CODE OF FEDERAL REGULATIONS
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The Code of Federal Regulations is a codification of the general and permanent rules published in the Federal Register by the Executive departments and agencies of the Federal Government. The Code is divided into 50 titles which represent broad areas subject to Federal regulation. Each title is divided into chapters which usually bear the name of the issuing agency. Each chapter is further subdivided into parts covering specific regulatory areas.
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Title 21—
For this volume, Jonn V. Lilyea was Chief Editor. The Code of Federal Regulations publication program is under the direction of Michael L. White, assisted by Ann Worley.
(This book contains parts 500 to 599)
Nomenclature changes to chapter I appear at 69 FR 13717, Mar. 24, 2004, and 69 FR 18803, Apr. 9, 2004.
21 U.S.C. 321, 331, 342, 343, 348, 351, 352, 353, 360b, 371.
The provisions of part 113 of this chapter shall apply to the manufacture, processing or packing of low-acid foods in hermetically sealed containers, and intended for use as food for animals.
The provisions of part 108 of this chapter shall apply to the issuance of emergency control permits for the manufacturer or packer of thermally processed low-acid foods packaged in hermetically sealed containers, and intended for use as food for animals.
(a) The Commissioner of Food and Drugs has determined that, in order to assure that anthelmintic drugs, including animal feeds bearing or containing such drugs, which do not carry the prescription statement are labeled to provide adequate directions for their effective use, labeling of these anthelmintic drugs shall bear, in addition to other required information, a statement that a veterinarian should be consulted for assistance in the diagnosis, treatment, and control of parasitism.
(b) The label and any labeling furnishing or purporting to furnish directions for use, shall bear conspicuously the following statement: “Consult your veterinarian for assistance in the diagnosis, treatment, and control of parasitism.”
(c) For drugs covered by approved new animal drug applications, the labeling revisions required for compliance with this section may be placed into effect without prior approval, as provided for in § 514.8(c)(3) of this chapter. For drugs listed in the index, the labeling revisions required for compliance with this section may be placed into effect without prior granting of a request for a modification, as provided for in § 516.161(b)(1) of this chapter.
(d) Labeling revisions required for compliance with this section shall be placed into effect by February 25, 1975, following which, any such drugs that are introduced into interstate commerce and not in compliance with this section will be subject to regulatory proceedings.
(a) Drugs are being offered in dosage forms that are designed to release the active ingredients over a prolonged period of time. There is a possibility of unsafe overdosage or ineffective dosage if such products are improperly made and the active ingredients are released at one time, over too short or too long a period of time, or not released at all. Drugs marketed in this form, which are referred to by such terms as timed-release, controlled-release, prolonged-release, sustained-release, or delayed-release drugs, are regarded as new animal drugs within the meaning of section 201(v) of the Federal Food, Drug, and Cosmetic Act.
(b) Timed-release dosage form animal drugs that are introduced into interstate commerce are deemed to be adulterated within the meaning of section 501(a)(5) of the act and subject to regulatory action, unless such animal drug is the subject of an approved new animal drug application, or listed in the index, as required by paragraph (a) of this section.
(c) The fact that the labeling of this kind of drug may claim delayed, prolonged, controlled, or sustained-release of all or only some of the active ingredients does not affect the new animal drug status of such articles. A new animal drug application or index listing is required in any such case.
(d) New animal drug applications for timed-release dosage form animal drugs must contain, among other things, data to demonstrate safety and effectiveness by establishing that the article is manufactured using procedures and controls to ensure release of the total dosage at a safe and effective rate. Data submitted in the new animal drug application must demonstrate that the formulation of the drug and the procedures used in its manufacture will ensure release of the active ingredient(s) of the drug at a safe and effective rate and that these release characteristics will be maintained until the expiration date of the drug. When the drug is intended for use in food-producing animals, data submitted must also demonstrate that, with respect to possible residues of the drug, food derived from treated animals is safe for consumption.
(a) New information requires a re- evaluation of the status of drugs containing methylene blue (tetramethylthionine chloride) for oral use in cats or dogs.
(1)(i) It has been demonstrated that two orally administered urinary antiseptic-antispasmodic preparations that contained methylene blue cause Heinz body hemolytic anemia in cats when used according to label directions. The specific cause of the reaction was determined to be the methylene blue contained in the preparations. The reaction can be severe enough to cause death of treated animals.
(ii) The Heinz body hemolytic anemia reaction to methylene blue has also been demonstrated in dogs under laboratory conditions. The precise mechanism by which methylene blue produces the characteristic erythrocytic inclusion bodies (Heinz bodies) and associated hemolytic anemia is unclear.
(2) The effectiveness of orally administered methylene blue as a urinary antiseptic is open to question. It appears that following oral administration,
(3) In view of the foregoing, the Commissioner has concluded that animal drugs containing methylene blue for oral use in cats or dogs are neither safe nor generally recognized as effective within the meaning of section 201(v) of the act and are therefore considered new animal drugs. Accordingly, all prior formal and informal opinions expressed by the Food and Drug Administration that such drugs are “not new drugs” or “no longer new drugs” are hereby revoked.
(b) Animal drugs that contain methylene blue for oral use in cats or dogs and not the subject of an approved new animal drug application (NADA) are deemed to be adulterated under the provisions of section 501(a) (5) and/or (6) and/or misbranded under section 502(a) of the act and subject to regulatory action as of April 10, 1978.
(c) Sponsors of animal drugs that contain methylene blue for oral use in cats or dogs and not the subject of an approved new animal drug application (NADA) may submit an application in conformity with § 514.1 of this chapter. Such applications will be processed in accordance with section 512 of the act. Submission of an NADA will not constitute grounds for continued marketing of this drug substance until such application is approved.
(d) New animal drug applications required by this regulation pursuant to section 512 of the act shall be submitted to the Food and Drug Administration. Center for Veterinary Medicine, Office of New Animal Drug Evaluation (HFV-100), 7500 Standish Pl., Rockville, MD 20855.
The Food and Drug Administration has determined that gentian violet is not generally recognized as safe for use in animal feed and is a food additive subject to section 409 of the Federal Food, Drug, and Cosmetic Act (the act), unless it is intended for use as a new animal drug, in which case it is subject to section 512 of the act. The Food and Drug Administration has determined that gentian violet is not prior sanctioned for any use in animal feed.
The Food and Drug Administration (FDA) has determined that gentian violet is not generally recognized as safe and effective for any veterinary drug use in food animals and is a new animal drug subject to section 512 of the Federal Food, Drug, and Cosmetic Act. FDA has determined that gentian violet is not exempted from new animal drug status under the “grandfather” provisions of the Drug Amendments of 1962 (21 U.S.C. 342).
(a) Investigations by the Food and Drug Administration, the Centers for Disease Control of the U.S. Public Health Service, the Animal Health Division of the Agricultural Research Service, U.S. Department of Agriculture, and by various State public health agencies have revealed that processed fish meal, poultry meal, meat meal, tankage, and other animal byproducts intended for use in animal feed may be contaminated with Salmonella bacteria, an organism pathogenic to man and animals. Contamination of these products may occur through inadequate heat treatment of the product during its processing or through recontamination of the heat-treated product during a time of improper storage or handling subsequent to processing.
(b) Articles used in food for animals are included within the definition of
(a) Polychlorinated biphenyls (PCB's) represent a class of toxic industrial chemicals manufactured and sold under a variety of trade names, including: Aroclor (United States); Phenoclor (France); Colphen (Germany); and Kanaclor (Japan). PCB's are highly stable, heat resistant, and nonflammable chemicals. Industrial uses of PCB's include, or did include in the past, their use as electrical transformer and capacitor fluids, heat transfer fluids, hydraulic fluids, plasticizers, and in formulations of lubricants, coatings, and inks. Their unique physical and chemical properties and widespread, uncontrolled industrial applications have caused PCB's to be a persistent and ubiquitous contaminant in the environment, causing the contamination of certain foods. In addition, incidents have occurred in which PCB's have directly contaminated animal feeds as a result of industrial accidents (leakage or spillage of PCB fluids from plant equipment). These accidents in turn cause the contamination of food intended for human consumption (meat, milk, and eggs). Investigations by the Food and Drug Administration have revealed that heat exchange fluids for certain pasteurization equipment used in processing animal feed contain PCB's. Although heat exchange fluids in such equipment are considered to be in
(b) The following special provisions are necessary to preclude accidental PCB contamination of animal feed:
(1) Coatings or paints for use on the contact surfaces of feed storage areas may not contain PCB's or any other harmful or deleterious substances likely to contaminate feed.
(2) New equipment or machinery for handling or processing feed in or around an establishment producing animal feed shall not contain PCB's.
(3) On or before Sept. 4, 1973, the management of establishments producing animal feed shall:
(i) Have the heat exchange fluid used in existing equipment or machinery for handling and processing feed sampled and tested to determine whether it contains PCB's, or verify the absence of PCB's in such formulations by other appropriate means. On or before Sept. 4, 1973, any such fluid formulated with PCB's must to the fullest extent possible commensurate with current good manufacturing practices, be replaced with a heat exchange fluid that does not contain PCB's.
(ii) Eliminate to the fullest extent possible commensurate with current good manufacturing practices from the animal feed producing establishment any PCB-containing lubricants for equipment or machinery used for handling or processing animal feed.
(iii) Eliminate to the fullest extent possible commensurate with current good manufacturing practices from the animal feed producing establishment any other PCB-containing materials, whenever there is a reasonable expectation that such materials could cause animal feed to become contaminated with PCB's either as a result of normal use or as a result of accident, breakage, or other mishap.
(iv) The toxicity and other characteristics of fluids selected as PCB replacements must be adequately determined so that the least potentially hazardous replacement should be used. In making this determination with respect to a given fluid, consideration should be given to (
(c) For the purpose of this section, the provisions do not apply to electrical transformers and condensers containing PCB's in sealed containers.
(d) For the purpose of this section, the term
(a) The Commissioner of Food and Drugs has determined that there are no adequate data to establish that animal drugs containing hexachlorophene are safe and effective for any animal use other than in topical products for use on non-food-producing animals as part of a product preservative system at a level not to exceed 0.1 percent; that there is no information on the potential risk to humans from exposure to hexachlorophene by persons who apply animal products containing the drug at levels higher than 0.1 percent; and that there is likewise no information on human exposure to animals on which these animal drugs have been used and no information on possible residues of hexachlorophene in edible products of food-producing animals treated with new animal drugs that contain any quantity of hexachlorophene.
(b) Animal drugs containing hexachlorophene for other than preservative use on non-food-producing animals at levels not exceeding 0.1 percent are considered new animal drugs and shall be the subject of new animal drug applications (NADA's).
(c) Any person currently marketing animal drugs that contain hexachlorophene other than as part of a product preservative system for products used on non-food-producing animals at a level not exceeding 0.1 percent shall submit a new animal drug application, supplement an existing application, or reformulate the product by September 29, 1977. Each application or supplemental application shall include adequate data to establish that the animal drug is safe and effective. If the animal drug is currently subject to an approved new animal drug application, each reformulation shall require an approved supplemental application. The interim marketing of these animal drugs may continue until the application has been approved, until it has been determined that the application is not approvable under the provisions of § 514.111 of this chapter, or until an existing approved application has been withdrawn.
(d) After September 29, 1977, animal drugs that contain hexachlorophene other than for preservative use on non-food-producing animals at a level not exceeding 0.1 percent that are introduced into interstate commerce shall be deemed to be adulterated within the meaning of section 501(a)(5) of the act (21 U.S.C. 351(a)(5)) unless such animal drug is the subject of a new animal drug application submitted pursuant to paragraph (c) of this section. Action to withdraw approval of new animal drug applications will be initiated if supplemental new animal drug applications have not been submitted in accordance with this section.
(e) New animal drug applications submitted for animal drugs containing hexachlorophene for use in or on food-
The Food and Drug Administration has determined that propylene glycol in or on cat food is not generally recognized as safe and is a food additive subject to section 409 of the Federal Food, Drug, and Cosmetic Act (the act). The Food and Drug Administration also has determined that this use of propylene glycol is not prior sanctioned.
(a) Among the representations on the label or labeling of an animal drug which will render the drug misbranded are any broad statements suggesting or implying that the drug is not safe and effective for use when used in accordance with labeling direction, or suggesting or implying that the labeling does not contain adequate warnings or adequate directions for use. Such statements include, but are not limited to:
(1) Any statement that disclaims liability when the drug is used in accordance with directions for use contained on the label or labeling.
(2) Any statement that disclaims liability when the drug is used under “abnormal” or “unforeseeable” conditions.
(3) Any statement limiting the warranty for the products to a warranty that the drug in the package contains the ingredients listed on the label.
(b) This regulation is not intended to prohibit any liability disclaimer that purports to limit the amount of damages or that sets forth the legal theory under which damages are to be recovered.
(c) Any person wishing to obtain an evaluation of an animal drug liability disclaimer under this regulation may submit it to Division of Compliance, (HFV-230), Center for Veterinary Medicine, Food and Drug Administration, 7500 Standish Pl., Rockville, MD 20855. A supplemental NADA providing appropriately revised labeling shall be submitted for any approved new animal drug the labeling of which is not in compliance with this regulation.
(a) The use of terms such as
(b) The unqualified use of the term
(c) An article so qualified as to be represented as a drug must be the subject of an approved new animal drug application unless the use of the article under the conditions set forth in its labeling is generally recognized as safe and effective among experts qualified by scientific training and experience to evaluate the safety and effectiveness of animal drugs.
(a) Section 201.105(c) of this chapter provides that in the case of certain drugs for which directions, hazards, warnings, and use information are commonly known to practitioners licensed by law, such information may be omitted from the dispensing package. Under this proviso, the Commissioner of Food and Drugs will offer an opinion, upon written request, stating reasonable grounds therefore on a proposal to omit such information from the dispensing package.
(b) The Commissioner of Food and Drugs has considered submitted material covering a number of drug products and has offered the opinion that the following drugs when intended for those veterinary uses for which they are now generally employed by the veterinary medical profession, should be exempt from the requirements of § 201.105(c) of this chapter, provided that they meet the conditions prescribed in this paragraph. Preparations that are not in dosage unit form (for example, solutions) will be regarded as meeting the conditions with respect to the maximum quantity of drug per dosage unit if they are prepared in a manner that enables accurate and ready administration of a quantity of drug not in excess of the stated maximum per dosage unit:
(a) Anaphylactoid reactions in cattle, horses, sheep, and swine occur occasionally from the injection of antibiotics, bacterins, and vaccines. Adequate directions for use of these antibiotics, bacterins, and vaccines can generally be written for use by the laity and thus are available to livestock producers. Epinephrine injection is effective for the treatment of anaphylactoid reactions in animals and would be of value in saving lives of animals if it were readily available at the time of administration of the causative agents. In connection with this problem the Food and Drug Administration has obtained the views of the Advisory Committee on Veterinary Medicine, and other experts, and has concluded that adequate directions for over-the-counter sale of epinephrine injection 1:1,000 can be prepared.
(b) In view of the above, the Commissioner of Food and Drugs has concluded that it is in the public interest to make epinephrine injection 1:1,000 available for sale without a prescription provided that it is packaged in vials not exceeding 10 milliliters and its label bears, in addition to other required information, the following statements in a prominent and conspicuous manner: “For emergency use only in treating
(c) The labeling must also bear a description of the symptoms of anaphylactoid shock including glassy eyes, increased salivation, grinding of the teeth, rapid breathing, muscular tremors, staggering gait, and collapse with death following. These symptoms may appear shortly after injection of a bacterin, vaccine, or antibiotic.
(a) The Federal Food, Drug, and Cosmetic Act requires that sponsored compounds intended for use in food-producing animals be shown to be safe and that food produced from animals exposed to these compounds be shown to be safe for consumption by people. The statute prohibits the use in food-producing animals of any compound found to induce cancer when ingested by people or animals unless it can be determined by methods of examination prescribed or approved by the Secretary (a function delegated to the Commissioner of Food and Drugs) that no residue of that compound will be found in the food produced from those animals under conditions of use reasonably certain to be followed in practice. This subpart identifies the steps a sponsor of a compound shall follow to secure the approval of the compound. FDA guidance documents contain the procedures and protocols FDA recommends for the implementation of this subpart. These guidance documents are available from the Division of Dockets Management (HFA-305), Food and Drug Administration, 5630 Fishers Lane, rm. 1061, Rockville, MD 20852. Requests for these guidance documents should be identified with Docket No. 1983D-0288.
(b) If FDA concludes on the basis of the threshold assessment that a sponsor shall conduct carcinogenicity testing on the sponsored compound, FDA will also determine whether and to what extent the sponsor shall conduct carcinogenicity testing on metabolites of the sponsored compound. The bioassays that a sponsor conducts must be designed to assess carcinogenicity and to determine the quantitative aspects of any carcinogenic response.
(c) If FDA concludes on the basis of the threshold assessment or at a later time during the approval process that the data show that the sponsored compound and its metabolites should not be subject to this subpart, FDA will continue to consider the compound for approval under the general safety provisions of the act for risks other than cancer.
(d) This subpart does not apply to essential nutrients.
(a) The definitions and interpretations contained in section 201 of the act apply to those terms when used in this subpart.
(b) The following definitions apply to this subpart:
(a) On the basis of the results of the chronic bioassays and other information, FDA will determine whether any of the substances tested are carcinogenic.
(b) If FDA concludes that the results of the bioassays do not establish carcinogenicity, then FDA will not subject the sponsored compound to the remainder of the requirements of this subpart.
(c) For each sponsored compound that FDA decides should be regulated as a carcinogen, FDA will analyze the data from the bioassays using a statistical extrapolation procedure.
(1) For each substance tested in separate bioassays, FDA will calculate the concentration of the residue of carcinogenic concern that corresponds to a maximum lifetime risk to the test animal of 1 in 1 million. FDA will designate the lowest value obtained as S
(2) From the appropriate residue chemistry data FDA will calculate the R
(3) FDA will conclude that the provisions of this subpart are satisfied when no residue of the compound is detectable (that is, the marker residue is below the LOD) using the approved regulatory method under the conditions of use of the sponsored compound, including any required preslaughter withdrawal period or milk discard time.
(a) For each edible tissue, the sponsor shall measure the depletion of the residue of carcinogenic concern until its concentration is at or below S
(b) In one or more edible tissues, the sponsor shall also measure the depletion of one or more potential marker residues until the concentration of the residue of carcinogenic concern is at or below S
(c) From these data, FDA will select a target tissue and a marker residue and designate the concentration of marker residue (R
(d) When a compound is to be used in milk- or egg-producing animals, milk or eggs must be the target tissue in addition to the tissue selected to monitor for residues in the edible carcass.
(a) The sponsor shall submit for evaluation and validation a regulatory method developed to monitor compliance with FDA's operational definition of no residue.
(b) The regulatory method must be able to confirm the identity of the marker residue in the target tissue at a minimum concentration corresponding to the R
(c) FDA will publish in the
In response to a petition or on the Commissioner's own initiative, the Commissioner may waive, in whole or in part, the requirements of this subpart except those provided under § 500.88. A petition for this waiver may be filed by any person who would be adversely affected by the application of the requirements to a particular compound. The petition shall explain and document why the requirements from which a waiver is requested are not reasonably applicable to the compound, and set forth clearly the reasons why the alternative procedures will provide the basis for concluding that approval of the compound satisfies the requirements of the anticancer provisions of the act. If the Commissioner determines that waiver of any of the requirements of this subpart is appropriate, the Commissioner will state the basis for that determination in the regulation approving marketing of the sponsored compound.
(a) This subpart E applies to all new animal drug applications, food additive petitions, and color additive petitions concerning any compound intended for use in food-producing animals (including supplemental applications and amendments to petitions).
(b) This subpart E also applies in the following manner to compounds already approved:
(1) For those compounds that FDA determines may induce cancer when ingested by man or animals, i.e., suspect
(2) For those compounds that FDA determines have been shown to induce cancer when ingested by man or animals, §§ 500.82 through 500.90 apply.
15 U.S.C. 1453, 1454, 1455; 21 U.S.C. 321, 331, 342, 343, 348, 371.
The term
(a) In the case of a rectangular package where one entire side properly can be considered to be the principal display panel side, the product of the height times the width of that side;
(b) In the case of a cylindrical or nearly cylindrical container, 40 percent of the product of the height of the container times the circumference;
(c) In the case of any otherwise shaped container, 40 percent of the total surface of the container:
(a) The term
(1) If the part of the label immediately contiguous and to the right of the principal display panel is too small to accommodate the necessary information or is otherwise unusable label space, e.g., folded flaps or can ends, the panel immediately contiguous and to the right of this part of the label may be used.
(2) If the package has one or more alternate principal display panels, the information panel is immediately contiguous and to the right of any principal display panel.
(3) If the top of the container is the principal display panel and the package has no alternate principal display panel, the information panel is any panel adjacent to the principal display panel.
(b) All information required to appear on the label of any package of food pursuant to §§ 501.4, 501.5, 501.8 and 501.17 shall appear either on the principal display panel or on the information panel, unless otherwise specified by regulations in this chapter.
(c) All information appearing on the principal display panel or the information panel pursuant to this section shall appear prominently and conspicuously, but in no case may the letters and/or numbers be less than
(1) Packaged foods are exempt from the type size requirements of this paragraph:
(i) The package is designed such that it has a surface area that can bear an information panel and/or an alternate principal display panel.
(ii) The area of surface available for labeling on the principal display panel of the package as this term is defined in § 501.1 is less than 10 square inches.
(iii) The label information includes a full list of ingredients in accordance with regulations in this part.
(iv) The information required by paragraph (b) of this section appears on the principal display panel or information panel label in accordance with the provisions of this paragraph (c) except that the type size is not less than
(2) Packaged foods are exempt from the type size requirements of this paragraph:
(i) The package is designed such that it has a single
(ii) The area of surface available for labeling on the principal display panel of the package as this term is defined in § 501.1 is less than 12 square inches and bears all labeling appearing on the package.
(iii) The label information includes a full list of ingredients in accordance with regulations in this part.
(iv) The information required by paragraph (b) of this section appears on the single, obvious principal display panel in accordance with the provisions of this paragraph (c) except that the type size is not less than
(3) Packaged foods are exempt from the type size requirements of this paragraph:
(i) The package is designed such that it has a total surface area available to bear labeling of less than 12 square inches.
(ii) The label information includes a full list of ingredients in accordance with regulations in this part.
(iii) The information required by paragraph (b) of this section appears on the principal display panel or information panel label in accordance with the provisions of this paragraph (c) except that the type size is not less than
(d) All information required to appear on the principal display panel or on the information panel pursuant to this section shall appear on the same panel unless there is insufficient space. In determining the sufficiency of the available space, any vignettes, design,
(e) All information appearing on the information panel pursuant to this section shall appear in one place without other intervening material.
(f) If the label of any package of food is too small to accommodate all of the information required by §§ 501.4, 501.5, 501.8, and 501.17, the Commissioner may establish by regulation an acceptable alternative method of disseminating such information to the public, e.g., a type size smaller than one-sixteenth inch in height, or labeling attached to or inserted in the package or available at the point of purchase. A petition requesting such a regulation, as an amendment to this paragraph shall be submitted pursuant to part 10 of this chapter.
(a) The principal display panel of a food in package form shall bear as one of its principal features a statement of the identity of the commodity.
(b) Such statement of identity shall be in terms of:
(1) The name now or hereafter specified in or required by any applicable Federal law or regulation; or, in the absence thereof,
(2) The common or usual name of the food; or, in the absence thereof,
(3) An appropriately descriptive term, or when the nature of the food is obvious, a fanciful name commonly used by the public for such food.
(c) Where a food is marketed in various optional forms (whole, slices, diced, etc.), the particular form shall be considered to be a necessary part of the statement of identity and shall be declared in letters of a type size bearing a reasonable relation to the size of the letters forming the other components of the statement of identity; except that if the optional form is visible through the container or is depicted by an appropriate vignette, the particular form need not be included in the statement. This specification does not affect the required declarations of identity under definitions and standards for foods promulgated pursuant to section 401 of the act.
(d) This statement of identity shall be presented in bold type on the principal display panel, shall be in a size reasonably related to the most prominent printed matter on such panel, and shall be in lines generally parallel to the base on which the package rests as it is designed to be displayed.
(e) Under the provisions of section 403(c) of the Federal Food, Drug, and Cosmetic Act, a food shall be deemed to be misbranded if it is an imitation of another food unless its label bears, in type of uniform size and prominence, the word
(1) A food shall be deemed to be an imitation and thus subject to the requirements of section 403(c) of the act if it is a substitute for and resembles another food but is nutritionally inferior to that food.
(2) A food that is a substitute for and resembles another food shall not be deemed to be an imitation provided it meets each of the following requirements:
(i) It is not nutritionally inferior to the food for which it substitutes and which it resembles.
(ii) Its label bears a common or usual name that complies with the provisions of § 502.5 of this chapter and that is not false or misleading, or in the absence of an existing common or usual name, an appropriately descriptive term that is not false or misleading. The label may, in addition, bear a fanciful name which is not false or misleading.
(3) A food for which a common or usual name is established by regulation (e.g., in a standard of identity pursuant to section 401 of the act, in a common or usual name regulation and may, in
(4) Nutritional inferiority includes:
(i) Any reduction in the content of an essential nutrient that is present in a measurable amount.
(ii) If the Commissioner concludes that a food is a substitute for and resembles another food but is inferior to the food imitated for reasons other than those set forth in this paragraph, he may propose appropriate revisions to this regulation or he may propose a separate regulation governing the particular food.
(f) A label may be required to bear the percentage(s) of a characterizing ingredient(s) or information concerning the presence or absence of an ingredient(s) or the need to add an ingredient(s) as part of the common or usual name of the food pursuant to part 502 of this chapter.
(a) Ingredients required to be declared on the label of a food, including foods that comply with standards of identity that require labeling in compliance with this part 501, except those exempted by § 501.100, shall be listed by common or usual name in descending order of predominance by weight on either the principal display panel or the information panel in accordance with the provisions of § 501.2.
(b) The name of an ingredient shall be a specific name and not a collective (generic) name, except that:
(1) Spices, flavorings, colorings and chemical preservatives shall be declared according to the provisions of § 501.22.
(2) An ingredient which itself contains two or more ingredients and which has an established common or usual name, conforms to a standard established pursuant to the Meat Inspection or Poultry Products Inspection Acts by the U.S. Department of Agriculture, or conforms to a definition and standard of identity established pursuant to section 401 of the Federal Food, Drug, and Cosmetic Act, shall be designated in the statement of ingredients on the label of such food by either of the following alternatives:
(i) By declaring the established common or usual name of the ingredient followed by a parenthetical listing of all ingredients contained therein in descending order of predominance except that, if the ingredient is a food subject to a definition and standard of identity established in this subchapter E, only the ingredients required to be declared by the definition and standard of identity need be listed; or
(ii) By incorporating into the statement of ingredients in descending order of predominance in the finished food, the common or usual name of every component of the ingredient without listing the ingredient itself.
(3) Skim milk, concentrated skim milk, reconstituted skim milk, and nonfat dry milk may be declared as
(4) Milk, concentrated milk, reconstituted milk, and dry whole milk may be declared as
(5) Bacterial cultures may be declared by the word
(6) Sweetcream buttermilk, concentrated sweetcream buttermilk, reconstituted sweetcream buttermilk, and dried sweetcream buttermilk may be declared as
(7) Whey, concentrated whey, reconstituted whey, and dried whey may be declared as
(8) Cream, reconstituted cream, dried cream, and plastic cream (sometimes known as concentrated milkfat) may be declared as
(9) Butteroil and anhydrous butterfat may be declared as
(10) Dried whole eggs, frozen whole eggs, and liquid whole eggs may be declared as
(11) Dried egg whites, frozen egg whites, and liquid egg whites may be declared as
(12) Dried egg yolks, frozen egg yolks, and liquid egg yolks may be declared as
(13) A livestock or poultry feed may be declared by a collective name listed in § 501.110 if it is an animal feed within the meaning of section 201(w) of the act and meets the requirements for the use of a collective name as prescribed in § 501.110 for certain feed ingredients.
(14) [Reserved]
(15) When all the ingredients of a wheat flour are declared in an ingredient statement, the principal ingredient of the flour shall be declared by the name(s) specified in §§ 137.105, 137.200, 137.220, 137.225 of this chapter, i.e., the first ingredient designated in the ingredient list of flour, or bromated flour, or enriched flour, or self-rising flour is
(c) When water is added to reconstitute, completely or partially, an ingredient permitted by paragraph (b) of this section to be declared by a class name, the position of the ingredient class name in the ingredient statement shall be determined by the weight of the unreconstituted ingredient plus the weight of the quantity of water added to reconstitute that ingredient, up to the amount of water needed to reconstitute the ingredient to single strength. Any water added in excess of the amount of water needed to reconstitute the ingredient to single strength shall be declared as
(a) The label of a food in packaged form shall specify conspicuously the name and place of business of the manufacturer, packer, or distributor.
(b) The requirement for declaration of the name of the manufacturer, packer, or distributor shall be deemed to be satisfied, in the case of a corporation, only by the actual corporate name, which may be preceded or followed by the name of the particular division of the corporation. In the case of an individual, partnership, or association, the name under which the business is conducted shall be used.
(c) Where the food is not manufactured by the person whose name appears on the label, the name shall be qualified by a phrase that reveals the connection such person has with such food; such as “Manufactured for ______,” “Distributed by ______,” or any other wording that expresses the facts.
(d) The statement of the place of business shall include the street address, city, state, and ZIP Code; however, the street address may be omitted if it is shown in a current city directory or telephone directory. The requirement for inclusion of the ZIP Code shall apply only to consumer commodity labels developed or revised after the effective date of this section. In the case of nonconsumer packages, the ZIP Code shall appear either on the label or the labeling (including invoice).
(e) If a person manufactures, packs, or distributes a food at a place other than his principal place of business, the label may state the principal place of business in lieu of the actual place where such food was manufactured or packed or is to be distributed, unless such statement would be misleading.
(a) The label of any package of a food which bears a representation as to the number of servings contained in such package shall bear in immediate conjunction with such statement, and in the same size type as is used for such statement, a statement of the net quantity (in terms of weight, measure, or numerical count) of each such serving; however, such statement may be expressed in terms that differ from the terms used in the required statement of net quantity of contents (for example, cupfuls, tablespoonfuls, etc.) when such differing term is common to cookery and describes a constant quantity.
(b) If there exists a voluntary product standard promulgated pursuant to the procedures found in 15 CFR part 10 by the Department of Commerce, quantitatively defining the meaning of the term
(a) A word, statement, or other information required by or under authority of the act to appear on the label may lack that prominence and conspicuousness required by section 403(f) of the act by reason (among other reasons) of:
(1) The failure of such word, statement, or information to appear on the part or panel of the label which is presented or displayed under customary conditions of purchase;
(2) The failure of such word, statement, or information to appear on two or more parts or panels of the label, each of which has sufficient space therefor, and each of which is so designed as to render it likely to be, under customary conditions of purchase, the part or panel displayed;
(3) The failure of the label to extend over the area of the container or package available for such extension, so as to provide sufficient label space for the prominent placing of such word, statement, or information;
(4) Insufficiency of label space (for the prominent placing of such word, statement, or information) resulting from the use of label space for any word, statement, design, or device which is not required by or under authority of the act to appear on the label;
(5) Insufficiency of label space (for the prominent placing of such word, statement, or information) resulting from the use of label space to give materially greater conspicuousness to any other word, statement, or information, or to any design or device; or
(6) Smallness or style of type in which such word, statement, or information appears, insufficient background contrast, obscuring designs or vignettes, or crowding with other written, printed, or graphic matter.
(b) No exemption depending on insufficiency of label space, as prescribed in regulations promulgated under section 403(e) or (i) of the act, shall apply if such insufficiency is caused by:
(1) The use of label space for any word, statement, design, or device which is not required by or under authority of the act to appear on the label;
(2) The use of label space to give greater conspicuousness to any word, statement, or other information that is required by section 403(f) of the act; or
(3) The use of label space for any representation in a foreign language.
(c)(1) All words, statements, and other information required by or under authority of the act to appear on the label or labeling shall appear thereon in the English language:
(2) If the label contains any representation in a foreign language, all words, statements, and other information required by or under authority of the act to appear on the label shall appear thereon in the foreign language.
(3) If any article of labeling (other than a label) contains any representation in a foreign language, all words, statements, and other information required by or under authority of the act to appear on the label or labeling shall appear on such article of labeling.
(a)
(2) In the case of products intended for use by children, the phrase “except under adult supervision” may be added at the end of the last sentence in the warning required by paragraph (a)(1) of this section.
(3) In the case of products packaged in glass containers, the word “break” may be substituted for the word “puncture” in the warning required by paragraph (a)(1) of this section.
(4) The words “Avoid spraying in eyes” may be deleted from the warning required by paragraph (a)(1) of this section in the case of a product not expelled as a spray.
(b)
(2) The warning required by paragraph (b)(1) of this section is not required for the following products:
(i) Products expelled in the form of a foam or cream, which contain less than 10 percent propellant in the container.
(ii) Products in a container with a physical barrier that prevents escape of the propellant at the time of use.
(iii) Products of a net quantity of contents of less than 2 ozs that are designed to release a measured amount of product with each valve actuation.
(iv) Products of a net quantity of contents of less than
(c)
(a) Among representations in the labeling of a food which render such food misbranded is a false or misleading representation with respect to another food or a drug, device, or cosmetic.
(b) The labeling of a food which contains two or more ingredients may be misleading by reason (among other reasons) of the designation of such food in such labeling by a name which includes or suggests the name of one or more but not all such ingredients, even though the names of all such ingredients are stated elsewhere in the labeling.
(c) Among representations in the labeling of a food which render such food misbranded is any representation that expresses or implies a geographical origin of the food or any ingredient of the food except when such representation is either:
(1) A truthful representation of geographical origin.
(2) A trademark or trade name provided that as applied to the article in question its use is not deceptively misdescriptive. A trademark or trade name comprised in whole or in part of geographical words shall not be considered deceptively misdescriptive if it:
(i) Has been so long and exclusively used by a manufacturer or distributor that it is generally understood by the consumer to mean the product of a particular manufacturer or distributor; or
(ii) Is so arbitrary or fanciful that it is not generally understood by the consumer to suggest geographic origin.
(3) A part of the name required by applicable Federal law or regulation.
(4) A name whose market significance is generally understood by the consumer to connote a particular class, kind, type, or style of food rather than to indicate geographical origin.
(a)(1) The term
(2) The term
(3) The term
(4) The term
(5) The term
(b) A food which is subject to the requirements of section 403(k) of the act shall bear labeling, even though such food is not in package form.
(c) A statement of artificial flavoring, artificial coloring, or chemical preservative shall be placed on the food, or on its container or wrapper, or on any two or all of these, as may be necessary to render such statement likely to be read by the ordinary individual under customary conditions of purchase and use of such food.
(d) A food shall be exempt from compliance with the requirements of section 403(k) of the act if it is not in package form and the units thereof are so small that a statement of artificial flavoring, artificial coloring, or chemical preservative, as the case may be, cannot be placed on such units with such conspicuousness as to render it likely to be read by the ordinary individual under customary conditions of purchase and use.
(e) A food shall be exempt while held for sale from the requirements of section 403(k) of the act (requiring label statement of any artificial flavoring, artificial coloring, or chemical preservatives) if said food, having been received in bulk containers at a retail establishment, is displayed to the purchaser with either (1) the labeling of the bulk container plainly in view or (2) a counter card, sign, or other appropriate device bearing prominently and conspicuously the information required to be stated on the label pursuant to section 403(k) of the act.
(f) A fruit or vegetable shall be exempt from compliance with the requirements of section 403(k) of the act with respect to a chemical preservative applied to the fruit or vegetable as a pesticide chemical prior to harvest.
(g) A flavor shall be labeled in the following way when shipped to a food manufacturer or processor (but not a consumer) for use in the manufacture of a fabricated food, unless it is a flavor for which a standard of identity has been promulgated, in which case it shall be labeled as provided in the standard:
(1) If the flavor consists of one ingredient, it shall be declared by its common or usual name.
(2) If the flavor consists of two or more ingredients, the label either may declare each ingredient by its common or usual name or may state “All flavor ingredients contained in this product are approved for use in a regulation of the Food and Drug Administration.” Any flavor ingredient not contained in one of these regulations, and any nonflavor ingredient, shall be separately listed on the label.
(3) In cases where the flavor contains a solely natural flavor(s), the flavor shall be so labeled, e.g.,
(h) The label of a food to which flavor is added shall declare the flavor in the statement of ingredients in the following way:
(1) Spice, natural flavor, and artificial flavor may be declared as
(2) An incidental additive in a food, originating in a spice or flavor used in the manufacture of the food, need not be declared in the statement of ingredients if it meets the requirements of § 501.100(a)(3).
(3) Substances obtained by cutting, grinding, drying, pulping, or similar processing of tissues derived from fruit, vegetable, meat, fish, or poultry, e.g., powdered or granulated onions, garlic powder, and celery powder, are commonly understood by consumers to be food rather than flavor and shall be declared by their common or usual name.
(4) Any salt (sodium chloride) used as an ingredient in food shall be declared by its common or usual name
(5) Any monosodium glutamate used as an ingredient in food shall be declared by its common or usual name
(6) Any pyroligneous acid or other artificial smoke flavors used as an ingredient in a food may be declared as
(i) If the label, labeling, or advertising of a food makes any direct or indirect representations with respect to the primary recognizable flavor(s), by word,
(1) If the food contains no artificial flavor which simulates, resembles or reinforces the characterizing flavor, the name of the food on the principal display panel or panels of the label shall be accompanied by the common or usual name of the characterizing flavor in letters not less than one-half the height of the letters used in the name of the food, except that:
(i) If the food is one that is commonly expected to contain a characterizing food ingredient, and the food contains natural flavor derived from such ingredient and an amount of characterizing ingredient insufficient to independently characterize the food, or the food contains no such ingredient, the
(ii) If none of the natural flavor used in the food is derived from the product whose flavor is simulated, the food in which the flavor is used shall be labeled either with the flavor of the product from which the flavor is derived or as
(iii) If the food contains both a characterizing flavor from the product whose flavor is simulated and other natural flavor which simulates, resembles or reinforces the characterizing flavor, the food shall be labeled in accordance with the introductory text and paragraph (i)(1)(i) of this section and the name of the food shall be immediately followed by the words
(2) If the food contains any artificial flavor which simulates, resembles or reinforces the characterizing flavor, the name of the food on the principal display panel or panels of the label shall be accompanied by the common or usual name(s) of the characterizing flavor, in letters not less than one-half the height of the letters used in the name of the food and the name of the characterizing flavor shall be accompanied by the word(s)
(3) Wherever the name of the characterizing flavor appears on the label (other than in the statement of ingredients) so conspicuously as to be easily seen under customary conditions of purchase, the words prescribed by this paragraph shall immediately and conspicuously precede or follow such name, without any intervening written, printed, or graphic matter, except:
(i) Where the characterizing flavor and a trademark or brand are presented together, other written, printed, or graphic matter that is a part of or is associated with the trademark or brand may intervene if the required words are in such relationship with the trademark or brand as to be clearly related to the characterizing flavor; and
(ii) If the finished product contains more than one flavor subject to the requirements of this paragraph, the statements required by this paragraph need appear only once in each statement of characterizing flavors present in such food.
(iii) If the finished product contains three or more distinguishable characterizing flavors, or a blend of flavors with no primary recognizable flavor, the flavor may be declared by an appropriately descriptive generic term in lieu of naming each flavor.
(4) A flavor supplier shall certify, in writing, that any flavor he supplies which is designated as containing no artificial flavor does not, to the best of his knowledge and belief, contain any artificial flavor, and that he has added no artificial flavor to it. The requirement for such certification may be satisfied by a guarantee under section 303(c)(2) of the act which contains such a specific statement. A flavor used shall be required to make such a written certification only where he adds to or combines another flavor with a flavor which has been certified by a flavor supplier as containing no artificial flavor, but otherwise such user may rely upon the supplier's certification and need make no separate certification. All such certifications shall be retained by the certifying party throughout the period in which the flavor is supplied and for a minimum of 3 years thereafter, and shall be subject to the following conditions:
(i) The certifying party shall make such certifications available upon request at all reasonable hours to any duly authorized officer, or employee of the Food and Drug Administration or any other employee acting on behalf of the Secretary of Health and Human Services. Such certifications are regarded by the Food and Drug Administration as reports to the government and as guarantees or other undertakings within the meaning of section 301(h) of the act and subject the certifying party to the penalties for making any false report to the government under 18 U.S.C. 1001 and any false guarantee or undertaking under section
(ii) Wherever possible, the Food and Drug Administration shall verify the accuracy of a reasonable number of certifications made pursuant to this section, constituting a representative sample of such certifications, and shall not request all such certifications.
(iii) Where no person authorized to provide such information is reasonably available at the time of inspection, the certifying party shall arrange to have such person and the relevant materials and records ready for verification as soon as practicable; provided that, whenever the Food and Drug Administration has reason to believe that the supplier or user may utilize this period to alter inventories or records, such additional time shall not be permitted. Where such additional time is provided, the Food and Drug Administration may require the certifying party to certify that relevant inventories have not been materially disturbed and relevant records have not been altered or concealed during such period.
(iv) The certifying party shall provide, to an officer or representative duly designated by the Secretary, such qualitative statement of the composition of the flavor or product covered by the certification as may be reasonably expected to enable the Secretary's representatives to determine which relevant raw and finished materials and flavor ingredient records are reasonably necessary to verify the certifications. The examination conducted by the Secretary's representative shall be limited to inspection and review of inventories and ingredient records for those certifications which are to be verified.
(v) Review of flavor ingredient records shall be limited to the qualitative formula and shall not include the quantitative formula. The person verifying the certifications may make only such notes as are necessary to enable him to verify such certification. Only such notes or such flavor ingredient records as are necessary to verify such certification or to show a potential or actual violation may be removed or transmitted from the certifying party's place of business:
(j) A food to which a chemical preservative(s) is added shall, except when exempt pursuant to § 501.100, bear a label declaration stating both the common or usual name of the ingredient(s) and a separate description of its function, e.g.,
(a) The following foods are exempt from compliance with the requirements of section 403(i)(2) of the act (requiring a declaration on the label of the common or usual name of each ingredient when the food is fabricated from two or more ingredients).
(1) An assortment of different items of food, when variations in the items that make up different packages packed from such assortment normally occur in good packing practice and when such variations result in variations in the ingredients in different packages, with respect to any ingredient that is not common to all packages. Such exemption, however, shall be on the condition that the label shall bear, in conjunction with the names of such ingredients as are common to all packages, a statement (in terms that are as informative as practicable and that are not misleading) indicating by name other ingredients which may be present.
(2) A food having been received in bulk containers at a retail establishment, if displayed to the purchaser with either (i) the labeling of the bulk container plainly in view or (ii) a counter card, sign, or other appropriate device bearing prominently and conspicuously the information required to be stated on the label pursuant to section 403(i)(2) of the act.
(3) Incidental additives that are present in a food at insignificant levels and do not have any technical or functional effect in that food. For the purposes of this paragraph (a)(3), incidental additives are:
(i) Substances that have no technical or functional effect but are present in a food by reason of having been incorporated into the food as an ingredient of another food, in which the substance did have a functional or technical effect.
(ii) Processing aids, which are as follows:
(
(
(
(iii) Substances migrating to food from equipment or packaging or otherwise affecting food that are not food additives as defined in section 201(s) of the act; or if they are food additives as so defined, they are used in conformity with regulations established pursuant to section 409 of the act.
(b) A food repackaged in a retail establishment is exempt from the following provisions of the act if the conditions specified are met.
(1) Section 403(e)(1) of the act (requiring a statement on the label of the name and place of business of the manufacturer, packer, or distributor).
(2) Section 403(g)(2) of the act (requiring the label of a food which purports to be or is represented as one for which a definition and standard of identity has been prescribed to bear the name of the food specified in the definition and standard and, insofar as may be required by the regulation establishing the standard the common names of the optional ingredients present in the food), if the food is displayed to the purchaser with its interstate labeling clearly in view, or with a counter card, sign, or other appropriate device bearing prominently and conspicuously the information required by these provisions.
(3) Section 403(i)(1) of the act (requiring the label to bear the common or usual name of the food), if the food is displayed to the purchaser with its interstate labeling clearly in view, or with a counter card, sign, or other appropriate device bearing prominently and conspicuously the common or usual name of the food, or if the common or usual name of the food is clearly revealed by its appearance.
(c) [Reserved]
(d) Except as provided by paragraphs (e) and (f) of this section, a shipment or other delivery of a food which is, in accordance with the practice of the trade, to be processed, labeled, or repacked in substantial quantity at an establishment other than that where originally processed or packed, shall be exempt, during the time of introduction into and movement in interstate commerce and the time of holding in such establishment, from compliance with the labeling requirements of section 403 (c), (e), (g), (h), (i), (j) and (k) of the act if:
(1) The person who introduced such shipment or delivery into interstate commerce is the operator of the establishment where such food is to be processed, labeled, or repacked; or
(2) In case such person is not such operator, such shipment or delivery is made to such establishment under a written agreement, signed by and containing the post office addresses of such person and such operator, and containing such specifications for the processing, labeling, or repacking, as the case may be, of such food in such establishment as will ensure, if such specifications are followed, that such
(e) Conditions affecting expiration of exemptions.
(1) An exemption of a shipment or other delivery of a food under paragraph (d)(1) of this section shall, at the beginning of the act of removing such shipment or delivery, or any part thereof, from such establishment become void ab initio if the food comprising such shipment, delivery, or part is adulterated or misbranded within the meaning of the act when so removed.
(2) An exemption of a shipment or other delivery of a food under paragraph (d)(2) of this section shall become void ab initio with respect to the person who introduced such shipment or delivery into interstate commerce upon refusal by such person to make available for inspection a copy of the agreement, as required by paragraph (d)(2) of this section.
(3) An exemption of a shipment or other delivery of a food under paragraph (d)(2) of this section shall expire:
(i) At the beginning of the act of removing such shipment or delivery, or any part thereof, from such establishment if the food comprising such shipment, delivery, or part is adulterated or misbranded within the meaning of the act when so removed; or
(ii) Upon refusal by the operator of the establishment where such food is to be processed, labeled, or repacked, to make available for inspection a copy of the agreement as required by such paragraph.
(f) [Reserved]
(g) The label declaration of a harmless marker used to identify a particular manufacturer's product may result in unfair competition through revealing a trade secret. Exemption from the label declaration of such a marker is granted, therefore, provided that the following conditions are met:
(1) The person desiring to use the marker without label declaration of its presence has submitted to the Commissioner of Food and Drugs full information concerning the proposed usage and the reasons why he believes label declaration of the marker should be subject to this exemption; and
(2) The person requesting the exemption has received from the Commissioner of Food and Drugs a finding that the marker is harmless and that the exemption has been granted.
The Commissioner of Food and Drugs, either on his own initiative or on behalf of any interested person who has submitted a petition pursuant to part 10 of this chapter may issue a proposal to amend § 501.4 to specify the manner in which an ingredient(s) shall be declared, i.e., by specific or class name, or § 501.100 to exempt an ingredient(s) from the requirements for label declaration.
(a) The principal display panel of a food in package form shall bear a declaration of the net quantity of contents. This shall be expressed in the terms of weight, measure, numerical count, or a combination of numerical count and weight or measure. The statement shall be in terms of fluid measure if the food is liquid, or in terms of weight if the food is solid, semisolid, or viscous, or a mixture of solid and liquid; except that such statement may be in terms of dry measure if the food is a fresh fruit, fresh vegetable, or other dry commodity that is customarily sold by dry measure. If there is a firmly established general consumer usage and trade custom of declaring the contents of a liquid by weight, or a solid, semisolid, or viscous product by fluid measure, it may be used. Whenever the Commissioner determines that an existing practice of declaring net quantity of contents by
(b)(1) Statements of weight shall be in terms of avoirdupois pound and ounce.
(2) Statements of fluid measure shall be in terms of the U.S. gallon of 231 cubic inches and quart, pint, and fluid ounce subdivisions thereof, and shall:
(i) In the case of frozen food that is sold and consumed in a frozen state, express the volume at the frozen temperature.
(ii) In the case of refrigerated food that is sold in the refrigerated state, express the volume at 40 °F (4 °C).
(iii) In the case of other foods, express the volume at 68 °F (20 °C).
(3) Statements of dry measure shall be in terms of the U.S. bushel of 2,150.42 cubic inches and peck, dry quart, and dry pint subdivisions thereof.
(c) When the declaration of quantity of contents by numerical count does not give adequate information as to the quantity of food in the package, it shall be combined with such statement of weight, measure, or size of the individual units of the foods as will provide such information.
(d) The declaration may contain common or decimal fractions. A common fraction shall be in terms of halves, quarters, eighths, sixteenths, or thirty-seconds; except that if there exists a firmly established general consumer usage and trade custom of employing different common fractions in the net quantity declaration of a particular commodity, they may be employed. A common fraction shall be reduced to its lowest terms; a decimal fraction shall not be carried out to more than two places. A statement that includes small fractions of an ounce shall be deemed to permit smaller variations than one which does not include such fractions.
(e) The declaration shall be located on the principal display panel of the label, and with respect to packages bearing alternate principal panels it shall be duplicated on each principal display panel.
(f) The declaration shall appear as a distinct item on the principal display panel, shall be separated (by at least a space equal to the height of the lettering used in the declaration) from other printed label information appearing above or below the declaration and (by at least a space equal to twice the width of the letter “N” of the style of type used in the quantity of contents statement) from other printed label information appearing to the left or right of the declaration. It shall not include any term qualifying a unit of weight, measure, or count (such as
(g) The declaration shall accurately reveal the quantity of food in the package exclusive of wrappers and other material packed therewith; provided that in the case of foods packed in containers designed to deliver the food under pressure, the declaration shall state the net quantity of the contents that will be expelled when the instructions for use as shown on the container are followed. The propellant is included in the net quantity declaration.
(h) The declaration shall appear in conspicuous and easily legible boldface print or type in distinct contrast (by typography, layout, color, embossing, or molding) to other matter on the package; except that a declaration of net quantity blown, embossed, or molded on a glass or plastic surface is permissible when all label information is so formed on the surface. Requirements of conspicuousness and legibility shall include the specifications that:
(1) The ratio of height to width (of the letter) shall not exceed a differential of 3 units to 1 unit (no more than 3 times as high as it is wide).
(2) Letter heights pertain to upper case or capital letters. When upper and lower case or all lower case letters are used, it is the lower case letter “o” or its equivalent that shall meet the minimum standards.
(3) When fractions are used, each component numeral shall meet one-half the minimum height standards.
(i) The declaration shall be in letters and numerals in a type size established in relationship to the area of the principal display panel of the package and shall be uniform for all packages of substantially the same size by complying with the following type specifications:
(1) Not less than
(2) Not less than
(3) Not less than
(4) Not less than
(j) On packages containing less than 4 pounds or 1 gallon and labeled in terms of weight or fluid measure:
(1) The declaration shall be expressed both in ounces, with identification by weight or by liquid measure and, if applicable (1 pound or 1 pint or more) followed in parentheses by a declaration in pounds for weight units, with any remainder in terms of ounces or common or decimal fractions of the pound (see examples set forth in paragraphs (m) (1) and (2) of this section), or in the case of liquid measure, in the largest whole units (quarts, quarts and pints, or pints, as appropriate) with any remainder in terms of fluid ounces or common or decimal fractions of the pint or quart (see examples in paragraphs (m) (3) and (4) of this section).
(2) If the net quantity of contents declaration appears on a random package, that is a package which is one of a lot, shipment, or delivery of packages of the same consumer commodity with varying weights and with no fixed weight pattern, it may, when the net weight exceeds 1 pound, be expressed in terms of pounds and decimal fractions of the pound carried out to not more than two decimal places. When the net weight does not exceed 1 pound, the declaration on the random package may be in decimal fractions of the pound in lieu of ounces (see example in paragraph (m)(5) of this section).
(3) The declaration may appear in more than one line. The term
(k) On packages containing 4 pounds or 1 gallon or more and labeled in terms of weight or fluid measure, the declaration shall be expressed in pounds for weight units with any remainder in terms of ounces or common or decimal fraction of the pound, or in the case of fluid measure, it shall be expressed in the largest whole unit (gallons followed by common or decimal fraction of a gallon or by the next smaller whole unit or units (quarts, or quarts and pints)) with any remainder in terms of fluid ounces or common or decimal fractions of the pint or quart (see paragraph (m)(6) of this section).
(l) [Reserved]
(m)
(2) A declaration of
(3) A declaration of 1 quart liquid measure shall be expressed as
(4) A declaration of 1
(5) On a random package, declaration of
(6) A declaration of 2
(n) For quantities, the following abbreviations and none other may be employed (periods and plural forms are optional):
(o) Nothing in this section shall prohibit supplemental statements at locations other than the principal display panel(s) describing in nondeceptive terms the net quantity of contents; provided, that such supplemental statements of net quantity of contents shall not include any term qualifying a unit of weight, measure, or count that tends to exaggerate the amount of the food contained in the package; for example,
(p) A separate statement of the net quantity of contents in terms of the metric system is not regarded as a supplemental statement and an accurate statement of the net quantity of contents in terms of the metric system of weight or measure may also appear on the principal display panel or on other panels.
(q) The declaration of net quantity of contents shall express an accurate statement of the quantity of contents of the package. Reasonable variations caused by loss or gain of moisture during the course of good distribution practice or by unavoidable deviations in good manufacturing practice will be recognized. Variations from stated quantity of contents shall not be unreasonably large.
(r) [Reserved]
(s) On a multiunit retail package, a statement of the quantity of contents shall appear on the outside of the package and shall include the number of individual units, the quantity of each individual unit, and, in parentheses, the total quantity of contents of the multiunit package in terms of avoirdupois or fluid ounces, except that such declaration of total quantity need not be followed by an additional parenthetical declaration in terms of the largest whole units and subdivisions thereof, as required by paragraph (j)(1) of this section. A multiunit retail package may thus be properly labeled:
(t) Where the declaration of net quantity of contents is in terms of net weight and/or drained weight or volume and does not accurately reflect the actual quantity of the contents or the product falls below the applicable standard of fill of container because of equipment malfunction or otherwise unintentional product variation, and the label conforms in all other respects to the requirements of this chapter (except the requirement that food falling below the applicable standard of fill of container shall bear the general statement of substandard fill specified in
(1) The purchaser shall sign a statement at the time of sale stating that he is aware that the product is mislabeled to include acknowledgement of the nature and extent of the mislabeling, e.g., “Actual net weight may be as low as __% below labeled quantity” and that any subsequent distribution by him of said product except for his own institutional use is unlawful. This statement shall be kept on file at the principal place of business of the manufacturer or processor for 2 years subsequent to the date of shipment of the product and shall be available to the Food and Drug Administration upon request.
(2) The product shall be labeled on the outside of its shipping container with the statement(s):
(i) When the variation concerns net weight and/or drained weight of volume—“Product Mislabeled. Actual net weight (drained weight or volume where appropriate) may be as low as __% below labeled quantity. This Product Not for Retail Distribution,” the blank to be filled in with the maximum percentage variance between the labeled and actual weight or volume of contents of the individual packages in the shipping container, and
(ii) When the variation is in regard to a fill of container standard—“Product Mislabeled. Actual fill may be as low as __% below standard of fill. This Product Not for Retail Distribution.”
(3) The statements required by paragraphs (t)(2) (i) and (ii) of this section, which may be consolidated where appropriate, shall appear prominently and conspicuously as compared to other printed matter on the shipping container and in boldface print or type on a clear, contrasting background in order to render them likely to be read and understood by the purchaser under ordinary conditions of purchase.
(a) An animal feed shall be exempt from the requirements of section 403(i)(2) of the act with respect to its label bearing the common or usual names of the animal feed ingredients listed in paragraph (b) of this section under the following prescribed conditions:
(1) The animal feed is intended solely for livestock and poultry.
(2) The label of the animal feed bears the collective name(s) prescribed in paragraph (b) of this section in lieu of the corresponding common or usual names of the individual feed ingredients contained therein.
(3) The label of the animal feed otherwise conforms to the requirements of section 403(i)(2) of the act.
(4) The ingredients of any feed listed in paragraph (b) of this section neither contain nor are food additives as defined in section 201(s) of the act unless provided for by and in conformity with applicable regulations established pursuant to section 409 of the act.
(b) Each collective name referred to in this paragraph may be used for the purpose of labeling where one or more of the ingredients listed for that collective name are present. The animal feed ingredients listed under each of the collective names are the products defined by the Association of American Feed Control Officials. The collective names are as follows:
(1)
(2)
(3)
(4)
(5)
(6)
21 U.S.C. 321, 343, 371.
(a) The common or usual name of a food, which may be a coined term, shall accurately identify or describe, in as simple and direct terms as possible, the basic nature of the food or its characterizing properties or ingredients. The name shall be uniform among all identical or similar products and may not be confusingly similar to the name of any other food that is not reasonably encompassed within the same name. Each class or subclass of food shall be given its own common or usual name that states, in clear terms, what it is in a way that distinguishes it from different foods.
(b) The common or usual name of a food shall include the percentage(s) of any characterizing ingredient(s) or component(s) when the proportion of such ingredient(s) or component(s) in the food has a material bearing on price or consumer acceptance or when the labeling or the appearance of the food may otherwise create an erroneous impression that such ingredient(s) or component(s) is present in an amount greater than is actually the case. The following requirements shall apply unless modified by a specific regulation in this part.
(1) The percentage of a characterizing ingredient or component shall be declared on the basis of its quantity in the finished product (i.e., weight/weight in the case of solids, or volume/volume in the case of liquids).
(2) The percentage of a characterizing ingredient or component shall be declared by the words “containing (or contains) __ percent (or %) __” or “__ percent (or %) __” with the first blank filled in with the percentage expressed as a whole number not greater than the actual percentage of the ingredient or component named and the second blank filled in with the common or usual name of the ingredient or component. The word “containing” (or “contains”), when used, shall appear on a line immediately below the part of the common or usual name of the food required by paragraph (a) of this section. For each characterizing ingredient or component, the words “__ percent (or %) __”shall appear following or directly below the word “containing” (or “contains”), or directly below the part of the common or usual name of the food required by paragraph (a) of this section when the word “containing” (or “contains”) is not used, in easily legible boldface print or type in distinct contrast to other printed or graphic matter, and in a height not less than the larger of the following alternatives:
(i) Not less than one-sixteenth inch in height on packages having a principal display panel with an area of 5 square inches or less and not less than one-eighth inch in height if the area of the principal display panel is greater than 5 square inches; or
(ii) Not less than one-half the height of the largest type appearing in the part of the common or usual name of the food required by paragraph (a) of this section.
(c) The common or usual name of a food shall include a statement of the presence or absence of any characterizing ingredient(s) or component(s) and/or the need for the user to add any characterizing ingredient(s) or component(s) when the presence or absence of such ingredient(s) or component(s) in the food has a material bearing on price or consumer acceptance or when the labeling or the appearance of the food may otherwise create an erroneous impression that such ingredient(s) or component(s) is present when it is not, and consumers may otherwise be misled about the presence or absence of the ingredient(s) or component(s) in the food. The following requirements shall apply unless modified by a specific regulation in this part.
(1) The presence or absence of a characterizing ingredient or component shall be declared by the words “containing (or contains) ____” or “containing (or contains) _____” or “no _____” or “does not contain _____”, with the blank being filled in with the common or usual name of the ingredient or component.
(2) The need for the user of a food to add any characterizing ingredient(s) or component(s) shall be declared by an appropriate informative statement.
(3) The statement(s) required under paragraph (c) (1) and/or (2) of this section shall appear following or directly below the part of the common or usual name of the food required by paragraphs (a) and (b) of this section, in easily legible boldface print or type in distinct contrast to other printed or graphic matter, and in a height not less than the larger of the alternatives established under paragraph (b)(2) (i) and (ii) of this section.
(d) A common or usual name of a food may be established by common usage or by establishment of a regulation in this part, in a standard of identity, or in other regulations in this chapter.
(a) The Commissioner of Food and Drugs, either on his own initiative or on behalf of any interested person who has submitted a petition, may publish a proposal to issue, amend, or revoke, under this part, a regulation prescribing a common or usual name for a food, pursuant to part 10 of this chapter.
(b) If the principal display panel of a food for which a common or usual name regulation is established is too small to accommodate all mandatory requirements, the Commissioner may establish by regulation an acceptable alternative, e.g., a smaller type size. A petition requesting such a regulation, which would amend the applicable regulation, shall be submitted pursuant to part 10 of this chapter.
21 U.S.C. 336, 342, 346, 346a, 348, 371.
(a)
(b) The definitions of terms contained in section 201 of the act are applicable to such terms when used in this part unless modified in this section.
(c) A
(d) An
(e)
(a) When appropriate under the criteria of § 509.6, a tolerance for an added poisonous or deleterious substance, which may be a food additive, may be established by regulation in subpart B of this part under the provisions of section 406 of the act. A tolerance may prohibit any detectable amount of the substance in food.
(b) When appropriate under the criteria of § 509.6, and under section 402(a)(1) of the act, a regulatory limit for an added poisonous or deleterious substance, which may be a food additive, may be established by regulation in subpart C of this part under the provisions of sections 402(a)(1) and 701(a) of the act. A regulatory limit may prohibit any detectable amount of the substance in food. The regulatory limit established represents the level at which food is adulterated within the meaning of section 402(a)(1) of the act.
(c)(1) When appropriate under the criteria of § 509.6, an action level for an added poisonous or deleterious substance, which may be a food additive, may be established to define a level of contamination at which a food may be regarded as adulterated.
(2) Whenever an action level is established or changed, a notice shall be published in the
(d) A regulation may be established in subpart D of this part to identify a food containing a naturally occurring poisonous or deleterious substance which will be deemed to be adulterated under section 402(a)(1) of the act. These regulations do not constitute a complete list of such foods.
The Commissioner of Food and Drugs, either on his own initiative or on behalf of any interested person who has submitted a petition, may issue a proposal to establish, revoke, or amend a regulation under this part. Any such petition shall include an adequate factual basis to support the petition, shall be in the form set forth in § 10.30 of this chapter, and will be published in the
(a) Use of an added poisonous or deleterious substance, other than a pesticide chemical, that is also a food additive will be controlled by a regulation issued under section 409 of the act when possible. When such a use cannot be approved under the criteria of section 409 of the act, or when the added poisonous or deleterious substance is not a food additive, a tolerance, regulatory limit, or action level may be established pursuant to the criteria in paragraphs (b), (c), or (d) of this section. Residues resulting from the use of an added poisonous or deleterious substance that is also a pesticide chemical will ordinarily be controlled by a tolerance established in a regulation issued under sections 406, 408, or 409 of the act by the U.S. Environmental Protection Agency (EPA). When such a regulation has not been issued, an action level for an added poisonous or deleterious substance that is also a pesticide chemical may be established by the Food and Drug Administration. The Food and Drug Administration will request EPA to recommend such an action level pursuant to the criteria established in paragraph (d) of this section.
(b) A tolerance for an added poisonous or deleterious substance in any food may be established when the following criteria are met:
(1) The substance cannot be avoided by good manufacturing practice.
(2) The tolerance established is sufficient for the protection of the public health, taking into account the extent of which the presence of the substance cannot be avoided and the other ways in which the consumer may be affected by the same or related poisonous or deleterious substances.
(3) No technological or other changes are foreseeable in the near future that might affect the appropriateness of the tolerance established. Examples of changes that might affect the appropriateness of the tolerance include anticipated improvements in good manufacturing practice that would change the extent to which use of the substance is unavoidable and anticipated studies expected to provide significant new toxicological or use data.
(c) A regulatory limit for an added poisonous or deleterious substance in any food may be established when each of the following criteria is met:
(1) The substance cannot be avoided by current good manufacturing practices.
(2) There is no tolerance established for the substance in the particular food under sections 406, 408, or 409 of the act.
(3) There is insufficient information by which a tolerance may be established for the substance under section 406 of the act or technological changes appear reasonably possible that may affect the appropriateness of a tolerance. The regulatory limit established represents the level at which food is adulterated within the meaning of section 402(a)(1) of the act.
(d) An action level for an added poisonous or deleterious substance in any food may be established when the criteria in paragraph (b) of this section are met, except that technological or other changes that might affect the appropriateness of the tolerance are foreseeable in the near future. An action level for an added poisonous or deleterious substance in any food may be established at a level at which the Food and Drug Administration may regard the food as adulterated within the meaning of section 402(a)(1) of the act, without regard to the criteria in paragraph (b) of this section or in section 406 of the act. An action level will be withdrawn when a tolerance or regulatory limit for the same substance and use has been established.
(e) Tolerances will be established under authority appropriate for action levels (sections 306, 402(a), and 701(a) of the act, together with section 408 or 409 of the act, if appropriate) as well as under authority appropriate for tolerances (sections 406 and 701 of the act). In the event the effectiveness of a tolerance is stayed pursuant to section 701(e)(2) of the act by the filing of an objection, the order establishing the tolerance shall be deemed to be an order establishing an action level until final action is taken upon such objection.
(a) Tolerances and action levels in this part are established at levels based on the unavoidability of the poisonous or deleterious substance concerned and do not establish a permissible level of contamination where it is avoidable.
(b) Compliance with tolerances, regulatory limits, and action levels does not excuse failure to observe either the requirement in section 402(a)(4) of the act that food may not be prepared, packed, or held under insanitary conditions or the other requirements in this chapter that food manufacturers must observe current good manufacturing practices. Evidence obtained through factory inspection or otherwise indicating such a violation renders the food unlawful, even though the amounts of poisonous or deleterious substances are lower than the currently established tolerances, regulatory limits, or action levels. The manufacturer of food must at all times utilize quality control procedures which will reduce contamination to the lowest level currently feasible.
(a) Polychlorinated biphenyls (PCB's) represent a class of toxic industrial chemicals manufactured and sold under
(b) The following special provisions are necessary to preclude the accidental PCB contamination of food-packaging materials:
(1) New equipment or machinery for manufacturing food-packaging materials shall not contain or use PCB's.
(2) On or before September 4, 1973, the management of establishments manufacturing food-packaging materials shall:
(i) Have the heat exchange fluid used in existing equipment for manufacturing food-packaging materials sampled and tested to determine whether it contains PCB's or verify the absence of PCB's in such formulations by other appropriate means. On or before Sept. 4, 1973, any such fluid formulated with PCB's must to the fullest extent possible commensurate with current good manufacturing practices be replaced with a heat exchange fluid that does not contain PCB's.
(ii) Eliminate to the fullest extent possible commensurate with current good manufacturing practices from the establishment any other PCB-containing equipment, machinery and materials wherever there is a reasonable expectation that such articles could cause food-packaging materials to become contaminated with PCB's either as a result of normal use or as a result of accident, breakage, or other mishap.
(iii) The toxicity and other characteristics of fluids selected as PCB replacements must be adequately determined so that the least potentially hazardous replacement is used. In making this determination with respect to a given fluid, consideration should be given to (
(c) The provisions of this section do not apply to electrical transformers and condensers containing PCB's in sealed containers.
(a) Polychlorinated biphenyls (PCB's) are toxic, industrial chemicals. Because of their widespread, uncontrolled industrial applications, PCB's have become a persistent and ubiquitous contaminant in the environment. As a result, certain foods and animal feeds, principally those of animal and marine origin, contain PCB's as unavoidable, environmental contaminants. PCB's are transmitted to the food portion (meat, milk, and eggs) of food producing animals ingesting PCB contaminated animal feed. In addition, a significant percentage of paper food-packaging materials contain PCB's which may migrate to the packaged food. The source of PCB's in paper food-packaging materials is primarily of certain types of carbonless copy paper (containing 3 to 5 percent PCB's) in waste paper stocks used for manufacturing recycled paper. Therefore, temporary tolerances for residues of PCB's as unavoidable environmental or industrial contaminants are established for a sufficient period of time following the effective date of this paragraph to permit the elimination of such contaminants at the earliest practicable time. For the purposes of this paragraph, the term
(1) 0.2 part per million in finished animal feed for food-producing animals (except the following finished animal feeds: feed concentrates, feed supplements, and feed premixes).
(2) 2 parts per million in animal feed components of animal origin, including fishmeal and other by-products of marine origin and in finished animal feed concentrates, supplements, and premixes intended for food-producing animals.
(3) 10 parts per million in paper food-packaging material intended for or used with finished animal feed and any components intended for animal feeds. The tolerance shall not apply to paper food-packaging material separated from the food therein by a functional barrier which is impermeable to migration of PCB's.
(b) A compilation entitled “Analytical Methodology for Polychlorinated Biphenyls, February 1973” for determining compliance with the tolerances established in this section is available from the Division of Dockets Management, Food and Drug Administration, 5630 Fishers Lane, rm. 1061, Rockville, MD 20852.
21 U.S.C. 321, 331, 351, 352, 353, 360b, 371, 379e.
As used in this part:
(a) The term
(b)
(c)
(d)
(e)
(f) The definitions and interpretations of terms contained in section 201 of the act shall be applicable to such terms when used in the regulations in this part.
(g) The term
(1) The composition of which is such that such drug is not generally recognized, among experts qualified by scientific training and experience to evaluate the safety and effectiveness of animal drugs, as safe and effective for use under the conditions prescribed, recommended, or suggested in the labeling thereof; except that such a drug not so recognized shall not be deemed to be a
(2) The composition of which is such that such drug, as a result of investigations to determine its safety and effectiveness for use under such conditions, has become so recognized but which has not, otherwise than in such investigations, been used to a material extent or for a material time under such conditions.
(h) The term
(i) The newness of an animal drug, including a new animal drug intended for use in or on animal feed, may arise by reason of: (1) The newness for its intended drug use of any substance of which the drug is comprised, in whole or in part, whether it be an active substance or a menstruum, excipient, carrier, coating, or other component; (2) the newness for its intended drug use of a combination of two or more substances, none of which is itself a new animal drug; (3) the newness for its intended drug use of the proportion of a substance in a combination, even though such combination containing such substance in other proportion is not a new animal drug; (4) the newness for its intended drug use in a different species of animal; (5) the newness of its intended drug use in diagnosing, curing, mitigating, treating, or preventing a disease, or to affect a structure or function of the animal body, even though such drug is not a new animal drug when used in another disease or to affect another structure or function of the body; or (6) the newness of a dosage, or method or duration of administration or application, or any other condition of use prescribed, recommended, or suggested in the labeling
(j)
(k)
An animal drug produced and distributed in full conformance with the animal virus, serum, and toxin law of March 4, 1913 (37 Stat. 832; 21 U.S.C. 151
(a) A new animal drug intended for use in the manufacture of animal feed shall be deemed to be unsafe unless at the time of its removal from the establishment of a manufacturer, packer, or distributor of such drug, such manufacturer, packer, or distributor has an unrevoked written statement from the consignee of such drug, or a notice from the Secretary, to the effect that with respect to the use of such drug in animal feed the consignee:
(1) Holds a license issued under § 515.20 of this chapter; or
(2) Will, if the consignee is not the user of the drug, ship such drug only to a holder of an approved application under § 515.10 of this chapter.
(b) The requirements of paragraph (a) of this section do not apply:
(1) Where such drugs are intended for export and/or
(2) When the use of such drug in the manufacture of a finished feed has been exempted from the requirements of section 512(m) of the act under the conditions specified by regulations published in part 558 of this chapter.
(a) Part 526 of this chapter provides for new animal drugs intended for intramammary use in animals and includes conditions of use intended to prevent the contamination of milk from the use of such drugs.
(b) Preparations containing antibiotics and other potent drugs labeled with directions for use in milk-producing animals will be misbranded under section 502(f)(2) of the act unless their labeling bears appropriate warnings and directions for use to avoid adulteration of milk under section 402(a)(2)(c)(ii) of the act.
(c) It is the position of the Food and Drug Administration that the labeling
(1) The article should not be administered to animals producing milk, since to do so would result in contamination of the milk; or
(2) The label should bear the following statement: “Warning: Milk that has been taken from animals during treatment and for __ hours after the latest treatment must not be used for food”, the blank being filled in with the figure that the manufacturer has determined by appropriate investigation is needed to insure that the milk will not carry violative residues resulting from use of the preparation. If the use of the preparation as recommended does not result in contamination of the milk, neither of the above warning statements is required.
Whenever the labeling of an antibiotic drug included in the regulations in this chapter suggests or recommends its use in milk-producing animals, the label of such drugs shall bear either the statement “Warning: Not for use in animals producing milk, since this use will result in contamination of the milk” or the statement “Warning: Milk that has been taken from animals during treatment and for __hours after the latest treatment must not be used for food”, the blank being filled in with the figure that the Commissioner has authorized the manufacturer of the drug to use. The Commissioner shall determine what such figures shall be from information submitted by the manufacturer and which the Commissioner considers is adequate to prove that period of time after the latest treatment that the milk from treated animals will contain no violative residues from use of the preparation. If the Commissioner determines from the information submitted that the use of the antibiotic drug as recommended does not result in its appearance in the milk, the Commissioner may exempt the drug from bearing either of the above warning statements.
(a) The Food and Drug Administration in the interest of fulfilling its responsibilities with regard to protection of the public health has requested an evaluation of the public health aspects of the use of antibiotics in veterinary medical and nonmedical uses. There is particular concern with regard to the potential hazards associated with the extensive use of antibiotics administered to food-producing animals. Accordingly, an ad hoc committee on the Veterinary Medical and Nonmedical Uses of Antibiotics was established by the Food and Drug Administration to study and advise the Commissioner of Food and Drugs on the uses of antibiotics in veterinary medicine and for various nonmedical purposes as such uses may affect the enforcement of the Federal Food, Drug, and Cosmetic Act with respect to their safety and effectiveness.
(b) Based upon an evaluation of the conclusions of said Committee and other relevant material, § 510.112 was published in the
(c) An evaluation of the data now available shows that use of many antibiotic preparations cause residues in edible products of treated animals for varying and, in some cases, for long periods of time following the last administration. Because of the accumulation of new information with regard to the development of resistance of bacteria to antibiotics, the ability of bacteria to
(d) Based on evaluation of information available, including the conclusions of the aforementioned ad hoc Committee, the Commissioner concludes that antibiotic preparations intended for use in food-producing animals, other than topical and ophthalmic preparations, are not generally recognized among qualified experts as having been shown to be safe for their intended use(s) within the meaning of section 201(s) of the Federal Food, Drug, and Cosmetic Act.
(e) Therefore, all exemptions from the provisions of section 409 of the act for use of antibiotics in food-producing animals based on sanctions or approvals granted prior to enactment of the Food Additives Amendment of 1958 (Pub. L. 85-929; 72 Stat. 1784) will be revoked and the uses which are concluded to be safe will be covered by food additive regulations. On those products for which there are inadequate residue data, actions will be initiated to withdraw approval of new-drug applications under the provisions of section 505 of the act. Antibiotic preparations, other than those for topical and ophthalmic application in food-producing animals, which are not covered by food additive regulations will be subject to regulatory action within 180 days after publication of the forthcoming revocation order.
(f) Because of the variation in the period of time that antibiotic residues may remain in edible products from treated animals, all injectable, intramammary infusion, intrauterine, and oral preparations, including medicated premixes intended for use in food-producing animals, are deemed to be new drugs as well as food additives.
(a) An ad hoc committee, Committee on the Veterinary Medical and Nonmedical Uses of Antibiotics, was formed by the Food and Drug Administration to study, and advise the Commissioner on, the use of antibiotics in veterinary medicine and for various nonmedical purposes as such uses may affect the enforcement of the Federal Food, Drug, and Cosmetic Act with respect to the safety and effectiveness of such substances. A copy of the report may be obtained from the Food and Drug Administration, Office of Public Affairs, Room 15-05, Parklawn Building, 5600 Fishers Lane, Rockville, MD 20857.
(b) On the basis of the report of the Committee and other information, sponsors of drugs containing any antibiotic intended for use in food-producing animals shall submit data for determining whether or not such antibiotics and their metabolites are present as residues in edible tissues, milk, and eggs from treated animals; however, in the case of a drug for which such data have already been submitted and for which a regulation has been promulgated under section 409 of the act, only such data as has been accumulated since the issuance of the regulation need be submitted.
(c) The required data shall be submitted within 180 days of the date of publication of this section in the
(d) Regulatory proceedings including revocation of prior sanctions, or actions to suspend or amend new drug or antibiotic approvals granted prior to passage of the Food Additives Amendment of 1958 (72 Stat. 1784), may be initiated with regard to the continued marketing of any antibiotic preparation on which the required information is not submitted within the period of time prescribed by paragraph (c) of this section.
(e) Questions relating to the acceptability of proposed research protocols and assay methods for determining the amount of antibiotic residues in food
Records and reports of clinical and other experience with the new animal drug will be maintained and reported, appropriately identified with the new animal drug application(s) or index listing(s) to which they relate, to the Center for Veterinary Medicine in duplicate in accordance with the following:
(a) Immediately upon receipt by the applicant, complete records or reports covering information of the following kinds:
(1) Information concerning any mixup in the new animal drug or its labeling with another article.
(2) Information concerning any bacteriological or any significant chemical, physical, or other change or deterioration in the drug, or any failure of one or more distributed batches of the drug to meet the specifications established for it in the new animal drug application or request for determination of eligibility for indexing.
(b) As soon as possible, and in any event within 15 working days of its receipt by the applicant, complete records or reports concerning any information of the following kinds:
(1) Information concerning any unexpected side effect, injury, toxicity, or sensitivity reaction or any unexpected incidence or severity thereof associated with clinical uses, studies, investigations, or tests, whether or not determined to be attributable to the new animal drug, except that this requirement shall not apply to the submission of information described in a written communication to the applicant from the Food and Drug Administration as types of information that may be submitted at other designated intervals.
(2) Information concerning any unusual failure of the new animal drug to exhibit its expected pharmacological activity.
Each applicant shall maintain in a single accessible location:
(a) A copy of the approved medicated feed mill license (Form FDA 3448) on the premises of the manufacturing establishment; and
(b) Approved or index listed labeling for each Type B and/or Type C feed being manufactured on the premises of the manufacturing establishment or the facility where the feed labels are generated.
(a) The Food and Drug Administration has received reports of side effects associated with the oral, injectable, and ophthalmic use of corticosteroid animal drugs. The use of these drugs administered orally or by injection has resulted in premature parturition when administered during the last trimester of pregnancy. Premature parturition
(b) In view of these potentially serious side effects, the Food and Drug Administration has concluded that the labeling on or within packaged corticosteroid-containing preparations intended for animal use shall bear conspicuously the following warning statement:
Additionally, corticosteroids administered to dogs, rabbits, and rodents during pregnancy have resulted in cleft palate in offspring. Corticosteroids administered to dogs during pregnancy have also resulted in other congenital anomalies, including deformed forelegs, phocomelia, and anasarca.
There has been an increasing interest in the use of injectable iron compounds for the prevention or treatment of iron-deficiency anemia in animals. Although some such preparations have been shown to be safe, such articles are regarded as new animal drugs within the meaning of the Federal Food, Drug, and Cosmetic Act. Accordingly, an approved new animal drug application is required prior to the marketing of such preparations within the jurisdiction of the act. In addition to the need for demonstrating the safety of such articles, the labeling of such preparations should not only recommend appropriate dosages of iron but also declare the amount (in milligrams) of available iron (Fe) per milliliter of the subject product.
(a)
(b)
(1) An original new animal drug application (NADA),
(2) A supplemental NADA, or
(3) An abbreviated NADA.
(c)
(1) Data, or reference to data in a master file (MF), showing that the target animal consumes the new animal drug in the Type C free-choice feed in an amount that is safe and effective (consumption/effectiveness data); and
(2) Data, or reference to data in an MF, showing the relevant ranges of conditions under which the drug will be chemically and physically stable in the Type C free-choice feed under field conditions.
(d)
(1) Directly in the NADA, by a sponsor; and/or
(2) To an MF that a sponsor may then reference in its NADA with written consent of the MF holder.
(e)
(1) The formula and/or specifications of the free-choice medicated feed, where the owner of this information requests such publication, or
(2) A statement that the approval has been granted for a proprietary formula and/or specifications.
(f)
(1) All free-choice medicated feeds that contain a Category II drug, and
(2) Free-choice medicated feeds that contain a Category I drug and use a proprietary formula and/or specifications.
(a) Section 512(i) of the act requires publication of names and addresses of sponsors of approved applications for new animal drugs.
(b) In this section each name and address is identified by a numerical drug labeler code. The labeler codes identify the sponsors of the new animal drug applications associated with the regulations published pursuant to section 512(i) of the act. The codes appear in the appropriate regulations and serve as a reference to the names and addresses listed in this section. The drug labeler code is established pursuant to section 510 of the act.
(c) The names, addresses, and drug labeler codes of sponsors of approved new animal drug applications are as follows:
For
At 72 FR 36595, July 5, 2007, § 510.600, in the table in paragraph (c)(2), was amended by removing the entry for “062749”; however, the amendment could not be incorporated because the entry does not exist.
21 U.S.C. 321, 351, 352, 353, 360b, 371.
(a)
(2) The person distributing or causing the distribution of new animal drugs for tests in vitro or in animals used only for laboratory research purposes under this exemption shall use due diligence to assure that the consignee is regularly engaged in conducting such tests and that the shipment of the new animal drug will actually be used for tests in vitro or in animals used only for laboratory research.
(3) The person who introduced such shipment or who delivered the new animal drug for introduction into interstate commerce shall maintain adequate records showing the name and post office address of the expert or expert organization to whom the new animal drug is shipped and the date, quantity, and batch or code mark of each shipment and delivery for a period of 2 years after such shipment and delivery. Upon the request of a properly authorized employee of the Department at reasonable times, he shall make such records available for inspection and copying.
(4) The exemption allowed in this paragraph shall not apply to any new animal drug intended for in vitro use in the regular course of diagnosing or treating disease, including antibacterial sensitivity discs impregnated with any new animal drug or drugs, which discs are intended for use in determining susceptibility of microorganisms to the new animal drug or drugs.
(b)
(1) The label shall bear the statements:
In the case of containers too small or otherwise unable to accommodate a label with sufficient space to bear the caution statements required by paragraph (a) or (b) of this section, the statements may be included on the carton label and other labeling on or within the package from which the new animal drug is to be dispensed.
(2) The person or firm distributing or causing the distribution of the new animal drug or animal feed containing a new animal drug shall use due diligence to assure that the new animal drug or animal feed containing a new animal drug will actually be used for tests in animals and is not used in humans.
(3) The person who introduced such shipment or who delivered the new animal drug or animal feed containing a new animal drug for introduction into interstate commerce shall maintain adequate records showing the name and post office address of the investigator to whom the new animal drug or animal feed containing a new animal drug is shipped and the date, quantity, and batch or code mark of each shipment and delivery for a period of 2 years after such shipment and delivery. Upon the request of a properly authorized employee of the Department at reasonable times, such records shall be made available for inspection and copying.
(4) Prior to shipment of the new animal drug for clinical tests in animals, the sponsor of the investigation shall
(i) The identity of the new animal drug.
(ii) All labeling and other pertinent information to be supplied to the investigators. When such pertinent information includes nonclinical laboratory studies, the information shall include, with respect to each nonclinical study, either a statement that the study was conducted in compliance with the requirements set forth in part 58 of this chapter, or, if the study was not conducted in compliance with such regulations, a brief statement of the reason for the noncompliance.
(iii) The name and address of each clinical investigator.
(iv) The approximate number of animals to be treated (or if not available, the amount of new animal drug to be shipped).
(v) If the new animal drug is given to food-producing animals, the statement shall contain the following additional information:
(
(
(
(vi) If a sponsor has transferred any obligations for the conduct of any clinical study to a contract research organization, a statement containing the name and address of the contract research organization, identification of the clinical study, and a listing of the obligations transferred. If all obligations governing the conduct of the study have been transferred, a general statement of this transfer—in lieu of a listing of the specific obligations transferred—may be submitted.
(5) Authorization for use of edible products derived from a treated food-producing animal may be granted under the provisions of this section and when the following specified conditions are met, except that in the case of an animal administered any unlicensed experimental veterinary biological product regulated under the viruses, serums, toxins statute (21 U.S.C., chapter V, sec. 151
(i) Data to show that consumption of food derived from animals treated at the maximum levels with the minimum withdrawal periods, if any, specified in accordance with paragraph (b)(4)(v)(
(ii) Data to show that food derived from animals treated at the maximum levels and with the minimum withdrawal periods, if any, specified in accordance with paragraph (b)(4)(v)(
(iii) The name and location of the packing plant where the animals will be processed, except that this requirement may be waived, on request, by the terms of the authorization.
(6) On written request of the Food and Drug Administration, the sponsor shall submit any additional information reported to or otherwise received by him with respect to the investigation deemed necessary to facilitate a determination whether there are
(7) The sponsor shall assure himself that the new animal drug is shipped only to investigators who:
(i) Are qualified by scientific training and/experience to evaluate the safety and/or effectiveness of the new animal drug.
(ii) Shall maintain complete records of the investigations, including complete records of the receipt and disposition of each shipment or delivery of the new animal drug under investigation. Copies of all records of the investigation shall be retained by the investigator for 2 years after the termination of the investigation or approval of a new animal drug application.
(iii) Shall furnish adequate and timely reports of the investigation to the sponsor.
(8) The sponsor:
(i) Shall retain all reports received from investigators for 2 years after the termination of the investigation or approval of a new animal drug application and make such reports available to a duly authorized employee of the Department for inspection at all reasonable times.
(ii) Shall provide for current monitoring of the investigation by a person qualified by scientific training and experience to evaluate information obtained from the investigation, and shall promptly investigate and report to the Food and Drug Administration and to all investigators any findings associated with use of the new animal drug that may suggest significant hazards pertinent to the safety of the new animal drug.
(iii) Shall not unduly prolong distribution of the new animal drug for investigational use.
(iv) Shall not, nor shall any person acting for or on behalf of the sponsor, represent that the new animal drug is safe or effective for the purposes for which it is under investigation. This requirement is not intended to restrict the full exchange of scientific information.
(v) Shall not commercially distribute nor test-market the new animal drug until a new animal drug application is approved pursuant to section 512(c) of the act.
(9) If the shipment or other delivery of the new animal drug is imported or offered for importation into the United States for clinical investigational use in animals, it shall also meet the following conditions:
(i) The importer of all such shipments or deliveries is an agent of the foreign exporter residing in the United States or the ultimate consignee, which person has, prior to such shipments and deliveries, informed the Food and Drug Administration of his intention to import the new animal drug as sponsor in compliance with the conditions prescribed in this subdivision; or
(ii) The new animal drug is shipped directly to a scientific institution with adequate facilities and qualified personnel to conduct laboratory or clinical investigations and is intended solely for use in such institutions and which institution has submitted a statement as sponsor of the investigation.
(10) The sponsor shall submit either a claim for categorical exclusion under § 25.30 or § 25.33 of this chapter or an environmental assessment under § 25.40 of this chapter.
(c)
(2) If, after evaluating all available information, including any explanation presented by the investigator, the
(3) Each “Notice of Claimed Investigational Exemption for a New Animal Drug” and each approved new animal drug application containing data reported by an investigator who has been determined to be ineligible to receive investigational-use new animal drugs will be examined to determine whether he has submitted unreliable data that are essential to the continuation of the investigation or essential to the approval of any new animal drug application.
(4) If the Commissioner determines, after the unreliable data submitted by the investigator are eliminated from consideration, that the data remaining are inadequate to support a conclusion that it is reasonably safe to continue the investigation, he shall first notify the sponsor, who shall have an opportunity for a regulatory hearing before the Food and Drug Administration pursuant to part 16 of this chapter on whether the exemption should be terminated. If a danger to the public health exists, however, he shall terminate the exemption forthwith and notify the sponsor of the termination. In such event the sponsor shall have an opportunity for a regulatory hearing before the Food and Drug Administration pursuant to part 16 (see 42 FR 15675, March 22, 1977) of this chapter on the question of whether the exemption should be reinstated.
(5) If the Commissioner determines, after the unreliable data submitted by the investigator are eliminated from consideration, that the data remaining are such that a new animal drug application would not have been approved, he will proceed to withdraw approval of the application in accordance with section 512(e) of the act.
(6) An investigator who has been determined to be ineligible may be reinstated as eligible to receive investigational-use new animal drugs when the Commissioner determines that he has presented adequate assurance that he will employ such new animal drugs solely in compliance with the exempting regulations in this section for investigational-use new animal drugs.
(d)
(1) The sponsor of the investigation has failed to comply with any of the conditions for the exemption established under this section, or
(2) The continuance of the investigation is unsafe or otherwise contrary to the public interest or the drug is being or has been used for purposes other than bona fide scientific investigation, he shall first notify the sponsor and invite his immediate correction. If the conditions of the exemption are not immediately met, the sponsor shall have an opportunity for a regulatory hearing before the Food and Drug Administration pursuant of part 16 of this chapter on whether the exemption should be terminated. If the exemption is terminated the sponsor shall recall or have destroyed the unused supplies of the new animal drug.
(e)
(f)
(2) A sponsor may transfer responsibility for any or all of the obligations set forth in this part to a contract research organization. Any such transfer
(3) A contract research organization that assumes any obligation of a sponsor shall comply with the specific regulations in this chapter applicable to this obligation and shall be subject to the same regulatory action as a sponsor for failure to comply with any obligation assumed under these regulations. Thus, all references to
(g)
21 U.S.C. 321, 331, 351, 352, 356a, 360b, 371, 379e, 381.
(a) Applications to be filed under section 512(b) of the act shall be submitted in the form described in paragraph (b) of this section. If any part of the application is in a foreign language, an accurate and complete English translation shall be appended to such part. Translations of literature printed in a foreign language shall be accompanied by copies of the original publication. The application must be signed by the applicant or by an authorized attorney, agent, or official. If the applicant or such authorized representative does not reside or have a place of business within the United States, the application must also furnish the name and post office address of, and must be
(b) Applications for new animal drugs shall be submitted in triplicate and assembled in the manner prescribed by paragraph (b)(15) of this section, and shall include the following information:
(1)
(2)
(i) Chemistry:
(
(
(
(ii) Scientific rationale and purpose the new animal drug is to serve:
(
(
(
(
(3)
(i) All labeling should be identified to show its position on, or the manner in which it is to accompany the market package.
(ii) Labeling for nonprescription new animal drugs should include adequate directions for use by the layman under all conditions of use for which the new animal drug is intended, recommended, or suggested in any of the labeling or advertising sponsored by the applicant.
(iii) Labeling for prescription veterinary drugs should bear adequate information for use under which veterinarians can use the new animal drug safely and for the purposes for which it is intended, including those purposes for which it is to be advertised or represented, in accord with § 201.105 of this chapter.
(iv) All labeling for prescription or nonprescription new animal drugs shall be submitted with any necessary use restrictions prominently and conspicuously displayed.
(v) Labeling for new animal drugs intended for use in the manufacture of medicated feeds shall include:
(
(
(vi) Draft labeling may be submitted for preliminary consideration of an application. Final printed labeling will ordinarily be required prior to approval of an application. Proposed advertising for veterinary prescription drugs may be submitted for comment or approval.
(4)
(i) A full list of the articles used as components of the new animal drug. This list should include all substances used in the synthesis, extraction, or other method of preparation of any new animal drug and in the preparation of the finished dosage form, regardless of whether they undergo chemical change or are removed in the process. Each component should be identified by its established name, if any, or complete chemical name, using structural formulas when necessary for specific identification. If any proprietary name is used, it should be followed by a complete quantitative statement of composition. Reasonable alternatives for any listed component may be specified.
(ii) A full statement of the composition of the new animal drug. The statement shall set forth the name and amount of each ingredient, whether active or not, contained in a stated quantity of the new animal drug in the form in which it is to be distributed (for example, amount per tablet or milliliter) and a batch formula representative of that to be employed for the manufacture of the finished dosage form. All components should be included in the batch formula regardless of whether they appear in the finished product. Any calculated excess of an ingredient over the label declaration should be designated as such and percent excess shown. Reasonable variation may be specified.
(iii) If it is a new animal drug produced by fermentation:
(
(
(
(
(
(
(5)
(i) If the applicant does not himself perform all the manufacturing, processing, packaging, labeling, and control operations for any new animal drug, he shall: Identify each person who will perform any part of such operations and designate the part; and provide a signed statement from each such person fully describing, directly or by reference, the methods, facilities, and controls he will use in his part of the operation. The statement shall include a commitment that no changes will be made without prior approval by the Food and Drug Administration, unless permitted under § 514.8.
(ii) A description of the qualifications, including educational background and experience, of the technical
(iii) A description of the physical facilities including building and equipment used in manufacturing, processing, packaging, labeling, storage, and control operations.
(iv) The methods used in the synthesis, extraction, isolation, or purification of any new animal drug. When the specifications and controls applied to such new animal drugs are inadequate in themselves to determine its identity, strength, quality, and purity, the methods should be described in sufficient detail, including quantities used, times, temperature, pH, solvents, etc., to determine these characteristics. Alternative methods or variations in methods within reasonable limits that do not affect such characteristics of the new animal drug may be specified. A flow sheet and indicated equations should be submitted when needed to explain the process.
(v) Precautions to insure proper identity, strength, quality, and purity of the raw materials, whether active or not, including:
(
(
(vi) The instructions used in the manufacturing, processing, packaging, and labeling of each dosage form of the new animal drug, including:
(
(
(
(
(
(
(vii) The analytical controls used during the various stages of the manufacturing, processing, packaging, and labeling of the new animal drug, including a detailed description of the collection of samples and the analytical procedures to which they are subjected. The analytical procedures should be capable of determining the active components within a reasonable degree of accuracy and of assuring the identity of such components.
(
(
(viii) An explanation of the exact significance of any batch control numbers used in the manufacturing, processing, packaging, and labeling of the new animal drug, including such control numbers that may appear on the label of the finished article. State whether these numbers enable determination of
(ix) Adequate information with respect to the characteristics of and the test methods employed for the container, closure, or other component parts of the drug package to assure their suitability for the intended use.
(x) A complete description of, and data derived from, studies of the stability of the new animal drug in the final dosage form, including information showing the suitability of the analytical methods used. A description of any additional stability studies underway or planned. Stability data for the finished dosage form of the new animal drug in the container in which it is to be marketed, including any proposed multiple dose container, and, if it is to be put into solution at the time of dispensing, for the solution prepared as directed. If the new animal drug is intended for use in the manufacture of Type C medicated feed as defined in § 558.3 of this chapter, stability data derived from studies in which representative formulations of the medicated feed articles are used. Similar data may be required for Type B medicated feeds as determined by the Food and Drug Administration on a case-by-case basis. Expiration dates shall be proposed for finished pharmaceutical dosage forms and Type A medicated articles. If the data indicate that an expiration date is needed for Type B or Type C medicated feeds, the applicant shall propose such expiration date. If no expiration date is proposed for Type B or Type C medicated feeds, the applicant shall justify its absence with data.
(xi) Additional procedures employed which are designed to prevent contamination and otherwise assure proper control of the product. An application may be refused unless it includes adequate information showing that the methods used in, and the facilities and controls used for, the manufacturing, processing, and packaging of the new animal drug are adequate to preserve its identity, strength, quality, and purity in conformity with good manufacturing practice and identifies each establishment, showing the location of the plant conducting these operations.
(6)
(i) Each sample shall consist of four identical, separately packaged subdivisions, each containing at least three times the amount required to perform the laboratory test procedures described in the application to determine compliance with its control specifications for identity and assays. Each of the samples submitted shall be appropriately packaged and labeled to preserve its characteristics, to identify the material and the quantity in each subdivision of the sample, and to identify each subdivision with the name of the applicant and the new animal drug application to which it relates. Included are:
(
(
(
(ii) The following information shall be included for the samples when requested:
(
(
(7)
(i) The kind of information required by this subdivision may include: Complete experimental protocols for determining drug residue levels in the edible products, and the length of time required for residues to be eliminated from such products following the drug's use; residue studies conducted under appropriate (consistent with the proposed usage) conditions of dosage, time, and route of administration to show levels, if any, of the drug and/or its metabolites in test animals during and upon cessation of treatment and at intervals thereafter in order to establish a disappearance curve; if the drug is to be used in combination with other drugs, possible effects of interaction demonstrated by the appropriate disappearance curve or depletion patterns after drug withdrawal under appropriate (consistent with the proposed usage) conditions of dosage, time, and route of administration; if the drug is given in the feed or water, appropriate consumption records of the medicated feed or water and appropriate performance data in the treated animal; if the drug is to be used in more than one species, drug residue studies or appropriate metabolic studies conducted for each species that is food-producing. To provide these data, a sufficient number of birds or animals should be used at each sample interval. Appropriate use of labeled compounds (e.g. radioactive tracers), may be utilized to establish metabolism and depletion curves. Drug residue levels ordinarily should be determined in muscle, liver, kidney, and fat and where applicable, in skin, milk, and eggs (yolk and egg white). As a part of the metabolic studies, levels of the drug or metabolite should be determined in blood where feasible. Samples may be combined where necessary. Where residues are suspected or known to be present in litter from treated animals, it may be necessary to include data with respect to such residues becoming components of other agricultural commodities because of use of litter from treated animals.
(ii) A new animal drug that has the potential to contaminate human food with residues whose consumption could present a risk of cancer to people must satisfy the requirements of subpart E of part 500 of this chapter.
(8)
(ii) An application may be refused unless it includes substantial evidence of the effectiveness of the new animal drug as defined in § 514.4.
(iii) An application may be refused unless it contains detailed reports of the investigations, including studies made on laboratory animals, in which the purpose, methods, and results obtained are clearly set forth of acute, subacute, and chronic toxicity, and unless it contains appropriate clinical laboratory results related to safety and
(iv) All information pertinent to an evaluation of the safety and effectiveness of the new animal drug received or otherwise obtained by the applicant from any source, including information derived from other investigations or commercial marketing (for example, outside the United States), or reports in the scientific literature, both favorable and unfavorable, involving the new animal drug that is the subject of the application and related new animal drugs shall be submitted. An adequate summary may be acceptable in lieu of a reprint of a published report that only supports other data submitted. Include any evaluation of the safety or effectiveness of the new animal drug that has been made by the applicant's veterinary or medical department, expert committee, or consultants.
(v) If the new animal drug is a combination of active ingredients or animal drugs, an application may be refused unless it includes substantial evidence of the effectiveness of the combination new animal drug as required in § 514.4.
(vi) An application shall include a complete list of the names and post office addresses of all investigators who received the new animal drug. This may be incorporated in whole or in part by reference to information submitted under the provisions of § 511.1 of this chapter.
(vii) Explain any omission of reports from any investigator to whom the investigational new animal drug has been made available. The unexplained omission of any reports of investigations made with the new animal drug by the applicant or submitted to him by an investigator or the unexplained omission of any pertinent reports of investigations or clinical experience received or otherwise obtained by the applicant from published literature or other sources that would bias an evaluation of the safety of the new animal drug or its effectiveness in use, constitutes grounds for the refusal or withdrawal of the approval of an application.
(viii) If a sponsor has transferred any obligations for the conduct of any clinical study to a contract research organization, the application is required to include a statement containing the name and address of the contract research organization, identifying the clinical study, and listing the obligations transferred. If all obligations governing the conduct of the study have been transferred, a general statement of this transfer—in lieu of a listing of the specific obligations transferred—may be submitted.
(ix) If original subject records were audited or reviewed by the sponsor in the course of monitoring any clinical study to verify the accuracy of the case reports submitted to the sponsor, a list identifying each clinical study so audited or reviewed.
(9)
(10)
(11)
(12)
(ii) The methods, facilities, and controls described under item 5 of this application conform to the current good manufacturing practice regulations in subchapter C of this chapter.
(iii) With respect to each nonclinical laboratory study contained in the application, either a statement that the study was conducted in compliance with the good laboratory practice regulations set forth in part 58 of this chapter, or, if the study was not conducted in compliance with such regulations, a brief statement of the reason for the noncompliance.
(13) [Reserved]
(14)
(15)
(i) Bind the original or ribbon copy of the application as copy No. 1.
(ii) Bind two identical copies as copy No. 2 and copy No. 3.
(iii) Identify each front cover with the name of the applicant, new animal drug, and the copy number.
(iv) Number each page of the application sequentially in the upper right hand corner or in another location so that the page numbers remain legible after the application has been bound, and organize the application consistent with paragraphs (b) (1) through (14) of this section. Each copy should bear the same page numbering, whether sequential in each volume or continuous and sequential throughout the application.
(v) Include complete labeling in each of the copies. It is suggested that labeling be identified by date of printing or date of preparation.
(vi) Submit separate applications for each different dosage form of the drug proposed. Repeating basic information pertinent to all dosage forms in each application is unnecessary if reference is made to the application containing such information. Include in each application information applicable to the specific dosage form, such as labeling, composition, stability data, and method of manufacture.
(vii) Submit in folders amendments, supplements, and other correspondence sent after submission of an original application. The front cover of these submissions should be identified with the name of the applicant, new animal drug, copy number, and the new animal drug application number, if known.
(c) When a new animal drug application is submitted for a new animal drug which has a stimulant, depressant, or hallucinogenic effect on the central nervous system, if it appears that the drug has a potential for abuse, the Commissioner shall forward that information to the Attorney General of the United States.
For
The definition and interpretation of terms contained in this section apply to those terms as used throughout subchapter E.
(1) An adverse event occurring in animals in the course of the use of an animal drug product by a veterinarian or by a livestock producer or other animal owner or caretaker.
(2) Failure of a new animal drug to produce its expected pharmacological or clinical effect (lack of expected effectiveness).
(3) An adverse event occurring in humans from exposure during manufacture, testing, handling, or use of a new animal drug.
(1) Intending to investigate a new animal drug under section 512(j) of the Federal Food, Drug, and Cosmetic Act (the act),
(2) Investigating a new animal drug under section 512(j) of the act,
(3) Intending to file a new animal drug application (NADA) or supplemental NADA under section 512(b)(1) of the act, or
(4) Intending to file an abbreviated new animal drug application (ANADA) under section 512(b)(2) of the act.
(a)
(b)
(2)
(i)
(ii) [Reserved]
(3)
(A) To determine that the parameters selected for measurement and the measured responses reliably reflect the effectiveness of the new animal drug;
(B) To determine that the results obtained are likely to be repeatable, and that valid inferences can be drawn to the target animal population; and
(C) To conclude that the new animal drug is effective for the intended use at the dose or dose range and associated conditions of use prescribed, recommended, or suggested in the proposed labeling.
(ii)
(c)
(i)
(ii)
(iii)
(iv)
(2)
(A) By substantial evidence, as defined in this section, that any active ingredient or animal drug intended only for the same use as another active ingredient or animal drug in the combination makes a contribution to the effectiveness of the combination new animal drug;
(B) That each active ingredient or animal drug intended for at least one use that is different from all the other active ingredients or animal drugs used in the combination provides appropriate concurrent use for the intended target animal population; and
(C) That the active ingredients or animal drugs are physically compatible and do not have disparate dosing regimens if FDA, based on scientific information, has reason to believe the active ingredients or animal drugs are physically incompatible or have disparate dosing regimens.
(ii) For combination new animal drugs intended for use in animal feed or drinking water that contain only active ingredients or animal drugs that have previously been separately approved for the particular uses and conditions of use for which they are intended in combination, the sponsor shall demonstrate:
(A) By substantial evidence, as defined in this section, that any active ingredient or animal drug intended only for the same use as another active ingredient or animal drug in the combination makes a contribution to the effectiveness of the combination new animal drug;
(B) For such combination new animal drugs that contain more than one antibacterial ingredient or animal drug, by substantial evidence, as defined in this section, that each antibacterial makes a contribution to labeled effectiveness;
(C) That each active ingredient or animal drug intended for at least one use that is different from all other active ingredients or animal drugs used in the combination provides appropriate concurrent use for the intended target animal population; and
(D) That the active ingredients or animal drugs intended for use in drinking water are physically compatible if FDA, based on scientific information, has reason to believe the active ingredients or animal drugs are physically incompatible.
(3)
(a)
(b)
(c)
(d)
(e)
(f)
(ii)
(iii)
(iv)
(2)
(g)
(1) FDA and the potential applicant mutually agree to modify, in part or in whole, the agreement and such modification is documented and provided to the potential applicant as described in paragraph (f)(1) of this section; or
(2) FDA by written order determines that a substantiated scientific requirement essential to the determination of safety or effectiveness of the new animal drug appeared after the conference.
(h)
(i) The potential applicant makes to FDA, before, during, or after the presubmission conference, any untrue statement of material fact; or
(ii) The potential applicant fails to follow any material term of the agreement; and
(2) A presubmission conference may no longer be valid if the potential applicant submits false or misleading data relating to a new animal drug to FDA.
(i)
The applicant may submit an amendment to an application that is pending, including changes that may alter the conditions of use, the labeling, safety, effectiveness, identity, strength, quality, or purity of the drug or the adequacy of the manufacturing methods, facilities, and controls to preserve them, in which case the unamended application may be considered as withdrawn and the amended application may be considered resubmitted on the date on which the amendment is received by the Food and Drug Administration. The applicant will be notified of such date.
The sponsor may withdraw his pending application from consideration as a new animal drug application upon written notification to the Food and Drug Administration. Such withdrawal may be made without prejudice to a future filing. Upon resubmission, the time limitation will begin to run from the date the resubmission is received by the Food and Drug Administration. The original application will be retained by the Food and Drug Administration although it is considered withdrawn. The applicant shall be furnished a copy at cost on request.
(a)
(2) The following definitions of terms apply to this part:
(i)
(ii)
(iii)
(iv)
(b)
(ii) The holder of an approved application under section 512 of the act must assess the effects of the change before distributing a drug made with a manufacturing change.
(iii) Notwithstanding the requirements of paragraphs (b)(2) and (b)(3) of this section, an applicant must make a change provided for in those paragraphs in accordance with a regulation or guidance that provides for a less burdensome notification of the change (for example, by submission of a supplement that does not require approval prior to distribution of the drug, or by notification in the next annual report described in paragraph (b)(4) of this section).
(iv) In each supplement and amendment to a supplement providing for a change under paragraph (b)(2) or (b)(3) of this section, the applicant must include a statement certifying that a field copy has been provided to the appropriate FDA district office. No field copy is required for a supplement providing for a change made to a drug manufactured outside of the United States.
(v) A supplement or annual report described in paragraph (b)(4) of this section must include a list of all changes contained in the supplement or annual report. For supplements, this list must be provided in the cover letter.
(2)
(ii) These changes include, but are not limited to:
(A) Except those described in paragraphs (b)(3) and (b)(4) of this section, changes in the qualitative or quantitative formulation of the drug, including inactive ingredients, or in the specifications provided in the approved application;
(B) Changes requiring completion of appropriate clinical studies to demonstrate the equivalence of the drug to the drug as manufactured without the change;
(C) Changes that may affect drug substance or drug product sterility assurance, such as changes in drug substance, drug product or component sterilization method(s) or an addition, deletion, or substitution of steps in an aseptic processing operation;
(D) Changes in the synthesis or manufacture of the drug substance that may affect the impurity profile and/or the physical, chemical, or biological properties of the drug substance;
(E) Changes in a drug product container closure system that controls the drug delivered to the animal or changes in the type or composition of a packaging component that may affect the impurity profile of the drug product;
(F) Changes solely affecting a natural product, a recombinant DNA-derived protein/polypeptide, or a complex or conjugate of a drug substance with a monoclonal antibody for the following:
(
(
(
(G) Changes to a drug under an application that is subject to a validity assessment because of significant questions regarding the integrity of the data supporting that application.
(iii) The applicant must obtain approval of a supplement from FDA prior to distribution of a drug made using a change under paragraph (b)(2) of this section. The supplement must be labeled “Prior Approval Supplement.” Except for submissions under paragraph (b)(2)(v) of this section, the following information must be contained in the supplement:
(A) A completed Form FDA 356V;
(B) A detailed description of the proposed change;
(C) The drug(s) involved;
(D) The manufacturing site(s) or area(s) affected;
(E) A description of the methods used and studies performed to assess the effects of the change;
(F) The data derived from such studies;
(G) Appropriate documentation (for example, updated master batch records, specification sheets) including previously approved documentation (with the changes highlighted) or references to previously approved documentation;
(H) For a natural product, a recombinant DNA-derived protein/polypeptide, or a complex or conjugate of a drug substance with a monoclonal antibody, relevant validation protocols and standard operating procedures must be provided in addition to the requirements in paragraphs (b)(2)(iii)(E) and (b)(2)(iii)(F) of this section;
(I) For sterilization process and test methodologies related to sterilization process validation, relevant validation protocols and a list of relevant standard operating procedures must be provided in addition to the requirements in paragraphs (b)(2)(iii)(E) and (b)(2)(iii)(F) of this section; and
(J) Any other information as directed by FDA.
(iv) An applicant may ask FDA to expedite its review of a supplement for public health reasons or if a delay in making the change described in it would impose an extraordinary hardship on the applicant. Such a supplement and its mailing cover must be plainly marked: “Prior Approval Supplement-Expedited Review Requested.”
(v)
(3)
(ii) These changes include, but are not limited to:
(A) A change in the container closure system that does not affect the quality of the drug except as otherwise described in paragraphs (b)(2) and (b)(4) of this section;
(B) Changes solely affecting a natural protein, a recombinant DNA-derived protein/polypeptide or a complex or conjugate of a drug substance with a monoclonal antibody, including:
(
(
(C) Relaxation of an acceptance criterion or deletion of a test to comply with an official compendium that is consistent with FDA statutory and regulatory requirements.
(iii) A supplement submitted under paragraph (b)(3)(i) or (b)(3)(vi) of this section is required to give a full explanation of the basis for the change and identify the date on which the change is made. The supplement submitted under paragraph (b)(3)(i) must be labeled “Supplement-Changes Being Effected in 30 Days.”
(iv) Pending approval of the supplement by FDA and except as provided in paragraph (b)(3)(vi) of this section, distribution of the drug made using the change may begin not less than 30 days after receipt of the supplement by FDA. The information listed in paragraphs (b)(2)(iii)(A) through (b)(2)(iii)(J) of this section must be contained in the supplement.
(v) The applicant must not distribute the drug made using the change if within 30 days following FDA's receipt of the supplement, FDA informs the applicant that either:
(A) The change requires approval prior to distribution of the drug in accordance with paragraph (b)(2) of this section; or
(B) Any of the information required under paragraph (b)(3)(iv) of this section is missing. In this case, the applicant must not distribute the drug made using the change until the supplement has been amended to provide the missing information.
(vi) The agency may designate a category of changes for the purpose of providing that, in the case of a change in such category, the holder of an approved application may commence distribution of the drug involved upon receipt by the agency of a supplement for the change. The information listed in paragraphs (b)(2)(iii)(A) through (b)(2)(iii)(J) of this section must be contained in the supplement. The supplement must be labeled “Supplement-Changes Being Effected.” These changes include, but are not limited to:
(A) Addition to a specification or changes in the methods or controls to provide increased assurance that the drug will have the characteristics of identity, strength, quality, purity, or potency that it purports or is represented to possess; and
(B) A change in the size and/or shape of a container for a nonsterile drug product, except for solid dosage forms, without a change in the labeled amount of drug product or from one container closure system to another.
(vii) If the agency disapproves the supplemental application, it may order the manufacturer to cease distribution of the drug(s) made with the manufacturing change.
(4)
(ii) These changes include but are not limited to:
(A) Any change made to comply with a change to an official compendium,
(B) The deletion or reduction of an ingredient intended to affect only the color of the drug product;
(C) Replacement of equipment with that of the same design and operating principles except for those equipment changes described in paragraph (b)(3)(ii)(B)(2) of this section;
(D) A change in the size and/or shape of a container containing the same number of dosage units for a nonsterile solid dosage form drug product, without a change from one container closure system to another;
(E) A change within the container closure system for a nonsterile drug product, based upon a showing of equivalency to the approved system under a protocol approved in the application or published in an official compendium;
(F) An extension of an expiration dating period based upon full shelf-life data on production batches obtained from a protocol approved in the application;
(G) The addition or revision of an alternative analytical procedure that provides the same or increased assurance of the identity, strength, quality, purity, or potency of the drug being tested as the analytical procedure described in the approved application, or deletion of an alternative analytical procedure; and
(H) The addition by embossing, debossing, or engraving of a code imprint to a solid oral dosage form drug product other than a modified release dosage form, or a minor change in an existing code imprint.
(iii) For changes under this category, the applicant is required to submit in the annual report:
(A) A completed Form FDA 356V;
(B) A statement by the holder of the approved application that the effects of the change have been assessed;
(C) A detailed description of the change(s);
(D) The manufacturing site(s) or area(s) involved;
(E) The date each change was implemented;
(F) Data from studies and tests performed to assess the effects of the change;
(G) For a natural product, recombinant DNA-derived protein/polypeptide, complex or conjugate of a drug substance with a monoclonal antibody, sterilization process or test methodology related to sterilization process validation, relevant validation protocols and/or standard operating procedures;
(H) Appropriate documentation (for example, updated master batch records, specification sheets, etc.) including previously approved documentation (with the changes highlighted) or references to previously approved documentation;
(I) Updated stability data generated on commercial or production batches according to an approved stability protocol or commitment; and
(J) Any other information as directed by FDA.
(c)
(2)
(A) Revision in labeling, such as updating information pertaining to effects, dosages, adverse reactions, contraindications, which includes information headed “adverse reactions,” “warnings,” “precautions,” and “contraindications,” except ones described in (c)(3) of this section;
(B) Addition of an intended use;
(C) If it is a prescription drug, any mailing or promotional piece used after the drug is placed on the market is labeling requiring a supplemental application, unless:
(
(
(
(D) Any other changes in labeling, except ones described in paragraph (c)(3) of this section.
(ii) The applicant must obtain approval of the supplement from FDA prior to distribution of the drug. The supplement must contain the following:
(A) A completed Form FDA 356V;
(B) A detailed description of the proposed change;
(C) The drug(s) involved;
(D) The data derived from studies in support of the change; and
(E) Any other information as directed by FDA.
(3)
(A) The addition to package labeling, promotional labeling, or prescription drug advertising of additional warning, contraindication, adverse reaction, and precaution information;
(B) The deletion from package labeling, promotional labeling, or drug advertising of false, misleading, or unsupported intended uses or claims for effectiveness; and
(C) Any other changes as directed by FDA.
(ii) Labeling changes (for example, design and style) that do not decrease safety of drug use proposed in supplemental applications may be placed into effect prior to written notice of approval from FDA of a supplemental application.
(iii) A supplement submitted under paragraph (c)(3) of this section must include the following information:
(A) A full explanation of the basis for the changes, the date on which such changes are being effected, and plainly marked on the mailing cover and on the supplement, “Supplement—Labeling Changes Being Effected”;
(B) Two sets of printed copies of any revised labeling to be placed in use, identified with the new animal drug application number; and
(C) A statement by the applicant that all promotional labeling and all drug advertising will promptly be revised consistent with the changes made in the labeling on or within the new animal drug package no later than upon approval of the supplemental application.
(iv) If the supplemental application is not approved and the drug is being distributed with the proposed labeling, FDA may initiate an enforcement action because the drug is misbranded under section 502 of the act and/or adulterated under section 501 of the act. In addition, under section 512(e) of the act, FDA may, after due notice and opportunity for a hearing, issue an order withdrawing approval of the application.
(4)
(d)
(e)
(f)
(a) For purposes of this section the
(b) The existence of an NADA file will not be disclosed by the Food and Drug Administration before an approval has been published in the
(c) If the existence of an NADA file has not been publicly disclosed or acknowledged, no data or information in the NADA file is available for public disclosure.
(d) If the existence of an NADA file has been publicly disclosed or acknowledged before an approval has been published in the
(e) After an approval has been published in the
(1) All safety and effectiveness data and information previously disclosed to the public, as defined in § 20.81 of this chapter.
(2) A summary or summaries of the safety and effectiveness data and information submitted with or incorporated by reference in the NADA file. Such summaries do not constitute the full reports of investigations under section 512(b)(1) of the act (21 U.S.C. 360b(b)(1)) on which the safety or effectiveness of the drug may be approved. Such summaries shall consist of the following:
(i) For an NADA approved prior to July 1, 1975, internal agency records that describe such data and information, e.g., a summary of basis for approval or internal reviews of the data and information, after deletion of:
(
(
(ii) For an NADA approved on or after July 1, 1975, a summary of such data and information prepared in one of the following two alternative ways shall be publicly released when the approval is published in the
(
(
(3) A protocol for a test or study, unless it is shown to fall within the exemption established for trade secrets and confidential commercial information in § 20.61 of this chapter.
(4) Adverse reaction reports, product experience reports, consumer complaints, and other similar data and information, after deletion of:
(i) Names and any information that would identify the person using the product.
(ii) Names and any information that would identify any third party involved with the report, such as a physician, hospital, or other institution.
(5) A list of all active ingredients and any inactive ingredients previously
(6) An assay method or other analytical method, unless it serves no regulatory or compliance purpose and is shown to fall within the exemption established in § 20.61 of this chapter.
(7) All correspondence and written summaries of oral discussions relating to the NADA, in accordance with the provisions of part 20 of this chapter.
(f) All safety and effectiveness data and information not previously disclosed to the public are available for public disclosure at the time any one of the following events occurs unless extraordinary circumstances are known:
(1) The NADA has been abandoned and no further work is being undertaken with respect to it.
(2) A final determination is made that the NADA is not approvable, and all legal appeals have been exhausted.
(3) Approval of the NADA is withdrawn, and all legal appeals have been exhausted.
(4) A final determination has been made that the animal drug is not a new animal drug.
(5) A final determination has been made that the animal drug may be marketed without submission of such safety and/or effectiveness data and information.
(g) The following data and information in an NADA file are not available for public disclosure unless they have been previously disclosed to the public as defined in § 20.81 of this chapter or they relate to a product or ingredient that has been abandoned and they no longer represent a trade secret or confidential commercial or financial information as defined in § 20.61 of this chapter:
(1) Manufacturing methods or processes, including quality control procedures.
(2) Production, sales, distribution, and similar data and information, except that any compilation of such data and information aggregated and prepared in a way that does not reveal data or information which is not available for public disclosure under this provision is available for public disclosure.
(3) Quantitative or semiquantitative formulas.
(h) For purposes of this regulation, safety and effectiveness data include all studies and tests of an animal drug on animals and all studies and tests on the animal drug for identity, stability, purity, potency, and bioavailability.
(a) The existence of an INAD notice will not be disclosed by the Food and Drug Administration unless it has previously been publicly disclosed or acknowledged.
(b) The availability for public disclosure of all data and information in an INAD file shall be handled in accordance with provisions established in § 514.11.
Among the reasons why an application for a new animal drug or animal feed bearing or containing a new animal drug may contain an untrue statement of a material fact are:
(a) Differences in:
(1) Conditions of use prescribed, recommended, or suggested by the applicant for the product from the conditions of such use stated in the application;
(2) Articles used as components of the product from those listed in the application;
(3) Composition of the product from that stated in the application;
(4) Methods used in or the facilities and controls used for the manufacture, processing, or packing of the product from such methods, facilities, and controls described in the application;
(5) Labeling from the specimens contained in the application; or
(b) The unexplained omission in whole or in part from an application or from an amendment or supplement to an application or from any record or report required under the provisions of section 512 of the act and § 514.80 or § 510.301 of this chapter of any information obtained from:
(1) Investigations as to the safety, effectiveness, identity, strength, quality, or purity of the drug, made by the applicant on the drug, or
(2) Investigations or experience with the product that is the subject of the application, or any related product, available to the applicant from any source if such information is pertinent to an evaluation of the safety, effectiveness, identity, strength, quality, or purity of the drug, when such omission would bias an evaluation of the safety or effectiveness of the product.
(c) Any nonclinical laboratory study contained in the application was not conducted in compliance with the good laboratory practice regulations as set forth in part 58 of this chapter, and the application fails to include a brief statement of the reason for the noncompliance.
The following table outlines the purpose for each paragraph of this section:
(a)
(2) Each applicant must submit reports of data, studies, and other information concerning experience with new animal drugs to the Food and Drug Administration (FDA) for each approved NADA and ANADA, as required in this section. A nonapplicant must submit data, studies, and other information concerning experience with new animal drugs to the appropriate applicant, as required in this section. The applicant, in turn, must report the nonapplicant's data, studies, and other information to FDA. Applicants and nonapplicants must submit data, studies, and other information described in this section from domestic, as well as foreign sources.
(3) FDA reviews the records and reports required in this section to facilitate a determination under section 512(e) of the Federal Food, Drug, and Cosmetic Act (21 U.S.C. 360b(e)) as to whether there may be grounds for suspending or withdrawing approval of the NADA or ANADA.
(4) The requirements of this section also apply to any approved Type A medicated article. In addition, the requirements contained in § 514.80(b)(1), (b)(2), (b)(4)(iv), and (b)(4)(v) apply to any approved Type A medicated article incorporated in animal feeds.
(5) The records and reports referred to in this section are in addition to those required by the current good manufacturing practice regulations in parts 211, 225, and 226 of this chapter.
(b)
(2)
(ii)
(3)
(4)
(i)
(ii)
(iii) Nonclinical laboratory studies and clinical data not previously reported.
(A) Copies of in vitro studies (e.g., mutagenicity) and other nonclinical laboratory studies conducted by or otherwise obtained by the applicant.
(B) Copies of published clinical trials of the new animal drug (or abstracts of them) including clinical trials on safety and effectiveness, clinical trials on new uses, and reports of clinical experience pertinent to safety conducted by or otherwise obtained by the applicant. Review articles, papers, and abstracts in which the drug is used as a research tool, promotional articles, press clippings, and papers that do not contain tabulations or summaries of original data are not required to be reported.
(C) Descriptions of completed clinical trials conducted by or for the applicant must be submitted no later than 1 year after completion of research. Supporting information is not to be reported.
(iv)
(B) Reports of adverse drug experiences in the literature must be noted in the periodic drug experience report. A bibliography of pertinent references must be included with the report. Upon FDA's request, the applicant must provide a full text copy of these publications.
(C) Reports of previously not reported adverse drug experiences that occur in postapproval studies must be reported separately from other experiences in the periodic drug experience report and clearly marked or highlighted.
(v)
(5)
(ii)
(iii)
(A) The distributor's current product labeling.
(
(
(B) A signed statement by the distributor stating:
(
(
(
(
(
(c)
(1) State when a report applies to multiple applications and identify all related applications for which the report is submitted by NADA or ANADA number.
(2) Ensure that the primary application contains a list of the NADA or ANADA numbers of all related applications.
(3) Submit a completed Form FDA 2301 to the primary application and each related application with reference to the primary application by NADA/ANADA number and submission date for the complete report of the common information.
(4) All other information specific to a particular NADA/ANADA must be included in the report for that particular NADA/ANADA.
(d)
(e)
(f)
(g)
(h)
(i)
(a) After the filed application has been evaluated, the applicant will be furnished written comment on any apparent deficiencies in the application.
(b) When the description of the methods used in, and the facilities and controls used for, the manufacture, processing, and packing of such new animal drug appears adequate on its face, but it is not feasible to reach a conclusion as to the safety and effectiveness of the new animal drug solely from consideration of this description, the applicant may be notified that an establishment inspection is required to verify their adequacy.
(c) A request for samples of a new animal drug or any edible tissues and byproducts of animals treated with such a drug, shall specify the quantity deemed adequate to permit tests of analytical methods to determine their adequacy for regulatory purposes. The request should be made as early in the 180-day period as possible to assure timely completion. The date used for computing the 180-day limit for the purposes of section 512(c) of the act shall be moved forward 1 day for each day after the mailing date of the request until all of the requested samples are received. If the samples are not received within 90 days after the request, the application will be considered withdrawn without prejudice.
(d) The information contained in an application may be insufficient to determine whether a new animal drug is safe or effective in use if it fails to include (among other things) a statement showing whether such drug is to be limited to prescription sale and exempt under section 502(f) of the act from the requirement that its labeling bear adequate directions for lay use. If such drug is to be exempt, the information may also be insufficient if:
(1) The specimen labeling proposed fails to bear adequate information for professional use including indications, effects, dosages, routes, methods, and frequency and duration of administration and any relevant hazards, contraindications, side effects, and precautions under which practitioners licensed by law to administer such drug can use the drug for the purposes for which it is intended, including all purposes for which it is to be advertised, or represented, in accordance with § 201.105 of this chapter, and information concerning hazards, contraindications, side effects, and precautions relevant with respect to any uses for which such drug is to be prescribed.
(2) The application fails to show that the labeling and advertising of such drug will offer the drug for use only under those conditions for which it is offered in the labeling that is part of the application.
(3) The application fails to show that all labeling that furnishes or purports to furnish information for professional use of such drug will contain, in the same language and emphasis, the information for use including indications, effects, dosages, routes, methods, and frequency and duration of administration and any relevant warnings, hazards, contraindications, side effects, and precautions, which is contained in the labeling that is part of the application in accordance with § 201.105 of this chapter.
(e) The information contained in an application will be considered insufficient to determine whether a new animal drug is safe and effective for use when there is a refusal or failure upon written notice to furnish inspectors authorized by the Food and Drug Administration an adequate opportunity to inspect the facilities, controls, and records pertinent to the application.
(f) On the basis of preliminary consideration of an application or supplemental application containing typewritten or other draft labeling in lieu of final printed labeling, an applicant may be informed that such application is approvable when satisfactory final printed labeling identical in content to such draft copy is submitted.
(g) When an application has been found incomplete on the basis of a need for the kind of information described in § 514.6, such application shall be considered withdrawn without prejudice to future filing on the date of issuance of the letter citing the inadequacies contained in the application, unless within
(a) The Commissioner shall forward for publication in the
(b) He shall notify the applicant by sending him a copy of the proposed publication as described in paragraph (a)(1) of this section.
(a) Within 180 days after a supplement to an approved application is filed pursuant to § 514.8, the Commissioner shall approve the supplemental application in accordance with procedures set forth in § 514.105(a)(1) and (2) if he/she determines that the application satisfies the requirements of applicable statutory provisions and regulations.
(b) The Commissioner will assign a supplemental application to its proper category to ensure processing of the application.
(1)
(i) A corporate change that alters the identity or address of the sponsor of the new animal drug application (NADA).
(ii) The sale, purchase, or construction of manufacturing facilities.
(iii) The sale or purchase of an NADA.
(iv) A change in container, container style, shape, size, or components.
(v) A change in approved labeling (color, style, format, addition, deletion, or revision of certain statements, e.g., trade name, storage, expiration dates, etc).
(vi) A change in promotional material for a prescription new animal drug not exempted by § 514.8(c)(2)(i)(C)(
(vii) Changes in manufacturing processes that do not alter the method of manufacture or change the final dosage form.
(viii) A change in bulk drug shipments.
(ix) A change in an analytical method or control procedures that do not alter the approved standards.
(x) A change in an expiration date.
(xi) Addition of an alternate manufacturer, repackager, or relabeler of the drug product.
(xii) Addition of an alternate supplier of the new drug substance.
(xiii) A change permitted in advance of approval as described under § 514.8(b)(3).
(2)
(i) A change in the active ingredient concentration or composition of the final product.
(ii) A change in quality, purity, strength, and identity specifications of the active or inactive ingredients.
(iii) A change in dose (amount of drug administered per dose).
(iv) A change in the treatment regimen (schedule of dosing).
(v) Addition of a new therapeutic claim to the approved uses of the product.
(vi) Addition of a new or revised animal production claim.
(vii) Addition of a new species.
(viii) A change in the prescription or over-the-counter status of a drug product.
(ix) A change in statements regarding side effects, warnings, precautions,
(x) A change in the drug withdrawal period prior to slaughter or in the milk discard time.
(xi) A change in the tolerance for drug residues.
(xii) A change in analytical methods for drug residues.
(xiii) A revised method of synthesis or fermentation of the new drug substance.
(xiv) Updating or changes in the manufacturing process of the new drug substance and/or final dosage form (other than a change in equipment that does not alter the method of manufacture of a new animal drug, or a change from one commercial batch size to another without any change in manufacturing procedure), or changes in the methods, facilities, or controls used for the manufacture, processing, packaging, or holding of the new animal drug (other than use of an establishment not covered by the approval that is in effect) that give increased assurance that the drug will have the characteristics of identity, strength, quality, and purity which it purports or is represented to possess.
(a) The date of receipt of an application for a new animal drug shall be the date on which the application shall be deemed to be filed.
(b) An application for a new animal drug shall not be considered acceptable for filing for any of the following reasons:
(1) It does not contain complete and accurate English translations of any pertinent part in a foreign language.
(2) Fewer than three copies are submitted.
(3) It is incomplete on its face in that it is not properly organized and indexed.
(4) On its face the information concerning required matter is so inadequate that the application is clearly not approvable.
(5) The new animal drug is to be manufactured, prepared, propagated, compounded, or processed in whole or in part in any State in an establishment that has not been registered or exempted from registration under the provisions of section 510 of the act.
(6) The sponsor does not reside or maintain a place of business within the United States and the application has not been countersigned by an attorney, agent, or other representative of the applicant, which representative resides in the United States and has been duly authorized to act on behalf of the applicant and to receive communications on all matters pertaining to the application.
(7) The new animal drug is a drug subject to licensing under the animal virus, serum, and toxin law of March 4, 1913 (37 Stat. 832; 21 U.S.C. 151
(8) It fails to include, with respect to each nonclinical laboratory study contained in the application, either a statement that the study was conducted in compliance with the good laboratory practice regulations set forth in part 58 of this chapter, or, if the study was not conducted in compliance with such regulations, a brief statement of the reasons for the noncompliance.
(9) [Reserved]
(10) The applicant fails to submit a complete environmental assessment under § 25.40 of this chapter or fails to provide sufficient information to establish that the requested action is subject to categorical exclusion under § 25.30 or § 25.33 of this chapter.
(c) If an application is determined not to be acceptable for filing, the applicant shall be notified within 30 days of receipt of the application and shall be given the reasons therefore.
(d) If the applicant disputes the findings that his application is not acceptable for filing, he may make written request that the application be filed over protest, in which case it will be filed as of the day originally received.
(a) The Commissioner shall, within 180 days after the filing of the application, inform the applicant in writing of his intention to issue a notice of opportunity for a hearing on a proposal to refuse to approve the application, if the Commissioner determines upon the basis of the application, or upon the basis of other information before him with respect to a new animal drug, that:
(1) The reports of investigations required to be submitted pursuant to section 512(b) of the act do not include adequate tests by all methods reasonably applicable to show whether or not such drug is safe for use under the conditions prescribed, recommended, or suggested in the proposed labeling thereof; or
(2) The results of such tests show that such drug is unsafe for use under such conditions or do not show that such drug is safe for use under such conditions; or
(3) The methods used in and the facilities and controls used for the manufacture, processing, and packing of such drug are inadequate to preserve its identity, strength, quality, and purity; or
(4) Upon the basis of the information submitted to the Food and Drug Administration as part of the application, or upon the basis of any other information before it with respect to such drug, it has insufficient information to determine whether such drug is safe for use under such conditions. In making this determination the Commissioner shall consider, among other relevant factors:
(i) The probable consumption of such drug and of any substance formed in or on food because of the use of such drug;
(ii) The cumulative effect on man or animal of such drug, taking into account any chemically or pharmacologically related substances;
(iii) Safety factors which, in the opinion of experts qualified by scientific training and experience to evaluate the safety of such drugs, are appropriate for the use of animal experimentation data; and
(iv) Whether the conditions of use prescribed, recommended, or suggested in the proposed labeling are reasonably certain to be followed in practice; or
(5) Evaluated on the basis of information submitted as part of the application and any other information before the Food and Drug Administration with respect to such drug, there is lack of substantial evidence as defined in § 514.4.
(6) Failure to include an appropriate proposed tolerance for residues in edible products derived from animals or a withdrawal period or other restrictions for use of such drug if any tolerance or withdrawal period or other restrictions for use are required in order to assure that the edible products derived from animals treated with such drug will be safe.
(7) Based on a fair evaluation of all material facts, the labeling is false or misleading in any particular; or
(8) Such drug induces cancer when ingested by man or animal or, after appropriate tests for evaluation of the safety of such drug, induces cancer in man or animal, except that this subparagraph shall not apply with respect to such drug if the Commissioner finds that, under the conditions of use specified in proposed labeling and reasonably certain to be followed in practice:
(i) Such drug will not adversely affect the animal for which it is intended; and
(ii) No residue of such drug will be found (by methods of examination prescribed or approved by the Commissioner by regulations) in any edible portion of such animal after slaughter or in any food yielded by, or derived from the living animals.
(9) The applicant fails to submit an adequate environmental assessment under § 25.40 of this chapter or fails to provide sufficient information to establish that the requested action is subject to categorical exclusion under § 25.30 or § 25.33 of this chapter.
(10) The drug fails to satisfy the requirements of subpart E of part 500 of this chapter.
(11) Any nonclinical laboratory study that is described in the application and that is essential to show that the drug is safe for use under the conditions prescribed, recommended, or suggested in its proposed labeling, was not conducted in compliance with the good
(b) The Commissioner, as provided in § 514.200 of this chapter, shall expeditiously notify the applicant of an opportunity for a hearing on the question of whether such application is approvable, unless by the 30th day following the date of issuance of the letter informing the applicant of the intention to issue a notice of opportunity for a hearing the applicant:
(1) Withdraws the application; or
(2) Waives the opportunity for a hearing; or
(3) Agrees with the Commissioner on an additional period to precede issuance of such notice of hearing.
(a) The Secretary may suspend approval of an application approved pursuant to section 512(c) of the act and give the applicant prompt notice of his action and afford the applicant the opportunity for an expedited hearing on a finding that there is an imminent hazard to the health of man or of the animals for which such new animal drug or animal feed is intended.
(b) The Commissioner shall notify in writing the person holding an application approved pursuant to section 512(c) of the act and afford an opportunity for a hearing on a proposal to withdraw approval of such application if he finds:
(1) That the application contains any untrue statement of a material fact; or
(2) That the applicant has made any changes from the standpoint of safety or effectiveness beyond the variations provided for in the application unless he has supplemented the application by filing with the Secretary adequate information respecting all such changes and unless there is in effect an approval of the supplemental application, or such changes are those for which written authorization or approval is not required as provided for in § 514.8. The supplemental application shall be treated in the same manner as the original application.
(3) That in the case of an application for use of a new animal drug approved or deemed approved pursuant to section 512(c) of the act:
(i) Experience or scientific data show that such drug is unsafe for use under the conditions of use upon the basis of which the application was approved; or
(ii) New evidence not contained in such application or not available to the Secretary until after such application was approved, or tests by new methods, or tests by methods not deemed reasonably applicable when such application was approved, evaluated together with the evidence available to the Secretary when the application was approved, shows that such drug is not shown to be safe for use under the conditions of use upon the basis of which the application was approved or that section 512 (d)(1)(H) of the act applies to such drug; or
(iii) On the basis of new information before him with respect to such drug, evaluated together with the evidence available to him when the application was approved, there is a lack of substantial evidence that such drug will have the effect it purports or is represented to have under the conditions of use prescribed, recommended, or suggested in the labeling thereof.
(4) That any nonclinical laboratory study that is described in the application and that is essential to show that the drug is safe for use under the conditions prescribed, recommended, or suggested in its proposed labeling, was not conducted in compliance with the good laboratory practice regulations as set forth in part 58 of this chapter and no reason for the noncompliance is provided or, if it is, the differences between the practices used in conducting the study and the good laboratory practice regulations do not support the validity of the study.
(c) The Commissioner may notify in writing the person holding an application approved pursuant to section 512(c) of the act and afford an opportunity for a hearing on a proposal to withdraw approval of such application if he finds:
(1) That the applicant has failed to establish a system for maintaining required records, or has repeatedly or deliberately failed to maintain such records or to make required reports in accordance with a regulation or order under section 512(l)(1) of the act, or the applicant has refused to permit access to, or copying, or verification of, such records as required by section 512(l)(2) of the act; or
(2) That on the basis of new information before him evaluated together with the evidence before him when the application was approved, the methods used in, or the facilities and controls used for, the manufacture, processing, and packing of such drug or animal feed are inadequate to assure and preserve its identity, strength, quality, and purity and were not made adequate within a reasonable time after receipt of written notice from the Secretary specifying the matter complained of; or
(3) That on the basis of new information before him, evaluated together with the evidence before him when the application was approved, the labeling of such drug, based on a fair evaluation of all material facts, is false or misleading in any particular and was not corrected within a reasonable time after receipt of written notice from the Secretary specifying the matter complained of.
(d) Approval of an application pursuant to section 512(c) of the act will be withdrawn on the basis of a request for its withdrawal submitted in writing by a person holding an approved new animal drug application on the grounds that the drug subject to such application is no longer being marketed and information is included in support of this finding, provided none of the conditions cited in paragraphs (a), (b), and (c) of this section pertain to the subject drug. A written request for such withdrawal shall be construed as a waiver of the opportunity for a hearing as otherwise provided for in this section. Withdrawal of approval of an application under the provisions of this paragraph shall be without prejudice.
(e) On the basis of the withdrawal of approval of an application for a new animal drug approved pursuant to section 512(c) of the act, the regulation published pursuant to section 512(i) of the act covering the conditions of use of such drug as provided for in the application shall be revoked.
When an approval of an application submitted pursuant to section 512 of the act is withdrawn by the Commissioner, he will give appropriate public notice of such action by publication in the
(a)
(b)
(1) The protocol for the study (protocol) and the report of the study results (study report) must include a clear statement of the study objective(s).
(2) The study is conducted in accordance with an appropriate standard of conduct that addresses, among other issues, study conduct, study personnel, study facilities, and study documentation. The protocol contains a statement acknowledging the applicability of, and intention to follow, a standard of conduct acceptable to FDA. The study report contains a statement describing adherence to the standard.
(3) The study is conducted with a new animal drug that is produced in accordance with appropriate manufacturing practices, which include, but are not necessarily limited to, the manufacture, processing, packaging, holding, and labeling of the new animal drug such that the critical characteristics of identity, strength, quality, purity, and physical form of the new animal drug are known, recorded, and reproducible, to permit meaningful evaluations of and comparisons with other studies conducted with the new animal drug. The physical form of a new animal drug includes the formulation and physical characterization (including delivery systems thereof, if any) of the new animal drug as presented to the animal. The protocol and study report must include an identification number which can be correlated with the specific formulation and production process used to manufacture the new animal drug used in the study.
(4) The study uses a design that permits a valid comparison with one or more controls to provide a quantitative evaluation of drug effects. The protocol and the study report must describe the precise nature of the study design, e.g., duration of treatment periods, whether treatments are parallel, sequential, or crossover, and the determination of sample size. Within the broad range of studies conducted to support a determination of the effectiveness of a new animal drug, certain of the controls listed below would be appropriate and preferred depending on the study conducted:
(i)
(ii)
(iii)
(iv)
(5) The study uses a method of selecting animals that provides adequate assurances that the animals are suitable for the purposes of the study. For example, the animals can reasonably be expected to have animal production characteristics typical of the class(es) of animals for which the new animal drug is intended, there is adequate assurance that the animals have the disease or condition being studied, or, in the case of prophylactic agents, evidence of susceptibility and exposure to the condition against which prophylaxis is desired has been provided. The protocol and the study report describe the method of selecting animals for the study.
(6) The study uses a method to assign a treatment or a control to each experimental unit of animals that is random and minimizes bias. Experimental units of animals are groups of animals that are comparable with respect to pertinent variables such as age, sex, class of animal, severity of disease, duration of disease, dietary regimen, level of animal production, and use of drugs or therapy other than the new animal drug. The protocol and the study report describe the method of assignment of animals to an experimental unit to account for pertinent variables and method of assignment of a treatment or a control to the experimental units. When the effect of such variables is accounted for by an appropriate design, and when, within the same animal, effects due to the test drug can be obtained free of the effects of such variables, the same animal may be used for both the test drug and the control using the controls set forth in paragraph (b)(4) of this section.
(7) The study uses methods to minimize bias on the part of observers and analysts of the data that are adequate to prevent undue influences on the results and interpretation of the study data. The protocol and study report explain the methods of observation and recording of the animal response variables and document the methods, such as “blinding” or “masking,” used in the study for excluding or minimizing bias in the observations.
(8) The study uses methods to assess animal response that are well defined and reliable. The protocol and study report describe the methods for conducting the study, including any appropriate analytical and statistical methods, used to collect and analyze the data resulting from the conduct of the study, describe the criteria used to assess response, and, when appropriate, justify the selection of the methods to assess animal response.
(9) There is an analysis and evaluation of the results of the study in accord with the protocol adequate to assess the effects of the new animal drug. The study report evaluates the methods used to conduct, and presents and evaluates the results of, the study as to their adequacy to assess the effects of the new animal drug. This evaluation of the results of the study assesses, among other items, the comparability of treatment and control groups with respect to pertinent variables and the effects of any interim analyses performed.
(c)
(2) Studies of a new animal drug conducted under field conditions shall, consistent with generally recognized scientific principles and procedures, use an appropriate control that permits comparison, employ procedures to minimize bias, and have the characteristics generally described in paragraph (b) of this section. However, because field studies are conducted under field conditions, it is recognized that the level of control over some study conditions need not or should not be the same as the level of control in laboratory studies. While not all conditions relating to a field study need to be or should be controlled, observations of the conditions under which the new animal drug is tested shall be recorded in sufficient detail to permit evaluation of the study. Adequate and well-controlled field studies shall balance the need to control study conditions with the need to observe the true effect of the new animal drug under closely approximated actual use conditions.
(d)
(e)
The Commissioner, upon his own initiative or upon request of an applicant stating reasonable grounds therefor and if he finds that the facts so require, may issue an order approving an application that previously has had its approval refused, suspended, or withdrawn.
All notices and orders under this subchapter E and section 512 of the act pertaining to new animal drug applications shall be served:
(a) In person by any officer or employee of the Department designated by the Commissioner; or
(b) By mailing the order by certified mail addressed to the applicant or respondent at his last known address in the records of the Food and Drug Administration.
(a) The notice to the applicant of opportunity for a hearing on a proposal by the Commissioner to refuse to approve an application or to withdraw the approval of an application will specify the grounds upon which he proposes to issue his order. On request of the applicant, the Commissioner will explain the reasons for his action. The notice of opportunity for a hearing will be published in the
(1) To avail himself of the opportunity for a hearing; or
(2) Not to avail himself of the opportunity for a hearing.
(b) If the applicant fails to file a written appearance in answer to the notice of opportunity for hearing, his failure will be construed as an election not to avail himself of the opportunity for the hearing, and the Commissioner without further notice may enter a final order.
(c) If the applicant elects to avail himself of the opportunity for a hearing, he is required to file a written appearance requesting the hearing within 30 days after the publication of the notice, giving the reason why the application should not be refused or should not be withdrawn, together with a well-organized and full-factual analysis of the clinical and other investigational data he is prepared to prove in support of his opposition to the Commissioner's proposal. A request for a hearing may not rest upon mere allegations or denials, but must set forth specific facts showing there is a genuine and substantial issue of fact that requires a hearing. When it clearly appears from the data in the application and from the reasons and a factual analysis in the request for the hearing that no genuine and substantial issue
(d) The hearing will be open to the public; however, if the Commissioner finds that portions of the application which serve as a basis for the hearing contain information concerning a method or process entitled to protection as a trade secret, the part of the hearing involving such portions will not be public, unless the respondent so specifies in his appearance.
Hearings relating to new animal drugs under section 512(d) and (e) of the act shall be governed by part 12 of this chapter.
(a) The transcript and record shall be certified by the Commissioner. In any case in which the Commissioner enters an order without a hearing pursuant to § 314.200(g) of this chapter, the request(s) for hearing together with the data and information submitted and the Commissioner's findings and conclusions shall be included in the record certified by the Commissioner.
(b) Judicial review of an order withdrawing approval of a new drug application, whether or not a hearing has been held, may be sought by a manufacturer or distributor of an identical, related, or similar drug product, as defined in § 310.6 of this chapter, in a United States court of appeals pursuant to section 505(h) of the act.
21 U.S.C. 360b, 371.
(a) Medicated feed mill license applications (Forms FDA 3448) may be obtained from the Public Health Service, Consolidated Forms and Publications Distribution Center, Washington Commerce Center, 3222 Hubbard Rd., Landover, MD 20785, or electronically from the Center for Veterinary Medicine home page at
(b) A completed medicated feed mill license must contain the following information:
(1) The full business name and address of the facility at which the manufacturing is to take place.
(2) The facility's FDA registration number as required by section 510 of the Federal Food, Drug, and Cosmetic Act (the act).
(3) The name, title, and signature of the responsible individual or individuals for that facility.
(4) A certification that the animal feeds bearing or containing new animal drugs are manufactured and labeled in accordance with the applicable regulations published under section 512(i) of the act or in accordance with the index listing published under section 572(e)(2) of the act.
(5) A certification that the methods used in, and the facilities and controls used for, manufacturing, processing, packaging, and holding such animal feeds conform to current good manufacturing practice as described in section 501(a)(2)(B) of the act and in part 225 of this chapter.
(6) A certification that the facility will establish and maintain all records required by regulation or order issued under sections 512(m)(5)(A) or 504(a)(3)(A) of the act, and will permit access to, or copying or verification of such records.
(7) A commitment that current approved or index listed Type B and/or Type C medicated feed labeling for each Type B and/or Type C medicated feed to be manufactured will be in the possession of the feed manufacturing facility prior to receiving the Type A medicated article containing such drug.
(8) A commitment to renew registration every year with FDA as required in §§ 207.20 and 207.21 of this chapter.
(c) Applications must be completed, signed, and submitted to the Division of Animal Feeds (HFV-220), Center for Veterinary Medicine, Food and Drug Administration, 7500 Standish Pl., Rockville, MD 20855.
(d) Applications that are facially deficient will be returned to the applicant. All reasons for the return of the application will be made known to the applicant.
(e) Upon approval, the original copy of the application will be signed by an authorized employee of FDA designated by the Commissioner of Food and Drugs, and a copy will be returned to the applicant.
(a) After approval of a medicated feed mill license application to manufacture animal feed, a supplemental application shall be submitted for a change in ownership and/or a change in mailing address of the facility site.
(b) Each supplemental application should be accompanied by a fully completed Form FDA 3448 and include an explanation of the change.
(c) Within 30 working days after a supplemental application has been filed, if the Commissioner of Food and Drugs determines that the application provides adequate information respecting the change in ownership and/or postal address of the facility site, then an authorized employee of the Food and Drug Administration designated by the Commissioner shall notify the applicant that it is approved by signing and mailing to the applicant a copy of the Form FDA 3448. Supplemental applications that do not provide adequate information shall be returned to the applicant and all reasons for the return of the application shall be made known to the applicant.
Within 90 days after an application has been filed under § 515.10, if the Commissioner of Food and Drugs (the Commissioner) determines that none of the grounds for denying approval specified in section 512(m)(3) of the Federal Food, Drug, and Cosmetic Act (the act) applies, an authorized employee of the Food and Drug Administration designated by the Commissioner shall notify the applicant that it is approved by signing and mailing to the applicant a copy of the Form FDA 3448.
(a) The Commissioner of Food and Drugs (the Commissioner) shall within 90 days, or such additional period as may be agreed upon by the Commissioner and the applicant, after the filing of an application under § 515.10, inform the applicant in writing of his/her intention to issue a notice of opportunity for a hearing on a proposal to refuse to approve the application, if the Commissioner determines upon the basis of the application, on the basis of a preapproval inspection, or upon the basis of any other information before him that:
(1) The application is incomplete, false, or misleading in any particular; or
(2) The methods used in and the facilities and controls used for the manufacturing, processing, and packaging of such animal feed are not adequate to preserve the identity, strength, quality, and purity of the new animal drug therein; or
(3) The facility manufactures animal feeds bearing or containing new animal drugs in a manner that does not accord with the specifications for manufacture or labels animal feeds bearing or containing new animal drugs in a manner that does not accord with the conditions or indications of use that are published under section 512(i) or 572(e)(2) of the act.
(b) The Commissioner, as provided in § 515.30, shall expeditiously notify the applicant of an opportunity for a hearing on the question of whether such application is approvable, unless by the 30th day following the date of issuance of the letter informing the applicant of the intention to issue a notice of opportunity for a hearing the applicant:
(1) Withdraws the application; or
(2) Waives the opportunity for a hearing; or
(3) Agrees with the Commissioner on an additional period to preceed issuance of such notice of hearing.
(a) The Secretary of Health and Human Services may suspend a medicated feed mill license approved under section 512(m)(2) of the Federal Food, Drug, and Cosmetic Act (the act) and give the person holding the medicated feed mill license application prompt notice of this action and afford the applicant the opportunity for an expedited hearing on a finding that there is an imminent hazard to the health of man or of the animals for which such animal feed is intended.
(b) The Commissioner of Food and Drugs (the Commissioner) shall notify in writing the person holding an application approved under section 512(m)(2) of the act and afford an opportunity for a hearing on a proposal to revoke approval of such application if the Commissioner finds:
(1) That the application contains any untrue statement of a material fact; or
(2) That the applicant has made any changes that would cause the application to contain any untrue statements of material fact or that would affect the safety or effectiveness of the animal feeds manufactured at the facility unless the applicant has supplemented the application by filing a supplemental application under § 515.11.
(c) The Commissioner may notify in writing the person holding an application approved under section 512(m)(2) of the act and afford an opportunity for a hearing on a proposal to revoke approval of such application if the Commissioner finds:
(1) That the applicant has failed to establish a system for maintaining required records, or has repeatedly or deliberately failed to maintain such records or to make required reports in accordance with a regulation or order under sections 512(m)(5)(A) or 504(a)(3)(A) of the act, or the applicant has refused to permit access to, or copying, or verification of, such records as required by sections 512(m)(5)(B) or 504(a)(3)(B) of the act; or
(2) That on the basis of new information before him, evaluated together with the evidence before him when such license was issued, the methods used in, or the facilities and controls used for, the manufacture, processing, packing, and holding of such animal feed are inadequate to assure and preserve the identity, strength, quality, and purity of the new animal drug therein, and were not made adequate within a reasonable time after receipt of written notice from the Commissioner specifying the matter complained of; or
(3) That on the basis of new information before him, evaluated together with the evidence before him when such license was issued, the labeling of any animal feeds, based on a fair evaluation of all material facts, is false or misleading in any particular and was not corrected within a reasonable time after receipt of written notice from the Commissioner specifying the matter complained of; or
(4) That on the basis of new information before him, evaluated together with the evidence before him when such license was issued, the facility has manufactured, processed, packed, or held animal feed bearing or containing a new animal drug adulterated under section 501(a)(6) of the act, and the facility did not discontinue the manufacture, processing, packing, or holding of such animal feed within a reasonable time after receipt of written notice from the Commissioner specifying the matter complained of.
A license issued under section 512(m)(2) of the Federal Food, Drug, and Cosmetic Act (the act) will be revoked on the basis of a request for its revocation submitted in writing by a responsible individual holding such license on the grounds that the facility no longer manufactures any animal feed covered under § 558.4(b) of this chapter. A written request for such revocation shall be construed as a waiver of the opportunity for a hearing as otherwise provided for in this section. Revocation of approval of a medicated feed mill license under the provisions of this paragraph shall be without prejudice.
When a license approved under section 512 of the Federal Food, Drug, and Cosmetic Act (the act) is revoked by the Commissioner of Food and Drugs (the Commissioner), the Commissioner will give appropriate public notice of such action by publication in the
The Commissioner of Food and Drugs (the Commissioner), upon his/her own initiative or upon request of an applicant stating reasonable grounds therefor and if the Commissioner finds that the facts so require, may issue an order approving a medicated feed mill license application that previously has had its approval refused, suspended, or revoked.
All notices and orders under this part 515 and section 512 of the Federal Food, Drug, and Cosmetic Act (the act) pertaining to medicated feed mill licenses shall be served:
(a) In person by any officer or employee of the Department of Health and Human Services designated by the Commissioner of Food and Drugs; or
(b) By mailing the order by certified mail addressed to the applicant or respondent at the applicant or respondent's last known address in the records of the Food and Drug Administration.
(a) The notice to the applicant of opportunity for a hearing on a proposal by the Commissioner of Food and Drugs (the Commissioner) to refuse to approve a medicated feed mill license application or to revoke the approval of a medicated feed mill license will specify the grounds upon which the Commissioner proposes to issue this order. On request of the applicant, the Commissioner will explain the reasons for the action. The notice of opportunity for a hearing will be published in the
(1) To avail himself of the opportunity for a hearing; or
(2) Not to avail himself of the opportunity for a hearing.
(b) If the applicant fails to file a written appearance in answer to the notice of opportunity for hearing, this failure will be construed as an election not to avail himself of the opportunity for the hearing, and the Commissioner without further notice may enter a final order.
(c) If the applicant elects to avail himself of the opportunity for a hearing, the applicant is required to file a written appearance requesting the hearing within 30 days after the publication of the notice, giving the reason why the application should not be refused or the medicated feed mill license should not be revoked, together with a well-organized and full-factual analysis of the information the applicant is prepared to prove in support of his opposition to the Commissioner's proposal. A request for a hearing may not rest upon mere allegations or denials, but must set forth specific facts showing there is a genuine and substantial issue of fact that requires a hearing. When it clearly appears from the information in the application and from the reasons and factual analysis in the request for the hearing that no genuine and substantial issue of fact precludes the refusal to approve the application or the revocation of approval of the application, the Commissioner will enter an order on this information, stating his/her findings and conclusions. If a hearing is requested and is justified by the applicant's response to the notice of opportunity for a hearing, the issues will be defined, an Administrative Law Judge will be named, and the Judge shall issue a written notice of the time and place at which the hearing will commence. In the case of denial of approval, such time shall be not more than 90 days after the expiration of such 30 days unless the Administrative Law Judge and the applicant otherwise agree; and, in the case of withdrawal of approval, such time shall be as soon as practicable.
(d) The hearing will be open to the public; however, if the Commissioner finds that portions of the application which serve as a basis for the hearing contain information concerning a method or process entitled to protection as a trade secret, the part of the hearing involving such portions will not be public, unless the respondent so specifies in the appearance.
Hearings relating to new animal drugs under section 512(m)(3) and (m)(4) of the Federal Food, Drug, and Cosmetic Act (the act) shall be governed by part 12 of this chapter.
The transcript and record shall be certified by the Commissioner of Food and Drugs (the Commissioner). In any case in which the Commissioner enters an order without a hearing under § 314.200(g) of this chapter, the request(s) for hearing together with the data and information submitted and the Commissioner's findings and conclusions shall be included in the record certified by the Commissioner.
21 U.S.C. 360ccc-1, 360ccc-2, 371.
(a) This part implements section 573 of the Federal Food, Drug, and Cosmetic Act (the act) (21 U.S.C. 360ccc-2) and contains the following subparts:
(1) Subpart A—General Provisions.
(2) Subpart B—Designation of a Minor Use or Minor Species New Animal Drug.
(3) Subpart C [Reserved]
(4) Subpart D [Reserved]
(b) References in this part to regulatory sections of the Code of Federal Regulations are to Chapter I of Title 21, unless otherwise noted.
This part establishes standards and procedures for implementing section 573 of the act, including designation of minor use or minor species new animal drugs and associated exclusive marketing rights.
(a) The definitions and interpretations contained in section 201 of the Federal Food, Drug, and Cosmetic Act (the act) (21 U.S.C. 321) apply to those terms when used in this part.
(b) The following definitions of terms apply to all subparts of part 516:
(i) The drug has been shown to be more effective, as assessed by effect on a clinically meaningful endpoint in adequate and well-controlled clinical trials, than a conditionally approved or approved MUMS drug, that is otherwise the same drug. Generally, this would represent the same kind of evidence needed to support a comparative effectiveness claim for two different drugs; in most cases, direct comparative clinical trials will be necessary; or
(ii) The drug has been shown to be safer than a conditionally-approved or approved MUMS drug, that is otherwise the same drug, in a substantial portion of the target population, for example, by the elimination of an ingredient or contaminant that is associated with relatively frequent adverse effects. In some cases, direct comparative clinical trials will be necessary.
(i) Part 520: Oral dosage form new animal drugs (excluding use in animal feeds as specified in part 558 of this chapter).
(ii) Part 522: Implantation or injectable dosage form new animal drugs.
(iii) Part 524: Ophthalmic and topical dosage form new animal drugs.
(iv) Part 526: Intramammary dosage forms.
(v) Part 529: Certain other dosage form new animal drugs.
(vi) Part 558: New animal drugs for use in animal feeds.
(i) If it is a MUMS drug composed of small molecules and contains the same active moiety as a prior designated, conditionally-approved, or approved MUMS drug, even if the particular ester or salt (including a salt with hydrogen or coordination bonds) or other noncovalent derivative such as a complex, chelate or clathrate is not the same, it is considered the same drug; except that, if the prior MUMS drug is conditionally approved or approved and the second MUMS drug is shown to be functionally superior to the conditionally approved or approved MUMS
(ii) If it is a MUMS drug composed of large molecules (macromolecules) and contains the same principal molecular structural features (but not necessarily all of the same structural features) as a prior designated, conditionally approved, or approved MUMS drug, it is considered the same drug; except that, if the prior MUMS drug is conditionally approved or approved and the second MUMS drug is shown to be functionally superior to the conditionally approved or approved MUMS drug for the same intended use, it is not considered the same drug. This criterion will be applied as follows to different kinds of macromolecules:
(A) Two protein drugs would be considered the same if the only differences in structure between them were due to post-translational events or infidelity of translation or transcription or were minor differences in amino acid sequence; other potentially important differences, such as different glycosylation patterns or different tertiary structures, would not cause the drugs to be considered different unless the subsequent drug is shown to be functionally superior.
(B) Two polysaccharide drugs would be considered the same if they had identical saccharide repeating units, even if the number of units were to vary and even if there were postpolymerization modifications, unless the subsequent drug is shown to be functionally superior.
(C) Two polynucleotide drugs consisting of two or more distinct nucleotides would be considered the same if they had an identical sequence of purine and pyrimidine bases (or their derivatives) bound to an identical sugar backbone (ribose, deoxyribose, or modifications of these sugars), unless the subsequent drug is shown to be functionally superior.
(D) Closely related, complex partly definable drugs with similar pharmacologic intent would be considered the same unless the subsequent drug is shown to be functionally superior.
(i) Two intended uses are considered the same if one of the intended uses falls completely within the scope of the other.
(ii) For intended uses associated with diseases or conditions with multiple causative organisms, two intended uses are not considered the same when they involve different causative organisms or different subsets of causative organisms of that disease or condition when the causative organisms involved can reliably be shown to be clinically significant causes of the disease or condition.
(iii) Two intended uses of a drug are not considered the same if they involve different intended species or different definable subpopulations (including “production classes”) of a species.
This subpart implements section 573 of the act. Specifically, this subpart sets forth the procedures and requirements for submissions to FDA of requests for designation of a new animal drug for a minor use or a minor species.
This subpart establishes standards and procedures for determining eligibility for designation and the associated incentives and benefits described in section 573 of the act, including a 7-year period of exclusive marketing rights.
The following definitions of terms apply only in the context of subpart B of this part:
All correspondence relating to a request for designation of a MUMS drug must be addressed to the Director of the Office of Minor Use and Minor Species Animal Drug Development. Submissions not including all elements specified in § 516.20 will be returned to the sponsor without review.
The person requesting designation must be the sponsor and the real party in interest of the development and the intended or actual production and sales of the drug or the permanent-resident U.S. agent for such a sponsor.
(a) A sponsor that submits a request for designation of a new animal drug intended for a minor use or minor species must submit each request in the form and containing the information required in paragraph (b) of this section. While a request for designation may involve multiple intended uses, each request for designation must constitute a separate submission. A sponsor may request MUMS-drug designation of a previously unapproved drug, or a new intended use or dosage form for an already conditionally approved or approved drug. Only one sponsor may receive MUMS-drug designation of the same drug, in the same dosage form, for the same intended use.
(b) A sponsor must submit two copies of a completed, dated, and signed request for designation that contains the following information:
(1) A request for designation of a new animal drug for a minor use or use in a minor species, which must be specific.
(2) The name and address of the sponsor; the name of the sponsor's primary contact person and/or permanent-resident U.S. agent including title, address, and telephone number; the generic and trade name, if any, of the drug; and the name and address of the source of the drug.
(3) A description of the proposed intended use for which the drug is being or will be investigated.
(4) A description of the drug and dosage form.
(5) A discussion of the scientific rationale for the intended use of the drug; specific reference, including date(s) of submission, to all data from nonclinical laboratory studies, clinical investigations, copies of pertinent unpublished and published papers, and other relevant data that are available to the sponsor, whether positive, negative, or inconclusive.
(6) A specific description of the product development plan for the drug, its dosage form, and its intended use.
(7) If the drug is intended for a minor use in a major species, documentation in accordance with § 516.21, with appended authoritative references, to demonstrate that such use is a minor use.
(8) A statement that the sponsor submitting the request is the real party in interest of the development and the intended or actual production and sales of the product.
(9) A statement that the sponsor acknowledges that, upon granting a request for MUMS designation, FDA will make information regarding the designation publicly available as specified in § 516.28.
So that FDA can determine whether a drug qualifies for MUMS-drug designation as a minor use in a major species under section 573 of the act, the sponsor shall include in its request to FDA for MUMS-drug designation under § 516.20 documentation demonstrating that the use is limited to a small number of animals (annualized). This documentation must include the following information:
(a) The estimated total number of animals to which the drug could potentially be administered on an annual basis for the treatment, control, or prevention of the disease or condition for which the drug is being developed, including animals administered the drug as part of herd or flock treatment, together with a list of the sources (including dates of information provided and literature citations) for the estimate.
(b) The estimated total number of animals referred to in paragraph (a) of this section may be further reduced to only a subset of the estimated total number of animals if administration of the drug is only medically justified for this subset. To establish this, requestors must demonstrate that administration of the drug to animals subject to the disease or condition for which the drug is being developed other than the subset is not medically justified. The sponsor must also include a list of the sources (including dates of information provided and literature citations) for the justification that administration of the drug to animals other than the targeted subset is medically inappropriate.
(c) An estimate of the potential market associated with the total number of animals established in paragraph (a) of this section compared to an estimate of the development costs of the proposed drug, in the proposed dosage form, for the proposed intended use.
Every foreign sponsor that seeks MUMS-drug designation shall name a permanent resident of the United States as the sponsor's agent upon whom service of all processes, notices, orders, decisions, requirements, and other communications may be made on behalf of the sponsor. Notifications of changes in such agents or changes of address of agents should preferably be provided in advance, but not later than 60 days after the effective date of such changes. The permanent-resident U.S. agent may be an individual, firm, or domestic corporation and may represent any number of sponsors. The name and address of the permanent-resident U.S. agent shall be provided to the Director of the Office of Minor Use and Minor Species Animal Drug Development.
A sponsor may request MUMS-drug designation at any time in the drug development process prior to the submission of an application for either conditional approval or approval of the
(a) FDA may grant the request for MUMS-drug designation if none of the reasons described in § 516.25 for refusal to grant such a request apply.
(b) When a request for MUMS-drug designation is granted, FDA will notify the sponsor in writing and will give public notice of the MUMS-drug designation in accordance with § 516.28.
(a) FDA will refuse to grant a request for MUMS-drug designation if any of the following reasons apply:
(1) The drug is not intended for use in a minor species or FDA determines that there is insufficient evidence to demonstrate that the drug is intended for a minor use in a major species.
(2) The drug is the same drug in the same dosage form for the same intended use as one that already has a MUMS-drug designation but has not yet been conditionally approved or approved.
(3) The drug is the same drug in the same dosage form for the same intended use as one that is already conditionally approved or approved. A drug that FDA has found to be functionally superior is not considered the same drug as an already conditionally approved or approved drug even if it is otherwise the same drug in the same dosage form for the same intended use.
(4) The sponsor has failed to provide:
(i) A credible scientific rationale in support of the intended use,
(ii) Sufficient information about the product development plan for the drug, its dosage form, and its intended use to establish that adherence to the plan can lead to successful drug development in a timely manner, and
(iii) Any other information required under § 516.20.
(b) FDA may refuse to grant a request for MUMS-drug designation if the request for designation contains an untrue statement of material fact or omits material information.
(a) At any time prior to conditional approval or approval of an application for a MUMS-designated drug, the sponsor may apply for an amendment to the designated intended use if the proposed change is due to new and unexpected findings in research on the drug, information arising from FDA recommendations, or other unforeseen developments.
(b) FDA will grant the amendment if it finds:
(1) That the initial designation request was made in good faith;
(2) That the amendment is intended to make the MUMS-drug designated intended use conform to the results of new and unexpected findings in research on the drug, information arising from FDA recommendations, or other unforeseen developments; and
(3) In the case of a minor use, that as of the date of the submission of the amendment request, the amendment would not result in the intended use of the drug no longer being considered a minor use.
(a) A sponsor may transfer sponsorship of a MUMS-designated drug to another person. A change of sponsorship will also transfer the designation status of the drug which will remain in effect for the new sponsor subject to the same conditions applicable to the former sponsor provided that at the time of a potential transfer, the new and former sponsors submit the following information in writing and obtain permission from FDA:
(1) The former sponsor shall submit a letter to FDA that documents the transfer of sponsorship of the MUMS-designated drug. This letter shall specify the date of the transfer. The former sponsor shall also certify in writing to FDA that a complete copy of the request for MUMS-drug designation, including any amendments to the request, and correspondence relevant to the MUMS-drug designation, has been provided to the new sponsor.
(2) The new sponsor shall submit a letter or other document containing the following information:
(i) A statement accepting the MUMS-drug designated file or application;
(ii) The date that the change in sponsorship is intended to be effective;
(iii) A statement that the new sponsor has a complete copy of the request for MUMS-drug designation, including any amendments to the request and any correspondence relevant to the MUMS-drug designation;
(iv) A statement that the new sponsor understands and accepts the responsibilities of a sponsor of a MUMS-designated drug established elsewhere in this subpart;
(v) The name and address of a new primary contact person or permanent resident U.S. agent; and
(vi) Evidence that the new sponsor is capable of actively pursuing approval with due diligence.
(b) No sponsor may relieve itself of responsibilities under the act or under this subpart by assigning rights to another person without:
(1) Assuring that the new sponsor will carry out such responsibilities; and
(2) Obtaining prior permission from FDA.
FDA will periodically update a publicly available list of MUMS-designated drugs. This list will be placed on file at the FDA Division of Dockets Management, and will contain the following information for each MUMS-designated drug:
(a) The name and address of the sponsor;
(b) The established name and trade name, if any, of the drug;
(c) The dosage form of the drug;
(d) The species and the proposed intended use for which MUMS-drug designation was granted; and
(e) The date designation was granted.
(a) The sponsor of a MUMS-designated drug must notify FDA of any decision to discontinue active pursuit of conditional approval or approval of such MUMS drug. FDA must terminate the designation upon such notification.
(b) A conditionally-approved or approved MUMS-designated drug sponsor must notify FDA at least 1 year before it intends to discontinue the manufacture of such MUMS drug. FDA must terminate designation upon such notification.
(c) MUMS designation shall terminate upon the expiration of any applicable period of exclusive marketing rights under this subpart.
(d) FDA may terminate designation if it independently determines that the sponsor is not actively pursuing conditional approval or approval with due diligence. At a minimum, due diligence must be demonstrated by:
(1) Submission of annual progress reports in a timely manner in accordance with § 516.30 that demonstrate that the sponsor is progressing in accordance with the drug development plan submitted to the agency under § 516.20 and
(2) Compliance with all applicable requirements of part 511 of this chapter.
(e) Designation of a conditionally approved or approved MUMS-designated drug and the associated exclusive marketing rights may be terminated if the sponsor is unable to provide sufficient quantities of the drug to meet the needs for which it is designated.
(f) FDA may also terminate MUMS-drug designation for any drug if the agency finds that:
(1) The request for designation contained an untrue statement of material fact; or
(2) The request for designation omitted material information required by this subpart; or
(3) FDA subsequently finds that the drug in fact had not been eligible for MUMS-drug designation at the time of submission of the request;
(4) The same drug, in the same dosage form, for the same intended use becomes conditionally approved or approved for another sponsor; or
(5) FDA withdraws the conditional approval or approval of the application for the new animal drug.
(g) For a conditionally approved or approved drug, termination of MUMS-drug designation also terminates the sponsor's exclusive marketing rights for the drug but does not withdraw the conditional approval or approval of the drug's application.
(h) Where a drug has been MUMS-designated for a minor use in a major species, its designation will not be terminated on the grounds that the number of animals to which the drug could potentially be administered on an annual basis for the treatment, control, or prevention of the disease or condition for which the drug is being developed, including animals administered the drug as part of herd or flock treatment, subsequently increases.
(i) When a MUMS-drug designation is terminated, FDA will notify the sponsor in writing and will give public notice of the termination of the MUMS-drug designation.
Within 14 months after the date on which a MUMS drug is granted designation and annually thereafter until approval, the sponsor of a MUMS-designated drug shall submit a brief progress report on the drug to the investigational new animal drug file addressed to the Director of the Office of Minor Use and Minor Species Animal Drug Development that includes the following information:
(a) A short account of the progress of drug development including a description of studies initiated, ongoing, and completed, and a short summary of the status or results of such studies;
(b) A description of the investigational plan for the coming year, as well as any anticipated difficulties in development, testing, and marketing; and
(c) A brief discussion of any changes that may affect the MUMS-designated drug status of the product. For example, situations in which testing data demonstrate that the proposed intended use is inappropriate due to unexpected issues of safety or effectiveness.
(a) After conditional approval or approval of an application for a MUMS-designated drug in the dosage form and for the intended use for which MUMS-drug designation has been granted, FDA will not conditionally approve or approve another application or abbreviated application for the same drug in the same dosage form for the same intended use before the expiration of 7 years after the date of conditional approval or approval as stated in the approval letter from FDA, except that such an application can be conditionally approved or approved sooner if, and at such time as, any of the following occurs:
(1) FDA terminates the MUMS-drug designation and associated exclusive marketing rights under § 516.29; or
(2) FDA withdraws the conditional approval or approval of the application for the drug for any reason; or
(3) The sponsor with exclusive marketing rights provides written consent to FDA to conditionally approve or approve another application before the expiration of 7 years; or
(4) The sponsor fails to assure a sufficient quantity of the drug in accordance with section 573 of the act and § 516.36.
(b) If an application for a MUMS drug cannot be approved until the expiration of the period of exclusive marketing of a MUMS-designated drug, FDA will so notify the sponsor in writing.
(a) FDA will send the sponsor (or the permanent-resident U.S. agent, if applicable) timely written notice recognizing exclusive marketing rights when an application for a MUMS-designated drug has been conditionally approved or approved. The written notice will inform the sponsor of the requirements for maintaining MUMS-designated drug exclusive marketing rights for the full 7-year term. This notice will generally be contained in the letter conditionally approving or approving the application.
(b) When an application is conditionally approved or approved for a MUMS-designated drug that qualifies for exclusive marketing rights, FDA will publish this information in the
(a) Under section 573 of the act, whenever FDA has reason to believe that sufficient quantities of a conditionally-approved or approved, MUMS-designated drug to meet the needs for which the drug was designated cannot be assured by the sponsor, FDA will so notify the sponsor of this possible insufficiency and will offer the sponsor the following options, one of which must be exercised by a time that FDA specifies:
(1) Provide FDA information and data regarding how the sponsor can assure the availability of sufficient quantities of the MUMS-designated drug within a reasonable time to meet the needs for which the drug was designated; or
(2) Provide FDA in writing the sponsor's consent for the conditional approval or approval of other applications for the same drug before the expiration of the 7-year period of exclusive marketing rights.
(b) If, within the time that FDA specifies, the sponsor fails to consent to the conditional approval or approval of other applications and if FDA finds that the sponsor has not shown that it can assure the availability of sufficient quantities of the MUMS-designated drug to meet the needs for which the drug was designated, FDA will issue a written order terminating designation of the MUMS drug and the associated exclusive marketing rights. This order will state FDA's findings and conclusions and will constitute final agency action. An order terminating designation and associated exclusive marketing rights may issue whether or not there are other sponsors that can assure the availability of alternative sources of supply. Such an order will not withdraw the conditional approval or approval of an application. Once terminated under this section, neither designation, nor exclusive marketing rights may be reinstated.
(a) FDA will not publicly disclose the existence of a request for MUMS-drug designation under section 573 of the act prior to final FDA action on the request unless the existence of the request has been previously publicly disclosed or acknowledged.
(b) Whether or not the existence of a pending request for designation has been publicly disclosed or acknowledged, no data or information in the request are available for public disclosure prior to final FDA action on the request.
(c) Except as provided in paragraph (d) of this section, upon final FDA action on a request for designation, the public availability of data and information in the request will be determined in accordance with part 20 of this chapter and other applicable statutes and regulations.
(d) In accordance with § 516.28, FDA will make a cumulative list of all MUMS-drug designations available to the public and update such list periodically. In accordance with § 516.29, FDA will give public notice of the termination of all MUMS-drug designations.
This subpart implements section 572 of the act and provides standards and procedures to establish an index of legally marketed unapproved new animal drugs. This subpart applies only to minor species and not to minor use in major species. This index is only available for new animal drugs intended for use in a minor species for which there is a reasonable certainty that the animal or edible products from the animal will not be consumed by humans or food-producing animals and for new animal drugs intended for use only in a hatchery, tank, pond, or other similar contained man-made structure in an early, nonfood life stage of a food-producing minor species, where safety for humans is demonstrated in accordance with the standard of section 512(d) of the act (including, for an antimicrobial new animal drug, with respect to antimicrobial resistance). The index shall not include a new animal drug that is
(a) Investigational exemptions for indexing purposes;
(b) Submissions to FDA of requests for determination of eligibility of a new animal drug for indexing;
(c) Establishment and operation of expert panels;
(d) Submissions to FDA of requests for addition of a new animal drug to the index;
(e) Modifications to index listings;
(f) Publication of the index; and
(g) Records and reports.
(a) The following definitions of terms apply only in the context of subpart C of this part:
(b) The definitions of the following terms are given in § 514.3 of this chapter:
Adverse drug experience.
Product defect/manufacturing defect.
Serious adverse drug experience.
Unexpected adverse drug experience.
(c) The definitions of the following terms are given in § 516.3 of this chapter:
Same dosage form.
Same drug.
Same intended use.
Unless directed otherwise by FDA, all correspondence relating to any aspect of the new animal drug indexing process described in this subpart must be addressed to the Director, OMUMS. The initial correspondence for a particular index listing should include the name and address of the authorized contact person. Notifications of changes in such person or changes of address of such person should be provided in a timely manner.
Every foreign requestor and holder shall name a permanent resident of the United States as their agent upon whom service of all processes, notices, orders, decisions, requirements, and other communications may be made on behalf of the requestor or holder. Notifications of changes in such agents or changes of address of agents should preferably be provided in advance, but not later than 60 days after the effective date of such changes. The permanent resident U.S. agent may be an individual, firm, or domestic corporation and may represent any number of requestors or holders. The name and address of the permanent-resident U.S. agent shall be submitted to the Director, OMUMS, and included in the index file.
(a) A requestor or potential requestor is entitled to one or more meetings to discuss the requirements for indexing a new animal drug.
(b) Requests for such meetings should be in writing, be addressed to the Director, OMUMS, specify the participants attending on behalf of the requestor or potential requestor, and
(c) Within 30 days of receiving a request for a meeting, FDA will attempt to schedule the meeting at a time agreeable to both FDA and the person making the request.
(a) Should FDA make an initial decision denying a request for determination of eligibility for indexing, terminating an investigational exemption, determining that a qualified expert panel does not meet the selection criteria, denying a request for addition to the index, or removing a new animal drug from the index, FDA will give written notice that specifies the grounds for the initial decision and provides an opportunity for an informal conference for review of the decision.
(b) The written notice will include information for scheduling the informal conference and state that a written request for a conference must be made within 60 days of the date FDA sends its notice.
(c) Within 45 days of receiving a request for an informal conference, FDA will schedule and hold the informal conference at a time agreeable to both FDA and the person making the request.
(d) Such an informal conference will be conducted by a presiding officer who will be the Director of the Center for Veterinary Medicine or his or her designee, excluding the Director of the Office of Minor Use and Minor Species Animal Drug Development and other persons significantly involved in the initial decision.
(e) The person requesting an informal conference must provide a written response to FDA's initial decision at least 2 weeks prior to the date of the scheduled meeting. Generally, this written response would be attached to the request for an informal conference. At the option of the person requesting an informal conference, such written response to FDA's initial decision may act in lieu of a face-to-face meeting. In this case, the informal conference will consist of a review by the presiding officer of the submitted written response.
(f) The purpose of an informal conference is to discuss scientific and factual issues. It will involve a discussion of FDA's initial decision and any written response to that decision.
(g) Internal agency review of a decision must be based on the information in the administrative file. If the person requesting an informal conference presents new information not in the file, the matter will be returned to the appropriate lower level in the agency for reevaluation based on the new information.
(h) Informal conferences under this part are not subject to the separation of functions rules in § 10.55 of this chapter.
(i) The rules of evidence do not apply to informal conferences. No motions or objections relating to the admissibility of information and views will be made or considered, but any party to the conference may comment upon or rebut all such data, information and views.
(j) [Reserved]
(k) The presiding officer will prepare a written report regarding the subject of the informal conference that states and describes the basis for his or her findings. Whenever time permits, the parties to the informal conference will have 30 days to review and comment on the report.
(l) The administrative record of the informal conference will consist of:
(1) The notice providing an opportunity for an informal conference and the written response to the notice.
(2) All written information and views submitted to the presiding officer at the conference or, at the discretion of the presiding officer, thereafter.
(3) The presiding officer's written report.
(4) All correspondence and memoranda of any and all meetings between the participants and the presiding officer.
(m) The administrative record of the informal conference is closed to the submission of information at the close of the conference, unless the presiding officer specifically permits additional time for further submission.
(n) The administrative record of the informal conference specified herein
(a) The investigational use of a new animal drug or animal feed bearing or containing a new animal drug intended solely for investigational use in minor species shall meet the requirements of part 511 of this chapter if the investigational use is for the purpose of:
(1) Demonstrating human food safety under section 572(a)(1)(B) of the act;
(2) Demonstrating safety with respect to individuals exposed to the new animal drug through its manufacture and use under section 572(c)(1)(F) of the act;
(3) Conducting an environmental assessment under section 572(c)(1)(E) of the act; or
(4) Obtaining approval of a new animal drug application or abbreviated new animal drug application under section 512(b) of the act.
(b) Correspondence and information associated with investigations described in paragraph (a) of this section shall not be sent to the Director, OMUMS, but shall be submitted to FDA in accordance with the provisions of part 511 of this chapter.
(c) The investigational use of a new animal drug or animal feed bearing or containing a new animal drug intended solely for investigational use in minor species, other than for an investigational use described in paragraph (a) of this section, shall meet the requirements of this section. For such investigations, all provisions of part 511 of this chapter apply with the following modifications:
(1) Under § 511.1(a)(1) of this chapter, the label statement is as follows:
“
(2) Under § 511.1(b)(1) of this chapter, the label statement is as follows:
“
(3) Under § 511.1(b)(4) of this chapter, the notice is titled “Notice of Claimed Investigational Exemption for a New Animal Drug for Index Listing” and is submitted in duplicate to the Director, OMUMS.
(4) Under § 511.1(c)(3) of this chapter, if an investigator is determined to be ineligible to receive new animal drugs, each “Notice of Claimed Investigational Exemption for a New Animal Drug for Index Listing” and each request for indexing shall be examined with respect to the reliability of information submitted by the investigator.
(5) Under § 511.1(c)(4) and (d)(2) of this chapter, with respect to termination of exemptions, the sponsor of an investigation shall not be granted an opportunity for a regulatory hearing before FDA pursuant to part 16 of this chapter. Instead, the sponsor shall have an opportunity for an informal conference as described in § 516.123.
(6) Under § 511.1(c)(5) of this chapter, if the Commissioner of Food and Drugs determines, after the unreliable data submitted by the investigator are eliminated from consideration, that the data remaining are such that a request for addition to the index would have been denied, FDA will remove the new animal drug from the index in accordance with § 516.167.
(d) The investigational use of a new animal drug or animal feed bearing or containing a new animal drug subject to paragraph (c) of this section shall not be subject to the good laboratory practice requirements in part 58 of this chapter.
(e) Correspondence and information associated with investigations described in paragraph (c) of this section shall be sent to the Director, OMUMS, in accordance with the provisions of this section.
(a) Each request for determination of eligibility:
(1) May involve only one drug (or one combination of drugs) in one dosage form;
(2) May not involve a new animal drug that is contained in or a product of a transgenic animal;
(3) May not involve the same drug in the same dosage form for the same intended use as a drug that is already approved or conditionally approved; and
(4) Must be submitted separately.
(b) A request for determination of eligibility for indexing may involve multiple intended uses and/or multiple minor species. However, if a request for determination of eligibility for indexing that contains multiple intended uses and/or multiple minor species cannot be granted in any part, the entire request will be denied.
(c) A requestor must submit two copies of a dated request signed by the authorized contact person for determination of eligibility for indexing that contains the following:
(1) Identification of the minor species or groups of minor species for which the new animal drug is intended;
(2) Information regarding drug components and composition;
(3) A statement of the intended use(s) of the new animal drug in the identified minor species or groups of minor species;
(4) A statement of the proposed conditions of use associated with the stated intended use(s) of the new animal drug, including the proposed dosage, route of administration, contraindications, warnings, and any other significant limitations associated with the intended use(s) of the new animal drug;
(5) A brief discussion of the need for the new animal drug for the intended use(s);
(6) An estimate of the anticipated annual distribution of the new animal drug, in terms of the total quantity of active ingredient, after indexing;
(7) Information to establish that the new animal drug is intended for use:
(i) In a minor species for which there is a reasonable certainty that the animal or edible products from the animal will not be consumed by humans or food-producing animals; or
(ii) In a hatchery, tank, pond, or other similar contained man-made structure in (which includes on) an early, non-food life stage of a food-producing minor species, and information to demonstrate food safety in accordance with the standards of section 512(d) of the act and § 514.111 of this chapter (including, for an antimicrobial new animal drug, with respect to antimicrobial resistance);
(8) A description of the methods used in, and the facilities and controls used for, the manufacture, processing and packing of the new animal drug sufficient to demonstrate that the requestor has established appropriate specifications for the manufacture and control of the new animal drug and that the requestor has an understanding of current good manufacturing practices;
(9) Either a claim for categorical exclusion under § 25.30 or § 25.33 of this chapter or an environmental assessment under § 25.40 of this chapter;
(10) Information sufficient to support the conclusion that the new animal drug is safe under section 512(d) of the act with respect to individuals exposed to the new animal drug through its manufacture and use; and
(11) The name and address of the contact person or permanent-resident U.S. agent.
(a) If a request for determination of eligibility for indexing contains all of the information required by § 516.129, FDA shall file it, and the filing date shall be the date FDA receives the request.
(b) If a request for a determination of eligibility lacks any of the information required by § 516.129, FDA will not file it, but will inform the requestor in writing within 30 days of receiving the request as to what information is lacking.
(a) FDA will deny a request for determination of eligibility for indexing if it determines upon the basis of the request evaluated together with any other information before it with respect to the new animal drug that:
(1) The same drug in the same dosage form for the same intended use is already approved or conditionally approved;
(2) There is insufficient information to demonstrate that the new animal drug is intended for use:
(i) In a minor species for which there is a reasonable certainty that the animal or edible products from the animal will not be consumed by humans or food-producing animals, or
(ii) In a hatchery, tank, pond, or other similar contained man-made structure in (which includes on) an early, non-food life stage of a food-producing minor species, and there is insufficient evidence to demonstrate safety for humans in accordance with the standard of section 512(d) of the act and § 514.111 of this chapter (including, for an antimicrobial new animal drug, with respect to antimicrobial resistance);
(3) The new animal drug is contained in or is a product of a transgenic animal;
(4) There is insufficient information to demonstrate that the requestor has established appropriate specifications for the manufacture and control of the new animal drug and that the requestor has an understanding of current good manufacturing practices;
(5) The requester fails to submit an adequate environmental assessment under § 25.40 of this chapter or fails to provide sufficient information to establish that the requested action is subject to categorical exclusion under § 25.30 or § 25.33 of this chapter;
(6) There is insufficient information to determine that the new animal drug is safe with respect to individuals exposed to the new animal drug through its manufacture or use; or
(7) The request for determination of eligibility for indexing fails to contain any other information required under the provisions of § 516.129.
(b) FDA may deny a request for determination of eligibility for indexing if it contains any untrue statement of a material fact or omits material information.
(c) When a request for determination of eligibility for indexing is denied, FDA will notify the requestor in accordance with § 516.137.
(a) FDA will grant the request for determination of eligibility for indexing if none of the reasons described in § 516.133 for denying such a request applies.
(b) When a request for determination of eligibility for indexing is granted, FDA will notify the requestor in accordance with § 516.137.
(a) Within 90 days after the filing of a request for a determination of eligibility for indexing based on § 516.129(c)(7)(i), or 180 days for a request based on § 516.129(c)(7)(ii), FDA shall grant or deny the request, and notify the requestor of FDA's decision in writing.
(b) If FDA denies the request, FDA shall provide due notice and an opportunity for an informal conference as described in § 516.123 regarding its decision. A decision of FDA to deny a request for determination of eligibility for indexing following an informal conference shall constitute final agency action subject to judicial review.
(a)
(b)
(2) A qualified expert panel member must certify that he or she has a working knowledge of section 572 of the act (the indexing provisions of the statute) and this subpart, and that he or she has also read and understood a clear written statement provided by the requestor stating his or her duties and responsibilities with respect to reviewing the new animal drug proposed for addition to the index.
(3) A qualified expert panel member may not be an FDA employee.
(4) A qualified expert panel must have at least three members.
(5) A qualified expert panel must have members with a range of expertise such that the panel, as a whole, is qualified by training and experience to evaluate the target animal safety and effectiveness of the new animal drug under consideration.
(6) Unless FDA makes a determination to allow participation notwithstanding an otherwise disqualifying financial interest, a qualified expert panel member must not have a conflict of interest or the appearance of a conflict of interest, as described in paragraph (g) of this section.
(c)
(i) Choose members for the qualified expert panel in accordance with selection criteria listed in paragraph (b) of this section.
(ii) Provide each potential expert panel member a copy of section 572 of the act (the indexing provisions of the statute) and this subpart and obtain certification that he or she has a working knowledge of the information.
(iii) Provide each potential expert panel member a written statement describing the purpose and scope of his or her participation on the qualified expert panel and obtain certification that he or she has read and understood the information. The written statement should describe the duties and responsibilities of qualified expert panels and their members established by paragraphs (e) and (f) of this section, including the need to prepare a written report under § 516.143.
(iv) Obtain information from each potential expert panel member demonstrating that he or she is qualified by training and experience to evaluate the target animal safety and effectiveness of the new animal drug under consideration. This information can be obtained from a comprehensive curriculum vitae or similar document.
(v) Notify each potential expert panel member that he or she must submit information relating to potential conflict of interest directly to FDA in a timely manner, as required in paragraph (e)(6) of this section.
(2) The requestor must submit, in writing, the names and addresses of the proposed qualified expert panel members and sufficient information about each proposed member for FDA to determine whether the panel meets the selection criteria listed in paragraphs (b)(1) through (b)(5) of this section.
(3) After FDA has determined that the qualified expert panel meets the selection criteria, the requestor must provide to the panel all information known by the requestor that is relevant to a determination of the target animal safety and the effectiveness of the new animal drug at issue. In addition, the requestor must notify FDA of the name of the qualified expert panel leader.
(4) The requestor must immediately notify FDA if it believes a qualified expert panel member no longer meets the selection criteria listed in paragraph (b) of this section or is otherwise not in compliance with the requirements of this section.
(5) If a qualified expert panel member cannot complete the review for which he or she was selected, the requestor must either choose a replacement or justify the continued work of the panel in the absence of the lost panelist. In either case, the requestor must submit sufficient information for FDA to determine whether the proposed revised qualified expert panel meets the selection criteria listed in paragraphs (b)(1) through (b)(5) of this section.
(6) The requestor must keep copies of all information provided to, or received from, qualified expert panel members, including the written report, for 2 years after the completion of the report, or the product is added to the index, whichever occurs later, and
(d)
(2) If FDA determines that a qualified expert panel no longer meets the selection criteria listed in paragraph (b) of this section or that the panel or its members are not in compliance with the requirements of this section, the agency will expeditiously inform the requestor, in writing, of this determination and provide due notice and an opportunity for an informal conference as described in § 516.123. A determination by FDA, following an informal conference, that a qualified expert panel no longer meets the selection criteria listed in paragraph (b) of this section or that the panel or its members are not in compliance with the requirements of this section shall constitute final agency action subject to judicial review.
(e)
(1) Continue to meet all selection criteria described in paragraph (b) of this section.
(2) Act in accordance with generally accepted professional and ethical business practices.
(3) Review all information relevant to a determination of the target animal safety and effectiveness of the new animal drug provided by the requestor. The panel should also consider all relevant information otherwise known by the panel members, including anecdotal information.
(4) Participate in the preparation of the written report of the findings of the qualified expert panel, described in § 516.143.
(5) Sign, or otherwise approve in writing, the written report. Such signature or other written approval will serve as certification that the written report meets the requirements of the written report in § 516.143.
(6) Provide the information relating to potential conflict of interest described in paragraph (g) of this section to FDA for its consideration. Such information should be submitted directly to the Director, OMUMS, when notified by the requestor.
(7) Immediately notify the requestor and FDA of any change in conflict of interest status.
(8) Certify at the time of submission of the written report that there has been no change in conflict of interest status, or identify and document to FDA any such change.
(f)
(2) The qualified expert panel leader serves as the principal point of contact between representatives of the agency and the panel.
(3) The qualified expert panel leader is responsible for submitting the written report and all notes or minutes relating to panel deliberations to the requestor.
(4) The qualified expert panel leader must maintain a copy of the written report and all notes or minutes relating to panel deliberations that are submitted to the requestor for 2 years after the report is submitted. Such records must be made available to a duly authorized employee of the agency for inspection at all reasonable times.
(g)
(2) Factors relevant to whether there is a conflict of interest or the appearance of a conflict of interest include whether the qualified expert panel member, their spouse, their minor children, their general partners, or any organizations in which they serve as an officer, director, trustee, general partner or employee:
(i) Is currently receiving or seeking funding from the requestor through a contract or research grant (either directly or indirectly through another entity, such as a university).
(ii) Has any employment, contractual, or other financial arrangement with the requestor other than receiving a reasonable fee for serving as a member of the qualified expert panel.
(iii) Has any ownership or financial interest in any drug, drug manufacturer, or drug distributor which will benefit from either a favorable or unfavorable evaluation or opinion.
(iv) Has any ownership or financial interest in the new animal drug being reviewed by the qualified expert panel.
(v) Has participated in the design, manufacture, or distribution of any drug that will benefit from either a favorable or unfavorable opinion of the qualified expert panel.
(vi) Has provided within 1 year any consultative services regarding the new animal drug being reviewed by the qualified expert panel.
(vii) Has entered into an agreement in which fees charged or accepted are contingent upon the panel member making a favorable evaluation or opinion.
(viii) Receives payment for services related to preparing information the requestor presents to the qualified expert panel, other than for services related to the written report described in § 516.143.
(3) To permit FDA to make a decision regarding potential conflict of interest, a potential qualified expert panel member must submit to the Director, OMUMS, the following information relating to themselves, their spouse, their minor children, their general partners, or any organizations in which they serve as an officer, director, trustee, general partner or employee, regarding the following issues to the extent that they are, in any way, relevant to the subject of the review of the qualified expert panel:
(i) Investments (for example, stocks, bonds, retirement plans, trusts, partnerships, sector funds, etc.), including for each the following: Name of the firm, type of investment, owner (self, spouse, etc.), number of shares / current value.
(ii) Employment (full or part time, current or under negotiation), including for each the following: Name of the firm, relationship (self, spouse, etc.), position in firm, date employment or negotiation began.
(iii) Consultant/advisor (current or under negotiation), including for each the following: Name of the firm, topic/issue, amount received, date initiated.
(iv) Contracts, grants, Cooperation Research and Development Agreement (CRADAs) (current or under negotiation), including for each the following: Type of agreement, product under study and indications, amount of remuneration (institution/self), time period, sponsor (government, firm, institution, individual), role of the person (site investigator, principal investigator, co-investigator, partner, no involvement, other), awardee.
(v) Patents/royalties/trademarks, including for each the following: Description, name of firm involved, income received.
(vi) Expert witness (last 12 months or under negotiation), including for each the following: For or against, name of firm, issue, amount received.
(vii) Speaking/writing (last 12 months or under negotiation), including for each the following: Firm, topic/issue, amount received (honorarium/travel), date.
(viii) Whether the potential qualified expert panel member, their spouse, their minor children, their general partners or any organizations in which they serve as an officer, director, trustee, general partner or employee, have had, at any time in the past, involvement of the kind noted in paragraph (g)(3)(i) through (g)(3)(vii) of this section with respect to the animal drug that is the subject of the qualified expert panel review.
(ix) Whether there are any other involvements (other kinds of relationships) that would give the appearance
(x) In all cases, a response of “no,” “none,” or “not applicable” is satisfactory when there is no relevant information to submit.
(xi) A certification statement signed by the potential qualified expert panel member to the effect that all information submitted is true and complete to the best of their knowledge, that they have read and understood their obligations as an expert panel member, and that they will notify FDA and the requestor of any change in their conflict of interest status.
(4) The fact that a qualified expert panel member receives a reasonable fee for services as a member of the qualified expert panel, provided that the fee is no more than commensurate with the value of the time that the member devotes to the review process, does not constitute a conflict of interest or the appearance of a conflict of interest.
The written report required in § 516.145(b)(3) shall:
(a) Be written in English by a qualified expert panel meeting the requirements of § 516.141;
(b) Describe the panel's evaluation of all available target animal safety and effectiveness information relevant to the proposed use of the new animal drug, including anecdotal information;
(c) For all information considered, including anecdotal information, include either a citation to published literature or a summary of the information;
(d) State the panel's opinion regarding whether the benefits of using the new animal drug for the proposed use in a minor species outweigh its risks to the target animal, taking into account the harm being caused by the absence of an approved or conditionally-approved new animal drug for the minor species in question;
(e) Be signed, or otherwise approved in writing, by all panel members, in accordance with § 516.141; and
(f) If the panel unanimously concludes that the benefits of using the new animal drug for the proposed use in a minor species outweigh its risks to the target animal, taking into account the harm being caused by the absence of an approved or conditionally-approved new animal drug for the minor species in question, the written report shall:
(1) Provide draft labeling that includes all conditions of use and limitations of use of the new animal drug deemed necessary by the panel to assure that the benefits of use of the new animal drug outweigh the risks, or provide narrative information from which such labeling can be written by the requestor; and
(2) Include a recommendation regarding whether the new animal drug should be limited to use under the professional supervision of a licensed veterinarian.
(a) A requestor may request addition of a new animal drug to the index only after the new animal drug has been granted eligibility for indexing.
(b) A requestor shall submit two copies of a dated request signed by the authorized contact for addition of a new animal drug to the index that contains the following:
(1) A copy of FDA's determination of eligibility issued under § 516.137;
(2) A copy of FDA's written determination that the proposed qualified expert panel meets the selection criteria provided for in § 516.141(b);
(3) A written report that meets the requirements of § 516.143;
(4) A proposed index entry that contains the information described in § 516.157;
(5) Proposed labeling, including representative labeling proposed to be used for Type B and Type C medicated feeds if the drug is intended for use in the manufacture of medicated feeds;
(6) Anticipated annual distribution of the new animal drug, in terms of the total quantity of active ingredient, after indexing;
(7) A written commitment to manufacture the new animal drug and animal feeds bearing or containing such new animal drug according to current good manufacturing practices;
(8) A written commitment to label, distribute, and promote the new animal drug only in accordance with the index entry;
(9) The name and address of the contact person or permanent-resident U.S. agent; and
(10) A draft Freedom of Information summary which includes the following information:
(i) A general information section that contains the name and address of the requestor and a description of the drug, route of administration, indications, and recommended dosage.
(ii) A list of the names and affiliations of the members of the qualified expert panel, not including their addresses or other contact information.
(iii) A summary of the findings of the qualified expert panel concerning the target animal safety and effectiveness of the drug.
(iv) Citations of all publicly-available literature considered by the qualified expert panel.
(v) For an early life stage of a food-producing minor species animal, a human food safety summary.
(c) Upon specific request by FDA, the requestor shall submit the information described in § 516.141 that it submitted to the qualified expert panel. Any such information not in English should be accompanied by an English translation.
(a) If a request for addition to the index contains all of the information required by § 516.145(b), FDA shall file it, and the filing date shall be the date FDA receives the request.
(b) If a request for addition to the index lacks any of the information required by § 516.145, FDA will not file it, but will inform the requestor in writing within 30 days of receiving the request as to what information is lacking.
(a) FDA will deny a request for addition to the index if it finds the following:
(1) The same drug in the same dosage form for the same intended use is already approved or conditionally approved;
(2) On the basis of new information, the new animal drug no longer meets the conditions for eligibility for indexing;
(3) The request for indexing fails to contain information required under the provisions of § 516.145;
(4) The qualified expert panel fails to meet any of the selection criteria listed in § 516.141(b);
(5) The written report of the qualified expert panel and other information available to FDA is insufficient to permit FDA to determine that the benefits of using the new animal drug for the proposed use in a minor species outweigh its risks to the target animal, taking into account the harm caused by the absence of an approved or conditionally-approved new animal drug for the minor species in question;
(6) On the basis of the report of the qualified expert panel and other information available to FDA, the benefits of using the new animal drug for the proposed use in a minor species do not outweigh its risks to the target animal, taking into account the harm caused by the absence of an approved or conditionally-approved new animal drug for the minor species in question; or
(7) The request contains any untrue statement of a material fact or omits material information.
(b) When a request for addition to the index is denied, FDA will notify the requestor in accordance with § 516.153.
(a) FDA will grant the request for addition of a new animal drug to the index if none of the reasons described in § 516.149 for denying such a request applies.
(b) When a request for addition of a new animal drug to the index is granted, FDA will notify the requestor in accordance with § 516.153.
(a) Within 180 days after the filing of a request for addition of a new animal drug to the index, FDA shall grant or
(b) If FDA denies the request for addition of a new animal drug to the index, FDA shall provide due notice and an opportunity for an informal conference as described in § 516.123. A decision of FDA to deny a request to index a new animal drug following an informal conference shall constitute final agency action subject to judicial review.
(a) The labeling of an indexed drug that is found to be eligible for indexing under § 516.129(c)(7)(i) shall state, prominently and conspicuously:
(b) The labeling of an indexed drug that was found to be eligible for indexing for use in an early, non-food life stage of a food-producing minor species animal, under § 516.129(c)(7)(ii), shall state, prominently and conspicuously:
(c) The labeling of an indexed drug shall contain such other information as may be prescribed in the index listing.
(a) FDA will make the list of indexed drugs available through the FDA Web site. A printed copy can be obtained by writing to the FDA Freedom of Information Staff or by visiting the FDA Freedom of Information Public Reading Room.
(b) The list will contain the following information for each indexed drug:
(1) The name and address of the person who holds the index listing;
(2) The name of the drug and the intended use and conditions of use for which it is indexed;
(3) Product labeling; and
(4) Conditions and any limitations that FDA deems necessary regarding use of the drug.
(a) After a drug is listed in the index, certain modifications to the index listing may be requested. Any modification of an index listing may not cause an indexed drug to be a different drug (or different combination of drugs) or a different dosage form. If such modification is requested, FDA will notify the holder that a new index listing is required for the new drug or dosage form.
(b) Modifications to the indexed drug will fall under one of three categories and must be submitted as follows:
(1)
(A) The addition to package labeling, promotional labeling, or prescription drug advertising of additional warning, contraindication, side effect, or cautionary information.
(B) The deletion from package labeling, promotional labeling, and drug advertising of false, misleading, or unsupported indications for use or claims for effectiveness.
(C) Changes in manufacturing methods or controls required to correct product or manufacturing defects that may result in serious adverse drug events.
(ii) The modifications described in paragraph (b)(1)(i) of this section must be submitted to the Director, OMUMS, in the form of a request for modification of an indexed drug, and must contain sufficient information to permit FDA to determine the need for the modification and whether the modification appropriately addresses the need.
(iii) FDA will take no action against an indexed drug or index holder solely because modifications of the kinds described in paragraph (b)(1)(i) of this section are placed into effect by the holder prior to receipt of a written notice granting the request if all the following conditions are met:
(A) A request to modify the indexed drug providing a full explanation of the basis for the modifications has been submitted, plainly marked on the mailing cover and on the request as follows:
(B) The holder specifically informs FDA of the date on which such modifications are to be effected and submits two printed copies of any revised labeling to be placed in use, and
(C) All promotional labeling and all drug advertising are promptly revised consistent with modifications made in the labeling on or within the indexed drug package.
(2)
(A) Addition of an intended use.
(B) Addition of a species.
(C) Addition or alteration of an active ingredient.
(D) Alteration of the concentration of an active ingredient.
(E) Alteration of dose or dosage regimen.
(F) Alteration of prescription or over-the-counter status.
(ii) Each modification described in paragraph (b)(2)(i) of this section must go through the same review process as an original index listing and is subject to the same standards for review.
(iii) Each submission of a request for a modification described in paragraph (b)(2)(i) of this section should contain only one type of modification unless one modification is actually necessitated by another, such as a modification of dose necessitated by a modification of the concentration of an active ingredient. Submissions relating to addition of an intended use for an existing species or addition of a species should be submitted separately, but each such submission may include multiple additional intended uses and/or multiple additional species.
(3)
(c) When changes affect the index listing, it will be updated accordingly.
(a) A holder may transfer ownership of a drug's index file to another person.
(1) The former owner shall submit in writing to FDA a statement that all rights in the index file have been transferred, giving the name and address of the new owner and the date of the transfer. The former owner shall also certify that a complete copy of the following, to the extent that they exist at the time of the transfer of ownership, has been provided to the new owner:
(i) The request for determination of eligibility;
(ii) The request for addition to the index;
(iii) Any modifications to the index listing;
(iv) Any records and reports under § 516.165; and
(v) All correspondence with FDA relevant to the indexed drug and its index listing.
(2) The new owner shall submit the following information in writing to FDA:
(i) The date that the change in ownership is effective;
(ii) A statement that the new owner has a complete copy of all documents listed in paragraph (a)(1) of this section to the extent that they exist at the time of the transfer of ownership;
(iii) A statement that the new owner understands and accepts the responsibilities of a holder of an indexed drug;
(iv) The name and address of a new primary contact person or permanent-resident U.S. agent; and
(v) A list of labeling changes associated with the change of ownership (e.g., a new trade name) as draft labeling, with complete final printed labeling to be submitted in the indexed drug annual report in accordance with §§ 516.161 and 516.165.
(b) Upon receiving the necessary information to support a change of ownership of a drug's index file, FDA will update its publicly-available listing in accordance with § 516.157.
(a)
(2) A holder is not required to report information under this section if the holder has reported the same information under § 514.80 of this chapter.
(3) The records and reports referred to in this section are in addition to those required by the current good manufacturing practice regulations in parts 211, 225, and 226 of this chapter.
(4) FDA will review the records and reports required in this section to determine, or facilitate a determination, whether there may be grounds for removing a drug from the index under section 572(f) of the act.
(b)
(2) The holder must, upon request from any authorized FDA officer or employee, at all reasonable times, permit such officer or employee to have access to copy and to verify all such records.
(c)
(2)
(3)
(i) The number of distributed units of each size, strength, or potency (e.g., 100,000 bottles of 100 5-milligram tablets; 50,000 10-milliliter vials of 5- percent solution) distributed during the reporting period. This information must be presented in two categories: Quantities distributed domestically and quantities exported. This information must include any distributor-labeled product.
(ii) If the labeling has changed since the last report, include a summary of those changes and the holder's and distributor's current package labeling, including any package inserts. For large-size package labeling or large shipping cartons, submit a representative copy (e.g., a photocopy of pertinent areas of large feed bags). If the labeling has not changed since the last report, include a statement of such fact.
(iii) A summary of any changes made during the reporting period in the methods used in, and facilities and controls used for, manufacture, processing, and packing. This information must be presented in the same level of detail that it was presented in the request for determination of eligibility for indexing. Do not include changes that have already been submitted under § 516.161.
(iv) Nonclinical laboratory studies and clinical data not previously reported under this section.
(v) Adverse drug experiences not previously reported under this section.
(vi) Any other information pertinent to safety or effectiveness of the indexed drug not previously reported under this section.
(4)
(i) The distributor's current product labeling. This must be identical to that in the index listing except for a different and suitable proprietary name (if used) and the name and address of the distributor. The name and address of the distributor must be preceded by an appropriate qualifying phrase such as “manufactured for” or “distributed by.”
(ii) A signed statement by the distributor stating:
(A) The category of the distributor's operations (e.g., wholesale or retail);
(B) That the distributor will distribute the drug only under the indexed drug labeling;
(C) That the distributor will promote the indexed drug only for use under the conditions stated in the index listing; and
(D) If the indexed drug is a prescription new animal drug, that the distributor is regularly and lawfully engaged in the distribution or dispensing of prescription products.
(5)
(a) After due notice to the holder of the index listing and an opportunity for an informal conference as described in § 516.123, FDA shall remove a new animal drug from the index if FDA finds that:
(1) The same drug in the same dosage form for the same intended use has been approved or conditionally approved;
(2) The expert panel failed to meet the requirements in § 516.141;
(3) On the basis of new information before FDA, evaluated together with the evidence available to FDA when the new animal drug was listed in the index, the benefits of using the new animal drug for the indexed use do not outweigh its risks to the target animal, taking into account the harm caused by the absence of an approved or conditionally-approved new animal drug for the minor species in question;
(4) Any of the conditions in § 516.133(a)(2), (5), or (6) are present;
(5) The manufacture of the new animal drug is not in accordance with current good manufacturing practices;
(6) The labeling, distribution, or promotion of the new animal drug is not in accordance with the index listing;
(7) The conditions and limitations of use associated with the index listing have not been followed; or
(8) Any information used to support the request for addition to the index contains any untrue statement of material fact.
(b) The agency may partially remove an indexing listing if, in the opinion of the agency, such partial removal would satisfactorily resolve a safety or effectiveness issue otherwise warranting removal of the listing under section 572(f)(1)(B) of the act.
(c) FDA may immediately suspend a new animal drug from the index if FDA determines that there is a reasonable probability that the use of the drug would present a risk to the health of humans or other animals. The agency will subsequently provide due notice and an opportunity for an informal conference as described in § 516.123.
(d) A decision of FDA to remove a new animal drug from the index following an informal conference, if any, shall constitute final agency action subject to judicial review.
(a) For purposes of this section, the index file includes all data and information submitted to or incorporated by reference into the index file, such as data and information related to investigational use exemptions under § 516.125, requests for determination of eligibility for indexing, requests for addition to the index, modifications to indexed drugs, changes in ownership, reports submitted under § 516.165, and master files. The availability for public disclosure of any record in the index file shall be handled in accordance with the provisions of this section.
(b) The existence of an index file will not be disclosed by FDA before an index listing has been made public by
(c) If the existence of an index file has not been publicly disclosed or acknowledged, no data or information in the index file are available for public disclosure.
(d) If the existence of an index file has been publicly disclosed or acknowledged before an index listing has been made public by FDA, no data or information contained in the file will be available for public disclosure before such index listing is made public, but the agency may, at its discretion, disclose a brief summary of such selected portions of the safety and effectiveness data as are appropriate for public consideration of a specific pending issue, e.g., at an open session of a Food and Drug Administration advisory committee or pursuant to an exchange of important regulatory information with a foreign government.
(e) After FDA sends a written notice to the requestor granting a request for addition to the index, the following data and information in the index file are available for public disclosure unless extraordinary circumstances are shown:
(1) All safety and effectiveness data and information previously disclosed to the public, as defined in § 20.81 of this chapter.
(2) A summary or summaries of the safety and effectiveness data and information submitted with or incorporated by reference in the index file. Such summaries do not constitute the full information described under section 572(c) and (d) of the act on which the safety or effectiveness of the drug may be determined. Such summaries will be based on the draft Freedom of Information summary submitted under § 516.145, which will be reviewed and, where appropriate, revised by FDA.
(3) A protocol for a test or study, unless it is shown to fall within the exemption established for trade secrets and confidential commercial information in § 20.61 of this chapter.
(4) Adverse reaction reports, product experience reports, consumer complaints, and other similar data and information, after deletion of the following:
(i) Names and any information that would identify the person using the product.
(ii) Names and any information that would identify any third party involved with the report, such as a veterinarian.
(5) A list of all active ingredients and any inactive ingredients previously disclosed to the public as defined in § 20.81 of this chapter.
(6) An assay method or other analytical method, unless it serves no regulatory or compliance purpose and is shown to fall within the exemption established in § 20.61 of this chapter.
(7) All correspondence and written summaries of oral discussions relating to the index file, in accordance with the provisions of part 20 of this chapter.
(f) The following data and information in an index file are not available for public disclosure unless they have been previously disclosed to the public as defined in § 20.81 of this chapter, or they relate to a product or ingredient that has been abandoned and they no longer represent a trade secret or confidential commercial or financial information as defined in § 20.61 of this chapter:
(1) Manufacturing methods or processes, including quality control procedures.
(2) Production, sales, distribution, and similar data and information, except that any compilation of such data and information aggregated and prepared in a way that does not reveal data or information which is not available for public disclosure under this provision is available for public disclosure.
(3) Quantitative or semiquantitative formulas.
(g) Subject to the disclosure provisions of this section, the agency shall regard the contents of an index file as confidential information unless specifically notified in writing by the holder of the right to disclose, to reference, or otherwise utilize such information on behalf of another named person.
(h) For purposes of this regulation, safety and effectiveness data include all studies and tests of an animal drug on animals and all studies and tests on the animal drug for identity, stability, purity, potency, and bioavailability.
(i) Safety and effectiveness data and information that have not been previously disclosed to the public are available for public disclosure at the time any of the following events occurs unless extraordinary circumstances are shown:
(1) No work is being or will be undertaken to have the drug indexed in accordance with the request.
(2) A final determination is made that the drug cannot be indexed and all legal appeals have been exhausted.
(3) The drug has been removed from the index and all legal appeals have been exhausted.
(4) A final determination has been made that the animal drug is not a new animal drug.
(a)
(b)
(c)
(d)
(e)
(ii)
(iii)
(2) [Reserved]
21 U.S.C. 360b.
(a)
(1) For No. 000856, use of 5-, 10-, or 25-milligram tablets as in paragraph (b) of this section.
(2) For No. 000010, use of 10- or 25-milligram tablets as in paragraph (c) of this section.
(b)
(1)
(2)
(3)
(c)
(1)
(2)
(3)
(a)
(b)
(c)
(2) It is administered orally at a dosage level of 5 to 15 milligrams per pound of body weight daily.
(3) For use only by or on the order of a licensed veterinarian.
(a)
(b)
(c)
(d)
(e)
(i)
(ii)
(iii)
(2)
(i)
(ii)
(iii)
(3)
(i)
(ii)
(iii)
(a)
(b)
(c)
(d)
(2)
(3)
(a)
(b)
(c)
(d) Conditions of use—(1)
(ii)
(iii)
(2)
(ii)
(iii)
(a)
(b)
(c)
(d)
Not for use in animals with glaucoma because of the occurrence of mydriasis.
(2) Dosage is administered by oral tablet every 8 to 12 hours, as follows:
(3) For use only by or on the order of a licensed veterinarian.
(a)
(b)
(c)
(2) It is administered at a dosage level of 1 to 2 milligrams per pound of body weight. The dosage can be repeated every 12 hours, as indicated.
(3) Not for use in animals intended for food purposes.
(4) For use only by or on the order of a licensed veterinarian.
(a)
(b)
(c)
(2) It is administered at a dosage level of one to two tablets per 10 pounds of body weight twice daily for 3 days.
(3) Federal law restricts this drug to use by or on the order of a licensed veterinarian.
(a)
(b)
(c)
(ii)
(iii)
(2)
(ii)
(iii)
(a)
(b)
(1)
(B)
(C)
(ii)
(B)
(C)
(2) [Reserved]
(c)
(1)
(ii)
(iii)
(2) [Reserved]
(a)
(b)
(c)
(d)
(2)
(3)
(a)
(b)
(c)
(d)
(2)
(3)
(a)
(b)
(c)
(d)
(2)
(3)
(a)
(b)
(c)
(ii)
(iii)
(2) [Reserved]
(a)
(b)
(c)
(ii)
(iii)
(2)
(ii)
(iii)
(a)
(b)
(c)
(ii)
(iii)
(2)
(ii)
(iii)
(a)
(b)
(c)
(ii)
(iii)
(2)
(ii)
(iii)
(a)
(b)
(c)
(2)
(3)
(a)
(b)
(c)
(ii)
(iii)
(2)
(ii)
(iii)
(a)
(b)
(c)
(ii)
(iii)
(2)
(ii)
(iii)
(a)
(b)
(c)
(d)
(2)
(3)
(a)
(b)
(c)
(d)
(i)
(ii)
(2)
(i)
(ii)
(a)
(2) Each gram of powder contains 200 mg amprolium (20 percent).
(3) Each ounce (28.4 grams) of crumbles contains 355 mg amprolium (1.25 percent).
(b)
(1) No. 016592 for use of products described in paragraph (a) of this section as in paragraph (e) of this section.
(2) No. 051311 for use of product described in paragraph (a)(1) of this section as in paragraph (e)(1) of this section.
(3) No. 059130 for use of product described in paragraph (a)(1) of this section as in paragraph (e)(2) of this section.
(c)
(d)
(e)
(i)
(ii)
(iii)
(2)
(i)
(B) As an aid in the treatment of coccidiosis caused by
(ii)
(a)
(b)
(c)
(d)
(2) It is administered for 7 days in drinking water at the rate of 12.5 milligrams of apramycin per kilogram (5.7 milligrams per pound) of body weight per day. Swine will normally consume 1 gallon per day of medicated water containing 375 milligrams of apramycin for each 66 pounds of body weight. Water consumption should be monitored to determine that the required amount of apramycin is being consumed. The drug concentration should be adjusted according to water consumption which varies depending on ambient temperature, humidity, and other factors.
(3) Prepare fresh medicated water daily.
(4) Do not slaughter treated swine for 28 days following treatment
(a)
(b)
(c)
(d)
(ii)
(iii)
(2)
(A)
(B)
(ii)
(A)
(B)
(3)
(ii)
(iii)
(4)
(ii)
(iii)
(a)
(b)
(c)
(2)
(3)
(a)
(b)
(c)
(d)
(A)
(B)
(ii)
(A)
(B)
(2)
(ii)
(iii)
(a)
(b)
(c)
(2) It is administered usually in a 2:1 sugar sirup containing a concentration of from 75 to 100 milligrams of fumagillin activity per gallon of sugar sirup.
(3) Colonies used for package production should be fed medicated sirup as a principal food supply for a month prior to stocking nuclei or shaking packages for market.
(4) The medicated sirup should not be fed immediately before or during the honey flow.
(a)
(b)
(c)
(d)
(2) It is administered to cats and dogs at the rate of 25 to 50 milligrams per kilogram of body weight. The drug should be given on an empty stomach and food should not be given for 3 hours following treatment.
(3) Tablets should not be crushed, mixed with food, or dissolved in liquid. Repeat treatments should not be given within 14 days. The drug should not be given to male dogs within 28 days prior to their use for breeding. Do not administer to dogs or cats having known heart conditions.
(4) For use only by or on the order of a licensed veterinarian.
(a)
(b)
(c)
(1)
(2)
(3)
(a)(1)
(2)
(3)
(ii)(
(
(
(iii) A veterinarian should be consulted before using in severely debilitated dogs or cats and also prior to repeated use in cases which present signs of persistent parasitism.
(b)(1)
(2)
(3)
(ii)(
(
(iii) A veterinarian should be consulted before using in severely debilitated dogs.
(a)
(b)
(c)
(2) It is administered by stomach tube or as a drench at a dose of 0.9 gram of cambendazole per 100 pounds of body weight (20 milligrams per kilogram).
(3) For animals maintained on premises where reinfection is likely to occur, re-treatments may be necessary. For most effective results, re-treat in 6 to 8 weeks.
(4) Not for use in horses intended for food.
(5) Caution: Do not administer to pregnant mares during first 3 months of pregnancy.
(6) Federal law restricts this drug to use by or on the order of a licensed veterinarian.
(a)
(b)
(c)
(2) Administer 20 milligrams cambendazole per kilogram body weight (6 ounces per 1,000 pounds) by mixing with normal grain ration given at one feeding. Doses for individual horses should be mixed and fed separately to assure that each horse will consume the correct amount.
(3) For animals maintained on premises where reinfection is likely to occur, re-treatments may be necessary. For most effective results, re-treat in 6 to 8 weeks.
(4) Not for use in horses intended for food.
(5) Caution: Do not administer to pregnant mares during first 3 months of pregnancy.
(6) Consult your veterinarian for assistance in the diagnosis, treatment, and control of parasitism.
(a)
(b)
(c)
(2) Administer 20 milligrams cambendazole per kilogram body weight (5 grams per 550 pounds (250 kilograms)) by depositing the paste on the back of the tongue using a dosing gun.
(3) For animals maintained on premises where reinfection is likely to occur, re-treatments may be necessary. For most effective results, re-treat in 6 to 8 weeks.
(4) Not for use in horses intended for food.
(5) Caution: Do not administer to pregnant mares during first 3 months of pregnancy.
(6) Consult your veterinarian for assistance in the diagnosis, treatment, and control of parasitism.
(a)
(2) Each chewable tablet contains 25, 75, or 100 mg carprofen.
(b)
(1) No. 000069 for use of products described in paragraph (a) of this section as in paragraph (d) of this section.
(2) Nos. 000115 and 062250 for use of product described in paragraph (a)(1) as in paragraph (d) of this section.
(c) [Reserved]
(d)
(2)
(3)
(a)
(b)
(c)
(2)
(a)
(b)
(c)
(2)
(3)
(a)
(b)
(c)
(i)
(ii)
(iii)
(2) For use in cats as follows:
(i)
(ii)
(iii)
(a)
(b)
(c)
(i)
(ii)
(2) For use in cats as follows:
(i)
(ii)
(3)
(a)
(b)
(c)
(2)
(3)
(a)(1)
(2)
(3)
(ii)
(iii)
(b)(1)
(2)
(3)
(ii)
(iii)
(a)
(b)
(1) Nos. 000069, 000185, and 050057 for capsules containing 50, 100, 250, or 500 mg chloramphenicol.
(2) No. 058034 for capsules containing 100 or 250 mg chloramphenicol.
(c)
(d)
(2)
(3)
(a)
(b)
(c)
(2)
(3)
(a)(1)
(2)
(3)
(ii)
(iii)
(
(b)(1)
(2)
(3)
(ii)
(iii)
(a)
(b)
(c)
(2)
(3)
(a)
(b)
(c)
(d)
(1)
(2)
(3)
(a)
(b)
(1) No. 048164 for use as in paragraph (d) of this section.
(2) No. 053501 for use as in paragraph (d)(5) of this section.
(3) No. 000010 for use as in paragraphs (d)(4)(i)(A), (d)(4)(i)(B), and (d)(4)(ii) through (iv) of this section.
(4) Nos. 021930 and 059130 for use as in paragraphs (d)(4)(i)(A), (d)(4)(i)(B), (d)(4)(ii), and (d)(4)(iii) of this section.
(c)
(d)
(i)
(
(
(B) [Reserved]
(ii) [Reserved]
(2) Use as chlortetracycline hydrochloride in a drench or drinking water as follows:
(i)
(
(
(B) [Reserved]
(ii) [Reserved]
(3) [Reserved]
(4) The following uses of chlortetracycline hydrochloride or chlortetracycline bisulfate in drinking water or drench were reviewed by the National Academy of Sciences/National Research Council (NAS/NRC) and found effective:
(i)
(
(
(B)
(
(
(C)
(
$(
(ii)
(
(
(B)
(
(
(iii)
(B)
(C)
(iv)
(B)
(C)
(5) Use in a drench or drinking water as follows:
(i)
(
(
(B)
(
(
(C)
(
(
(ii)
(
(
(B)
(
(
(iii)
(B)
(C)
(iv)
(B)
(C)
(a)
(b)
(c)
(d)
(e)
(i)
(ii)
(2)
(i)
(ii)
(3)
(i)
(ii)
(a)
(2) Each tablet contains the equivalent of 25, 75, or 150 mg clindamycin as the hydrochloride salt.
(3) Each capsule contains the equivalent of 25, 75, or 150 mg clindamycin as the hydrochloride salt.
(b)
(1) Nos. 000009 and 059130 for use of capsules described in paragraph (a)(1) of this section.
(2) No. 051311 for use of tablets described in paragraph (a)(2) of this section.
(3) No. 043806 for use of tablets described in paragraph (a)(3) of this section.
(c)
(2)
(3)
(a)
(b)
(c)
(d)
(ii)
(2) Cats—(i)
(ii)
(a)
(b)
(c) [Reserved]
(d)
(ii)
(iii)
(2) [Reserved]
(a) Specifications. Each tablet contains 5, 20, 40, or 80 milligrams (mg) clomipramine hydrochloride.
(b)
(c)
(2)
(3)
(a)
(b)
(c)
(2)
(3)
(a)
(b)
(c) [Reserved]
(d)
(2)
(3)
(a)
(b)
(c)
(d)
(2)
(3)
(a) [Reserved]
(b)
(c)
(d)
(2)
(3)
(a)
(b)
(c)
(d)
(2)
(3)
(a)
(b)
(c) [Reserved]
(d)
(i) 1 to 2 mg/kilograms (kg) (0.45 to 0.91 mg/pound (lb), for use as in paragraph (d)(2)(i) of this section.
(ii) 3 to 4 mg/kg (1.4 to 1.8 mg/lb) for up to 7 days, for use as in paragraph (d)(2)(ii) of this section.
(2)
(ii) For the control of postoperative pain and inflammation associated with orthopedic surgery in dogs weighing 4 or more pounds (1.8 kg).
(3)
(a)
(b)
(c)
(2) The drug is administered at a dosage level of 5 to 10 milligrams per animal the first day then 5 milligrams per day as required by drench or by sprinkling on a small amount of feed.
(3) Clinical and experimental data have demonstrated that corticosteroids
(4) Federal law restricts this drug to use by or on the order of a licensed veterinarian. A withdrawal period has not been established for this product in preruminating calves. Do not use in calves to be processed for veal.
(a)(1)
(2)
(3)
(ii) Administered orally, 5 to 10 milligrams for the first day, then 5 milligrams per day as required.
(iii) Do not use in viral infections during the viremic stage. With bacterial infections, appropriate antibacterial therapy should be used.
(iv) Do not use in animals with chronic nephritis and hypercorticalism (cushingoid syndrome), except for emergency therapy.
(v) Clinical and experimental data have demonstrated that corticosteroids administered orally or by injection to animals may induce the first stage of parturition when administered during the last trimester of pregnancy and may precipitate premature parturition followed by dystocia, fetal death, retained placenta, and metritis.
(vi) Federal law restricts this drug to use by or on the order of a licensed veterinarian. A withdrawal period has not been established for this product in preruminating calves. Do not use in calves to be processed for veal.
(b)(1)
(2)
(3)
(ii)
(iii)
(
(
(a)
(b)
(c)
(2)
(3)
(ii) Clinical and experimental data have demonstrated that corticosteriods administered orally or parenterally to animals may induce the first stage of parturition when administered during the last trimester of pregnancy; and they may precipitate premature parturition followed by dystocia, fetal death, retained placenta, and metritis.
(iii) Do not use in viral infections. Anti-inflammatory action of corticosteriods may mask signs of infection. Do not use in animals with tuberculosis, chronic nephritis, cushingoid syndrome, or peptic ulcers, except for emergency therapy.
(iv) Federal law restricts this drug to use by or on the order of a licensed veterinarian.
(a)
(b)
(c)
(2) Dissolve each packet in two quarts of warm water and administer to each calf as follows:
(i)
(ii)
(3) The product should not be used in animals with severe dehydration (down, comatose, or in a state of shock). Such animals need intravenous therapy. Oral therapy in these cases is too slow. Animals which cannot drink after initial intravenous therapy may need to be dosed with a stomach tube or esophageal tube. Adequate colostrum intake during the first 12 hours is essential for healthy, vigorous calves. Antibacterial therapy is often indicated in bacterial scours due to
(a)
(b)
(c)
(2) It is administered orally at a dosage level of 0.5 to 1.0 milliliter per pound of body weight by gavage or stomach tube. It is administered rectally at a dosage level of 0.5 to 1.0 milliliter per pound of body weight diluted with 1 part of the drug to 5 parts of water.
(3) Federal law restricts this drug to use by or on the order of a licensed veterinarian.
(a)
(b)
(2) For single and multiple dose, see 000010, 000061, and 038782 in § 510.600(c) of this chapter.
(c)
(d)
(ii) Divided dose of 100 milligrams of dichlorophene and 120 milligrams of toluene per 5 pounds of body weight (20 and 24 milligrams per pound) daily for 6 days.
(2)
(3)
For
(a)
(b)
(c)
(d)
(2)
(3)
(a)
(b) [Reserved]
(c)
(d)
(e)
(2) The preparation should be added to the indicated amount of feed as set forth in paragraph (e)(2) of this section and administered shortly after mixing, as follows:
(3) Do not use this product on animals either simultaneously or within a
(f)
(2) The drug is in capsule form for direct administration and in pellet form for administration in about one-third of the regular canned dog food ration or in ground meat. Dogs may be treated with any combination of capsules and/or pellets so that the animal receives a single dose equaling 12 to 15 milligrams of the active ingredient per pound of body weight. One-half of the single recommended dosage may be given, and the other half may be administered 8 to 24 hours later. This split dosage schedule should be used in animals which are very old, heavily parasitized, anemic, or otherwise debilitated. The drug should not be used in dogs weighing less than 2 pounds.
(3) In some dogs, efficacy against
(4) Do not use in dogs infected with
(5) Do not use with other anthelmintics, taeniacides, antifilarial agents, muscle relaxants, or tranquilizers.
(6) The drug is a cholinesterase inhibitor. Not for use simultaneously or within a few days before or after treatment with or exposure to cholinesterase-inhibiting drugs, pesticides, or chemicals.
(7) Federal law restricts this drug to use by or on the order of a licensed veterinarian.
(g)
(2) For a satisfactory diagnosis, a microscopic fecal examination should be performed by a veterinarian or a diagnostic laboratory prior to worming.
(3) It is administered in the grain portion of the ration at a dosage of 14.2 milligrams to 18.5 milligrams per pound of body weight as a single dose. It may be administered at one-half of the single recommended dosage and repeated 8 to 12 hours later in the treatment of very aged, emaciated or debilitated subjects or those reluctant to consume medicated feed. In suspected cases of severe ascarid infection sufficient to cause concern over mechanical blockage of the intestinal tract, the split dosage should be utilized.
(4) Do not use in horses which are severely debilitated, suffering from diarrhea or severe constipation, infectious disease, toxemia or colic. Do not administer in conjunction with or within 1 week of administration of muscle relaxant drugs, phenothiazine derived tranquilizers or central nervous system depressant drugs. Horses should not be subjected to insecticide treatment for 5 days prior to or after treating with the drug. Do not administer to horses afflicted with chronic alveolar emphysema (heaves) or related respiratory conditions. The product is a cholinesterase inhibitor and should not be used simultaneously or within a few days before or after treatment with or exposure to cholinesterase inhibiting drugs, pesticides or chemicals.
(5) Do not use in animals other than horses, ponies, and mules. Do not use in horses, ponies, and mules intended for food purposes. Do not allow fowl access to feed containing this preparation or to fecal excrement from treated animals.
(h)
(2) The product is in the form of a gel which is administered directly from a syringe onto the horse's tongue. The product is administered at a dosage level of 20 milligrams of dichlorvos per kilogram of body weight for the removal of bots and ascarids. The same dosage level is repeated every 21 to 28 days for the control of bots and ascarids. For the control of bots only, the repeat dosage is 10 milligrams per kilogram of body weight every 21 to 28 days during bot fly season.
(3) Do not use this product in animals simultaneously or within a few days before or after treatment with or exposure to cholinesterase-inhibiting drugs, pesticides or chemicals. Do not administer in conjunction with or within 1 week of administration of muscle-relaxant drugs, phenothiazine derived tranquilizers, or central nervous system depressants.
(4) Do not use in horses which are severly debilitated or suffering from diarrhea or severe constipation, infectious disease, toxemia, or colic. Do not administer to horses affected with chronic alveolar emphysema (heaves) or other respiratory conditions.
(5) Do not use in horses intended for food purposes.
(6) Federal law restricts this drug to use by or on the order of a licensed veterinarian.
(i)
(2) It is administered orally at 5 milligrams of dichlorvos per pound of body weight.
(3) Dogs and puppies: Removal and control of intestinal roundworms (
(4) Cats and kittens: Removal and control of intestinal roundworms (
(5) Dichlorvos is a cholinesterase inhibitor. Do not use simultaneously with or within a few days before or after treatment with or exposure to cholinesterase-inhibiting drugs, pesticides, or chemicals.
(6) Do not use in animals under 10 days of age or 1 pound of body weight.
(7) Do not administer to animals showing signs of constipation, mechanical blockage of the intestinal tract, impaired liver function, or recently exposed to or showing signs of infectious disease.
(8) Do not use in dogs or puppies infected with
(9) Federal law restricts this drug to use by or on the order of a licensed veterinarian.
(a)
(b)
(c)
(2)
(3)
(a)
(b)
(c)
(2)
(3)
(a)
(2) See 053501 in § 510.600(c) of this chapter for use of 100, 200, and 300 milligram tablets for prevention of heartworm disease in dogs and as an aid in the treatment of ascarid infections in dogs.
(3) See 061623 in § 510.600(c) of this chapter for use of 50, 100, 200, 300, or 400 milligram tablets for prevention of heartworm disease in dogs, as an aid in the control of ascarid infections in dogs, and as an aid in the treatment of ascarid infections in dogs and cats.
(4) See 017030 in § 510.600(c) of this chapter for use of 50, 100, 200, 300, and 400 milligram tablets for prevention of heartworm disease in dogs and as an aid in the treatment of ascarid infections in dogs and cats.
(5) See 000081 in § 510.600(c) of this chapter for use of 60, 120, or 180 milligram tablets for prevention of heartworm disease in dogs, as an aid in the control of ascarid infections in dogs, and as an aid in the treatment of ascarid infections in dogs and cats.
(6) See No. 000010 in § 510.600(c) of this chapter for use of 50, 100, 200, 300, or 400 milligram tablets for prevention of heartworm disease in dogs, as an aid in the control of ascarid infections in dogs, and as an aid in the treatment of ascarid infections in dogs and cats.
(b)
(ii) Three milligrams per pound of body weight daily as an aid in the control of ascarid infections (
(iii) Twenty-five to 50 milligrams per pound of body weight as an aid in the treatment of ascarid infections in dogs (
(2)
(a)(1)
(2)
(3)
(ii) For prevention of heartworm and ascarid infections in dogs, the drug may be added to the daily diet at a dosage rate of 3.0 milligrams per pound of body weight per day or given directly by mouth at the same dosage rate. For treatment of ascarid infections in dogs and cats, the drug is administered at a dosage level of 25 to 50 milligrams per pound of body weight preferably administered immediately after feeding.
(iii) Older dogs should be proven negative for the presence of
(iv) Federal law restricts this drug to use by or on the order of a licensed veterinarian.
(b)(1)
(2)
(ii) See No. 017030 for use as in paragraphs (b)(3)(ii) (
(3)
(ii)
(
(
(iii)
(c)(1)
(2)
(3)
(ii) The drug is administered (
(iii) Dogs older than 8 months of age may be infected with
(iv) Federal law restricts this drug to use by or on the order of a licensed veterinarian.
(a)
(b)
(1) For 015579, use of 30 or 120 milligram tablets as in paragraph (c)(2)(i) of this section.
(2) For 000069, use of 60, 120, or 180 milligram tablets as in paragraph (c)(2)(ii) of this section.
(3) For 061690, use of 45 or 150 milligram tablets as in paragraph (c)(2)(iii) of this section.
(4) For 061133, use of 60-, 120-, or 180-milligram tablets as in paragraph (c)(2)(i) of this section.
(5) For 000061, use of 60-milligram tablets as in paragraph (c)(2)(i) of this section.
(6) For 000010, use of 30, 60, 120, or 180 milligram tablets as in paragraph (c)(2)(i) of this section.
(7) [Reserved]
(c)
(2)
(ii) For prevention of infection with
(iii) For prevention of heartworm disease (
(3)
For
(a)
(b)
(c)
(2)
(a)
(b)
(c)
(2)
(3)
(a)
(b)
(c) [Reserved]
(d)
(ii)
(iii)
(2) [Reserved]
(a)
(b)
(c)
(2)
(3)
(a)
(b)
(c)
(d)
(2) The drug is contraindicated in animals sensitive to dithiazanine iodide and should be used cautiously, if at all, in dogs with reduced renal function.
(3) Federal law restricts this drug to use by or on the order of a licensed veterinarian.
(e) Use for treating dogs for large roundworms, hookworms, whipworms, and strongyloides as provided for in this section has been NAS/NRC reviewed and deemed effective. Applications for these uses need not include effectiveness data as specified by § 514.111 of this chapter, but may require bioequivalency and safety information.
(a)
(b)
(c)
(d)
(2) The drug is contraindicated in animals sensitive to dithiazanine iodide and should be used cautiously, if at all, in dogs with reduced renal function.
(3) Federal law restricts this drug to use by or on the order of a licensed veterinarian.
(e) Use for treating dogs for large roundworms, hookworms, whipworms, and strongyloides as provided for in this section has been NAS/NRC reviewed and deemed effective. Applications for these uses need not include effectiveness data as specified by § 514.111 of this chapter, but may require bioequivalency and safety information.
(a)
(b)
(c)
(d)
(2)
(3)
(a)
(b)
(c)
(2) It is administered orally to horses at a dosage level of 1 to 2 milligrams per pound of body weight per day divided into 3 or 4 equal doses. It is administered orally to dogs and cats at a dosage level of 2 to 3 milligrams per pound of body weight per day divided into 3 or 4 equal doses.
(3) Not for use in horses intended for food.
(4) Federal law restricts this drug to use by or on the order of a licensed veterinarian.
(a)
(b)
(c)
(ii)
(iii)
(2) [Reserved]
(a)
(b)
(c) [Reserved]
(d)
(2)
(3)
(a)
(b)
(c)
(ii)
(2)
(ii)
(3)
(a)
(b)
(c)
(d)
(1)
(ii)
(iii)
(2)
(ii)
(iii)
(3)
(ii)
(iii)
(a)
(b)
(c)
(2) It is administered once daily at a dosage level of 2 to 5 milligrams of ethylisobutrazine hydrochloride per pound of body weight.
(3) It is not to be used in conjunction with organophosphates and/or procaine
(4) Federal law restricts this drug to use by or on the order of a licensed veterinarian.
(a)
(b)
(c) [Reserved]
(d)
(ii)
(iii)
(2) [Reserved]
(a)
(b)
(c)
(d)
(2)
(3)
(ii) [Reserved]
(iii) For animals maintained on premises where reinfection is likely to occur, retreatment may be necessary. For most effective results, retreat in 6 to 8 weeks.
(iv) Not for use in horses intended for food.
(v) Consult your veterinarian for assistance in the diagnosis, treatment, and control of parasitism.
(a)
(b)
(c)
(2)
(3)
(d)
(1) Combine 1 part febantel suspension with 5 parts trichlorfon liquid.
(2) Allow animal to consume a portion of daily grain ration; administer mixture by stomach tube at rate of 18 milliliters per 100 pounds of body weight.
(a)
(b)
(c)
(ii) Puppies and kittens (less than 6 months of age): 15 milligrams of febantel and 1.5 milligrams of praziquantel per kilogram of body weight (1 gram of paste per 5 pounds body weight) administered by mouth on a full stomach once daily for 3 days.
(2)
(ii) Cats and kittens: For removal of hookworms (
(3)
(4)
(a)
(b)
(c)
(ii)
(2)
(ii) For removal of hookworms (
(3)
(a)
(b)
(c)
(d)
(ii)
(iii)
(2)
(ii)
(iii)
(3)
(ii) For the removal and control of stomach worm (4th-stage inhibited larvae/type II ostertagiasis),
(iii)
(4)
(ii)
(iii)
(e)
(a)
(b)
(c)
(d)
(ii)
(iii)
(2)
(ii)
(iii)
(3)
(ii)
(A) Lion (
(B) Cheetah (
(C) Puma (
(D) Black Bear (
(E) Polar Bear (
(iii)
(a)
(b)
(c)
(d)
(e)
(B) For control of arteritis caused by the fourth-stage larvae of S. vulgaris: 4.6 mg/lb of body weight daily for 5 days. Treatment should be initiated in the spring and repeated in 6 months.
(C) For treatment of encysted mucosal cyathostome (small strongyle) larvae including early third-stage (hypobiotic), late third-stage, and fourth-stage larvae: 4.6 mg/lb of body weight daily for 5 consecutive days.
(D) Fenbendazole paste 10 percent may be used concomitantly with approved forms of trichlorfon for the indications provided in paragraph (e)(1)(i)(A) of this section and for treating infections of stomach bots as provided in § 520.2520.
(ii)
(2)
(ii)
(iii)
(a)
(2) Each 4-ounce packet contains 1.7 grams (1.5 percent) of fenbendazole plus other inert ingredients.
(b)
(2) See No. 051311 in § 510.600(c) of this chapter for use of the 1.5-percent product.
(c)
(d)
(1)
(2)
(3)
(a)
(2) Each pound of protein block contains 750 milligrams of fenbendazole.
(b)
(c)
(d)
(2)
(3)
(a)
(b)
(c)
(2)
(3)
(a)
(b)
(c)
(2)
(3)
(a)
(b)
(c)
(d)
(2)
(3)
(a)
(b)
(c)
(ii)
(2)
(ii)
(3)
(a)
(b)
(c)
(2)
(3)
(a)
(b)
(c)
(2)
(3)
(a)
(b)
(c)
(2)
(3)
(a)
(2) Each bolus contains 2 grams (g) furosemide.
(3) Each packet of powder contains 2 g furosemide.
(4) Each milliliter of syrup contains 10 mg furosemide.
(b)
(1) No. 000010 for tablets in paragraph (a)(1) of this section for conditions of use in paragraphs (d)(2)(i), (d)(2)(ii)(A), and (d)(3) of this section.
(2) No. 057926 for tablets in paragraph (a)(1) of this section for conditions of use in paragraphs (d)(2)(i), (d)(2)(ii)(A), and (d)(3) of this section; for boluses in paragraph (a)(2) of this section and powder in paragraph (a)(3) of this section for conditions of use in paragraph (d)(1) of this section; and for syrup in paragraph (a)(4) of this section for conditions of use in paragraphs (d)(2)(i) and (d)(2)(ii)(A).
(3) Nos. 058829 and 059130 for use of syrup in paragraph (a)(4) of this section for conditions of use in paragraph (d)(2)(i) and (d)(2)(ii)(A) of this section.
(c)
(d)
(1)
(ii)
(iii)
(2)
(ii)
(B) For treatment of edema (pulmonary congestion, ascites) associated with cardiac insufficiency.
(3)
(ii)
(a)
(b)
(c)
(d)
(2)
(3)
(a)
(b)
(c)
(d)
(2)
(3)
(a)
(b)
(c)
(d)
(2)
(3)
(a)
(2) Each bolus contains 2.5 grams griseofulvin.
(3) Each tablet contains 125 or 500 milligrams griseofulvin.
(b)
(1) No. 000061 for use of products described in paragraph (a) for use as in paragraph (d) of this section.
(2) No. 059130 for use of the powder described in paragraph (a)(1) for use as in paragraphs (d)(1)(i)(A) and (d)(1)(ii) of this section.
(c)
(d)
(B) For treating ringworm infection caused by
(ii)
(2) Dogs and cats: (i)
(A) Daily (single or divided) dose:
(B) Weekly (single) dose: If experience indicates that treatment is more effective for the drug given in large doses, administer at intervals of 7 to 10 days, a dose equal to 10 milligrams/pound of body weight × body weight × number of days between treatments. Dosage should be adjusted according to response. Administer additional dose after the animal is free of infection.
(ii)
(a)
(b)
(c)
(d)
(e)
(f)
(1)
(ii)
(iii)
(
(a)
(b)
(c)
(d)
(e)
(2) It is administered by giving one bolus per approximately 500 pounds
(3) For most effective results, re-treat animals in 3 to 4 weeks. If reinfection is likely to occur, additional re-treatments may be necessary.
(4) Do not use any drug, pesticide or other chemical having cholinesterase inhibiting activity either simultaneously or within a few days before or after treatment with haloxon.
(5) Do not treat animals within one week of slaughter.
(6) Do not treat dairy animals of breeding age or older.
(a)
(b)
(c)
(ii)
(iii)
(2)
(ii)
(3)
(a)
(b)
(c)
(ii)
(iii)
(2)
(ii)
(iii)
(a)
(b)
(c)
(ii)
(iii)
(2)
(ii)
(iii)
(a)
(b)
(c)
(2)
(3)
(a)
(b)
(c)
(2)
(3)
(a)
(b)
(c)
(2)
(3)
(a)
(b)
(1) No. 050604 for use of a 1.87-percent paste as in (e)(1)(i), (e)(1)(ii)(A), and (e)(1)(iii) of this section and a 0.153-percent paste for use as in paragraph (e)(2) of this section.
(2) No. 059130 for use of a 1.87-percent paste for use as in paragraph (e)(1)(i), (e)(1)(ii)(B), and (e)(1)(iii) of this section.
(3) No. 061623 for use of a 1.87 percent paste for use as in paragraph (e)(1)(i), (e)(1)(ii)(C), and (e)(1)(iii) of this section.
(4) Nos. 051311 and 054925 for use of a 1.87 percent paste as in paragraphs (e)(1)(i), (e)(1)(ii)(A), and (e)(1)(iii) of this section.
(c)
(d)
(e)
(ii)
(A) Large Strongyles (adults):
(B) Large Strongyles (adult) (
(C) Large strongyles (adults)—
(iii)
(2)
(ii)
(iii)
(a)
(2) Each chewable contains 55 or 165 mcg ivermectin.
(b)
(1) No. 050604 for use of tablets or chewables described in paragraph (a)(1) as in paragraph (d)(1) and chewables described in paragraph (a)(2) as in paragraph (d)(2) of this section.
(2) Nos. 051311 and 059130 for use of tablets described in paragraph (a)(1) as in paragraph (d)(1) of this section.
(c)
(d)
(i)
(ii)
(2)
(i)
(ii)
(a)
(b)
(c)
(d)
(2)
(a)
(2) Each mL of micellar solution contains 0.8 mg ivermectin.
(b)
(1) Nos. 050604, 054925, and 059130 for use of product described in paragraph (a)(1) of this section as in paragraphs (e)(1)(i), (e)(1)(ii)(A), and (e)(1)(iii) of this section.
(2) Nos. 058005 and 058829 for use of product described in paragraph (a)(1) of this section as in paragraphs (e)(1)(i), (e)(1)(ii)(B), and (e)(1)(iii) of this section.
(3) Nos. 050604 and 058829 for use of product described in paragraph (a)(2) of this section as in paragraph (e)(2) of this section.
(c)
(d)
(e)
(ii)
(A) Large Strongyles (adults):
(B) Large Strongyles (
(iii)
(2)
(ii)
(iii)
(a)
(b)
(c)
(ii)
(iii)
(2) [Reserved]
(a)
(b)
(c)
(d)
(2)
(3)
(a)
(1) 0.0155 mg (1.55 percent) ivermectin and 0.0775 mg (7.75 percent) praziquantel.
(2) 0.0187 mg (1.87 percent) ivermectin and 0.1403 mg (14.03 percent) praziquantel.
(b)
(1) No. 050604 for use of product described in paragraph (a)(1) of this section as in paragraphs (d)(1)(i), (d)(2)(i) and (d)(3) of this section.
(2) No. 051311 for use of product described in paragraph (a)(2) of this section as in paragraphs (d)(1)(ii), (d)(2)(ii), and (d)(3) of this section.
(c)
(d)
(ii) 200 mcg/kg ivermectin (91 mcg/lb) and 1.5 mg/kg praziquantel (681 mcg/lb) body weight.
(2)
(i) Tapeworms—
(ii) Tapeworms—
(3)
(a)
(1) 34 micrograms (mcg) ivermectin, 28.5 milligrams (mg) pyrantel pamoate, and 28.5 mg praziquantel;
(2) 68 mcg ivermectin, 57 mg pyrantel pamoate, and 57 mg praziquantel;
(3) 136 mcg ivermectin, 114 mg pyrantel pamoate, and 114 mg praziquantel; or
(4) 272 mcg ivermectin, 228 mg pyrantel pamoate, and 228 mg praziquantel.
(b)
(c)
(i) 6 to 12 lb: one tablet as described in paragraph (a)(1) of this section.
(ii) 12.1 to 25 lb: one tablet as described in paragraph (a)(2) of this section.
(iii) 25.1 to 50 lb: one tablet as described in paragraph (a)(3) of this section.
(iv) 50.1 to 100 lb: one tablet as described in paragraph (a)(4) of this section.
(v) Greater than 100 lb: use the appropriate combination of tablets.
(2)
(3)
(a)
(2) Each tablet contains 100 mg kanamycin (as the sulfate), 250 mg bismuth subcarbonate, and 500 mg activated attapulgite.
(b)
(c)
(2)
(3)
(a)
(b)
(1) No. 000061 for use of 46.8- and 544.5-g packages as in paragraph (e)(1)(i), (e)(1)(ii)(B), and (e)(1)(iii) of this section; for 11.7-, 46.8-, and 544.5-g packages as in paragraph (e)(2)(i), (e)(2)(ii)(B), and (e)(2)(iii) of this section; and for an 18.15-g package as in paragraph (e)(3) of this section.
(2) No. 053501 for use of a 46.8-g package as in paragraph (e)(1)(i), (e)(1)(ii)(A), and (e)(1)(iii) of this section; for 11.7- and 46.8-g packages as in paragraph (e)(2)(i), (e)(2)(ii)(A), and (e)(2)(iii) of this section; and for 9.075- and 18.15-g packages as in paragraph (e)(3) of this section.
(3) No. 057561 for use of 46.8- and 544.5-g packages as in paragraphs (e)(1)(i), (e)(1)(ii)(A), and (e)(1)(iii) and (e)(2)(i), (e)(2)(ii)(A), and (e)(2)(iii) of this section.
(4) No. 059130 for use of 46.8-, 362.7-, and 544.5-g packages as in paragraphs (e)(1)(i), (e)(1)(ii)(B), (e)(1)(iii), (e)(2)(i), (e)(2)(ii)(B), and (e)(2)(iii) of this section; and for use of an 18.15-g package as in paragraph (e)(3) of this section.
(c)
(d)
(e)
(1)
(ii)
(B) Effective against the following adult nematode infections: Stomach worms (
(iii)
(2)
(ii)
(B) Effective against the following adult nematode infections: Stomach worms (
(iii)
(3)
(ii)
(iii)
(a)
(b)
(c)
(d)
(e)
(f)
(i)
(ii)
(iii)
(2) It is used in a tablet for sheep as follows:
(i)
(ii)
(iii)
(a)
(2) The drug is a soluble powder which when reconstituted with water contains in each fluid ounce 0.45 gram of levamisole hydrochloride and piperazine dihydrochloride equivalent to 5.0 grams of piperazine base.
(b)
(c) [Reserved]
(d)
(1)
(2)
(a)
(b)
(c)
(d)
(1)
(2)
(3)
(a)
(b)
(c)
(d)
(1)
(2)
(3)
(a)
(b)
(c)
(d)
(ii)
(iii)
(2)
(ii)
(iii)
(a)
(b)
(c)
(d)
(e)
(f)
(2)
(3)
(a)
(b)
(c)
(2) It is administered orally to dogs and cats at a dosage level of 10 mgs per pound of body weight every 12 hours, or 7 mgs per pound of body weight every 8 hours. Treatment may be continued for
(3) Federal law restricts this drug to use by or on the order of a licensed veterinarian.
(a)
(b)
(c)
(d)
(ii)
(iii)
(2)
(ii)
(iii)
(a)
(1) Lincomycin hydrochloride monohydrate and spectinomycin sulfate tetrahydrate.
(2) Lincomycin hydrochloride monohydrate and spectinomycin dihydrochloride pentahydrate.
(b)
(1) No. 000009 for use of product described in paragraph (a)(1) of this section.
(2) Nos. 057561, 059130, and 061623 for use of product described in paragraph (a)(2) of this section.
(c)
(d)
(2)
(a)
(b)
(c)
(2) It is administered orally to dogs at levels up to 12.8 micrograms per kilogram of body weight per day. Dosage should be adjusted according to the severity of the condition and the response of the patient. Dosage at the total replacement level (12.8µg per kilogram of body weight) should be considered for initiating therapy and then titrated downward for optimum maintenance effect. Twice daily administration is recommended.
(3) Federal law restricts this drug to use by or on the order of a licensed veterinarian.
(a)
(2) Flavored tablets containing 45, 90, 204.9, or 409.8 milligrams (mg) lufenuron for use as in paragraphs (c)(1)(i), (c)(1)(ii)(A) or (c)(1)(ii)(B), and (c)(1)(iii) of this section.
(3) Flavored tablets containing 90 or 204.9 mg lufenuron for use as in paragraphs (c)(2)(i), (c)(2)(ii)(A) or (c)(2)(ii)(B), and (c)(2)(iii) of this section.
(4) Flavored tablets containing 135 or 270 mg lufenuron for use as in paragraphs (c)(2)(i), (c)(2)(ii)(A), and (c)(2)(iii) of this section.
(b)
(c)
(ii)
(B) The concurrent use of flavored lufenuron tablets described in paragraph (a)(2) of this section as in paragraph (c)(1)(ii)(A) of this section with nitenpyram tablets as in § 520.1510(d)(1) of this chapter is indicated to kill adult fleas and prevent flea eggs from hatching.
(iii)
(2)
(ii)
(B) The concurrent use of flavored lufenuron tablets described in paragraph (a)(3) of this section as in paragraph (c)(2)(ii)(A) of this section with nitenpyram tablets as in § 520.1510(d)(2) of this chapter is indicated to kill adult fleas and prevent flea eggs from hatching.
(iii)
(a)
(b)
(c)
(2)
(3)
(a)
(b)
(c) [Reserved]
(d)
(2)
(3)
(a)
(b)
(c)
(2)
(a)
(b)
(c)
(d)
(ii)
(iii)
(
(
(2)
(ii)
(iii)
(a)
(b)
(c)
(2)
(3)
(a)
(b)
(c)
(2)
(3)
(a)
(b)
(c)
(d)
(2) It is administered orally at a dosage of 1 milligram per pound of body weight (1 gram per 1,000 pounds) once daily for 5 to 7 days by addition to the daily grain ration.
(3) Treatment beyond the initial 5- to 7-day period may be indicated. A maintenance dosage level should be individualized for each animal.
(4) This drug should not be administered to horses with active gastrointestinal, hepatic, or renal disease.
(5) Not for use in horses intended for food.
(6) Federal law restricts this drug to use by or on the order of a licensed veterinarian.
(a)
(b)
(c)
(2)
(3)
(a)
(b)
(c)
(2) It is administered orally, intact, or crushed and mixed with food as follows:
(i) For the postponement of estrus by proestrus treatment, 1 milligram per pound of body weight per day for 8 days.
(ii) For the postponement of estrus by anestrus treatment, 0.25 milligram per pound of body weight per day for 32 days.
(iii) For alleviation of false pregnancy, 1 milligram per pound of body weight per day for 8 days.
(3) Full dosage regimen must be completed to produce the desired effect.
(4) Examination of vaginal smears is recommended to confirm detection of proestrus.
(5) Do not administer for more than two consecutive treatments.
(6) Once therapy is started, the animal should be confined for 3 to 8 days or until cessation of bleeding, since dogs in proestrus accept a male.
(7) Do not use prior to or during first estrus cycle.
(8) Do not use in pregnant animals.
(9) Do not use in the presence of a disease of the reproductive system or with mammary tumors.
(10) Should estrus occur within 30 days after cessation of treatment, mating should be prevented.
(11) Federal law restricts this drug to use by or on the order of a licensed veterinarian.
(a)
(b)
(c)
(2)
(3)
(a)
(b)
(c)
(d)
(2) Dosage is based upon severity of symptoms and response noted. The usual initial dose in 60 milligrams per pound of body weight in two or three equally divided doses followed by 30 to 60 milligrams per pound of body weight each following day, usually not to exceed 14 to 21 days.
(3) For use only by or on the order of a licensed veterinarian.
(a)
(b)
(c) [Reserved]
(d)
(2)
(a)
(b)
(c)
(d)
(2) Systemic therapy with methylprednisolone is contraindicated in animals with arrested tuberculosis, peptic ulcer, acute psychoses, or cushingoid syndrome. The presence of active tuberculosis, diabetes, osteoporosis, chronic psychotic reactions, predisposition to thrombophlebitis, hypertension, congestive heart failure, or renal insufficiency necessitates carefully controlled use of corticosteroids. Some of these conditions occur only rarely in dogs and cats but should be kept in mind.
(3) Anti-inflammatory action of corticosteroids may mask signs of infection.
(e)
(2)
(3)
(a)
(b)
(c)
(d)
(2) Systemic therapy with methylprednisolone is contraindicated in animals with tuberculosis, chronic nephritis, peptic ulcer, or Cushingoid syndrome. The presence of diabetes mellitus, osteoporosis, predisposition to thrombophlebitis, hypertension, congestive heart failure, or renal insufficiency necessitates carefully controlled use of corticosteroids.
(3) Anti-inflammatory action of corticosteroids may mask signs of infection.
(e)
(2)
(3)
(a)
(b)
(c)
(d)
(1)
(i)
(ii)
(2)
(i)
(ii)
(a)
(b)
(c)
(2)
(3)
(a)
(2)
(b)
(c) [Reserved]
(d)
(ii)
(iii)
(2)
(ii)
(iii)
(a)
(2) Flavored tablets containing: 2.3 mg milbemycin oxime and 46 mg lufenuron, 5.75 mg milbemycin oxime and 115 mg lufenuron, 11.5 mg milbemycin oxime and 230 mg lufenuron, or 23 mg milbemycin oxime and 460 mg lufenuron.
(b)
(c) [Reserved]
(d)
(ii)
(B) The concurrent use of flavored milbemycin oxime and lufenuron tablets described in paragraph (a)(2) of this section as in paragraph (d)(1)(ii)(A) of this section with nitenpyram tablets as in § 520.1510(d)(1) of this chapter is indicated to kill adult fleas and prevent flea eggs from hatching.
(iii)
(2) [Reserved]
Monensin, as the base or the sodium salt, contains a minimum of 90 percent monensin activity derived from monensin A and a minimum of 95 percent derived from monensin A plus B. Using thin layer chromatography, the
(a)(1)
(2)
(3)
(4)
(ii)
(iii)
(b) [Reserved]
(c)(1)
(2)
(3)
(4)
(ii)
(iii)
(d)(1)
(2)
(3)
(4)
(ii)
(iii)
For
(a)
(b)
(c)
(d)
(2)
(3)
(a)
(b)
(c)
(d)
(2)
(3)
(a)
(b)
(c)
(d)
(2)
(3)
(a)
(b)
(c) [Reserved]
(d)
(2)
(3)
(a)
(b)
(c)
(d)
(2)
(3)
(a)
(b)
(c)
(d)
(2)
(3)
(a)
(b)
(c)
(d)
(e)
(2)
(3)
(a)
(b)
(c)
(2)(i) For oral maintenance therapy following initial intravenous dosage, administer 10 milligrams naproxen per kilogram of animal body weight twice daily as top dressing in the animal's feed for up to 14 consecutive days. The initial intravenous dosage is 5 milligrams per kilogram of body weight.
(ii) For oral dosage only, administer 10 milligrams naproxen per kilogram of animal body weight twice daily as a top dressing in the animal's feed for up to 14 consecutive days.
(3) Not for use in horses intended for food.
(4) Federal law restricts this drug to use by or on the order of a licensed veterinarian.
(a)
(2) Each milliliter of solution contains 200 milligrams (mg) neomycin sulfate (equivalent to 140 mg neomycin base).
(b)
(1) Nos. 000069 and 054925 for use of product described in paragraph (a)(1) as in paragraph (e)(1) of this section.
(2) Nos. 000009, 046573, 058005, and 061623 for use of product described in paragraph (a)(1) as in paragraphs (e)(1) and (e)(2) of this section.
(3) Nos. 000009, 054925, 058005, and 059130 for use of product described in paragraph (a)(2) as in paragraph (e)(1) of this section.
(c)
(d)
(e)
(ii)
(iii)
(2)
(ii)
(iii)
(a)
(b)
(c)
(2)
(3)
(a)
(b)
(c)
(d)
(B) One 11.4-mg tablet for dogs weighing less than 25 lb or one 57 mg tablet for dogs weighing more than 25 lbs, once or twice weekly, for use as in paragraph (d)(1)(ii)(B) of this section.
(ii)
(B) The concurrent use of nitenpyram tablets as in paragraph (d)(1)(i)(B) of this section with either flavored lufenuron tablets as in § 520.1288(c)(1) of this chapter or flavored milbemycin and lufenuron tablets as in § 520.1446(d)(1) of this chapter is indicated to kill adult fleas and prevent flea eggs from hatching.
(2)
(B) One 11.4-mg tablet, once or twice weekly, for use as in paragraph (d)(2)(ii)(B) of this section.
(ii)
(B) The concurrent use of nitenpyram tablets as in paragraph (d)(2)(i)(B) of this section with flavored lufenuron tablets as in § 520.1288(c)(2) of this chapter is indicated to kill adult fleas and prevent flea eggs from hatching.
(a)
(b)
(c)
(d)
(ii) For prevention of gastric ulcers using the premarked syringe, one dose per day for 8 or 28 days. Each dose delivers at least 1 mg/kg of body weight. Horses over 1,200 lb body weight should receive two doses per day.
(2)
(ii) For prevention of gastric ulcers in horses.
(3)
(a)
(b)
(c)
(2)
(3)
(a)
(2)
(b)
(c)
(2)
(3)
(ii)
(a)(1)
(2)
(3)
(ii)
(iii)
(b)(1)
(2)
(3)
(4)
(ii)
(iii)
(a)
(1) 90.6 milligrams (mg) oxfendazole (9.06 percent).
(2) 225.0 mg oxfendazole (22.5 percent).
(b)
(c)
(d)
(e)
(i)
(ii)
(iii)
(2)
(i)
(ii)
(iii)
(a)
(b)
(c)
(2)
(3)
(a)
(b)
(c)
(2)
(3)
(a)
(b)
(c)
(2)
(3)
(a)
(2) Carbomycin: The antibiotic substance produced by growth of
(b)
(c)
(d)
(e)
(1)
(2)
(3)
(a)
(b)
(c)
(2) The drug is administered orally to dogs and cats at a dosage level of 25-50 milligrams per pound of body weight per day in divided doses at 12-hour intervals. The drug can be used for continuation of compatible antibiotic therapy following parenteral oxytetracycline administration where rapidly attained, sustained antibiotic blood levels are required. The duration of treatment required to obtain favorable response will depend to some extent on the severity and degree of involvement and the susceptibility of the infectious agent. Clinical response to antibiotic therapy usually occurs within 48 to 72 hours. If improvement is not observed within that period, the diagnosis and course of treatment should be reconsidered. To assure adequate treatment, administration of the drug should continue for at least 48 hours following favorable clinical response.
(3) Federal law restricts this drug to use by or on the order of a licensed veterinarian.
(a)
(b)
(c)
(d)
(ii)
(2)(i)
(ii)
(3)
(a)
(1) Each 18.14 grams of powder contains 1 gram of oxytetracycline hydrochloride (OTC HCl) (packets: 4, 6.4, and 16 oz.).
(2) Each 4.43 grams of powder contains 1 gram of OTC HCl (packets: 4 and 16 oz.).
(3) Each 1.32 grams of powder contains 1 gram of OTC HCl (packets: 2.39, 4.78, and 9.55 oz.; jars: 2.25 lbs.; and pails: 4.5 lbs.).
(4) Each 2.73 grams of powder contains 1 gram of OTC HCl (packets: 2.46 and 9.87 oz; pail: 3.09 lb).
(5) Each 4.2 grams of powder contains 1 gram of OTC HCl (packets: 3.8 and 15.2 oz; pails: 4.74 and 23.7 lb).
(6) Each 1.32 grams of powder contains 1 gram of OTC HCl (packet: 4.78 oz.; pail: 5 lb). Each 2.73 grams of powder contains 1 gram of OTC HCl (packet: 9.87 oz).
(7) Each 1.32 grams of powder contains 1 gram of OTC HCl (packet: 4.78 and 9.6 oz.; pails: 2 and 5 lb); each 18.1 grams of powder contains 1 gram of OTC HCl (packet: 6.4 oz.; pails: 2 and 5 lb).
(8) Each 135.5-gram packet (4.78 ounce) contains 102.4 grams of OTC HCl. Each 677.5-gram packet (23.9 ounce) contains 512 grams of OTC HCl.
(9) Each 2.73 grams of powder contains 1 gram of OTC HCl (packets: 9.87 and, 19.75 oz, and 3.91 lb; pails: 3.09 and 5 lb).
(10) Each 2.73 grams of powder contains 1 gram of OTC HCl (packets: 9.87 and 19.74 oz; pails: 5 lb).
(b)
(1) No. 000069 for use of OTC HCl concentrations in paragraphs (a)(1), (a)(2), and (a)(3) of this section in chickens, turkeys, swine, cattle, sheep, and honey bees.
(2) No. 046573 for use of OTC HCl concentration in paragraph (a)(4) of this section in chickens, turkeys, and swine.
(3) No. 000010 for use of OTC HCl concentration in paragraph (a)(5) of this section in turkeys and chickens.
(4) No. 057561 for use of OTC HCl concentration in paragraph (a)(6) of this section in chickens, turkeys, and swine.
(5) No. 059130 for use of OTC HCl concentration in paragraph (a)(7) of this section in chickens, turkeys, swine, cattle, sheep, and honeybees.
(6) No. 048164 for use of OTC HCl concentrations in paragraph (a)(8) of this section in chickens, turkeys, swine, cattle, and sheep.
(7) No. 061623 for use of OTC HCl concentration in paragraph (a)(9) of this section in chickens, turkeys, and swine.
(8) No. 059320 for use of OTC concentration in paragraph (a)(10) of this section in chickens, turkeys, and swine as in paragraph (d) of this section.
(c)
(d)
(i)
(
(
(B)(
(
(
(ii)
(
(
(B)(
(
(
(C)(
(
(
(iii)
(B)
(C)
(iv)
(B)
(C)
(v)
(B)
(C)
(2) It is used in the food of honey bees as follows:
(i)
(ii)
(iii)
For
(a)
(b)
(c)
(d)
(1)
(i)
(ii)
(2)
(i)
(ii)
(a)
(b)
(c)
(2)
(3)
(a)
(b)
(c)
(d)
(2)
(3)
(a)
(b)
(c)
(d)
(2)
(3)
(a)
(b)
(1) No. 000061 for use of 100- or 400-mg or 1-g tablets, or 2- or 4-g boluses, in dogs and horses.
(2) Nos. 000010 and 059130 for use of 100- or 200-mg or 1-g tablets in dogs and horses.
(3) Nos. 000856, 058829, and 061623 for use of 100-mg or 1-g tablets in dogs and horses.
(4) No. 055246 for use of 100-mg tablets in dogs.
(5) No. 000143 for use of 1-g tablets in horses.
(c)
(ii)
(iii)
(2)
(ii)
(iii)
(a)
(b)
(c)
(d)
(ii)
(iii)
(a)
(2) Each gram of paste contains 0.35 grams phenylbutazone.
(b)
(1) Nos. 000061 and 010797 for use of product described in paragraph (a)(1) of this section.
(2) No. 064847 for use of product described in paragraph (a)(2) of this section.
(c)
(2)
(3)
(a)
(b)
(c)
(d)
(2)
(3)
(a)
(2) Each 10 g of powder contains 1 g phenylbutazone.
(b)
(1) No. 027053 for use of product described in paragraph (a)(1) of this section.
(2) No. 057699 for use of product described in paragraph (a)(2) of this section.
(c)
(2)
(3)
(a)
(b)
(c)
(2)
(3)
(a)
(b)
(c)
(2)
(3)
(a)
(b)
(c)
(2)
(3)
(a)
(b)
(c)
(2)
(3)
(a)
(b)
(c)
(2) The contents of 1 capsule should be mixed with the food of the animal for each 5 pounds, or fraction thereof of body weight, except dogs weighing over 25 pounds should be given the contents of 6 capsules. The drug should be mixed in
(3) Severely debilitated animals should not be wormed except on the advice of a veterinarian.
(a)
(b)
(c)
(2)
(ii)
(3)
(a)
(b)
(c)
(2)
(3)
(a)
(b)
(c)
(d)
(2)
(3)
(a)
(b)
(c)
(d)
(ii)
(iii)
(2)
(ii)
(iii)
(3)
(ii)
(iii)
(a)
(b)
(1) No. 000069 for use as in paragraphs (d)(1) and (d)(3) of this section.
(2) No. 051311 for use as in paragraph (d)(4) of this section.
(3) No. 067949 for use as in paragraph (d)(2) of this section.
(4) No. 066104 for use as in paragraph (d)(3) of this section.
(c) [Reserved]
(d)
(2) For control of legume (alfalfa, clover) bloat in cattle. Administer, in molasses block containing 6.6 percent poloxalene, at the rate of 0.8 oz. of block (1.5 grams poloxalene) per 100 lbs. of body weight per day.
(3) For prevention of legume (alfalfa, clover) and wheat pasture bloat in cattle. A 53-percent poloxalene top dressing on individual rations of ground feed. Dosage is 1 gram of poloxalene per 100 pounds of body weight daily. If bloating conditions are severe, the dose is doubled. Treatment should be started 2 to 3 days before exposure to bloat-producing conditions. Repeat use of the drug if animals are exposed to bloat-producing conditions for more than 12 hours after the last treatment. Do not exceed the double dose in any 24-hour period.
(4) For control of legume (alfalfa, clover) and wheat pasture bloat in cattle. Administer in molasses block containing 6.6 percent poloxalene, at the rate of 0.8 ounce of block (1.5 grams of poloxalene) per 100 pounds of body weight per day. Provide access to
(a)
(b)
(c)
(2)
(3)
(a)
(b)
(c)
(2)
(3)
(a)
(1) 34 milligrams (mg) praziquantel.
(2) 11.5 or 23 mg praziquantel.
(b)
(1) No. 000859 for use of the product described in paragraph (a)(1) of this section, as in paragraph (c)(1) of this section; and for use of the product described in paragraph (a)(2) of this section, as in paragraph (c)(2) of this section.
(2) No. 059130 for use of the product described in paragraph (a)(1) of this section, as in paragraph (c)(1) of this section.
(c)
(ii)
(B) For removal of the canine cestode
(iii)
(B) If labeled for use as in paragraph (c)(1)(ii)(B) of this section: Federal law restricts this drug to use by or on the order of a licensed veterinarian.
(2)
(ii)
(iii)
(a)
(2) Each chewable tablet contains 30 mg praziquantel and 30 mg pyrantel pamoate or 114 mg praziquantel and 114 mg pyrantel pamoate.
(b)
(1) See No. 000859 for use of tablet described in paragraph (a)(1) of this section for use as in paragraph (d)(1) of this section.
(2) See No. 051311 for use of tablets described in paragraph (a)(2) of this section for use as in paragraph (d)(2) of this section.
(c)
(d)
(ii)
(iii)
(2)
(ii)
(a)
(1) Tablet No. 1: 22.7 milligrams praziquantel, 22.7 milligrams pyrantel base, and 113.4 milligrams febantel; or
(2) Tablet No. 2: 68 milligrams praziquantel, 68 milligrams pyrantel base, and 340.2 milligrams febantel.
(3) Tablet No. 3: 136 milligrams (mg) praziquantel, 136 mg pyrantel base, and 680.4 mg febantel.
(b)
(c)
(ii)
(iii)
(a)
(b)
(c)
(2) Do not use in viral infections. Systemic therapy with prednisolone is contraindicated in animals with peptic ulcer, corneal ulcer, and Cushingoid syndrome. The presence of diabetes, osteoporosis, predisposition to thrombophlebitis, hypertension, congestive heart failure, renal insufficiency, and active tuberculosis necessitates carefully controlled use. Some of the above conditions occur only rarely in dogs but should be kept in mind.
(3) Anti-inflammatory action of corticosteroids may mask signs of infection.
(d)
(2)
(3)
(a)
(b)
(c)
(2)
(3)
(a)
(1) 3.33 milligrams of prochlorperazine (as the dimaleate) and 1.67 milligrams of isopropamide (as the iodide), or
(2) 10 milligrams of prochlorperazine (as the dimaleate) and 5 milligrams of isopropamide (as the iodide).
(b)
(c)
(2)(i) Capsules described in paragraph (a)(1) of this section are administered orally to dogs weighing from 4 to 15 pounds at the rate of 1 capsule twice daily. These capsules are administered orally to dogs weighing from 16 to 30 pounds at the rate of 1 or 2 capsules twice daily. For dogs weighing less than 4 pounds, administer orally an appropriate fraction of the contents of one of these capsules.
(ii) Capsules described in paragraph (a)(2) of this section are given to dogs weighing 30 pounds and over at the rate of 1 capsule twice daily.
(3) For use only by or on the order of a licensed veterinarian.
(a)
(1) Capsule No. 1: 3.33 milligrams of prochlorperazine (as the dimaleate), 1.67 milligrams of isopropamide (as the iodide), and 25 milligrams of neomycin base (as the sulfate); or
(2) Capsule No. 3: 10 milligrams of prochlorperazine (as the dimaleate), 5 milligrams of isopropamide (as the iodide), and 75 milligrams of neomycin base (as the sulfate).
(b)
(c)
(2)
(3)
(a)(1)
(2)
(3)
(4) [Reserved]
(5)
(ii) Do not use in horses intended for food.
(iii) Federal law restricts this drug to use by or on the order of a licensed veterinarian.
(b) [Reserved]
(a)
(b)
(c)
(d)
(2) It is administered at the rate of 0.5 to 2 milligrams of propiopromazine hydrochloride per pound of body weight once or twice daily depending upon the degree of tranquilization desired.
Not for use with organophosphates and/or procaine hydrochloride, as phenothiazine may potentiate the toxicity of organophosphates and the activity of procaine hydrochloride. Overdosage may produce significant depression.
(3) For use only by or on the order of a licensed veterinarian.
(a)
(b)
(c)
(2)
(ii) In puppies and adult dogs and in lactating bitches after whelping. To prevent reinfection of
(3)
(a)
(b)
(c)
(1)
(2)
(3)
(a)
(2) Each mL contains pyrantel pamoate equivalent to 2.27 or 4.54 mg pyrantel base.
(3) Each mL contains pyrantel pamoate equivalent to 4.54 mg pyrantel base.
(b)
(1) Nos. 000069, 058829, and 059130 for use of the product described in paragraph (a)(1) as in paragraph (d)(1) of this section.
(2) Nos. 000069, 010237, 058829, and 059130 for use of the products described in paragraph (a)(2) as in paragraph (d)(2) of this section.
(3) No. 023851 for use of the product described in paragraph (a)(3) as in paragraph (d)(2) of this section.
(c)
(d)
(i)
(ii)
(iii)
(2)
(i)
(B)
(C)
(ii)
(B)
(C)
(a)
(2) Each mL contains 226 mg pyrantel base (as pyrantel pamoate).
(3) Each mL contains 171 mg pyrantel base (as pyrantel pamoate).
(b)
(1) No. 000069 for use of product described in paragraph (a)(1) of this section as in paragraph (d)(1)(i) and (d)(2) of this section.
(2) No. 059130 for use of product described in paragraph (a)(2) of this section as in paragraph (d) of this section.
(3) No. 061623 for use of product described in paragraph (a)(3) of this section as in paragraph (d)(1)(i) and (d)(2) of this section.
(c)
(d)
(1)
(ii) 6 mg/lb body weight as single oral dose for the removal and control of mature infections of tapeworms (
(2)
(a)
(2) Pyrantel tartrate pellets colt and horse wormer contains 1.25 percent pyrantel tartrate.
(b)
(2) See No. 051311 in § 510.600(c) of this chapter, for conditions of use provided for in paragraph (d)(3) of this section.
(c)
(d)
(i) For the removal and control of infections from the following mature parasites: Large strongyles (
(ii) It is administered as a single dose at 0.57 gram of pyrantel tartrate per 100 pounds of body weight mixed with the usual grain ration.
(iii) It is recommended that severely debilitated animals not be treated with this drug. Do not administer by stomach tube or dose syringe. The drug should be used immediately after the package is opened.
(iv) Warning: Not for use in horses and ponies to be slaughtered for food purposes.
(2) Swine:
(i) For the removal and control of large roundworms (
(ii) It is added to feed at 0.4 gram pyrantel tartrate per pound of nonpelleted ration. The ration is administered as a single treatment as the sole ration at the rate of 1 pound per 40 pounds of animal weight for animals up to 200 pounds. Animals 200 pounds and over are administered 5 pounds of ration per animal.
(iii) Fast pigs over night for optimum results. Water should be made available to animals during fasting and treatment periods. Consult veterinarian before using in severely debilitated animals. The drug should be used immediately after the package is opened.
(iv) Warning: Do not treat within 24 hours of slaughter.
(3) Horses and colts:
(i) For the removal and control of infections from the following mature parasites: Large strongyles (
(ii) It is administered as a single dose at 12.5 milligrams of pyrantel tartrate per 2.2 pounds of body weight mixed with the usual grain ration.
(iii) It is recommended that severely debilitated animals not be treated with this drug.
(iv) Warning: Do not use in horses or colts intended for food.
(a)
(b)
(c)
(d)
(e)
(ii)
(iii)
(2)
(ii)
(iii)
(a)(1)
(2)
(3)
(4)
(5)
(
(
(ii)
(
(
(b)(1)
(2)
(3)
(4)
(5)
(
(
(ii) [Reserved]
(c)(1)
(2)
(3)
(4)
(ii)
(iii)
(a)
(b)
(c)
(d)
(2)
(3)
(a)
(b)
(c) [Reserved]
(d)
(i)
(ii)
(2)
(i)
(ii)
(a)
(b)
(c)
(2) The capsules are administered orally with the larger capsules administered at a dosage level of 1 capsule per 20 pounds of body weight to a maximum of 5 capsules with the dosage repeated at 3 day intervals until a satisfactory therapeutic response is observed. A maintenance dosage is then administered consisting of 1 capsule per 40 pounds of body weight, with a minimum of 1 capsule per 40 pounds of body weight, with a minimum of 1 capsule, given every 3 days, or 7 days, or longer, as required to maintain improvement or an asymptomatic condition. For dogs under 20 pounds of body weight, the small capsules are administered orally at a dosage level of 1 per 5 pounds of body weight with a minimum of 1 capsule which dosage is repeated at 3 day intervals until a satisfactory response is observed then a maintenance regimen is initiated with 1 capsule per 10 pounds of body weight, minimum of 1 capsule, every 3 days, or 7 days, or longer as required to maintain continued improvement or an asymptomatic condition.
(3) Federal law restricts this drug to use by or on the order of a licensed veterinarian.
(a)
(b)
(c)
(2)
(3)
(a)
(b)
(c)
(d)
(1)
(ii) As an aid in controlling infectious synovitis due to
(iii) As an aid in the prevention or control of losses due to CRD associated with
(2)
(a)
(b)
(c)
(d)
(2)
(3)
(a)
(b)
(c)
(2)
(3)
(a)
(b)
(c)
(2) Administered orally to cats and small breeds of dogs,
(3) Federal law restricts this drug to use by or on the order of a licensed veterinarian.
(a)
(b)
(c)
(2) Administered orally to small breeds of dogs,
(3) Federal law restricts this drug to use by or on the order of a licensed veterinarian.
(a)
(b)
(c)
(d)
(1)
(ii)
(iii)
(2)
(ii)
(iii)
(a)
(b)
(c)
(d)
(2)
(3)
(a)
(b)
(c)
(d)
(2)
(3)
(a)
(b)
(c)
(d)
(e)
(2)
(3)
(a)
(b)
(c)
(d)
(1)
(2)
(3)
(a)
(b)
(c)
(d)
(e)
(1)
(2)
(3)
(a)
(b)
(c)
(d)
(e)
(1)
(ii)
(iii)
(2)
(
(
(ii)
(
(
(a)
(b)
(c)
(2) It is administered orally at a dosage level of 500 milligrams per 10 to 15 pounds of body weight daily, in two or three divided doses.
(3) The administration of the drug should be discontinued if a response is not noted within 7 to 10 days.
(4) Federal law restricts this drug to use by or on the order of a licensed veterinarian.
(a)
(b)
(c)
(2)
(3)
(a)
(b)
(c)
(d)
(B) As an aid in the control of acute fowl cholera caused by
(ii)
(2)
(B) As an aid in the control of acute fowl cholera caused by
(ii)
(a)
(2) For soluble powder, each 107 grams contain the equivalent of 94.6 grams of sulfadimethoxine (as the sodium salt); see Nos. 000069, 054925, 057561, 059130, and 061623 in § 510.600(c) of this chapter.
(b)
(c)
(d)
(1)
(ii)
(iii)
(2)
(ii)
(iii)
(3)
(ii)
(iii) Administer 2.5 grams per 100 pounds of body weight for first day, then 1.25 grams per 100 pounds of body weight per day for the next 4 consecutive days; in drinking water or drench; available as a sulfadimethoxine soluble powder or a 12.5 percent sulfadimethoxine sodium solution (3.75 grams sulfadimethoxine per fluid ounce); if no improvement within 2 to 3 days, reevaluate diagnosis; do not treat beyond 5 days; withdraw 7 days before slaughter. A withdrawal period has not been established for this product in preruminating calves. Do not use in calves to be processed for veal.
(a)
(1) To 000069, approval for use as in paragraphs (d)(1), (d)(2), and (d)(3) of this section.
(2) To 000061, approval for use as in paragraph (d)(2).
(b)
(c) [Reserved]
(d) It is used as follows:
(1)
(ii)
(iii)
(2)
(ii)
(iii)
(3)
(ii)
(iii)
(a)
(b)
(c)
(1) It is intended for use in the treatment of sulfonamide susceptible bacterial infections in dogs and cats and enteritis associated with coccidiosis in dogs.
(2) On the first day of treatment administer an oral dose of 25 milligrams per pound of body weight, then follow with a daily dosage of 12.5 milligrams per pound of body weight. Length of treatment will depend upon clinical response. Continue treatment until patient is asymptomatic for 48 hours. Maintain adequate water intake during the treatment period.
(3) For use only by or on the order of a licensed veterinarian.
(a)
(b)
(c)
(2)
(3)
(a)
(b)
(c)
(d)
(e)
(1)
(ii)
(iii)
(2)
(ii)
(iii)
(a)
(b)
(c)
(d)
(e)
(1)
(i)
(ii)
(2)
(i)
(ii)
(a)(1)
(2)
(3)
(ii)
(A)
(B)
(iii)
(b)(1)
(2)
(3)
(ii)
(iii)
(a)(1)
(2)
(ii)
(iii)
(b)(1)
(2)
(ii)
(iii)
(c)(1)
(2)
(ii)
(iii)
(d)(1)
(2)
(ii)
(iii)
(e)(1)
(2)
(ii)
(iii)
(f)(1)
(2)
(ii)
(iii)
(g)
(h)(1)
(2)
(ii)
(iii)
(a)
(b)
(2)
(3)
(a)
(b)
(c)
(2)
(i)
(ii)
(iii)
(3)
(d)
(a)
(b)
(c)
(d)
(ii)
(iii)
(2)
(ii)
(iii)
(3)
(ii)
(iii)
(4)
(ii)
(iii)
(a)
(b)
(c)
(2) It is administered at a dosage level of one tablet for each 20 pounds of body weight given three times per day. The drug should be given until all signs are alleviated. To reduce the possibility of a relapse, it is suggested that therapy be continued for a further period of a week to 10 days.
(3) Federal law restricts this drug to use by or on the order of a licensed veterinarian.
(a)
(2) Aklomide: 2-Chloro-4-nitrobenzamide.
(b)
(i) Melting point range: 260 °C. to 261 °C.
(ii) Assay (by sodium nitrite titration): 97 to 100.5 percent.
(iii) Moisture (Method No. 6.123, “Toluene Distillation Method—Official Final Action” in “Official Methods of Analysis of the Association of Official Analytical Chemists,” 13th Ed., 1980, p. 83. Copies are available from the AOAC INTERNATIONAL, 481 North Frederick Ave., suite 500, Gaithersburg, MD 20877, or at the National Archives and Records Administration (NARA). For information on the availability of this material at NARA, call 202-741-6030, or go to:
(iv) Molecular weight: 335.34.
(v) Soluble in 0.1
(2) Aklomide conforms to the following specifications:
(i) Minimum melting point: 170 °C.
(ii) Moisture content: Not to exceed 1.0 percent.
(iii) Purity: Not less than 98 percent on an anhydrous basis.
(c)
(d)
(e)
(1)
(2)
(3)
(a)
(1) To No. 059130 for use of a 25-percent sulfaquinoxaline soluble powder and a 20-percent sulfaquinoxaline sodium solution as provided for in paragraph (c) of this section.
(2) To No. 051311 for use of 3.44- and 12.85-percent sulfaquinoxaline sodium solutions as provided for in paragraphs (c)(1), (c)(2), (c)(3), (c)(4)(i), and (c)(4)(ii) of this section.
(3) To No. 046573 for use of a 31.92-percent sulfaquinoxaline solution (sodium and potassium salts) as provided for in paragraphs (c)(1), (c)(2), (c)(3), (c)(4)(i), and (c)(4)(ii) of this section.
(4) No. 053501 for use of a 28.62-percent sulfaquinoxaline sodium solution as provided in paragraphs (c)(1), (c)(2), and (c)(3) of this section.
(b)
(c)
(1)
(ii) Administer at the 0.04 percent level for 2 or 3 days, skip 3 days then administer at the 0.025 percent level for 2 more days. If bloody droppings appear, repeat treatment at the 0.025 percent level for 2 more days. Do not change litter unless absolutely necessary. Do not give flushing mashes.
(2)
(ii) Administer at the 0.025 percent level for 2 days, skip 3 days, give for 2 days, skip 3 days and give for 2 more days. Repeat if necessary. Do not change litter unless absolutely necessary. Do not give flushing mashes.
(3)
(ii) Administer at the 0.04 percent level for 2 or 3 days. Move birds to clean ground. If disease recurs, repeat treatment. If cholera has become established as the respiratory or chronic form, use feed medicated with sulfaquinoxaline. Poultry which have survived typhoid outbreaks should not be kept for laying house replacements or breeders unless tests show they are not carriers.
(4)
(ii) Administer at the 0.015-percent level for 3 to 5 days in drinking water
(iii) In lieu of treatment as provided in paragraph (e)(4)(ii) of this section, administer 1 teaspoon of 25-percent sulfaquinoxaline soluble powder per day for each 125 pounds of body weight for 3 to 5 days in drinking water.
(d)
(a)-(b) [Reserved]
(c)
(d)
(e)
(1) For the control and treatment of outbreaks of coccidiosis in cattle and calves caused by
(2) Give one teaspoon of 25 percent sulfaquinoxaline soluble powder for each 125 pounds of body weight for 3 to 5 days as a drench.
(f)
(a)
(b)
(c)
(2)
(3)
(a)
(b)
(c)
(2)
(3)
(a)
(b)
(1) No. 000009: 250 mg per capsule.
(2) No. 000069: 125, 250, or 500 mg per capsule.
(3) No. 000185: 50, 100, 250, or 500 mg per capsule.
(c)
(2)
(3)
(a)
(b)
(c)
(2)
(3)
(a)
(b)
(c)
(d)
(i)
(ii)
(iii)
(2)
(i)
(ii)
(a)
(b)
(1) No. 000069: 25 grams per pound as in paragraphs (d)(3) and (d)(4) of this section.
(2) Nos. 000010 and 046573: 102.4 and 324 grams per pound as in paragraph (d) of this section.
(3) No. 053501: 102.4 and 324 grams per pound as in paragraphs (d)(1) and (d)(2) of this section.
(4) No. 046573: 102.4 and 324 grams per pound as in paragraph (d)(3) of this section.
(5) Nos. 054925, 057561, 059130, and 061623: 324 grams per pound as in paragraph (d) of this section.
(c)
(d)
(1)
(ii)
(iii)
(2)
(ii)
(iii)
(3)
(ii)
(iii)
(4)
(ii)
(iii)
(a)
(b)
(c)
(ii)
(iii)
(iv)
(2)
(ii)
(iii)
(a)
(b)
(c)
(2)
(3)
(a)
(b)
(c)
(2)
(3)
(a)
(b)
(c)
(2)
(3)
(a)
(b)
(c)
(d)
(2) Suckling puppies or recently weaned puppies weighing less than 5 pounds should not be treated with the drug. Animals that are severely infected, exhibiting evidence of intestinal hemorrhage, debilitation, and anemia, should be given supportive treatment.
(3) Federal law restricts this drug to use by or on the order of a licensed veterinarian.
(a)
(b)
(c)
(1) No. 051311 for use as in paragraph (e)(1)(i) of this section.
(2) No. 050604 for use as in paragraph (e)(1)(ii) of this section.
(3) No. 021930 for use as in paragraph (e)(2) of this section.
(d)
(e)
(1)
(
(
(
(ii)
(
(
(
(
(
(
(2)
(ii)
(iii)
(iv)
(a)
(b)
(c)
(d)
(e)
(1)
(i)
(
(
(ii)
(
(
(2)
(i)
(ii)
(iii)
(3)
(i)
(
(
(ii)
(
(
(4)
(i)
(ii)
(iii)
(5)
(i)
(ii)
(iii)
(a)
(b)
(c)
(d)
(e)
(1)
(i)
(
(
(ii)
(
(
(2)
(i)
(ii)
(iii)
(3)
(i)
(ii)
(iii)
(a)
(b)
(c)
(2) Do not use in horses intended to be used for food purposes.
(3) For use by or on the order of a licensed veterinarian.
(a)
(b)
(c)
(2) Administer 2 grams of thiabendazole with 1.8 grams of trichlorfon per 100 pounds of body weight sprinkled on the animals' usual daily ration of feed, or may be mixed in 5 to 10 fluid ounces of water and administered by stomach tube or drench.
(3) Do not re-treat more than once every 30 days, preferably every 6 to 8 weeks.
(4) Do not treat animals if sick or debilitated; less than 4 months of age; or mares in last month of pregnancy.
(5) Do not administer intravenous anesthetics, especially muscle relaxants, within 2 weeks of use.
(6) Not for animals intended for food use.
(7) Do not use within a few days before or after treatment with or exposure to cholinesterase-inhibiting drugs, pesticides, or chemicals.
(8) If the label bears directions for administration of the drug by stomach tube or drench it shall also bear the statement: Caution; Federal law restricts this drug to use by or on the order of a licensed veterinarian.
(a)
(b)
(c)
(2)
(3)
(a)
(2) Each gram of soluble powder contains 450 milligrams (mg) tiamulin hydrogen fumarate.
(b)
(c)
(d)
(2) Do not use in swine weighing over 250 pounds (lb).
(e)
(i) 3.5 mg per (/) lb of body weight daily for treatment of swine dysentery associated with
(ii) 10.5 mg/lb of body weight daily for treatment of swine pneumonia due to
(2)
(a)
(b)
(c)
(ii)
(iii)
(2) [Reserved]
(a)
(b)
(c)
(ii)
(iii)
(2) [Reserved]
(a)
(b)
(c)
(d)
(2) An initial daily dosage of 0.05 milligram per pound of body weight is usually sufficient to control symptoms, although up to 0.1 milligram per pound of body weight may be given daily if response to the smaller dose is inadequate. As soon as feasible, and in any case within 2 weeks, dosage should be reduced gradually to maintenance levels of 0.0125 to 0.025 milligram per pound of body weight per day. Therapy should be discontinued by a gradual reduction in dosage after the condition has been controlled for several days. Therapy may be initiated with a single dose of sterile triamcinolone acetonide suspension veterinary in which case the tablet dosage should be administered beginning 5 to 7 days after the injection or when symptoms reappear.
(3) The labeling shall comply with the requirements of § 510.410 of this chapter.
(4) Federal law restricts this drug to use by or on the order of a licensed veterinarian.
(a)
(b)
(c)
(d)
(2) It is administered at a dosage of 0.005 to 0.01 milligram triamcinolone acetonide per pound of body weight twice daily, sprinkled (top-dressed) on a small portion of feed. Treatment may be initiated with a single dose of sterile triamcinolone acetonide suspension USP followed after 3 or 4 days with the use of triamcinolone acetonide oral powder.
(3) The labeling shall comply with the requirements of § 510.410 of this chapter.
(4) Not for use in horses intended for food.
(5) Federal law restricts this drug to use by or on the order of a licensed veterinarian.
(a)
(2) For atropine: Atropine N.F.
(b)
(c)
(2) It is administered in distilled water as sole source of drinking water continuously for 7 to 14 days at 1.67 grams of trichlorfon and 7.7 milligrams of atropine per liter.
(3) Prepare fresh solution every 3 days. Do not use simultaneously with other drugs, insecticides, pesticides, or chemicals having cholinesterase activity, nor within 7 days before or after treatment with any other cholinesterase inhibitor.
(4) Restricted to use by or on the order of a licensed veterinarian.
(a)
(b)
(c)
(d)
(e)
(2)
(3)
(a)
(b)
(c)
(d)
(e)
(2)
(3)
(a)
(b)
(c)
(d)
(2)
(3)
(a)
(b)
(c)
(2) The drug is administered orally to dogs and cats at a dosage level of 1 to 2 milligrams per pound of body weight daily; an initial dosage at the 2-milligrams level is suggested followed by daily doses at the 1-milligram level. Frequently, the drug may be withdrawn after 4 to 5 days, with drug effect continuing after withdrawal.
(3) Do not use in conjunction with organophosphates and/or procaine hydrochloride, because phenothiazines may potentiate the toxicity of organophosphates and the activity of procaine hydrochloride.
(4) Federal law restricts this drug to use by or on the order of a licensed veterinarian.
(a)
(b)
(c)
(2) The drug is administered orally at an initial dosage level of
(3) Do not use the drug in cases of viral infections involving corneal ulceration or dendritic ulceration of the cornea.
(4) Clinical and experimental data have demonstrated that corticosteroids administered orally or parenterally to animals may induce the first stage of parturition when administered during the last trimester of pregnancy and may precipitate premature parturition followed by dystocia, fetal death, retained placenta, and metritis.
(5) Federal law restricts this drug to use by or on the order of a licensed veterinarian.
(a)
(b)
(c)
(2)
(3)
(a)
(b)
(c)
(2) The drug is given orally at 30 milligrams per kilogram of body weight per day (14 milligrams per pound per day), or as follows:
(3) The drug is given once daily. Alternatively, especially in severe infections, the initial dose may be followed by one-half the recommended daily dose every 12 hours. If no improvement is seen in 3 days, discontinue therapy and reevaluate diagnosis.
(4) Administer for 2 to 3 days after symptoms have subsided. Do not treat for more than 14 consecutive days.
(5) During long term treatment, periodic platelet counts and white and red blood cell counts are recommended.
(6) The drug should not be used in patients showing marked liver parenchymal damage or blood dyscrasia, nor in those with a history of sulfonamide sensitivity.
(7) Federal law restricts this drug to use by or on the order of a licensed veterinarian.
(a)
(b)
(1) No. 000856 for product administered as in paragraph (c)(1)(i) of this section.
(2) No. 000061 for product administered as in paragraph (c)(1)(ii) of this section.
(c)
(i) 5 g of paste (335 mg trimethoprim and 1,665 mg sulfadiazine) per 150 pounds (68 kilograms) of body weight per day.
(ii) 3.75 g of paste (250 mg trimethoprim and 1,250 mg sulfadiazine) per 110 pounds (50 kilograms) of body weight per day.
(2)
(3)
(a)
(b)
(c)
(2)
(3)
(a)
(b)
(c)
(2)
(3)
(a)
(b)
(c)
(d)
(e)
(ii)
(iii)
(2)
(ii)
(iii)
(3)
(ii)
(iii)
(4)
(ii)
(iii)
21 U.S.C. 360b.
(a)
(b)
(1)
(2)
(c)
(1)
(2)
(3)
(a)
(b)
(c)
(2) It is administered intramuscularly or intraperitoneally to dogs at a level of 5 to 15 milligrams per pound of body weight daily preferably administered in two or more divided doses.
(3) For use only by or on the order of a licensed veterinarian.
(a)
(b)
(c)
(1)
(2)
(3)
(a)
(b)
(c)
(2)
(3)
(a)
(b)
(c)
(d)
Not for use in animals with glaucoma because of the occurrence of mydriasis.
(2) Dosage is administered by subcutaneous or intramuscular injection every 8 to 12 hours, as follows:
(3) For use only by or on the order of a licensed veterinarian.
(a)
(b)
(c)
(2) It is administered intramuscularly or intravenously to dogs and cats at a level of 1 to 2 milligrams per pound of body weight. It is administered intramuscularly or intravenously to horses at a level of 0.25 milligrams per pound of body weight. Dosage can be repeated every 12 hours, as indicated.
(3) Not for use in animals intended for food purposes.
(4) For use only by or on the order of a licensed veterinarian.
(a)
(b)
(c) [Reserved]
(d)
(ii)
(iii)
(2) [Reserved]
(a)(1)
(2) Each vial contains 25 grams of amoxicillin as the trihydrate. The powder is reconstituted with sterile water for injection USP to a concentration of 250 milligrams per milliliter for use as in paragraph (e).
(b)
(c)
(d)
(2)
(ii)
(3)
(e)
(2)
(3)
(a)
(1)
(2)
(3)
(B)
(C)
(ii)
(B)
(C)
(iii)
(B)
(C)
(iv)
(B)
(C)
(b)
(1)
(2)
(3)
(ii)
(iii)
(a)
(b)
(2) See 010515 in § 510.600(c) of this chapter for use of 100 and 250 milligrams per milliliter ampicillin suspension.
(c)
(d)
(ii)
(iii)
(2)
(ii)
(iii)
(3)
(ii)
(iii)
(a)
(b)
(c)
(2)
(3)
(a)
(b)
(c)
(d)
(2) It is administered intravenously at 0.1 milliliter per pound of body weight (1.0 milliliter for every 10 pounds) twice a day for 2 days. For dogs in poor condition, particularly those with evidence of reduced liver function, a more conservative dosage schedule of 0.1 milliliter per pound of body weight daily for 15 days is recommended.
(3) Restricted to use only by or on the order of a licensed veterinarian.
(a)
(b)
(c)
(2)
(3)
(a)
(b)
(c)
(2)
(3)
(a)
(b)
(c)
(d)
(a)
(b)
(c)
(ii) It is administered by intramuscular injection at a dosage of 0.25 to 0.5 milliliter per 20 pounds of body weight, depending on the severity of the condition. Frequency of dosage depends on recurrence of pruritic symptoms. Dosage may be repeated every 3 weeks or when symptoms recur, not to exceed a total of 4 injections.
(2)
(ii) It is administered aseptically by intraarticular injection at a dosage of 2.5 to 5 milliliters per joint, depending on the severity of the condition and the joint size. Dosage may be repeated upon recurrence of clinical signs. Injection into the joint cavity should be preceded by withdrawal of synovial fluid.
(iii) Not for use in horses intended for food.
(3)
(4)
(a)
(b)
(c)
(2)
(3)
(a)
(b)
(c)
(2) The drug is administered subcutaneously at the rate of 0.1 milliliter per pound of body weight. In problem cases, retreatment for whipworms may be necessary in approximately 3 months. For hookworms, a second injection should be given 21 days after the initial treatment.
(3) Federal law restricts this drug to use by or on the order of a licensed veterinarian.
(a)
(1) 0.5 milligrams (mg);
(2) 2 mg; or
(3) 10 mg
(b)
(1) No. 000856 for use of the product described in paragraph (a)(1) as in paragraph (d)(1) of this section; for use of the product described in paragraph (a)(2) as in paragraph (d)(2) of this section; and for use of the product described in paragraph (a)(3) as in paragraph (d)(3) of this section.
(2) No. 059130 for use of the product described in paragraph (a)(2) as in paragraph (d)(2) of this section.
(3) Nos. 057926 and 059130 for use of the product described in paragraph (a)(3) as in paragraph (d)(3) of this section.
(c)
(d)
(ii)
(2)
(ii)
(3)
(ii)
(iii)
(a)
(b)
(c)
(2)
(3)
(a)
(b)
(c)
(2)
(3)
(a)
(b)
(c) [Reserved]
(d)
(2)
(3)
(a)
(1) Each milliliter (mL) contains 100 milligrams (mg) ceftiofur equivalents.
(2) Each mL contains 200 mg ceftiofur equivalents.
(b)
(c)
(d)
(e)
(i)
(ii)
(iii)
(2)
(i)
(ii)
(iii)
(a)
(b)
(c)
(d) Special considerations. Federal law restricts this drug to use by or on the order of a licensed veterinarian.
(e)
(ii)
(iii)
(2)
(ii)
(iii)
(a)
(b)
(c)
(d)
(e)
(ii)
(iii)
(2)
(ii)
(iii)
(3)
(ii)
(4)
(ii)
(5)
(ii)
(6)
(ii)
(7)
(ii)
(iii)
(8)
(ii)
(a) [Reserved]
(b)(1)
(2)
(3)
(ii) For intravenous use only. The drug is administered at a dosage level of 20 to 50 milliliters per 100 pounds of body weight for general anesthesia until the desired effect is produced. Cattle usually require a lower dosage on the basis of body weight. When used as a sedative-relaxant, it is administered at a level of one-fourth to one-half of the anesthetic dosage level.
(iii) Federal law restricts this drug to use by or on the order of a licensed veterinarian.
(a)
(b)
(c)
(2)
(3)
(a)(1)
(2)
(3)
(i)
(ii)
(
(
(
(
(iii) Do not administer to pregnant animals where the calf is not to be aborted.
(iv) Women of childbearing age, asthmatics, and persons with bronchial and other respiratory problems should exercise extreme caution when handling this product. Cloprostenol is readily absorbed through the skin and may cause abortion and/or bronchiospasms. Accidental spillage on the skin should be washed off immediately with soap and water.
(v) Federal law restricts this drug to use by or on the order of a licensed veterinarian.
(b)(1)
(2)
(3)
(4)
(ii)
(iii)
(a)
(b)
(c) [Reserved]
(d)
(i)
(ii)
(iii)
(2) [Reserved]
(a)(1)
(2)
(3)
(4)
(ii) It is administered to cattle initially at 200 to 600 units followed by a dose daily or every other day of 200 to 300 units and to small animals at one unit per pound of body weight to be repeated as indicated.
(iii) For use only by or on the order of a licensed veterinarian.
(b)(1)
(2)
(3)
(ii) For diagnostic use: Administer at one unit per pound of body weight intramuscularly. For therapeutic use: Administer at one unit per pound of body weight intramuscularly or subcutaneously, initially, to be repeated as indicated.
(iii) Federal law restricts this drug to use by or on the order of a licensed veterinarian.
(c)
(a)
(b)
(c)
(2)
(3)
(a)
(b)
(c)
(d)
(2)
(3)
(a)
(b)
(c) [Reserved]
(d)
(ii)
(iii)
(2) [Reserved]
(a)
(b)
(c) [Reserved]
(d)
(ii)
(iii)
(2) [Reserved]
(a)
(b)
(c)
(2)
(3)
(a)(1)
(2)
(i) Nos. 000061, 059130, and 061623 for use as in paragraph (a)(3) of this section.
(ii) No. 058005 for use as in paragraphs (a)(3)(i)(C), (a)(3)(i)(D), (a)(3)(ii)(A), and (a)(3)(iii) of this section.
(3)
(A)
(B)
(C)
(D)
(ii)
(A) For the treatment of primary bovine ketosis and as an anti-inflammatory agent in cattle and horses;
(B) As an anti-inflammatory agent in dogs and cats.
(iii)
(b)(1)
(2)
(i) No. 061623 for use of 2.0 milligrams dexamethasone or 4.0 milligrams dexamethasone sodium phosphate injections.
(ii) No. 000402 for use of 2.0 milligrams dexamethasone or 4.0 milligrams dexamethasone sodium phosphate injections.
(3)
(ii) The drug is administered intravenously at 0.25 to 1 milligram initially. The dose may be repeated for 3 to 5 days or until a response is noted. If continued treatment is required, oral therapy may be substituted. When therapy is withdrawn after prolonged use, the daily dose should be reduced gradually over several days.
(iii) Clinical and experimental data have demonstrated that corticosteroids administered orally or parenterally to animals may induce the first stage of parturition when administered during the last trimester of pregnancy and may precipitate premature parturition followed by dystocia, fetal death, retained placenta, and metritis.
(iv) Federal law restricts this drug to use by or on the order of a licensed veterinarian.
(c)(1)
(2)
(3)
(ii) The drug is administered intravenously at a dosage of 2.5 to 5.0 milligrams. If permanent corticosteroid effect is required, oral therapy may be substituted. When therapy is withdrawn after prolonged use, the daily dose should be reduced gradually over several days.
(iii) Clinical and experimental data have demonstrated that corticosteroids administered orally or parenterally to animals may induce the first stage of parturition when administered during the last trimester of pregnancy and may precipitate premature parturition followed by dystocia, fetal death, retained placenta, and metritis.
(iv) Not for use in horses intended for food.
(v) Federal law restricts this drug to use by or on the order of a licensed veterinarian.
(d)(1)
(2)
(i) Nos. 000069 and 059130 for intravenous or intramuscular use of 2.0 milligrams dexamethasone injection.
(ii) No. 000069 for intravenous use of 2.0 milligrams dexamethasone injection.
(3)
(ii) It is administered intravenously or intramuscularly as follows: dogs—0.25 to 1 milligram; cats—0.125 to 0.5 milligram; horses—2.5 to 5 milligrams.
(iii) Clinical and experimental data have demonstrated that corticosteroids administered orally or by injection to animals may induce the first stage of parturition when administered during the last trimester of pregnancy and may precipitate premature parturition followed by dystocia, fetal death, retained placenta, and metritis.
(iv) Not for use in horses intended for food.
(v) Federal law restricts this drug to use by or on the order of a licensed veterinarian.
(e)(1)
(2)
(3)
(ii) Administer intravenously as follows: Dogs—0.25 to 1 milligram initially; may be repeated for 3 to 5 days or until response is noted. Horses—2.5 to 5 milligrams. If permanent glucocorticoid effect is required, oral therapy may be substituted. When therapy is to be withdrawn after prolonged use, the daily dose should be reduced gradually over several days.
(iii) Clinical and experimental data have demonstrated that corticosteroids administered orally or by injection may induce the first stage of parturition when administered during the last trimester of pregnancy and may precipitate premature parturition followed by dystocia, fetal death, retained placenta, and metritis.
(iv) Do not use in viral infections. Anti-inflammatory action of corticosteroids may mask signs of infections. Except when used for emergency therapy, the product is contraindicated in animals with tuberculosis, chronic nephritis, cushingoid syndrome, or peptic ulcers.
(v) Not for use in horses intended for food.
(vi) Federal law restricts this drug to use by or on the order of a licensed veterinarian.
For
(a)
(b)
(c)
(2) It is recommended for intramuscular administration as follows: Dogs—0.25 to 1 milligram; cats—0.125 to 0.5 milligram; horses—5 to 20 milligrams. Dosage may be repeated.
(3) Clinical and experimental data have demonstrated that corticosteriods administered orally or parenterally to animals may induce the first stage of parturition when administered during the last trimester of pregnancy and may precipitate premature parturition following by dystocia, fetal death, retained placenta, and metritis.
(4) Not for use in horses intended for food.
(5) Federal law restricts this drug to use by or on the order of a licensed veterinarian.
(a)
(b)
(c)
(B) For use as a preanesthetic to general anesthesia, administer 125 µg/m
(ii)
(2)
(ii)
(iii)
(a)
(b)
(c)
(2) For excretion urography administer 0.5 to 1.0 milliliter per pound of body weight to a maximum of 30 milliliters intravenously. For cystography remove urine, administer 5 to 25 milliliters directly into the bladder via catheter. For urethrography administer 1.0 to 5 milliliters via catheter into the urethra to provide desired contrasts delineation. For angiocardiography (including aortography) rapidly inject 5 to 10 milliliters directly into the heart via catheter or intraventricular puncture. For cerebral angiography rapid injection of 3 to 10 milliliters via carotid artery. For peripheral arteriography and/or venography and selective coronary arteriography rapidly inject 3 to 10 milliliters intravascularly into the vascular bed to be delineated. For lymphography slowly inject 1.0 to 10 milliliters directly into the lymph vessel to be delineated. For arthrography slowly inject 1.0 to 5 milliliters directly into the joint to be delineated. For discography slowly inject 0.5 to 1.0 milliliter directly into the disc to be delineated. For sialography slowly inject 0.5 to 1.0 milliliter into the duct to be delineated. For delineation of fistulous tracts slowly inject quantity necessary to fill the tract. For delineation of peritoneal hernias inject 0.5 to 1.0 milliliter per pound of body weight directly into the peritoneal cavity.
(3) Federal law restricts this drug to use by or on the order of a licensed veterinarian.
(a)
(b)
(c)
(d)
(2)
(3)
(a)
(b)
(c)
(2) Women of child-bearing age, asthmatics, and persons with bronchial and other respiratory problems should exercise extreme caution when handling this product. Dinoprost tromethamine is readily absorbed through the skin and can cause abortion and bronchiospasms. Accidental spillage on the skin should be washed off immediately with soap and water.
(d)
(ii)
(iii)
(2)
(B)
(ii)
(B)
(iii)
(B)
(iv)
(B)
(v) Dinoprost solution as provided by No. 000009 in § 510.600(c) of this chapter may be used concurrently with progesterone intravaginal inserts as in § 529.1940 of this chapter.
(3)
(ii)
(a)
(b)
(c)
(d)
(2) It is administered intramuscularly or intravenously at a suitable dosage level depending upon the species.
(3) For use in wild or exotic animals only. Do not use in domestic food-producing animals. Do not use 30 days before, or during, the hunting season in free-ranging wild animals that might be used for food.
(4) Federal law restricts this drug to use by or on the order of a licensed veterinarian. Distribution is restricted to veterinarians engaged in zoo and exotic animal practice, wildlife management programs and researchers.
(a)
(b)
(c)
(d)
(ii)
(iii)
(2)
(ii)
(iii)
(a)
(b)
(c)
(2)
(3)
(a)
(b)
(c) [Reserved]
(d)
(ii)
(iii)
(a)
(b)
(c)
(2) It is administered to horses at a dosage level of 25 mg per hundred pounds of body weight. It is administered to dogs and cats at a dosage level of 0.5 to 1 mg per pound of body weight. Doses may be repeated at 8 to 12 hours, if necessary, to produce desired effect. Intravenous route is not recommended for dogs and cats and should be injected slowly in horses. Intramuscular and subcutaneous administration should be by divided injection sites.
(3) Not for use in horses intended for food.
(4) Federal law restricts this drug to use by or on the order of a licensed veterinarian.
(a)
(b)
(c)
(2) It is administered as follows:
(i) For analgesia and tranquilization administer according to response desired, as follows:
(
(
(ii) For general anesthesia administer according to response desired, as follows:
(
(
(3) For use only by or on the order of a licensed veterinarian.
(a)
(b)
(c)
(2)
(3)
(a)
(1) 22.7 milligrams (mg) enrofloxacin or
(2) 100 mg enrofloxacin.
(b)
(c)
(d)
(e)
(i)
(ii)
(2)
(i)
(ii)
(iii)
(a)
(b)
(2) Each mL of solution contains 200 mg erythromycin base.
(c)
(d)
(i)
(ii)
(iii)
(2)
(i)
(ii)
(iii)
(3)
(i)
(ii)
(iii)
(a)
(b)
(c)
(d)
(1)
(2)
(3)
(a)
(1) No. 000856 for use as in paragraph (c)(1)(i), (c)(2), and (c)(3) of this section.
(2) No. 021641 for use as in paragraph (c) of this section.
(b)
(c)
(1)
(ii) 20 mg estradiol benzoate and 200 mg testosterone propionate (one implant consisting of 9 pellets, each of 8 pellets containing 2.5 mg estradiol benzoate and 25 mg testosterone propionate, and 1 pellet containing 29 mg tylosin tartrate) per implant dose.
(2)
(3)
(a)
(1) An implant containing 6.0 milligrams of norgestomet.
(2) An injectable solution (sesame oil) containing 3.0 milligrams of
(b)
(c)
(2)
(3)
(a)
(b)
(c)
(2) It is administered intramuscularly at a dosage level of 2 to 5 milligrams of ethylisobutrazine hydrochloride per pound of body weight for profound tranquilization. It is administered intravenously at a dosage level of 1 to 2 milligrams of ethylisobutrazine hydrochloride per pound of body weight to effect.
(3) It is not to be used in conjunction with organophosphates and/or procaine hydrochloride because phenothiazines may potentiate the toxicity of organophosphates and the activity of procaine hydrochloride.
(4) Federal law restricts this drug to use by or on the order of a licensed veterinarian.
(a)
(b)
(c)
(2)
(3)
(a)
(b)
(c)
(d)
(2) It is administered intramuscularly by hand syringe or syringe dart at a suitable dosage level depending upon the species.
(3) Do not use the drug unless diprenorphine hydrochloride injection, veterinary, as provided for in § 522.723, is available for use in reversing the effects of etorphine hydrochloride injection, veterinary.
(4) For use in wild or exotic animals only. Do not use in domestic food-producing animals. Do not use 30 days before, or during, the hunting season in free-ranging wild animals that might be used for food.
(5) Federal law restricts this drug to use by or on the order of a licensed veterinarian. Distribution is restricted to veterinarians engaged in zoo and exotic animal practice, wildlife management programs, and researchers.
(a)
(1) 390 milligrams (mg) of pentobarbital sodium and 50 mg phenytoin sodium.
(2) 400 mg secobarbital sodium and 25 mg dibucaine hydrochloride.
(b)
(1) Nos. 000061, 051311, and 054925 for use of product described in paragraph (a)(1) of this section.
(2) No. 000856 for use of product described in paragraph (a)(2) of this section.
(c)
(d)
(2)
(3)
(a)
(2)
(b)
(c)
(d)
(e)
(ii)
(iii)
(2)
(ii)
(iii)
(a)
(b)
(c)
(d)
(A)
(B) [Reserved]
(ii)
(A)
(B) [Reserved]
(iii)
(2) [Reserved]
(a)
(b)
(c)
(d)
(2) The drug is administered intraarticularly at a dosage level of 6 to 10 milligrams per injection. The dosage level is dependent upon the size of the involved synovial structure and the degree of severity of the condition under treatment. The dosage is limited to a single injection per week in any one synovial structure.
(3) Clinical and experimental data have demonstrated that corticosteroids administered orally and parenterally to animals during the last trimester of pregnancy may induce the first stage of parturition and may precipitate premature parturition followed by dystocia, fetal death, retained placenta, and metritis. The drug is not to be used in horses intended for slaughter for food purposes.
(4) For use only by or on the order of a licensed veterinarian.
(a)
(b)
(c)
(d)
(2) The drug is administered intramuscularly at the following recommended daily dosage:
(3) For use only by or on the order of a licensed veterinarian.
(a)
(b)
(c)
(1)
(ii)
(iii)
(
(
(
(
(
(2)
(ii)
(iii)
(3)
(ii)
(iii)
(a)
(b)
(1) See No. 000061 for use as in paragraph (e) of this section.
(2) See Nos. 057561, 059130, and 061623 for use as in paragraphs (e)(1), (e)(2)(i)(A), (e)(2)(ii)(A), and (e)(2)(iii), of this section.
(3) See No. 000856 for use as in paragraph (e)(1) of this section.
(4) See No. 055529 for use as in paragraphs (e)(1) and (e)(2) of this section.
(c)
(d)
(e)
(ii)
(iii)
(2)
(B) 2.2 mg/kg (1.0 mg/lb) of body weight given once by intravenous administration.
(ii)
(B) For control of pyrexia associated with acute bovine mastitis.
(iii)
(3)
(ii)
(iii)
(a)
(b)
(c)
(2)
(3)
(a)(1)
(2)
(3)
(ii)
(iii)
(b)(1)
(2)
(3)
(ii)
(iii)
(a)
(b)
(c)
(2)
(3)
(a)
(2) Each mL of solution contains 50 mg furosemide diethanolamine.
(b)
(1) No. 000010 as described in paragraph (a)(1) of this section for use as in paragraphs (d)(1) and (d)(2)(ii) of this section.
(2) No. 061623 as described in paragraph (a)(2) of this section for use as in paragraph (d)(2)(ii) of this section.
(3) No. 059130 as described in paragraph (a)(2) for use as in paragraphs (d)(1), (d)(2)(i), and (d)(3) of this section.
(4) No. 057926 as described in paragraph (a)(2) for use as in paragraphs (d)(1), (d)(2)(iii), and (d)(3) of this section.
(c)
(d)
(ii)
(2)
(A)
(B)
(ii)
(A)
(B)
(3)
(ii)
(iii)
(A)
(B)
(a)
(b)
(c)
(2) The exact dosage to be administered must be determined after evaluating the animal's condition and will vary according to the size of the animal and the degree of shock. A suggested dosage range for small animals such as dogs is 4 to 8 cubic centimeters per pound body weight. The suggested dosage range for large animals such as sheep, calves, cows, or horses is 2 to 4 cubic centimeters per pound of body weight. It is administered intravenously at a rate of 10 cubic centimeters per minute in small animals and 20 to 30 cubic centimeters per minute in large animals. The solution is administered aseptically and must be between 50 to 70 °F. when injected.
(3) A few animals will exhibit signs of allergic reaction. This solution can cause transient reversible nephrosis. This product is not intended to replace whole blood in cases of anemia and should not be used in the presence of renal dysfunction. Unused portions remaining in bottles should be discarded.
(4) For use only by or on the order of a licensed veterinarian.
(a)
(b)
(1) No. 000061 for use of 5 mg per milliliter (/mL) solution in swine as in paragraph (d)(4), 50 mg/mL solution in dogs and cats as in paragraph (d)(1), 50
(2) No. 058005 for use of 5 mg/mL solution in swine as in paragraph (d)(4) of this section.
(3) No. 000010 for use of 50 mg/mL solution in dogs as in paragraph (d)(5) of this section.
(4) No. 059130 for use of 100 mg/mL solution in turkeys as in paragraph (d)(2) and in chickens as in paragraph (d)(3) of this section.
(c)
(d)
(ii)
(
(iii)
(2)
(ii)
(iii)
(3)
(ii)
(iii)
(4)
(ii)
(iii)
(5)
(ii)
(iii)
(a)
(b)
(c)
(2)
(3)
(a)
(b)
(c)
(2)
(3)
(a)
(b)
(c)
(1)
(2)
(3)
(a)
(b)
(c)
(2)
(ii)
(3)
(i)
(ii)
(a)(1)
(2)
(i) Nos. 000402 and 053501 for use of 10,000 U.S.P. units intramuscularly, 2,500 to 5,000 U.S.P. units intravenously, and 500 to 2,500 U.S.P. units intrafollicularly in cattle.
(ii) Nos. 058639 and 063323 for use of 10,000 U.S.P. units intramuscularly and 500 to 2,500 U.S.P. units intrafollicularly in cattle.
(iii) No. 057926 for use of 10,000 U.S.P. units intramuscularly in cattle and finfish.
(3)
(4)
(
(
(ii)
(iii)
(5)
(ii)
(iii)
(b) [Reserved]
(a)
(b)
(c)
(2) A solution is prepared by dissolving the drug in sterile water for injection to make a solution containing 50 milligrams of guaifenesin per milliliter of solution. It is administered by rapid intravenous infusion at a fixed dosage of 1 milliliter of prepared solution per pound of body weight.
(3) Not to be used in horses intended for food.
(4) Federal law restricts this drug to use by or on the order of a licensed veterinarian.
(a)
(b)
(c) [Reserved]
(d)
(2) Administer rapidly at a dosage of 1 milliliter per pound of body weight.
(3) No to be used in horses intended for food.
(4) Federal law restricts this drug to use by or on the order of a licensed veterinarian.
(a)
(b)
(c) [Reserved]
(d)
(2)
(3)
(a)(1)
(2)
(3)
(ii)
(iii)
(b)(1)
(2)
(3)
(ii)
(iii)
(c)(1)
(2)
(3)
(ii)
(iii)
(d)(1)
(2)
(3)
(ii)
(iii)
(e)(1)
(i) 10 milligrams (mg) hyaluronate sodium; or
(ii) 10 mg hyaluronate sodium with benzyl alcohol as a preservative.
(2)
(3)
(ii)
(iii)
(f)(1)
(2)
(3)
(ii)
(iii)
(a)
(b)
(c)
(2)
(3)
(a)
(b)
(c)
(1)
(2)
(3)
(a)
(b)
(c) [Reserved]
(d)
(ii)
(iii)
(2) [Reserved]
(a)
(b)
(c)
(ii) Adjust the once-daily dose described in paragraph (c)(1)(i) of this section at appropriate intervals based on clinical signs, urinalysis results, and glucose curve/spot check values until adequate glycemic control has been attained. Twice-daily therapy should be initiated if the duration of insulin action is determined to be inadequate. If twice-daily treatment is initiated, the two doses should be 25 percent less than the once daily dose required to attain an acceptable nadir.
(2)
(3)
(a)
(1) 100 milligrams (mg) of elemental iron derived from:
(i) Ferric hydroxide;
(ii) Ferric oxide; or
(iii) Elemental iron.
(2) 200 mg of elemental iron derived from ferric hydroxide.
(b)
(1) Nos. 042552 and 059130 for use of product described in paragraph (a)(1)(i) of this section as follows:
(i) For prevention of iron deficiency anemia, inject 100 mg (1 mL) by intramuscular injection at 2 to 4 days of age.
(ii) For treatment of iron deficiency anemia, inject 100 mg (1 mL) by intramuscular injection. Dosage may be repeated in approximately 10 days.
(2) No. 000856 for use of product described in paragraph (a)(1)(i) of this section as follows:
(i) For the prevention of anemia due to iron deficiency, administer an initial intramuscular injection of 100 mg at 2 to 4 days of age. Dosage may be repeated in 14 to 21 days.
(ii) For the treatment of anemia due to iron deficiency, administer an intramuscular injection of 200 mg.
(3) Nos. 000061 and 062408 for use of product described in paragraph (a)(1)(i) of this section as follows:
(i) For the prevention of iron deficiency anemia, administer intramuscularly an amount of drug containing 100 to 150 mg of elemental iron to animals from 1 to 3 days of age.
(ii) For the treatment of iron deficiency anemia, administer intramuscularly an amount of drug containing 100 to 200 mg of elemental iron per animal. Dosage may be repeated in 10 days to 2 weeks.
(4) Nos. 051311 and 053501 for use of product described in paragraph (a)(1)(ii) of this section as follows:
(i) For prevention of iron deficiency anemia, administer 1 mL by intramuscular injection at 2 to 5 days of age. Dosage may be repeated at 2 weeks of age.
(ii) For treatment of iron deficiency anemia, administer 1 to 2 mL by intramuscular injection at 5 to 28 days of age.
(5) No. 053501 for use of product described in paragraph (a)(1)(iii) of this section as follows:
(i) For prevention of anemia due to iron deficiency, administer 100 mg by intramuscular or subcutaneous injection at 2 to 4 days of age.
(ii) For treatment of anemia due to iron deficiency, administer 100 mg by intramuscular or subcutaneous injection up to 4 weeks of age.
(6) Nos. 058005 and 059130 for use of product described in paragraph (a)(1)(iii) of this section as follows:
(i) For prevention of anemia due to iron deficiency, administer 100 mg by intramuscular injection at 2 to 4 days of age.
(ii) For treatment of anemia due to iron deficiency, administer 100 mg by intramuscular injection. Treatment may be repeated in 10 days.
(7) Nos. 042552 and 059130 for use of product described in paragraph (a)(2) of this section as follows:
(i) For prevention of baby pig anemia due to iron deficiency, intramuscularly inject 200 mg of elemental iron (1 mL) at 1 to 3 days of age.
(ii) For treatment of baby pig anemia due to iron deficiency, intramuscularly inject 200 mg of elemental iron at the first sign of anemia.
(8) No. 062408 for use of product described in paragraph (a)(2) of this section as follows:
(i) For prevention of iron deficiency anemia, administer 200 mg intramuscularly on or before 3 days of age.
(ii) For treatment of iron deficiency anemia, administer 200 mg intramuscularly.
(a)
(2) Each mL of solution contains 10 mg ivermectin.
(3) Each mL of solution contains 2.7 mg ivermectin.
(b)
(1) No. 050604 for use of the product described in paragraph (a)(1) of this section as in paragraph (e)(1) of this section; the product described in paragraph (a)(2) of this section as in paragraphs (e)(2)(i), (e)(2)(ii)(A), (e)(2)(ii)(C), (e)(2)(iii), (e)(3), (e)(4) and (e)(5) of this section; and the product described in paragraph (a)(3) of this section as in paragraphs (e)(3) and (e)(6) of this section.
(2) No. 055529 for use of the product described in paragraph (a)(2) of this section as in paragraphs (e)(2)(i), (e)(2)(ii)(A), (e)(2)(ii)(C), (e)(2)(iii), (e)(3), (e)(4) and (e)(5) of this section.
(3) No. 059130 for use of the product described in paragraph (a)(2) of this section as in paragraphs (e)(2)(i), (e)(2)(ii)(A), (e)(2)(ii)(B), (e)(2)(iii), (e)(3), (e)(4), and (e)(5) of this section.
(c)
(d)
(2) Labeling shall bear the following precaution: “This product should not be used in other animal species as severe adverse reactions, including fatalities in dogs, may result.”
(e)
(ii)
(iii)
(2)
(ii)
(B) For control of infections of
(C) For control of infections and to protect from reinfection with
(iii)
(3)
(ii)
(iii)
(4)
(ii)
(iii)
(5)
(ii)
(iii)
(6)
(ii)
(a)
(b)
(c)
(d)
(e)
(2)
(3)
(a)
(b)
(c)
(2) It is administered subcutaneously or intramuscularly at 5 milligrams per pound of body weight per day in equally divided doses at 12-hour intervals.
(3) Its label shall bear an appropriate expiration date.
(4) Restricted to use by or on the order of a licensed veterinarian.
(a)
(b)
(c)
(d)
(ii)
(2)
(ii)
(a)
(b)
(c)
(d)
(e)
(2) It is administered intramuscularly at a recommended dose from 15 to 20 milligrams ketamine base per pound of body weight, depending on the effect desired.
(3) Federal law restricts this drug to use by or on the order of a licensed veterinarian.
(a)
(b)
(c)
(2)
(3)
(a)
(b)
(c)
(2)
(ii) The 18.2 percent injection is used as an anthelmintic in cattle for treatment of the following parasites: stomach worms (
(3)
(a)
(1) 25, 50, 100, or 300 milligrams (mg) lincomycin.
(2) 25, 100, or 300 mg lincomycin.
(3) 300 mg lincomycin.
(4) 100 or 300 mg lincomycin.
(b)
(1) No. 000009 for use of concentrations in paragraph (a)(1) of this section as in paragraph (e) of this section.
(2) Nos. 058005 and 059130 for use of concentrations in paragraph (a)(2) of this section as in paragraph (e)(2) of this section.
(3) No. 046573 for use of concentration in paragraph (a)(3) of this section as in paragraph (e)(2) of this section.
(4) No. 061623 for use of concentrations in paragraph (a)(4) of this section as in paragraph (e)(2) of this section.
(c)
(d)
(e)
(1)
(ii)
(iii)
(2)
(ii)
(iii)
(a)
(b)
(c) [Reserved]
(d)
(ii)
(iii)
(2) [Reserved]
(a)
(b)
(c)
(d)
(2)
(3)
(a)
(b)
(c)
(2)
(3)
(a)
(b)
(c)
(2)
(3)
(a)
(b)
(c)
(2)
(3)
(a)
(b)
(c)
(2)
(3)
(a)
(b)
(c)
(ii)
(iii)
(2)
(ii)
(iii)
(a)
(b)
(c)
(2)
(3)
(a)
(b)
(c)
(ii)
(2)
(3)
(a)
(b)
(c)
(2) Systemic therapy with methylprednisolone acetate, as with other corticoids, is contraindicated in animals with arrested tuberculosis, peptic ulcer, and Cushing's syndrome. The presence of active tuberculosis, diabetes mellitus, osteoporosis, renal insufficiency, predisposition to thrombophlebitis, hypertension, or congestive heart failure necessitates carefully controlled use of corticosteroids. Intrasynovial, intratendinous, or other injections of corticosteroids for local effect are contraindicated in the presence of acute infectious conditions. Exacerbation of pain, further loss of joint motion, with fever and malaise following injection may indicate that the condition has become septic. Appropriate antibacterial therapy should be instituted immediately.
(d)
(ii)
(2)
(3)
(a)
(b)
(c)
(d)
(2)
(3)
(a)
(b)
(c) [Reserved]
(d)
(2)
(3)
(a)
(b)
(c)
(2)
(3)
(a)
(b)
(c)
(2) It is administered by intravenous, intramuscular, or subcutaneous injection at an initial dose of 0.04 milligram per kilogram of body weight. When given intravenously, the dosage may be repeated at 2- to 3-minute intervals as necessary. Onset of action by intramuscular or subcutaneous injection is slightly longer than it is by intravenous injection, and repeated dosages must be administered accordingly.
(3) For use only by or on the order of a licensed veterinarian.
(a)
(b)
(c)
(2)
(3)
(a)
(b)
(c)
(2)
(3)
(a)
(b)
(c)
(2)
(3)
(a)
(b)
(c)
(2) It is administered to cattle and horses at a dosage level of 1 milligram per 100 pounds of body weight subcutaneously. It is administered to sheep at a dosage level of 1 to 1
(3) The drug is contraindicated in mechanical, intestinal or urinary obstruction, late pregnancy, and in animals treated with other cholinesterase inhibitors.
(4) Not for use in animals producing milk, since this use will result in contamination of the milk.
(5) Federal law restricts this drug to use by or on the order of a licensed veterinarian.
(a)
(b)
(c)
(2) The drug is administered by parenteral injection dependent upon the area of response desired. An injection of 1 milliliter will produce a response of approximately 15 square centimeters. Do not inject more than 2 milliliters per injection site. Regardless of the number of injection sites, the total volume used should not exceed 10 milliliters.
(3) Not for use in horses intended for food.
(4) Federal law restricts this drug to use by or on the order of a licensed veterinarian.
(a)
(b)
(c)
(ii) It is administered by deep intramuscular injection at a dosage level of 5 milligrams every other day for 2 weeks and twice weekly for 2 to 3 more weeks. Severe cases, both acute and chronic, may benefit more from daily therapy initially. Dosage may be continued beyond 5 weeks if satisfactory improvement has not been achieved.
(iii) Not for use in horses intended for food.
(2)
(ii) It is administered by subcutaneous injection at a dosage level of 5 milligrams every day for 6 days, and thereafter, every other day for 8 days. In less severe conditions, shorter courses of therapy may be indicated.
(3) Federal law restricts this drug to use by or on the order of a licensed veterinarian.
(a)
(b)
(c)
(2) Do not mix with a barbiturate in the same syringe to preclude precipitation.
(3) It tends to depress respiration. Naloxone hydrochloride and other narcotic antagonists are used to counter over-dosing.
(4) Federal law restricts this drug to use by or on the order of a licensed veterinarian.
(a)
(b)
(c)
(d)
(e)
(B) 5 mg/lb BW/day intramuscularly or intravenously for treatment of anaplasmosis caused by
(C) 9 mg/lb BW intramuscularly or subcutaneously as single dosage where retreatment of calves and yearlings for bacterial pneumonia is impractical, for treatment of infectious bovine keratoconjunctivitis (pinkeye) caused by
(ii)
(2)
(B) 3 to 5 mg/lb BW/day intramuscularly for treatment of bacterial enteritis (scours, colibacillosis) caused by
(C) 9 mg/lb BW as a single dosage where retreatment for pneumonia is impractical.
(ii)
For
(a)
(b)
(c)
(d)
(e)
(B) 5 mg/lb BW/day intramuscularly, subcutaneously, or intravenously for treatment of severe foot-rot, and advanced cases of other indicated diseases.
(C) 9 mg/lb BW intramuscularly or subcutaneously as single dosage where retreatment of calves and yearlings for bacterial pneumonia is impractical or for treatment of infectious bovine keratoconjunctivitis (pinkeye) caused by
(D) 9 to 13.6 mg/lb BW intramuscularly or subcutaneously as single dosage where retreatment of calves and yearlings for bacterial pneumonia is impractical or for treatment of infectious bovine keratoconjunctivitis (pinkeye) caused by
(E) 13.6 mg/lb BW intramuscularly or subcutaneously as a single dosage for control of respiratory disease in cattle at high risk of developing BRD associated with
(ii)
(2)
(B) 3 to 5 mg/lb BW/day intramuscularly for treatment of bacterial enteritis (scours, colibacillosis) caused by
(C) 9 mg/lb BW as a single dosage where retreatment for pneumonia is impractical.
(ii)
(a)(1)
(2)
(3)
(ii) It is administered by intramuscular injection of 3 to 5 milligrams of oxytetracycline hydrochloride per pound of body weight per day. Leptospirosis, severe foot-rot and severe forms of the indicated diseases should be treated with 5 milligrams per pound of body weight per day. Treatment should be continued for 24 to 48 hours following remission of disease symptoms; however, not to exceed a total of 4 consecutive days. Only 2 milliliters of the drug should be injected per site in case of calves weighing 100 pounds or less and not more than 10 milliliters should be injected per site in adult cattle.
(iii) Discontinue treatment with the drug at least 20 days prior to slaughter of the animal. When administered to animals within 30 days of slaughter, muscle discoloration may necessitate trimming of injection site and surrounding tissues.
(iv) For use only in beef cattle, beef calves, nonlactating dairy cattle, and dairy calves.
(b)(1)
(2)
(3)
(
(
(ii)
(
(
(c)(1)
(2)
(3)
(ii) It is administered to cattle at a dosage level of 3 to 5 milligrams per pound of body weight per day. It may be administered intramuscularly or intravenously from a 50 milligram per milliliter solution. It is administered intravenously from a 100 milligram per milliliter solution. Severe foot-rot and the severe forms of the indicated diseases should be treated with 5 milligrams per pound of body weight. Treatment should be continued 24 to 48 hours following remission of disease symptoms, however, not to exceed a total of 4 consecutive days. If no improvement is noted within 24 hours, consult a veterinarian. When injecting the drug intramuscularly, do not inject more than 10 milliliters per site in adult cattle. Reduce the amount injected at each site according to the size of the animal. For very small calves do not use more than 2 milliliters per injection site.
(iii) Not for use in lactating dairy cattle. Discontinue treatment at least 19 days prior to slaughter. When administered intramuscularly within 30 days of slaughter, muscle discoloration may necessitate trimming of the injection site and surrounding tissues.
(d)(1)
(2)
(3)
(
(
(
(ii) In swine as follows:
(
(
(iii) In poultry (broilers, turkeys, and breeding chickens) as follows:
(
(
(
(iv) Treatment of all diseases should be instituted early. Treatment should continue for 24 to 48 hours beyond the remission of disease symptoms, but not exceed a total of 4 consecutive days. If no improvement is noted within 24 to 48 hours, diagnosis and therapy should be reevaluated.
(v) When injecting intramuscularly in adult livestock, do not inject more than 10 milliliters at any one site. The volume administered per injection site should be reduced according to age and body size so that 1 or 2 milliliters are injected in smaller animals such as small calves and young pigs. Intravenous administration is recommended in cattle when daily dosage exceeds 50 milliliters.
(vi) Treatment must be discontinued at least 5 days prior to slaughter for chickens and turkeys and at least 22 days prior to slaughter for cattle and swine. When administered intramuscularly to animals within 30 days of slaughter, muscle discoloration may necessitate trimming of the injection site(s) and surrounding tissues during the dressing procedure.
(vii) Not for use in lactating dairy animals. Do not administer to laying hens unless the eggs are used for hatching only.
(e)(1)
(2)
(3)
(
(
(ii)
(
(
(f) [Reserved]
(g)(1)
(2)
(3)
(i)
(
(
(ii)
(
(
(h)(1)
(2)
(3)
(ii)
(iii)
(i)(1)
(2)
(3)
(ii)
(iii)
(j) [Reserved]
(k)(1)
(2)
(3)
(ii)
(iii)
For
(a)
(b)
(c)
(2) The drug is administered intramuscularly at a recommended daily dosage to dogs at 5 milligrams per pound of body weight administered in divided doses at 6 to 12 hour intervals. Therapy should be continued for at least 24 hours after all symptoms have subsided.
(3) Federal law restricts this drug to use by or on the order of a licensed veterinarian.
(a)
(b)
(c)
(ii)
(2)
(3)
(a)
(b)
(1) Nos. 000856, 010515, 049185, 061623 for use as in paragraph (d)(1) of this section.
(2) Nos. 010515, 059130, and 061623 for use as in paragraphs (d)(2)(i), (d)(2)(ii)(A), and (d)(2)(iii) of this section.
(3) Nos. 000856 and 049185 for use as in paragraphs (d)(2)(i), (d)(2)(ii)(B), and (d)(2)(iii) of this section.
(c)
(d)
(B)
(C)
(ii)
(iii)
(2)
(ii)
(B) As in paragraph (d)(2)(ii)(A) of this section; and prophylaxis of bovine shipping fever in 300- to 500-pound beef calves.
(iii)
(a)
(b)
(1) Nos. 010515, 053501, and 059130 for use as in paragraph (d) of this section.
(2) Nos. 055529 and 061623 for use as in paragraph (d)(2) of this section.
(c)
(d)
(ii)
(iii)
(2)
(A) For Nos. 010515, 053501, 059130, and 061623: Continue treatment at least 48 hours after symptoms disappear.
(B) For No. 055529: Continue treatment at least 1 day after symptoms disappear (usually 2 or 3 days).
(ii)
(iii)
(A) For Nos. 053501 and 061623: Do not exceed 7 days of treatment in nonlactating dairy and beef cattle, sheep, and swine, or 5 days in lactating cattle. Discontinue treatment for the following number of days before slaughter: Nonruminating cattle (calves)—7; all other cattle—4; sheep—8; and swine—6.
(B) For Nos. 010515, 055529, and 059130: Treatment should not exceed 4 consecutive days. Discontinue treatment for the following number of days before slaughter: Cattle—10; sheep—9; and swine—7. A withdrawal period has not been established for this product in preruminating calves. Do not use in calves to be processed for veal.
(a)
(b)
(c)
(d)
(2)
(3)
(a)
(b)
(c)
(ii)
(iii)
(2)
(ii)
(iii)
(a)(1)
(2)
(3)
(ii) The drug is administered intravenously “to effect”. For general surgical anesthesia, the usual dose is 11 to 13 milligrams per pound of body weight. For sedation, the usual dose is approximately 2 milligrams per pound
(iii) Federal law restricts this drug to use by or on the order of a licensed veterinarian.
(b) [Reserved]
(a)
(b)
(2) Approval for use of the 200 milligrams per milliliter drug for use in horses: See sponsor Nos. 000010 and 058005 in § 510.600(c) of this chapter.
(3) Approval for use of the 100 milligrams per milliliter drug in dogs and horses: See sponsor No. 000856 in § 510.600(c) of this chapter.
(c)
(2) It is administered intravenously at a dosage level of 10 milligrams per pound of body weight daily in 3 divided doses, not to exceed 800 milligrams daily regardless of weight. Limit intravenous administration to 2 successive days. Oral medication may follow.
(3) Federal law restricts this drug to use by or on the order of a licensed veterinarian.
(d)
(2) It is administered intravenously at a dosage level of 1 to 2 grams per 1,000 pounds of body weight daily in 3 divided doses, not to exceed 4 grams daily. Limit intravenous administration to not more than 5 successive days.
(3) Not for use in animals intended for food.
(4) Federal law restricts this drug to use by or on the order of a licensed veterinarian.
For
(a)
(b)
(c)
(2) Preferably given by intravenous injection, it may be administered subcutaneously; dosage is as follows: Cattle and horses, 25 mg; swine, 5 mg; sheep, 2.5 mg, and dogs, 1.0 mg. Treatment may be repeated in 1 to 4 weeks, or as indicated.
(3) Federal law restricts this drug to use by or on the order of a licensed veterinarian.
(a)
(b)
(c)
(d)
(ii)
(B)
(iii)
(2)
(ii)
(a)
(b)
(c)
(d)
(2) It is administered as soon as possible after exposure to the poison. Before administration of the sterile pralidoxime chloride, atropine is administered intravenously at a dosage rate of 0.05 milligram per pound of body weight, followed by administration of an additional 0.15 milligram of atropine per pound of body weight administered intramuscularly. Then the appropriate dosage of sterile pralidoxime chloride is administered slowly intravenously. The dosage rate for sterile pralidoxime chloride when administered to horses is 2 grams per horse. When administered to dogs and cats, it is 25 milligrams per pound of body weight. For small dogs and cats, sterile pralidoxime chloride may be administered either intraperitoneally or intramuscularly. A mild degree of atropinization should be maintained for at least 48 hours. Following severe poisoning, a second dose of sterile pralidoxime chloride may be given after 1 hour if muscle weakness has not been relieved.
(3) For use only by or on the order of a licensed veterinarian.
(a)
(b)
(c)
(ii)
(iii)
(2)
(ii)
(iii)
(a)
(b)
(c)
(d)
(2) The drug is administered to horses intra-articularly at a dosage level of 50 to 100 milligrams. The dose may be repeated when necessary. If no response is noted after 3 or 4 days, the possibility must be considered that the condition is unresponsive to prednisolone therapy. The drug is administered to dogs and cats intramuscularly at a dosage level of 10 to 50 milligrams. The dosage may be repeated when necessary. If the condition is of a chronic nature, an oral corticosteroid may be given as a maintenance dosage. The drug may be given intra-articularly to dogs and cats at a dosage level of 5 to 25 milligrams. The dose may be repeated when necessary after 7 days for two or three doses.
(3) The labeling shall comply with the requirements of § 510.410 of this chapter for corticosteroids.
(4) Not for use in horses intended for food.
(5) Federal law restricts this drug to use by or on the order of a licensed veterinarian.
(a)
(b)
(c)
(2)
(3)
(a)
(b)
(c)
(d)
(2)(i) The dosage for horses is 50 to 100 milligrams as an initial dose given intravenously over a period of one-half to 1 minute, or intramuscularly, and may be repeated in inflammatory, allergic, or other stress conditions at intervals of 12, 24, or 48 hours, depending upon the size of the animal, the severity of the condition and the response to treatment.
(ii) In dogs, the drug is administered intravenously at a range of 2.5 to 5 milligrams per pound of body weight as an initial dose followed by maintenance doses at 1, 3, 6, or 10 hour intervals, as determined by the condition of the animal, for treatment of shock.
(iii) In dogs and cats, the drug may be given intramuscularly for treatment of inflammatory, allergic and less severe stress conditions, where immediate effect is not required, at 1 to 5 milligrams ranging upward to 30 to 50 milligrams in large breeds of dogs. Dosage may be repeated in 12 to 24 hours and continued for 3 to 5 days if necessary. If permanent corticosteroid effect is required oral therapy with prednisolone tablets may be substituted.
(3) Federal law restricts this drug to use by or on the order of a licensed veterinarian.
(a)
(b)
(c)
(2) It is administered to horses intramuscularly at a dosage level of 100 to 300 milligrams and intrasynovially at a dosage level of 50 to 100 milligrams. It is administered intramuscularly to dogs and cats at a dosage level of 1 milligram per 5 pounds of body weight and intrasynovially at a dosage level of 10 to 20 milligrams. Intramuscular retreatment of horses in 24 to 48 hours may be necessary, depending on the general condition of the animal and the severity and duration of the disease.
(3) Clinical and experimental data have demonstrated that corticosteroids administered orally or parenterally to animals may induce the first stage of parturition when administered late in pregnancy and may precipitate premature parturition followed by dystocia, fetal death, retained placenta, and metritis.
(4) Federal law restricts this drug to use by or on the order of a licensed veterinarian.
(a) [Reserved]
(b)(1)
(2)
(3)
(
(
(ii)
(iii)
(a)
(b)
(c)
(2) Dosage is administered by subcutaneous injection twice daily as follows:
(3) For use only by or on the order of a licensed veterinarian.
(a)
(1) No. 000856 for use as in paragraphs (c)(1)(i)(A), (c)(1)(ii), (c)(1)(iii), (c)(2)(i)(A), (c)(2)(ii), (c)(2)(iii), and (c)(3) of this section.
(2) No. 021641 for use as in paragraphs (c)(1) and (c)(2) of this section.
(b)
(c)
(1)
(B) 100 mg progesterone and 10 mg estradiol benzoate (one implant consisting of 5 pellets, each of 4 pellets containing 25 mg progesterone and 2.5 mg estradiol benzoate, and 1 pellet containing 29 mg tylosin tartrate) per implant dose.
(ii)
(iii)
(2)
(B) 200 mg progesterone and 20 mg estradiol benzoate (one implant consisting of 9 pellets, each of 8 pellets containing 25 mg progesterone and 2.5 mg estradiol benzoate, and 1 pellet containing 29 mg tylosin tartrate) per implant dose.
(ii)
(iii)
(3)
(ii)
(iii)
(a)
(b)
(1) No. 000856 for use as in paragraphs (c)(1)(i)(A), (c)(1)(ii)(A), (c)(1)(iii), and (c)(2) of this section.
(2) No. 061623 for use as in paragraphs (c)(1)(i)(B), (c)(1)(ii)(B), and (c)(1)(iii) of this section.
(c)
(B) 0.2 to 0.5 mg/lb body weight intravenously as required.
(ii)
(B) For use as a tranquilizer and preanesthetic.
(iii)
(2)
(ii)
(iii)
(a)
(b)
(c)
(d)
(2) It is not to be used in conjunction with organophosphates and/or procaine hydrochloride since phenothiazines may potentiate the toxicity of organophosphates and the activity of procaine hydrochloride.
(3) For use only by or on the order of a licensed veterinarian.
(a)
(b)
(c)
(ii) The drug is administered by intravenous injection as follows: For induction of general anesthesia without the use of preanesthetics the dosage is 5.5 to 7.0 milligrams per kilogram (2.5 to 3.2 milligrams per pound); for the maintenance of general anesthesia without the use of preanesthetics the dosage is 1.1 to 3.3 milligrams per kilogram (0.5 to 1.5 milligrams per pound). The use of preanesthetic medication reduces propofol dose requirements.
(iii) Adequate data concerning safe use of propofol in pregnant and breeding dogs have not been obtained. Doses may need adjustment for geriatric or debilitated patients. Federal law restricts this drug to use by or on the order of a licensed veterinarian.
(2)
(ii) The drug is administered by intravenous injection as follows: For induction of general anesthesia without the use of preanesthetics the dosage is 8.0 to 13.2 milligrams per kilogram (3.6 to 6.0 milligrams per pound). For the maintenance of general anesthesia without the use of preanesthetics the dosage is 1.1 to 4.4 milligrams per kilogram (0.5 to 2.0 milligrams per pound). The use of preanesthetic medication reduces propofol dose requirements.
(iii) Adequate data concerning safe use of propofol in pregnant and breeding cats have not been obtained. Doses may need adjustment for geriatric or debilitated patients. Federal law restricts this drug to use by or on the order of a licensed veterinarian.
(a)
(b)
(c)
(2) It is administered at a dose of 5 micrograms per kilogram of body weight as a single subcutaneous injection.
(3) Not for use in horses intended for food.
(4) Federal law restricts this drug to use by or on the order of a licensed veterinarian.
(a)
(b)
(c)
(2)(i) It is administered intramuscularly, subcutaneously, or intravenously. Local injection at the site of insect bites may be indicated in severe cases. Intravenous injections must be given slowly to avoid symptoms of overdosage. Dosage may be repeated every 6 to 12 hours whenever necessary. Horses, 40 to 60 milligrams
(ii) It is administered intravenously. Intravenous injections must be given slowly to avoid symptoms of overdosage. Dosage may be repeated every 6 to 12 hours if necessary. Horses, 40 to 60 milligrams per 100 pounds body weight; foals, 20 milligrams per 100 pounds body weight.
(3) Do not use in horses intended for food purposes.
(4) Federal law restricts this drug to use by or on the order of a licensed veterinarian.
(a)
(b)
(c)
(2)
(3)
(a)(1)
(2)
(3)
(ii) The drug is administered by intravenous or deep intramuscular injection in divided doses in 2 or more sites in the gluteal or cervical muscles at a dosage level of 1 milliliter per 100 pounds of body weight and may be repeated at 5 to 10 day intervals.
(iii) Do not use in horses intended for food.
(iv) Federal law restricts this drug to use by or on the order of a licensed veterinarian.
(b)(1)
(2)
(3)
(ii) The drug is administered subcutaneously or intramuscularly in divided doses in 2 or more sites at a dosage level of 1 milliliter per 20 pounds of body weight with a minimum dosage of
(iii) Federal law restricts this drug to use by or on the order of a licensed veterinarian.
(c)(1)
(2)
(3)
(ii)
(iii)
(d)(1)
(2)
(3)
(ii)
(iii)
(e)(1)
(2)
(3)
(ii)
(iii)
(a)
(b)
(c)
(2)
(3)
(a)
(1) 5 milligrams when used as provided in paragraph (d)(1) of this section.
(2) [Reserved]
(3) 100 milligrams when used as provided in paragraphs (d) (2), (3), and (4) of this section.
(b)
(c)
(d)
(1) Subcutaneously in the treatment of 1-to-3-day-old turkey poults at the rate of 1 to 2 milligrams per poult as an aid in the prevention of mortality associated with Arizona group infection.
(2) Subcutaneously in the treatment of 1-to-3-day old:
(i) Turkey poults at the rate of 5 milligrams per poult as an aid in the control of chronic respiratory disease (CRD) associated with
(ii) Baby chicks at the rate of 2.5 to 5 milligrams per chick as an aid in the control of mortality and to lessen severity of infections caused by
(3) Intramuscularly in the treatment of dogs:
(i) At a dosage level of 2.5 milligrams to 5.0 milligrams per pound of body weight twice daily. Treatment may be continued for 4 days. For treatment of infections caused by gram-negative and gram-positive organisms susceptible to spectinomycin.
(ii) Federal law restricts this drug to use by or on the order of a licensed veterinarian.
(4) Administer single injection of 0.1 milliliter (10 milligrams) subcutaneously in nape of neck of 1- to 3-day-old turkey poults as an aid in control of airsacculitis associated with
(a)
(b)
(c)
(d)
(2)
(3)
(a)
(b)
(c)
(2) Administered to dogs and cats by deep intramuscular injection in the thigh at weekly intervals, for several weeks. For cats and small breeds of dogs, 25 milligrams. For larger dogs, 50 milligrams.
(3) Administered to horses by deep intramuscular injection in the gluteal region at weekly intervals, for not more than 4 weeks; 25 milligrams per 100 pounds of body weight.
(4) Not for use in horses intended for food.
(5) Federal law restricts this drug to use by or on the order of a licensed veterinarian.
(a)
(b)
(c)
(d)
(e)
(1)
(2)
(3)
(a)(1)
(2)
(ii) See No. 057561 for conditions of use as in paragraph (a)(3) of this section.
(iii) See No. 059130 for use as in paragraph (a)(3)(iii) of this section.
(3)
(
(
(
(ii) It is used or intended for use in horses as follows:
(
(
(
(
(iii) It is used or intended for use in cattle as follows:
(
(
(
(
(b) [Reserved]
(c)(1)
(2)
(3)
(ii) It is administered by subcutaneous, intramuscular, or intravenous injection at an initial dose of 25 milligrams per pound of body weight followed by 12.5 milligrams per pound of body weight every 24 hours thereafter. Continue treatment until the animal is free from symptoms for 48 hours.
(iii) For use by or on the order of a licensed veterinarian.
(d)
(a)
(b)
(c)
(d)
(e)
(1)
(2)
(3)
(a)
(b)
(c)
(d)
(e)
(2)
(3)
(a)
(b)
(c)
(d)
(e)
(2) It is administered by subcutaneous injection as follows:
(3) A second injection may be given 3 days later if symptoms persist.
(4) Not for use in laying hens; do not treat chickens within 5 days of slaughter; do not treat turkeys within 7 days of slaughter.
(a)
(b)
(c)
(2) It is administered intravenously. The drug is injected slowly to dogs, cats, cattle, sheep, and swine. For horses, it is recommended that a pre-anesthetic sedation be administered to the horse 30 minutes before the drug is administered. The drug is then injected rapidly and completely. The drug is used at the following dosage levels:
(3) Federal law restricts this drug to use by or on the order of a licensed veterinarian.
(a)
(b)
(c)
(2) When diluted aseptically to the desired concentration and administered intravenously to effect, the average single dose is:
(i) Dogs and cats: 8 milligrams per pound of body weight (when used with a preanesthetic, generally one-half the normal dose).
(ii) Swine: 40 milligrams per 5 pounds of body weight.
(iii) Horses: Light anesthesia, 1 gram per 500 pounds to 1,100 pounds of body weight; deep anethesia, 1 gram per 300 pounds of body weight (40 milligrams per 12 pounds of body weight).
(iv) Cattle: Short duration, 20 milligrams per 5 pounds of body weight; longer duration, 40 milligrams per 7 pounds of body weight.
(3) Federal law restricts this drug to use by or on the order of a licensed veterinarian.
(4) NAS/NRC status: The conditions of use specified in this paragraph are NAS/NRC reviewed and found effective. Applications for these uses need not include effectiveness data as specified in § 514.111 of this chapter, but may require bioequivalency and safety information.
(a)
(b)
(c)
(2) It is administered as follows:
(i) For brief anesthesia (6 to 10 minutes) a dosage of 6 to 9 milligrams per pound of body weight is suggested.
(ii) To obtain anesthesia of 15 to 25 minutes duration the suggested dosage is 10 to 12 milligrams per pound of body weight.
(iii) Use of a preanesthetic tranquilizer or morphine will decrease the dosage of sodium thiopental required, provide for smoother induction and smoother recovery, and sometimes prolong the recovery period. If morphine is used as a preanesthetic agent the dose of the barbiturate can be reduced as much as 40 to 50 percent. When a tranquilizer is administered the barbiturate dosage can be reduced 10 to 25 percent.
(3) Federal law restricts this drug to use by or on the order of a licensed veterinarian.
(a)
(b)
(c)
(2) It is administered as follows:
(i) For total anesthesia, it is given at approximately 10 to 12 milligrams per pound of body weight over a period of 3.5 to 5 minutes.
(ii) When preanesthetic medication is used, it is important to wait at least an hour before administering thiopental and sodium pentobarbital for injection, and the dosage necessary for anesthesia is reduced. Usually
(3) Federal law restricts this drug to use by or on the order of a licensed veterinarian.
(a)
(b)
(c)
(2)
(i) In healthy dogs: An initial intramuscular dosage of 3 to 4.5 milligrams per pound of body weight for diagnostic purposes; 4.5 to 6 milligrams per pound of body weight for minor procedures of short duration such as repair of lacerations and wounds, castrations, and other procedures requiring mild to moderate analgesia. Supplemental doses when required should be less than the initial dose and the total dose given should not exceed 12 milligrams per pound of body weight. The maximum total safe dose is 13.6 milligrams per pound of body weight.
(ii) In healthy cats: An initial intramuscular dosage of 4.4 to 5.4 milligrams per pound of body weight is recommended for such procedures as dentistry, treatment of abscesses, foreign body removal, and related types of surgery; 4.8 to 5.7 milligrams per pound of body weight for minor procedures requiring mild to moderate analgesia, such as repair of lacerations, castrations, and other procedures of short duration. Initial dosages of 6.5 to 7.2 milligrams per pound of body weight are recommended for ovariohysterectomy and onychectomy. When supplemental doses are required, such individual supplemental doses should be given in increments that are less than the initial dose and the total dose given (initial dose plus supplemental doses) should not exceed the maximum allowable safe dose of 32.7 milligrams per pound of body weight.
(3)
(a)
(b)
(c)
(d)
(2) Federal law restricts this drug to use by or on the order of a licensed veterinarian.
(e)
(ii)
(iii)
(2)
(ii)
(iii)
(a)
(b)
(c)
(1)
(ii)
(iii)
(2) [Reserved]
(a)
(1) No. 021641 for use as in paragraph (c) of this section.
(2) No. 057926 for use as in paragraphs (c)(1)(i)(A), (c)(1)(ii), (c)(1)(iii), (c)(2)(i)(A), (c)(2)(ii), and (c)(2)(iii) of this section.
(b)
(c)
(A) 140 milligrams (mg) trenbolone acetate (one implant consisting of 7 pellets, each pellet containing 20 mg trenbolone acetate) per implant dose.
(B) 140 mg trenbolone acetate (one implant consisting of 8 pellets, each of 7 pellets containing 20 milligrams trenbolone acetate, and 1 pellet containing 29 mg tylosin tartrate) per implant dose.
(ii)
(iii)
(2)
(A) 200 mg trenbolone acetate (one implant consisting of 10 pellets, each pellet containing 20 mg trenbolone acetate) per implant dose.
(B) 200 mg of trenbolone acetate (one implant consisting of 11 pellets, each of 10 pellets containing 20 mg of trenbolone acetate, and 1 pellet containing 29 mg of tylosin tartrate) per implant dose.
(ii)
(iii)
(a) [Reserved]
(b)
(1) No. 021641 for use as in paragraphs (d)(1)(i)(A), (d)(1)(i)(B), (d)(1)(i)(C), (d)(1)(i)(D), (d)(1)(i)(E), (d)(1)(i)(F), (d)(1)(ii), (d)(1)(iii), (d)(2), and (d)(3) of this section.
(2) No. 057926 for use as in paragraphs (d)(1)(i)(A), (d)(1)(i)(C), (d)(1)(i)(D), (d)(1)(i)(G), (d)(1)(ii), (d)(1)(iii), (d)(2)(i)(A), (d)(2)(i)(C), (d)(2)(i)(D),
(3) No. 000856 for use as in paragraphs (d)(1)(i)(A), (d)(1)(i)(D), (d)(1)(ii), (d)(1)(iii), (d)(3)(i)(A), (d)(3)(ii), and (d)(3)(iii) of this section.
(d)
(B) 120 mg trenbolone acetate and 24 mg estradiol (one implant consisting of 7 pellets, each of 6 pellets containing 20 mg trenbolone acetate and 4 mg estradiol, and 1 pellet containing 29 mg tylosin tartrate) per implant dose.
(C) 200 mg trenbolone acetate and 20 mg estradiol (one implant consisting of 10 pellets, each pellet containing 20 mg trenbolone acetate and 2 mg estradiol) per implant dose.
(D) 80 mg trenbolone acetate and 16 mg estradiol (one implant consisting of 4 pellets, each pellet containing 20 mg trenbolone acetate and 4 mg estradiol) per implant dose.
(E) 200 mg trenbolone acetate and 20 mg estradiol (one implant consisting of 11 pellets, each of 10 pellets containing 20 mg trenbolone acetate and 2 mg estradiol, and 1 pellet containing 29 mg tylosin tartrate) per implant dose.
(F) 80 mg trenbolone acetate and 16 mg estradiol (one implant consisting of 5 pellets, each of 4 pellets containing 20 mg trenbolone acetate and 4 mg estradiol, and 1 pellet containing 29 mg tylosin tartrate) per implant dose.
(G) 200 milligram (mg) trenbolone acetate and 40 mg estradiol (one implant consisting of 10 pellets, each pellet containing 20 mg trenbolone acetate and 4 mg estradiol) per implant dose.
(ii)
(iii)
(2)
(B) 140 mg trenbolone acetate and 14 mg estradiol (one implant consisting of 8 pellets, each of 7 pellets containing 20 mg trenbolone acetate and 2 mg estradiol, and 1 pellet containing 29 mg tylosin tartrate) per implant dose for use as in paragraphs (d)(2)(ii)(A) of this section.
(C) 80 mg trenbolone acetate and 8 mg estradiol (one implant consisting of 4 pellets, each pellet containing 20 mg trenbolone acetate and 2 mg estradiol) per implant dose for use as in paragraph (d)(2)(ii)(B) of this section.
(D) 200 mg trenbolone acetate and 20 mg estradiol (one implant consisting of 10 pellets, each pellet containing 20 mg trenbolone acetate and 2 mg estradiol) per implant dose for use as in paragraph (d)(2)(ii)(A) of this section.
(E) 80 mg trenbolone acetate and 8 mg estradiol (one implant consisting of 5 pellets, each of 4 pellets containing 20 mg trenbolone acetate and 2 mg
(F) 200 mg trenbolone acetate and 20 mg estradiol (one implant consisting of 11 pellets, each of 10 pellets containing 20 mg trenbolone acetate and 2 mg estradiol, and 1 pellet containing 29 mg tylosin tartrate) per implant dose.
(ii)
(B) For increased rate of weight gain.
(iii)
(3)
(B) 40 mg trenbolone acetate and 8 mg estradiol (one implant consisting of 3 pellets, each of 2 pellets containing 20 mg trenbolone acetate and 4 mg estradiol, and 1 pellet containing 29 mg tylosin tartrate) per implant dose.
(ii)
(iii)
For
(a)
(1) 8 pellets, each pellet containing 25 milligrams (mg) trenbolone acetate and 3.5 mg estradiol benzoate.
(2) 4 pellets, each pellet containing 25 mg trenbolone acetate and 3.5 mg estradiol benzoate.
(b)
(c)
(d)
(A)
(B)
(C)
(ii) For an implant as described in paragraph (a)(2) of this section:
(A)
(B)
(C)
(2)
(ii)
(iii)
(a)
(b)
(c)
(
(
(ii)
(
(2)
(3)
(ii) Do not use in animals with tuberculosis, chronic nephritis, or cushingoid syndrome, except for emergency therapy.
(iii) Not for use in horses intended for food.
(iv) Clinical and experimental data have demonstrated that corticosteroids administered orally or parenterally to animals may induce the first stage of parturition when administered during the last trimester of pregnancy and may precipitate premature parturition followed by dystocia, fetal death, retained placenta, and metritis.
(v) Do not use in the treatment of laminitis.
(vi) Intra-articular injection in equine leg injuries may produce osseous metaplasia.
(vii) Federal law restricts this drug to use by or on the order of a licensed veterinarian.
(a)
(b)
(c)
(2) The drug is administered to dogs either intravenously at a dosage level of 0.5 to 1 milligram per pound of body weight daily, or intramuscularly at a dosage level of 1 to 2 milligrams per pound of body weight daily. It is administered to cats intramuscularly at a dosage level of 2 to 4 milligrams per pound of body weight daily. It is administered to horses intravenously or intramuscularly at a dosage level of 10 to 15 milligrams per 100 pounds of body weight daily to a maximum dose of 100 milligrams.
(3) Not for use in horses intended for food.
(4) Do not use in conjunction with organophosphates and/or procaine hydrochloride, because phenothiazines may potentitate the toxicity of organophosphates and the activity of procaine hydrochloride.
(5) Federal law restricts this drug to use by or on the order of a licensed veterinarian.
(a)
(1) 40 milligrams (mg) trimethoprim suspended in a solution containing 200 mg sulfadiazine; or
(2) 80 mg trimethoprim suspended in a solution containing 400 mg sulfadiazine (as the sodium salt).
(b)
(c)
(d)
(ii)
(2)
(ii)
(iii)
(a)
(b)
(c)
(d)
(ii)
(2)
(3)
(a)
(b)
(c)
(d)
(ii)
(iii)
(2)
(ii)
(iii)
(a)
(b)
(2) See No. 000010 in § 510.600(c) of this chapter for use as in paragraphs (e)(1) and (2) of this section.
(c)
(d)
(e)
(ii)
(iii)
(2)
(ii)
(iii)
(3)
(ii)
(
(iii)
(a)
(1) 20 milligrams (mg) xylazine.
(2) 100 mg xylazine.
(3) 300 mg xylazine.
(b)
(1) No. 000010 for use of product described in paragraph (a)(2) of this section as in paragraph (d)(2) of this section.
(2) No. 000856 for use of product described in paragraph (a)(2) of this section as in paragraphs (d)(2), (d)(3)(i), (d)(3)(ii)(A), and (d)(3)(iii) of this section.
(3) Nos. 000859 and 061651 for use of product described in paragraph (a)(1) of this section as in paragraph (d)(1); and product described in paragraph (a)(2) of this section as in paragraphs (d)(2), (d)(3)(i), (d)(3)(ii)(A), and (d)(3)(iii) of this section.
(4) No. 061690 for use of product described in paragraph (a)(1) of this section as in paragraph (d)(1) of this section; product described in paragraph (a)(2) of this section as in paragraphs (d)(2), (d)(3)(i), (d)(3)(ii)(A), and (d)(3)(iii) of this section; and product described in paragraph (a)(3) of this section as in paragraphs (d)(3)(i), (d)(3)(ii)(B), and (d)(3)(iii) of this section.
(c)
(d)
(ii)
(2)
(ii)
(iii)
(3)
(A) Elk (
(B) Mule deer (
(C) Fallow deer (
(ii)
(B) To produce sedation, accompanied by a shorter period of analgesia. May be used to calm and facilitate handling of fractious animals for diagnostic procedures, for minor surgical procedures, for therapeutic medication for sedation and relief of pain following injury or surgery, and as a preanesthetic to local anesthetic. At the recommended dosages, can be used in conjunction with local anesthetics, such as procaine or lidocaine.
(iii)
(a)
(b)
(1)
(2)
(3)
(c)
(1)
(2)
(3)
(a)
(b)
(c)
(d)
(ii)
(B) For increased rate of weight gain in suckling calves.
(iii)
(2)
(ii)
(iii)
(3)
(ii)
(iii)
(4)
(ii)
(iii)
(a)
(b)
(c)
(2)
(3)
21 U.S.C. 360b.
(a)
(b)
(c)
(2)
(3)
(a)
(1) To 000009; each gram contains 500 units of bacitracin, 3.5 milligrams of neomycin, and 10,000 units of polymyxin B.
(2) To 000061 and 025463; each gram contains 400 units of bacitracin zinc, 3.5 milligrams of neomycin, and 10,000 units of polymyxin B sulfate.
(b)
(2)
(3)
(a)
(1) To 000061; each gram of ointment contains 400 units of bacitracin zinc, 10,000 units of polymyxin B sulfate, 5 milligrams of neomycin sulfate (equivalent to 3.5 milligrams of neomycin base), and 10 milligrams of hydrocortisone.
(2) To 025463; each gram of ointment contains 400 units of bacitracin zinc, 10,000 units of polymyxin B sulfate, 5 milligrams of neomycin sulfate (equivalent to 3.5 milligrams of neomycin base), and 10 milligrams of hydrocortisone acetate.
(b)
(2)
(3)
(a)
(b)
(c)
(i) Every 3 hours around the clock for 48 hours after which night instillations may be omitted.
(ii) Four to six times daily to affected eye for the first 72 hours depending upon the severity of the condition. A small amount of ointment should be placed in the lower conjunctival sac.
(2)
(3)
(a)
(b)
(c)
(2)
(3)
(a)
(b)
(c)
(2)
(3)
(a)
(b)
(c)
(2)
(a)
(b)
(c)
(2)
(3)
(a)
(b)
(c)
(2)
(3)
(a)
(b)
(c)
(2) The cream is applied twice daily to affected areas by rubbing into lesions. Treatment should be continued for a few days after clinical recovery to avoid possible relapses.
(3) After application to cutaneous areas, a change in color from dark green to pink is due to the liberation of free myxin from its copper complex.
(4) If no response is seen within seven days, diagnosis and therapy should be reevaluated. If any adverse local reaction is observed after topical application, discontinue treatment.
(5) Federal law restricts this drug to use by or on the order of a licensed veterinarian.
(a)
(b)
(c)
(2)
(3)
(a)
(b)
(c)
(2)
(3)
(a)
(b)
(c)
(i) In horses administered 2 or 3 times daily in an amount not to exceed 100 milliliters per day. Total duration of therapy should not exceed 30 days.
(ii) In dogs administered 3 or 4 times daily in an amount not to exceed 20 milliliters per day. Total duration of therapy should not exceed 14 days.
(2) Not for use in horses and dogs intended for breeding purposes nor in horses slaughtered for food. Other topical medications should only be used when the dimethyl sulfoxide treated area is thoroughly dry. Do not administer by any other route.
(3) For use by or on the order of a licensed veterinarian.
(a)
(b)
(c)
(2)
(ii)
(3)
(a)
(b)
(c)
(d)
(e)
(2)
(3)
(a)
(b)
(c)
(2)
(3)
(a)
(b)
(c)
(2)
(3)
(a)
(b)
(c)
(d)
(2)
(3)
(a)
(b)
(c)
(d)
(e)
(f)
(2) It is used at the rate of 1 ounce per 200 pounds body weight, not to exceed a total dosage of 4 ounces, applied from the shoulder to the tail head as a single treatment. It is applied as soon as possible after heel fly activity ceases. Do not use on lactating dairy cows or dry dairy cows within 21 days of freshening, calves less than 3 months
(3) Do not slaughter within 35 days after treatment. Swine should be eliminated from area where run-off occurs.
(a)
(b)
(2)
(3)
(4)
(5)
(ii) It is used at the rate of one-half fluid ounce per 100 pounds of body weight placed on the backline of the animal. Only one application per season should be made for grub control and this will also provide initial control of lice. A second application for lice control may be made if animals become reinfested, but no sooner than 35 days after the first treatment. Proper timing of treatment is important for grub control; cattle should be treated as soon as possible after heel-fly activity ceases. Cattle should not be slaughtered within 35 days following a single treatment. If a second application is made for lice control, cattle should not be slaughtered within 45 days of the second treatment. The drug must not be used within 28 days of freshening of dairy cattle. If freshening should occur within 28 days after treatment, do not use milk as human food for the balance of the 28-day interval. Do not treat lactating dairy cattle; calves less than 3 months old; or sick, convalescent, or stressed livestock. Do not treat cattle for 10 days before or after shipping, weaning, or dehorning or after exposure to contagious infectious diseases.
(c)
(2)
(3)
(4)
(5)
(ii) It is applied as a single application placed on the backline of animals as follows:
(iii) Do not treat dairy cattle of breeding age; calves less than 3 months old; sick, convalescent, or severely stressed livestock.
(iv) Do not treat cattle for 10 days before or after shipping, weaning, dehorning, or after exposure to contagious or infectious diseases.
(v) Do not slaughter within 45 days of treatment.
(d)
(2)
(3)
(4)
(ii)
(iii)
(a)
(b)
(c)
(ii)
(2)
(3)
(ii) The drug is contraindicated in infectious tuberculous lesions of the eye, early acute stages of viral diseases of the cornea and conjunctiva, herpes simplex lesions of the eye, and fungal infections of the conjunctiva and eyelids.
(iii) The usual precautions and contraindications for corticosteroids and adrenocorticoids are applicable with this drug. Corticosteroids may inhibit essential inflammatory responses intrinsic to the fundamental healing mechanism. Adrenocorticoid compounds have been reported to cause an increase in intraocular pressure. Intraocular pressure should be checked frequently. Ocular reexaminations should be made at frequent intervals during long-term therapy.
(iv) Federal law restricts this drug to use by or on the order of a licensed veterinarian.
(a)
(b)
(c)
(2) A small amount is applied to the affected area two or three times daily.
(3) Federal law restricts this drug to use by or on the order of a licensed veterinarian.
(a)
(b)
(c)
(2) A small amount of solution is applied to the affected area 2 or 3 times daily.
(3) Federal law restricts this drug to use by or on the order of a licensed veterinarian.
(a)
(b)
(c)
(2) A small amount is applied to the infected area two or three times daily.
(3) Federal law restricts this drug to use by or on the order of a licensed veterinarian.
(a)
(b)
(c)
(2) It is administered by instillation of 1 to 2 milliliters into each anal sac following expression of anal sac contents. It may be necessary to repeat treatment at 60-day intervals to maintain an odor-free state. The total dosage used should not exceed 2 milliliters per anal sac per treatment.
(3) For use only by or on the order of a licensed veterinarian.
(a)
(b)
(c)
(2) It is administered at 4 to 6 drops (0.2 milliliter) twice daily into the ear canal for a maximum period of 14 days. The total dosage used should not exceed 17 milliliters. The ear canal should be cleansed by some appropriate method prior to instillation of the solution and the ear should be massaged gently following instillation.
(3) There should be careful initial evaluation and followup of infected ears. Incomplete response or exacerbation of corticosteroid-responsive lesions may be due to the presence of an infection which requires identification or antibiotic sensitivity testing, and the use of the appropriate antimicrobial agent. As with any corticosteroid, animals with a generalized infection should not be treated with this product without proper supportive antimicrobial therapy. Preparations with dimethyl sulfoxide should not be used in pregnant animals. For use by or on the order of a licensed veterinarian.
(a)
(b)
(2) See No. 017135 for use of the 4 percent product as in paragraph (c)(2)(iv) of this section.
(c)
(2)
(ii)
(iii) [Reserved]
(iv)
(3)
(a)
(b)
(c)
(2) Administer 1 or 2 drops into the conjunctival sac 2 to 4 times a day.
(3) Federal law restricts this drug to use by or on the order of a licensed veterinarian.
(a)
(b)
(c)
(ii) For the treatment of infected superficial lesions caused by bacteria sensitive to gentamicin in dogs and cats, apply a sufficient amount of the drug to cover the treatment area twice daily for 7 to 14 days.
(2)
(a)
(b)
(c)
(2)
(3)
(a)
(b)
(c)
(2)(i) For the treatment of acute and chronic canine otitis externa the drug is administered by instillation of 3 to 8 drops into the ear canal twice daily for 7 days. The external ear and ear canal should be properly cleaned and dried before treatment. Remove foreign material, debris, crusted exudates, etc., with suitable nonirritating solutions. Excessive hair should be clipped from the treatment area of the external ear.
(ii) For the treatment of canine infected superficial lesions, the lesion and adjacent area should be properly cleaned before treatment. Excessive hair should be removed. A sufficient amount of the drug should be applied to cover the treatment area. The drug should be administered twice daily for 7 to 14 days.
(3) If hypersensitivity to any of the components occurs, treatment should be discontinued and appropriate therapy instituted. Concomitant use of drugs known to induce ototoxicity should be avoided. Observe patients for signs of adrenocorticoid overdosage. The antibiotic susceptibility of the pathogenic organism should be determined prior to use of this preparation. Administration of recommended doses beyond 7 days may result in delayed wound healing. Animals treated longer than 7 days should be monitored closely.
(4) For use by or on the order of a licensed veterinarian.
(a)
(b)
(c)
(2) One actuation of the sprayer delivers 0.7 milliliter containing 0.75 milligram gentamicin. The sprayer should be held upright 3 to 6 inches from the affected eye, with the opening directed towards the eye, and pumped once. It is advisable to treat once a day for up to 3 days.
(3) Conditions other than bacterial infections of the bovine eye and infectious keratoconjunctivitis caused by
(a)
(b) See Nos. 000061, 054925, and 058829 in § 510.600(c) of this chapter.
(c)
(2)
(3)
(a)
(b)
(1) No. 000061 for use of 7.5- or 15-gram (g) tubes, 12.5-, 30-, or 215-g bottles.
(2) No. 054925 for use of 7.5- or 15-g tubes; 10-, 15-, 25-, or 215-g bottles.
(3) No. 059130 for use of 10-, 20-, 40-, or 215-g bottles.
(3) No. 059130 for use of 10-, 20-, or 215-g bottles.
(4) No. 025463 for use of 7.5- or 15-g tubes, or 215-g bottles.
(c)
(i) From 7.5- or 15-g tubes; 10-, 12.5-, 15-, 25-, or 30-g bottles: 4 drops for dogs weighing less than 30 pounds (lb) or 8 drops for dogs weighing 30 lb or more.
(ii) From 20-, 40-, or 215-g bottles: 2 drops for dogs weighing less than 30 lb or 4 drops for dogs weighing 30 lb or more.
(ii) From 20- or 215-g bottles: 2 drops for dogs weighing less than 30 lb or 4 drops for dogs weighing 30 lb or more.
(2)
(3)
(a)
(b)
(c)
(2)
(a)
(b)
(c)
(2)
(3)
(a)
(2) Each milliliter of solution contains 100 mg imidacloprid and 10 mg moxidectin for use as in paragraph (d)(2) of this section.
(b)
(c)
(d)
(ii)
(2)
(ii)
(a)
(b)
(1) No. 050604 for use as in paragraphs (e)(1), (e)(2)(i), (e)(2)(iii), and (e)(3) of this section.
(2) Nos. 051311, 054925, 055529, 058829, 059130, and 066916 for use as in paragraphs (e)(1), (e)(2)(i), (e)(2)(ii), and (e)(3) of this section.
(c)
(d)
(e)
(2)
(3)
(a)
(b)
(c)
(2)
(3)
(a)
(b)
(c)
(a)
(b)
(c)
(a)
(i) Its potency is not less than 863 micrograms of amphomycin per milligram;
(ii) Its moisture content is not more than 10 percent; and
(iii) Its pH in a 2-percent aqueous suspension is 6.0 to 7.5.
(2) The drug is in a water-miscible ointment or cream base and each gram of ointment or cream contains: 5.0 milligrams of kanamycin activity as the sulfate, 5.0 milligrams of amphomycin activity as the calcium salt, and 10.0 milligrams of hydrocortisone acetate.
(b)
(c)
(2) The ointment should be applied to the affected areas of the skin at least twice daily. In severe or widespread lesions it may be desirable to apply the ointment more than twice daily. After some improvement is observed, treatment can usually be reduced to once daily. Before application, hair in the affected area should be closely clipped and the area should be thoroughly cleansed of crusts, scales, dirt, or other detritus. When treating infections of the anal gland, the drug should be introduced into the orifice of the gland and not through any fistulous tract. If no response is evident in 7 days, diagnosis and therapy should be reevaluated.
(3) For use only by or on the order of a licensed veterinarian.
(a)
(b)
(c)
(d)
(2)
(3)
(a)
(b)
(c)
(2)
(3)
(a)
(2) Each gram of lotion or spray contains miconazole nitrate equivalent to 1 percent miconazole base.
(b)
(1) No. 000061 for use of cream, lotion, and spray;
(2) Nos. 054925 and 058829 for use of lotion and spray.
(c)
(2)
(3)
(a)
(b)
(c)
(2)
(3)
(a)
(b)
(c)
(d)
(e)
(2)
(3)
(a)
(b)
(c)
(2)
(3)
(a)
(b)
(c)
(2) The drug is applied four times each day.
(3) The drug is applied by inserting the tip of the tube beneath the lower lid and by expressing a small quantity of ointment into the conjunctival sac. The tip of the tube should not come in contact with the eye surface.
(4) Severe infections should be supplemented by systemic therapy.
(5) Prolonged administration of the drug may permit overgrowth of organisms that are not susceptible to neomycin. If new infections due to bacteria or fungi appear during therapy, appropriate measures should be taken.
(6) Federal law restricts this drug to use by or on the order of a licensed veterinarian.
(a)
(b)
(c)
(2) Federal law restricts this drug to use by or on the order of a licensed veterinarian.
(a)
(b)
(c)
(2) In treatment of otitis externa and other inflammatory conditions of the external ear canal, a quantity of ointment sufficient to fill the external ear canal may be applied one to three times daily. When used on the skin or mucous membranes, the affected area should be cleansed, and a small amount of the ointment applied and spread or rubbed in gently. The involved area may be treated one to three times a day and these daily applications continued in accordance with the clinical response.
(3) Tetracaine and neomycin have the potential to sensitize. Care should be taken to observe animals being treated for evidence of hypersensitivity or allergy to the drug. If such signs are noted, therapy with the drug should be stopped. Treatment should be limited to the period when local anesthesia is essential to control self-inflicted trauma.
(4) Federal law restricts this drug to use by or on the order of a licensed veterinarian.
(a)
(b)
(c)
(2) Tetracaine and neomycin have the potential to sensitize. Care should be taken to observe animals being treated for evidence of hypersensitivity or allergy to the product. If such signs are noted, therapy with the product should be stopped. Incomplete response or exacerbation of corticosteroid responsive lesions may be due to the presence of nonsusceptible organisms or to prolonged use of antibiotic-containing preparations resulting in overgrowth of nonsusceptible organisms, particularly Monilia.
(3) Federal law restricts this drug to use by or on the order of a licensed veterinarian.
(a)
(b)
(c)
(2) The recommended dosage is 1 to 2 drops per eye every 6 hours.
(3) In treating ophthalmological conditions associated with bacterial infections the drug is contraindicated in
(4) Federal law restricts this drug to use by or on the order of a licensed veterinarian.
(a)
(b)
(c)
(2) Incomplete response or exacerbation of corticosteroid responsive lesions may be due to the presence of nonsusceptible organisms or to prolonged use of antibiotic-containing preparations resulting in overgrowth of nonsusceptible organisms, particularly Monilia. Thus, if improvement is not noted within 2 or 3 days, or if redness, irritation, or swelling persists or increases, the diagnosis should be redetermined and appropriate therapeutic measures initiated. Tetracaine and neomycin have the potential to sensitize. Care should be taken to observe animals being treated for evidence of hypersensitivity or allergy. If such signs are noted, therapy should be stopped.
(3) Federal law restricts this drug to use by or on the order of a licensed veterinarian.
(a)
(b)
(c)
(2) In treating dermatoses affecting areas other than the ear, the surface of the lesions should be well moistened (two to four drops per square inch) twice daily. In treating otitis externa, five to 15 drops of the drug should be instilled in the ear twice daily. The drug is limited to 7 days maximum duration of administration.
(3) For use only by or on order of a licensed veterinarian.
(a)
(b)
(c)
(d)
(2)
(3)
(a)
(b)
(c)
(2)
(3)
(a)
(b)
(c)
(2)
(3)
(a)
(b)
(1) See Nos. 000010, 000069, 050749, 054925, 058005, and 061623 for use on dogs, cats, or horses.
(2) See No. 017135 for use on dogs and horses.
(c) [Reserved]
(d)
(2)
(3)
For
(a)
(b)
(c)
(2)
(3)
(a)
(b)
(c)
(2)
(a)
(b)
(c)
(ii) For otic use: Clean ear canal of impacted cerumen, remove any foreign bodies such as grass awns and ticks, and instill three to five drops of petrolatum base ointment. Preliminary use of a local anesthetic may be advisable.
(iii) For infected anal glands and cystic areas: Drain gland or cyst and fill with petrolatum base ointment.
(2)
(ii) Otitis, cysts, and anal gland infections: Use petrolatum base ointment in dogs and cats for the treatment of acute and chronic otitis and interdigital cysts, and in dogs for anal gland infections.
(3)
(a)
(b)
(c)
(2) It is to be administered as follows:
(i) For conjunctivitis and keratitis: Apply one drop of ointment to the affected eye(s) two or three times daily. Treatment may be continued for up to 2 weeks if necessary.
(ii) For bovine infectious kerato-conjunctivitis: Apply small line of ointment to the affected eye(s) once daily. Treatment may be continued for up to 2 weeks if necessary.
(iii) Frequency of administration is dependent on the severity of the condition. For mild inflammations, applications may range from once daily to once a week; for severe conditions the drug may be applied as often as two to three times daily. Frequency of treatment may be decreased as improvement occurs.
(3) For use only by or on the order of a licensed veterinarian.
(a)
(b)
(c)
(2) A small quantity should be sprayed on the affected surface by holding the container about 6 inches
(3) Keep away from eyes or other mucous membranes; avoid inhaling; use with adequate ventilation; in case of deep or puncture wounds or serious burns, consult a veterinarian.
(a)
(b)
(c)
(2) It is administered topically to the eye two to four times daily.
(3) Allergic reactions may occasionally occur. Treatment should be discontinued if reactions are severe. If new infections due to nonsensitive bacteria or fungi appear during therapy, appropriate measures should be taken.
(a)
(b)
(c)
(i)
(
(
(ii)
(iii)
(2)
(3)
(ii) Control of Lone Star Ticks and hornflies requires two treatments, 7 days apart.
(4)
(d)
(a)
(b)
(c)
(a)
(b)
(c)
(2) For beginning treatment of acute ocular inflammations 1 or 2 drops may be placed in the conjunctival sac 3 to 6 times during a 24 hour period. When improvement occurs, the dosage may be reduced to 1 drop 2 to 4 times daily. In otitis externa, 2 to 6 drops may be placed in the external ear canal 2 or 3 times daily.
(3) All topical ophthalmic preparations containing corticosteroids with or without an anti-microbial agent are contraindicated in the initial treatment of corneal ulcers. They should not be used until infection is under control and corneal regeneration is well underway.
(4) Federal law restricts this drug to use by or on the order of a licensed veterinarian.
(a)
(b)
(c)
(2) A small quantity of the ointment should be expressed into the conjunctival sac 4 times a day (at intervals of 1 to 8 hours) for a few days until there is a favorable response, then the frequency of application may be reduced to twice daily as long as the condition remains under control. Treatment may require from a few days to several weeks.
(3) All topical ophthalmic preparations containing corticosteroids with or without an antimicrobial agent are contraindicated in the initial treatment of corneal ulcers. They should not be used until the infection is under control and corneal regeneration is well underway.
(4) For use only by or on the order of a licensed veterinarian.
(a)
(b)
(c)
(d)
(2) It is administered as follows:
(i) For removal of sutures: Instill one to two drops 2 or 3 minutes before removal of stitches.
(ii) For removal of foreign bodies from eye, ear, and nose: For ophthalmic use, instill three to five drops in the eye prior to examination; for otic use, instill five to 10 drops in the ear; for nasal use, instill five to 10 drops in each nostril every 3 minutes for three doses.
(iii) For tonometry: Instill one to two drops immediately before measurement.
(iv) As an aid in treatment of otitis: Instill two drops into the ear every 5 minutes for three doses.
(v) For minor surgery: Instill one or more drops as required.
(vi) For catheterization: Instill two to three drops with a blunt 20-gauge needle immediately before inserting catheter.
(3) For use only by or on the order of a licensed veterinarian.
(a)
(b)
(c) [Reserved]
(d)
(2)
(3)
(a)
(b)
(c)
(2)
(3)
(a)
(b)
(c)
(2) A small amount of the cream is applied to the affected areas once or twice a day for 2 to 4 weeks. The areas to be treated are first cleared of exudate and the hair clipped if the areas are not already denuded. The cream is massaged into each lesion and immediate surrounding area until the cream is no longer visible.
(3) If no response is seen after 2 weeks of treatment with the drug the diagnosis should be reviewed.
(4) Federal law restricts this drug to use by or on the order of a licensed veterinarian.
(a)
(b)
(c)
(2)
(3)
(a)
(b)
(c)
(2)
(3)
(a)(1)
(2)
(b)(1)
(2)
(c)
21 U.S.C. 360b.
(a)
(b)
(c)
(d)
(2)
(3)
(a)
(b)
(c)
(d)
(e)
(ii)
(iii)
(2)
(ii)
(iii)
(a)
(b)
(c)
(d)
(2)
(3)
(a)
(b)
(c)
(d)
(2)
(3)
(a)
(b)
(c)
(1)
(2)
(3)
(d)
(1)
(2)
(3)
(a)
(b)
(c)
(1)
(2)
(3)
(d)
(1)
(2)
(3)
(a)
(b)
(c)
(d)
(2)
(3)
(a)
(b)
(c)
(d)
(2)
(3)
(a)
(2) Each 12-milliliter, single-dose, disposable syringe contains 600 milligrams of erythromycin (as the base), 0.90 milligram of butylated hydroxyanisole, and 0.90 milligram of butylated hydroxytoluene.
(3) The vehicle is triglyceride of saturated fatty acids from coconut oil.
(4) The drug may or may not be sterile.
(b)
(c)
(ii) Dry cows: After milking, cleaning, and disinfecting, infuse contents of a single 12-milliliter syringe into each infected quarter at the time of drying off.
(2)
(3)
(a)
(b)
(c)
(2)
(3)
(a)(1)
(2)
(3)
(4)
(ii)
(iii)
(b)(1)
(2)
(3)
(4)
(ii)
(iii)
(a)
(b)
(c)
(1)
(2)
(i)
(A)
(B)
(ii)
(d)
(1)
(2)
(3)
(e)
(1)
(2)
(3)
(4)
(a)
(b)
(c)
(d)
(2)
(3)
(a)
(b)
(c)
(d)
(2)
(3)
(a)
(b)
(c)
(ii)
(iii)
(2)
(ii)
(iii)
(a)
(b)
(c)
(d)
(2)
(3)
21 U.S.C. 360b.
(a)
(b)
(c)
(d)
(2)
(3)
(a)
(b)
(c)
(2)
(3)
(a)
(b)
(c)
(2)
(3)
(a)
(1) For 2,000-dose packet, add contents of one 2,000-dose packet of reconstitution powder to 490 milliliters of deionized water. Mix. Add contents of one 2,000-dose packet of lyophilized culture. Mix thoroughly.
(2) For 5,000-dose packet, add contents of one 5,000-dose packet of reconstitution powder to 1,250 milliliters of deionized water. Mix. Add contents of one 5,000-dose packet of lyophilized culture. Mix thoroughly. Allow to stand for 45 minutes before use. Use within 5 hours of reconstitution.
(b)
(c) [Reserved]
(d)
(2)
(3)
(a)
(b)
(c)
(2)
(a)
(b)
(1) Nos. 049968, 050378, and 067188 for use as in paragraphs (d)(1)(iii), (d)(1)(iv), (d)(1)(v), (d)(2)(iii), (d)(2)(iv), (d)(2)(v), and (d)(3).
(2) No. 051212 for use as in paragraphs (d)(1)(i), (d)(1)(ii), (d)(2)(i), (d)(2)(ii), and (d)(3).
(c) [Reserved]
(d)
(1)
(ii) Select finfish eggs. For control of fungi of the family Saprolegniaceae on salmon, trout, and esocid eggs.
(iii) Penaeid shrimp. For control of external protozoan parasites
(iv) All finfish. For control of external protozoa
(v) All finfish eggs: For control of fungi of the family Saprolegniaceae.
(2)
(i) For control of external parasites on select finfish:
(ii) For control of fungi of the Saprolegniaceae on salmon, trout, and esocid eggs: Apply in constant flow water supply of incubating facilities for 15 minutes. Concentration of formalin used is 1,000 to 2,000 microliters per liter.
(iii) For control of external protozoan parasites on shrimp:
(iv) For control of external parasites on all finfish:
(v) For control of fungi of the family Saprolegniaceae on all finfish eggs: Eggs of all finfish except Acipenseriformes, 1,000 to 2,000 µL/L (ppm) for 15 minutes; eggs of Acipenseriformes, up to 1,500 µL/L (ppm) for 15 minutes.
(3)
(a)
(b)
(c)
(2)
(3)
(a)
(b)
(c)
(2) The drug is added to clean water to provide a dip solution with a gentamicin concentration of 250 to 1,000 parts per million. A concentration of 500 parts per million is recommended. Clean eggs should be held submerged in the gentamicin solution under a vacuum of about 27.5 to 38 centimeters of mercury for 5 minutes followed by additional soaking in gentamicin solution for approximately 10 minutes at atmospheric pressure. Eggs can also be treated by warming them for 3 to 6 hours at approximately 100 °F. then immediately submerging them in gentamicin solution maintained at about 40 °F., keeping the eggs submerged for 10 to 15 minutes.
(3) For use in the dipping treatment of turkey-hatching eggs only. Eggs which have been dipped in the drug shall not be used for food.
(a)
(b)
(c)
(2)
(3)
(a)
(b)
(c)
(ii) Freshwater-reared salmonids: 100 mg/L for 30 minutes or 50 to 100 mg/L for 60 minutes once per day on alternate days for three treatments in a continuous flow water supply or as a static bath.
(iii) Coolwater species of freshwater-reared finfish fingerlings and adults (except northern pike & paddlefish) and channel catfish fingerlings and adults: 50 to 75 mg/L for 60 minutes once per day on alternate days for three treatments in continuous flow water supply or as a static bath. Coolwater species of freshwater-reared finfish fry (except northern pike, pallid sturgeon & paddlefish) and channel catfish fry: 50 mg/L for 60 minutes once per day on alternate days for three treatments in continuous flow water supply or as a static bath.
(2)
(3)
(a)
(b)
(c)
(1)
(ii)
(2)
(3)
(a)
(2) Each gram of powder contains 753 mg oxytetracycline hydrochloride.
(b)
(1) Nos. 046573 and 061623 for use of product in paragraph (a)(1) of this section.
(2) Nos. 000069 and 059130 for use of product described in paragraph (a)(2) of this section.
(c)
(d)
(2)
(a)
(b)
(c)
(d)
(2) This product is approved with the concurrent use of dinoprost solution on day 6 of the 7-day administration period when used for indications listed in paragraph (e)(2)(i) of this section. See § 522.690(c) of this chapter.
(e)
(2)
(ii) For synchronization of the return to estrus in lactating dairy cows inseminated at the immediately preceding estrus.
(3)
(a)
(b)
(c)
(2)
(3)
(a)
(b)
(c)
(2)
(3)
(a)
(b)
(c)
(2) It is used as follows:
(i) For fish the drug is added to ambient water at a concentration of from 15 to 330 milligrams per liter depending upon the degree of anesthetization or sedation desired, the species and size of the fish, and the temperature and softness of the water. Preliminary tests of solutions must be made with small numbers of fish to determine the desired rates of sedation or anesthesia and the appropriate exposure times for the specific lots of fish under prevailing conditions.
(ii) For amphibians and other aquatic coldblooded animals, the drug is added to ambient water in concentrations of from 1:1000 to 1:20,000 depending upon species and stage of development.
(iii) Do not use within 21 days of harvesting fish for food. Use in fish intended for food should be restricted to Ictaluridae, Salmonidae, Esocidae, and Percidae, and water temperature should exceed 10 °C. (50 °F.). In other fish and in cold-blooded animals, the drug should be limited to hatchery or laboratory use.
15 U.S.C. 1453, 1454, 1455; 21 U.S.C. 321, 331, 351, 352, 353, 355, 357, 360b, 371, 379e.
This part applies to the extralabel use in an animal of any approved new animal drug or approved new human drug by or on the lawful order of a licensed veterinarian within the context of a valid veterinary-client-patient relationship.
The purpose of this part is to establish conditions for extralabel use or intended extralabel use in animals by or on the lawful order of licensed veterinarians of Food and Drug Administration approved new animal drugs and approved new human drugs. Such use is limited to treatment modalities when the health of an animal is threatened or suffering or death may result from failure to treat. This section implements the Animal Medicinal Drug Use Clarification Act of 1994 (the AMDUCA) (Pub. L. 103-396).
(a)
(b)
(c) The phrase
(d) The phrase
(e) The phrase
(f) A
(g) A
(h)
(i) A
(1) A veterinarian has assumed the responsibility for making medical judgments regarding the health of (an) animal(s) and the need for medical treatment, and the client (the owner of the animal or animals or other caretaker) has agreed to follow the instructions of the veterinarian;
(2) There is sufficient knowledge of the animal(s) by the veterinarian to initiate at least a general or preliminary diagnosis of the medical condition of the animal(s); and
(3) The practicing veterinarian is readily available for followup in case of adverse reactions or failure of the regimen of therapy. Such a relationship can exist only when the veterinarian has recently seen and is personally acquainted with the keeping and care of the animal(s) by virtue of examination of the animal(s), and/or by medically appropriate and timely visits to the premises where the animal(s) are kept.
Nothing in this part shall be construed as permitting the advertising or
(a) As a condition of extralabel use permitted under this part, to permit FDA to ascertain any extralabel use or intended extralabel use of drugs that the agency has determined may present a risk to the public health, veterinarians shall maintain the following records of extralabel uses. Such records shall be legible, documented in an accurate and timely manner, and be readily accessible to permit prompt retrieval of information. Such records shall be adequate to substantiate the identification of the animals and shall be maintained either as individual records or, in food animal practices, on a group, herd, flock, or per-client basis. Records shall be adequate to provide the following information:
(1) The established name of the drug and its active ingredient, or if formulated from more than one ingredient, the established name of each ingredient;
(2) The condition treated;
(3) The species of the treated animal(s);
(4) The dosage administered;
(5) The duration of treatment;
(6) The numbers of animals treated; and
(7) The specified withdrawal, withholding, or discard time(s), if applicable, for meat, milk, eggs, or any food which might be derived from any food animals treated.
(b) A veterinarian shall keep all required records for 2 years or as otherwise required by Federal or State law, whichever is greater.
(c) Any person who is in charge, control, or custody of such records shall, upon request of a person designated by FDA, permit such person designated by FDA to, at all reasonable times, have access to, permit copying, and verify such records.
An approved new animal drug or human drug intended to be used for an extralabel purpose in an animal is not unsafe under section 512 of the act and is exempt from the labeling requirements of section 502(f) of the act if such use is:
(a) By or on the lawful written or oral order of a licensed veterinarian within the context of a valid veterinarian-client-patient relationship; and
(b) In compliance with this part.
In addition to uses which do not comply with the provision set forth in § 530.10, the following specific extralabel uses are not permitted and result in the drug being deemed unsafe within the meaning of section 512 of the act:
(a) Extralabel use in an animal of an approved new animal drug or human drug by a lay person (except when under the supervision of a licensed veterinarian);
(b) Extralabel use of an approved new animal drug or human drug in or on an animal feed;
(c) Extralabel use resulting in any residue which may present a risk to the public health; and
(d) Extralabel use resulting in any residue above an established safe level, safe concentration or tolerance.
Any human or animal drug prescribed and dispensed for extralabel use by a veterinarian or dispensed by a pharmacist on the order of a veterinarian shall bear or be accompanied by labeling information adequate to assure the safe and proper use of the product. Such information shall include the following:
(a) The name and address of the prescribing veterinarian. If the drug is dispensed by a pharmacy on the order of a veterinarian, the labeling shall include the name of the prescribing veterinarian and the name and address of the dispensing pharmacy, and may include
(b) The established name of the drug or, if formulated from more than one active ingredient, the established name of each ingredient;
(c) Any directions for use specified by the veterinarian, including the class/species or identification of the animal or herd, flock, pen, lot, or other group of animals being treated, in which the drug is intended to be used; the dosage, frequency, and route of administration; and the duration of therapy;
(d) Any cautionary statements; and
(e) The veterinarian's specified withdrawal, withholding, or discard time for meat, milk, eggs, or any other food which might be derived from the treated animal or animals.
(a) This part applies to compounding of a product from approved animal or human drugs by a veterinarian or a pharmacist on the order of a veterinarian within the practice of veterinary medicine. Nothing in this part shall be construed as permitting compounding from bulk drugs.
(b) Extralabel use from compounding of approved new animal or human drugs is permitted if:
(1) All relevant portions of this part have been complied with;
(2) There is no approved new animal or approved new human drug that, when used as labeled or in conformity with criteria established in this part, will, in the available dosage form and concentration, appropriately treat the condition diagnosed. Compounding from a human drug for use in food-producing animals will not be permitted if an approved animal drug can be used for the compounding;
(3) The compounding is performed by a licensed pharmacist or veterinarian within the scope of a professional practice;
(4) Adequate procedures and processes are followed that ensure the safety and effectiveness of the compounded product;
(5) The scale of the compounding operation is commensurate with the established need for compounded products (e.g., similar to that of comparable practices); and
(6) All relevant State laws relating to the compounding of drugs for use in animals are followed.
(c) Guidance on the subject of compounding may be found in guidance documents issued by FDA.
(a) The following conditions must be met for a permitted extralabel use in food-producing animals of approved new animal and human drugs:
(1) There is no approved new animal drug that is labeled for such use and that contains the same active ingredient which is in the required dosage form and concentration, except where a veterinarian finds, within the context of a valid veterinarian-client-patient relationship, that the approved new animal drug is clinically ineffective for its intended use.
(2) Prior to prescribing or dispensing an approved new animal or human drug for an extralabel use in food animals, the veterinarian must:
(i) Make a careful diagnosis and evaluation of the conditions for which the drug is to be used;-
(ii) Establish a substantially extended withdrawal period prior to marketing of milk, meat, eggs, or other edible products supported by appropriate scientific information, if applicable;
(iii) Institute procedures to assure that the identity of the treated animal or animals is carefully maintained; and
(iv) Take appropriate measures to assure that assigned timeframes for withdrawal are met and no illegal drug residues occur in any food-producing animal subjected to extralabel treatment.
(b) The following additional conditions must be met for a permitted extralabel use of in food-producing animals an approved human drug, or of an animal drug approved only for use in animals not intended for human consumption:
(1) Such use must be accomplished in accordance with an appropriate medical rationale; and
(2) If scientific information on the human food safety aspect of the use of the drug in food-producing animals is not available, the veterinarian must take appropriate measures to assure that the animal and its food products will not enter the human food supply.
(c) Extralabel use of an approved human drug in a food-producing animal is not permitted under this part if an animal drug approved for use in food-producing animals can be used in an extralabel manner for the particular use.
(a) FDA may prohibit the extralabel use of an approved new animal or human drug or class of drugs in food-producing animals if FDA determines that:
(1) An acceptable analytical method needs to be established and such method has not been established or cannot be established; or
(2) The extralabel use of the drug or class of drugs presents a risk to the public health.
(b) A prohibition may be a general ban on the extralabel use of the drug or class of drugs or may be limited to a specific species, indication, dosage form, route of administration, or combination of factors.
(a) FDA may establish a safe level for extralabel use of an approved human drug or an approved new animal drug when the agency finds that there is a reasonable probability that an extralabel use may present a risk to the public health. FDA may:
(1) Establish a finite safe level based on residue and metabolism information from available sources;
(2) Establish a safe level based on the lowest level that can be measured by a practical analytical method; or
(3) Establish a safe level based on other appropriate scientific, technical, or regulatory criteria.
(b) FDA may require the development of an acceptable analytical method for the quantification of residues above any safe level established under this part. If FDA requires the development of such an acceptable analytical method, the agency will publish notice of that requirement in the
(c) The extralabel use of an animal drug or human drug that results in residues exceeding a safe level established under this part is an unsafe use of such drug.
(d) If the agency establishes a safe level for a particular species or category of animals and a tolerance or safe concentration is later established through an approval for that particular species or category of animals, for that species or category of animals, the safe level is superseded by the tolerance or safe concentration for that species or category of animals.
(a) FDA may issue an order establishing a safe level for a residue of an extralabel use of an approved human drug or an approved animal drug. The agency will publish in the
(1) A statement setting forth the agency's finding that there is a reasonable probability that extralabel use in animals of the human drug or animal drug may present a risk to the public health;
(2) A statement of the basis for that finding; and
(3) A request for public comments.
(b) A current listing of those drugs for which a safe level for extralabel drug use in food-producing animals has been established, the specific safe levels, and the availability, if any, of a specific analytical method or methods for drug residue detection will be codified in § 530.40.
(a) FDA may issue an order announcing a specific analytical method or methods for the quantification of extralabel use drug residues above the
(b) Copies of analytical methods for the quantification of extralabel use drug residues above the safe levels established under § 530.22 will be available upon request from the Communications and Education Branch (HFV-12), Division of Program Communication and Administrative Management, Center for Veterinary Medicine, 7500 Standish Pl., Rockville, MD 20855. When an analytical method for the detection of extralabel use drug residues above the safe levels established under § 530.22 is developed, and that method is acceptable to the agency, FDA will incorporate that method by reference.
(a) FDA may issue an order prohibiting extralabel use of an approved new animal or human drug in food-producing animals if the agency finds, after providing an opportunity for public comment, that:
(1) An acceptable analytical method required under § 530.22 has not been developed, submitted, and found to be acceptable by FDA or that such method cannot be established; or
(2) The extralabel use in animals presents a risk to the public health.-
(b) After making a determination that the analytical method required under § 530.22 has not been developed and submitted, or that such method cannot be established, or that an extralabel use in animals of a particular human drug or animal drug presents a risk to the public health, FDA will publish in the
(1) Specify the nature and extent of the order of prohibition and the reasons for the prohibition;
(2) Request public comments; and
(3) Provide a period of not less than 60 days for comments.
(c) The order of prohibition will become effective 90 days after date of publication of the order unless FDA publishes a notice in the
(d) The agency may publish an order of prohibition with a shorter comment period and/or delayed effective date than specified in paragraph (b) of this section in exceptional circumstances (e.g., where there is immediate risk to the public health), provided that the order of prohibition states that the comment period and/or effective date have been abbreviated because there are exceptional circumstances, and the order of prohibition sets forth the agency's rationale for taking such action.
(e) If FDA publishes a notice in the
(f) A current listing of drugs prohibited for extralabel use in animals will be codified in § 530.41.
(g) After the submission of appropriate information (i.e., adequate data, an acceptable method, approval of a new animal drug application for the prohibited extralabel use, or information demonstrating that the prohibition was based on incorrect data), FDA may, by publication of an appropriate notice in the
(h) FDA may prohibit extralabel use of a drug in food-producing animals without establishing a safe level.
(a) Because extralabel use of animal and human drugs in nonfood-producing animals does not ordinarily pose a threat to the public health, extralabel use of animal and human drugs is permitted in nonfood-producing animal practice except when the public health is threatened. In addition, the provisions of § 530.20(a)(1) will apply to the use of an approved animal drug.
(b) If FDA determines that an extralabel drug use in animals not intended for human consumption presents a risk to the public health, the agency may publish in the
(a) In accordance with § 530.22, the following safe levels for extralabel use of an approved animal drug or human drug have been established: [Reserved]
(b) In accordance with § 530.22, the following analytical methods have been accepted by FDA: [Reserved]
(a) The following drugs, families of drugs, and substances are prohibited for extralabel animal and human drug uses in food-producing animals.
(1) Chloramphenicol;
(2) Clenbuterol;
(3) Diethylstilbestrol (DES);
(4) Dimetridazole;
(5) Ipronidazole;
(6) Other nitroimidazoles;
(7) Furazolidone.
(8) Nitrofurazone.
(9) Sulfonamide drugs in lactating dairy cattle (except approved use of sulfadimethoxine, sulfabromomethazine, and sulfaethoxypyridazine);
(10) Fluoroquinolones; and
(11) Glycopeptides.
(12) Phenylbutazone in female dairy cattle 20 months of age or older.
(b) The following drugs, families of drugs, and substances are prohibited for extralabel animal and human drug uses in nonfood-producing animals: [Reserved]
(c) [Reserved]
(d) The following drugs, or classes of drugs, that are approved for treating or preventing influenza A, are prohibited from extralabel use in chickens, turkeys, and ducks:
(1) Adamantanes.
(2) Neuraminidase inhibitors.
21 U.S.C. 342, 360b, 371.
(a) Tolerances established in this part are based upon residues of drugs in edible products of food-producing animals treated with such drugs. Consideration of an appropriate tolerance for a drug shall result in a conclusion either that:
(1) Finite residues will be present in the edible products—in which case a finite tolerance is required; or
(2) It is not possible to determine whether finite residues will be incurred but there is reasonable expectation that they may be present—in which case a tolerance for negligible residue is required; or
(3) The drug induces cancer when ingested by man or animal or, after tests which are appropriate for the evaluation of the safety of such drug, has been shown to induce cancer in man or animal; however, such drug will not adversely affect the animals for which it is intended, and no residue of such drug will be found by prescribed methods of analysis in any edible portion of such animals after slaughter or in any food yielded by or derived from the living animal—in which case the accepted method of analysis shall be published or cited, if previously published and available elsewhere, in this part; or
(4) It may or may not be possible to determine whether finite residues will be incurred but there is no reasonable expectation that they may be present—in which case the establishment of a tolerance is not required; or
(5) The drug is such that it may be metabolized and/or assimilated in such form that any possible residue would be indistinguishable from normal tissue constituents—in which case the establishment of a tolerance is not required.
(b) No tolerance established pursuant to paragraph (a)(1) of this section will be set at any level higher than that reflected by the permitted use of the drug.
(c) Any tolerance required pursuant to this section will, in addition to the toxicological considerations, be conditioned on the availability of a practicable analytical method to determine the quantity of residue. Such method must be sensitive to and reliable at the established tolerance level or, in certain instances, may be sensitive at a higher level where such level is also deemed satisfactory and safe in light of the toxicity of the drug residue and of the unlikelihood of such residue's exceeding the tolerance.
A tolerance of 0.1 part per million is established for negligible residues of 2-acetylamino-5-nitrothiazole in the edible tissues of turkeys.
Tolerances are established for combined residues of aklomide (2-chloro-4-nitrobenzamide) and its metabolite (4-amino-2-chlorobenzamide) in uncooked edible tissues of chickens as follows:
(a) 4.5 parts per million in liver and muscle.
(b) 3 parts per million in skin with fat.
(a)
(b)
(1)
(ii)
(2)
(ii)
(3)
(ii) [Reserved]
(c)
(a)
(b)
(ii)
(2) [Reserved]
A tolerance of 0.01 part per million is established for negligible residues of amoxicillin in milk and in the uncooked edible tissues of cattle.
A tolerance of 0.01 p/m is established for negligible residues of ampicillin in the uncooked edible tissues of swine and cattle and in milk.
Tolerances are established as follows for residues of amprolium (1-(4-amino-2-
(a) In the edible tissues and in eggs of chickens and turkeys:
(1) 1 part per million in uncooked liver and kidney.
(2) 0.5 part per million in uncooked muscle tissue.
(3) In eggs:
(i) 8 parts per million in egg yolks.
(ii) 4 parts per million in whole eggs.
(b) In the edible tissues of calves:
(1) 2.0 parts per million in uncooked fat.
(2) 0.5 part per million in uncooked muscle tissue, liver, and kidney.
(c) In the edible tissues of pheasants:
(1) 1 part per million in uncooked liver.
(2) 0.5 part per million in uncooked muscle.
A tolerance of 0.1 part per million is established for parent apramycin (marker residue) in kidney (target tissue) of swine. The acceptable daily intake (ADI) for total residues of apramycin is 25 micrograms per kilogram of body weight per day.
Tolerances for total residues of combined arsenic (calculated as As) in food are established as follows:
(a) In edible tissues and in eggs of chickens and turkeys:
(1) 0.5 part per million in uncooked muscle tissue.
(2) 2 parts per million in uncooked edible by-products.
(3) 0.5 part per million in eggs.
(b) In edible tissues of swine:
(1) 2 parts per million in uncooked liver and kidney.
(2) 0.5 part per million in uncooked muscle tissue and by-products other than liver and kidney.
(a)
(b)
Tolerances are established for residues of buquinolate as follows:
(a) In edible tissues of chickens:
(1) 0.4 part per million in uncooked liver, kidney, and skin with fat.
(2) 0.1 part per million in uncooked muscle.
(b) In eggs:
(1) 0.5 part per million in uncooked yolk.
(2) 0.2 part per million in uncooked whole eggs.
A tolerance of 30 parts per billion is established for residues of quinoxaline-2-carboxylic acid (marker residue) in liver (target tissue) of swine.
A tolerance of zero is established for residues of carbomycin in the uncooked edible tissues of chickens.
(a)
(2)
(b)
(2)
(i)
(ii)
(iii)
(3)
(i)
(ii)
(iii)
(iv)
A tolerance of 0.02 parts per million (ppm) is established for residues of cephapirin in the milk and 0.1 ppm in the uncooked edible tissues of dairy cattle.
A tolerance of zero is established for residues of chlorhexidine in the uncooked edible tissues of calves.
A tolerance of zero is established for residues of chlorobutanol in milk from dairy animals.
(a)
(b)
(2) A tolerance is established for residues of chlortetracycline in eggs of 0.4 ppm.
Tolerances for residues of clopidol (3,5-dichloro-2,6-dimethyl-4-pyridinol) in food are established as follows:
(a) In cereal grains, vegetables, and fruits: 0.2 part per million.
(b) In chickens and turkeys:
(1) 15 parts per million in uncooked liver and kidney.
(2) 5 parts per million in uncooked muscle.
(c) In cattle, sheep, and goats:
(1) 3 parts per million in uncooked kidney.
(2) 1.5 parts per million in uncooked liver.
(3) 0.2 part per million in uncooked muscle.
(d) In swine: 0.2 part per million in uncooked edible tissues.
(e) In milk: 0.02 part per million (negligible residue).
(a)
(b)
(ii)
(2) [Reserved]
A tolerance of 0.01 part per million is established for negligible residues of cloxacillin in the uncooked edible tissues of cattle and in milk.
A tolerance for residues of colistimethate in the edible tissues of chickens is not required.
(a)
(b)
(ii)
(2) [Reserved]
(a)
(b)
(1) 1 part per million (ppm) in skeletal muscle.
(2) 2 ppm in other tissues.
A tolerance of 0.1 part per million is established for negligible residues of dichlorvos (2,2-dichlorovinyl dimethyl phosphate) in the edible tissues of swine.
(a)
(b)
(ii)
(iii)
(2)
(ii)
(iii)
Tolerances are established for residues of dihydrostreptomycin in uncooked, edible tissues of cattle and swine of 2.0 parts per million (ppm) in kidney and 0.5 ppm in other tissues, and 0.125 ppm in milk.
No residues of 3,5-dinitrobenzamide may be found in the uncooked edible tissues of chickens as determined by the following method of analysis:
I.
II.
B. Acetyl-(
C. Alumina—activated F-20, 80-200 mesh, Aluminum Co. of America, or equivalent substance.
D. Ammonium sulfamate.
E. Ammonium sulfamate solution 1.25 grams of ammonium sulfamate per 100 milliliters of water. Refrigerate when not in use. Prepare fresh weekly.
F. Cation-exchange resin—Dowex 50W-X8, 200-400 mesh, Baker Analyzed Reagent, or equivalent, prepared as follows:
1. Place 500 grams of resin into a 3-liter beaker.
2. Add 2,000 milligrams of 6
3. Heat and stir while on a bath at 80 °C. for 6 hours. Discontinue heating and continue stirring overnight.
4. Filter the resin on a Buchner funnel (24 cm.) fitted with Whatman No. 1 paper.
5. Wash the resin bed with four 500-milliliter portions of 6
6. Wash the resin bed with 500-milliliter portions of deionized water until the effluent has a pH of 5 or higher.
7. Wash the resin bed with three 400-milliliter portions of specially denatured alcohol 3A. Drain thoroughly.
8. Make a slurry of resin in 1,250 milliliters of specially denatured alcohol 3A.
G. Chloroform.
H. Coupling reagent—0.25 gram of
I. 3,5-Dinitrobenzamide (3,5-DNBA standard). Add to boiling specially denatured alcohol 3A until a saturated solution is obtained and treat with activated carbon, filtered and crystallize by cooling to room temperature. The 3,5-DNBA therefrom is treated a second time with activated carbon and then recrystallized three more times from specially denatured alcohol 3A. The third crystallization is washed with diethyl ether and dried in a vacuum desiccator, melting point range 185 °C.-186 °C.
J. Ethyl alcohol—absolute, A.C.S.
K. Eluting reagent A. The formula and volume required in procedure step V-D is dependent on the adsorptive strength of the Al
1. Prepare a column (see procedure step V-D for determining formula and volume to eluting reagent A).
2. Transfer 1 milliliter of APNPS standard (100 micrograms per milliliter) in 75 milliliters of chloroform to the column.
3. Wash the column with 100 milliliters of chloroform and discard the eluate.
4. Pass through 100 milliliters of solution consisting of specially denatured alcohol 3A and ethyl alcohol 1:1 (volume to volume). Collect one 50-milliliter and five 10-milliliter portions; these make up the first, second, third, fourth, fifth, and sixth portions of eluate.
5. Place in beakers under a stream of air on a water bath (90 °C.) until the solvents are evaporated.
6. Add 10 milliliters of 4
7. Add the Bratton-Marshall reagents.
8. All fractions show a slight color. Note the portion containing the first significant increase in pink color.
a. If the color increases in the second, third, or fourth portions of eluate, the formula in procedure step V-D is suitable and, depending on the portion, 45, 55, or 65 milliliters, respectively, should be used in procedure step V-D4. Thereby, the APNPS is retained on the column and the benzamides are eluted.
b. If the color increases in the first portion, the eluting strength of the reagent is too strong. Return the test, substituting 1:4 (volume to volume) in procedure step V-D4. If 1:4 (volume to volume) is too strong, rerun with ethyl alcohol in procedure step V-D. If none of these are suitable, another lot of Al
c. If the color increases in the fifth or sixth portion, the eluting strength of the reagent is too weak. Rerun the test, substituting in procedure step V-D4, respectively, 4:1 (volume to volume), specially denatured alcohol 3A: methyl alcohol, 4:1 (volume to volume), until a suitable formula is found. If none of these are suitable, another lot of Al
L. Hydrochloric acid, 4
M. Diatomaceous earth—Hyflo Super Cel, Johns-Manville Co., or equivalent substance.
N.
O. Sodium hydroxide solution, 10
P. Sodium nitrite solution—0.25 grams of sodium nitrite per 100 milliliters of water. Refrigerate when not in use. Prepare fresh weekly.
Q. Specially denatured alcohol, formula 3A-100 parts of 190-proof ethyl alcohol plus 5 parts of commercial methyl alcohol.
R. Titanium(ous) chloride-20 percent solution.
III.
B. Autotransformer—type 500B, or equivalent. To regulate speed of mixer.
C. Centrifuge.
D. Centrifuge tubes—50-milliliter size with glass stopper.
E. Chromatography tubes—Corning No. 38460, 20 millimeters A 400 millimeters and having a tapered 29/42 joint with coarse, fritted disc, or equivalent tubes.
F. Evaporator—vacuum, rotary, thin film.
G. Ion-exchange column—as described by Thiegs et al. in “Determination of 3-amino-5-nitro-
H. Glycerol manostat. For regulating pressure on columns: To Al
I. Motor speed control. For regulating speed on 1-quart blender.
J. Volumetric flasks—50 milliliter size, actinic ware.
K. Mixer—Vortex Jr. Model K-500-1, Scientific Industries, Inc., or equivalent mixer.
L. One-quart blender.
M. Water bath (45 °C.-50° C.).
N. Water bath (90 °C.).
IV.
2. Dissolve and dilute with acetone to volume.
3. Dilute 1 milliliter to 100 milliliters.
4. Add 5.0 milliliters of water to each of six centrifuge tubes.
5. Add standard to each of the tubes to contain one of the following amounts: 0.0, 1.0, 2.0, 3.0, 5.0, and 10.0 micrograms of 3,5-DNBA.
B. Prepare each tube for colorimetric measurement as follows:
1. Place the tube in a hot water bath (90 °C.) until 5.0 milliliters remain. Cool to room temperature.
2. While mixing on Vortex mixer, or equivalent, regulated with an autotransformer, add 2 drops of TiCl
3. Add 2 milliliters of HCl, mix, and allow to stand for 5 minutes.
4. Transfer to 50-milliliter volumetric flask and dilute with 4
5. Cool to 0 °C.-5 °C. by placing in a freezer or ice bath.
6. Perform the Bratton-Marshall reaction in subdued light as follows:
a. Add 1 milliliter of sodium nitrite reagent, mix, and allow to stand for 1 minute.
b. Add 1 milliliter of ammonium sufamate reagent, mix, and allow to stand for 1 minute.
c. Add 1 milliliter of coupling reagent, mix, and allow to stand for 10 minutes.
d. Dilute to volume with 4
C. Perform colorimetric measurement at 530 millimicrons as follows:
1. Fill two matched 100-millimeter cells with 4
2. Adjust dark current.
3. Adjust to zero absorbance.
4. Replace acid in cell of sample side of compartment with standard to be measured.
5. The standard curve should be run five different times. Plot equivalent concentration in tissue versus mean absorbance at each concentration. If computer is available, a better procedure is to calculate the equation of the standard curve by means of least squares.
V.
2. Weight 100 ±0.5 grams of each replicate sample in a 150-milliliter beaker. Analyze each sample in triplicate and average the results. Reproducibility of ±10 percent between such analyses has been obtained.
3. Transfer the sample to a 1-quart blender jar. For kidney and liver tissues, make a slurry with acetone in the weighing beaker. Transfer with several rinses of acetone.
4. Blend the sample for 5 minutes with 250 milliliters of acetone and a 100-milliliter beakerful of diatomaceous earth.
5. Filter through a Buchner funnel containing a wetted Whatman No. 5 filter paper (12.5 cm.) into a 1-liter suction flask.
6. Rinse the blender jar into the funnel with three 25-milliliter portions of acetone.
7. Transfer the pulp and paper from the funnel to the aforementioned blender jar.
8. Add 250 milliliters of chloroform.
9. Blend for 3 minutes.
10. Filter through the aforementioned apparatus of procedure step V-A5. For rapid filtration of skin and blood samples, prepare funnel by adding diatomaceous earth and tamping evenly over paper to a thickness of 3 to 5 millimeters.
11. Rinse the blender jar into the funnel with three 25-milliliter rinses of chloroform.
B. Phasic separation. 1. Pour the combined filtrates into a 1-liter separatory funnel.
2. Rinse the suction flask twice with 25 milliliters of chloroform.
3. Mix the funnel contents by gently rocking and swirling for 30 seconds.
4. Let stand 10 minutes to allow phases to separate.
a. The upper (aqueous) phase (30 to 50 milliliters) is not always emulsion-free. Losses from emulsions have not been significant.
b. If an upper (aqueous) phase does not appear, add an additional 100 milliliters of chloroform and 10 milliliters of water and repeat procedure step V-B3.
5. Withdraw the lower phase into a 1-liter round-bottom flask, and discard upper phase. Withdraw nearly all of the lower phase, let stand for 2 to 3 minutes, then withdraw the remainder.
C. Evaporation. Attach the flask on a thin-film rotary evaporator connected to a vacuum supply, and place in a water bath maintained at 45 °C.-50 °C. until an oily residue remains. Do not overheat the sample or allow to go to dryness.
D. Adsorption chromatography. 1. Prepare a chromatography column using a column with calibrated etchings to indicate appropriate adsorbent and solvent levels as follows:
a. Fill tube to a depth of 60 millimeters with Al
b. Tap walls gently with hands.
c. Add anhydrous sodium sulfate to an additional depth of 25 millimeters.
d. Wet and wash column with 50 milliliters of chloroform.
i. During chromatography, make each addition to the tube when the liquid level has reached the top of the sodium sulfate layer.
ii. Increase the percolation rates by applying a slight air pressure to the top of the column.
2. Transfer the residue from procedure step V-C to the column with four 15-milliliter rinses of chloroform. Then rinse the walls of the tube and sodium sulfate layer with three 5-milliliter portions of chloroform. Percolation rate: 15 to 25 milliliters per minute. No color from sample should be seen in sodium sulfate layer after final rinse.
3. Wash column with 100 milliliters of chloroform. Discard eluate.
4. Add 75 milliliters of eluting reagent A and collect eluate A in a 250-milliliter beaker for cation-exchange chromatography.
a. Refer to “Eluting reagent A” under “Reagents” (II-K) for determining formula and volume.
b. Percolation rate: 8 to 12 milliliters per minute.
E. Cation-exchange chromatography—No. 1. 1. Prepare an ion-exchange column as follows:
a. Add a uniform slurry of resin to the column to obtain a 4 to 5 centimeter bed depth after settling.
i. Obtain a uniform slurry using a magnetic stirrer. To add the required amount of resin, calibrate the slurry and transfer it with a 10-milliliter pipette to deliver a reproducible volume.
ii. Increase the flow rate to 2 to 4 milliliters per minute by applying air pressure to the column. A glycerol manostat adjusted to 30 inches and attached between an air supply and column provides adequate pressure.
b. Wash the resin with 10 milliliters of eluting reagent A. Discard eluate.
2. Pass eluate A from procedure step V-D4 through the column. Collect in a 250-milliliter beaker.
3. Pass 50 milliliters of specially denatured alcohol 3A through the column. Combine with the eluate of procedure step V-E2.
F. Reduction. 1. Place the eluate A fraction from procedure step V-E3 on a hot water bath (90 °C.) and evaporate with a stream of air until 5 to 10 milliliters remain. Do not overheat the sample or allow the sample to go to dryness.
2. Transfer to centrifuge tube and rinse beaker three times with 3 milliliters of specially denatured alcohol 3A.
3. Evaporate on a hot water bath (90 °C.) under a stream of air until alcohol has evaporated. Do not overheat the sample or allow the sample to go to dryness.
4. Remove the tube from the water bath and immediately add 5.0 milliliters of water.
5. While mixing, add 2 drops of titanium chloride and 4 drops of 10
a. Mix on Vortex Jr. mixer, or equivalent, regulated with autotransformer.
b. Precipitate of insoluble tissue substances and white titanium salts is present after reduction is complete.
6. Dilute to 50 milliliters with specially denatured alcohol 3A and mix.
7. Centrifuge for 5 minutes at 2,000 r.p.m.
G. Cation-exchange chromatography—No. 2. 1. Prepare resin column by procedure step V-E.
2. Pass the centrifugate of procedure step V-F7 through column. Use three rinses of specially denatured alcohol 3A, each 5 milliliters, to aid in transferring of sample.
3. Pass 50 milliliters of specially denatured alcohol 3A through the column.
4. Pass 50 milliliters of deionized water through the column.
5. Elute arylamine residue from the resin with 40 to 43 milliliters of 4
H. Color development and measurement. 1. Cool to 0 °C.-5 °C. by placing in a freezer or ice bath.
2. Perform the Bratton-Marshall reaction in subdued light as follows:
a. Add 1 milliliter of sodium nitrite reagent, mix, and allow to stand for 1 minute.
b. Add 1 milliliter of ammonium sulfamate reagent, mix, and allow to stand for 1 minute.
c. Add 1 milliliter of coupling reagent, mix, and allow to stand for 10 minutes.
d. Dilute to volume with 4
3. Perform colorimetric measurement at 530 millimicrons as follows:
a. Fill two matched 100-millimeter cells with 4
b. Adjust dark current.
c. Adjust to zero absorbance.
d. Replace acid in cell of sample side of compartment with sample to be measured.
e. Record absorbance observed.
I. Calculations. Determine parts per billion (observed) from the standard curve.
(a)
(b)
(2)
(a)
(b)
(2) [Reserved]
The acceptable daily intake for enrofloxacin is 3 micrograms per kilogram of body weight per day.
(a)
(b) [Reserved]
Tolerances for residues of erythromycin in food are established as follows:
(a) 0.1 part per million in uncooked edible tissues of beef cattle and swine.
(b) Zero in milk.
(c) 0.025 part per million in uncooked eggs.
(d) 0.125 part per million (negligible residue) in uncooked edible tissues of chickens and turkeys.
No residues of estradiol, resulting from the use of estradiol or any of the related esters, are permitted in excess of the following increments above the concentrations of estradiol naturally present in untreated animals:
(a) In uncooked edible tissues of heifers, steers, and calves:
(1) 120 parts per trillion for muscle.
(2) 480 parts per trillion for fat.
(3) 360 parts per trillion for kidney.
(4) 240 parts per trillion for liver.
(b) In uncooked edible tissues of lambs:
(1) 120 parts per trillion for muscle.
(2) 600 parts per trillion for fat, kidney, and liver.
Tolerance for residues of ethopabate converted to metaphenetidine are established in the edible tissues of chickens as follows:
(a) 1.5 parts per million in uncooked liver and kidney.
(b) 0.5 part per million in uncooked muscle.
A tolerance of zero is established for residues of ethylenediamine in milk.
Tolerances are established for residues of famphur including its oxygen analog in or on meat, fat, or meat byproducts of cattle at 0.1 part per million.
(a)
(b)
(ii)
(iii)
(2)
(ii)
(3)
(ii)
(4)
(ii)
A tolerance for marker residue of fenprostalene in cattle is not needed. The safe concentrations for the total residues of fenprostalene in the uncooked edible tissues of cattle are 10 parts per billion in muscle, 20 parts per billion in liver, 30 parts per billion in
(a)
(b)
(ii)
(2)
(ii)
(3)
(4)
(b)
(c)
(a)
(b)
(i)
(ii)
(iii)
(2)
(i)
(ii)
(c)
A tolerance of zero is established for residues of furazolidone in the uncooked edible tissues of swine.
(a) A tolerance of 0.1 part per million is established for negligible residues of gentamicin sulfate in the uncooked edible tissues of chickens and turkeys.
(b) Tolerances are established for total residues of gentamicin in edible tissues of swine as follows: 0.1 part per million in muscle, 0.3 part per million in liver, and 0.4 part per million in fat and kidney. A microbiological determinative procedure and an HPLC confirmatory procedure for gentamicin have been developed to assay gentamicin in kidney at 0.4 ppm. Since residues of gentamicin as the parent compound and total residues are equal, the marker (parent drug) residue concentration of 0.4 ppm in kidney corresponds to 0.4 ppm of total residue.
(a)
(b)
The marker residue selected to monitor for total residues of halofuginone hydrobromide in broilers and turkeys is parent halofuginone hydrobromide and the target tissue selected is liver.
A tolerance of 0.1 part per million is established for negligible residues of haloxon (3-chloro-7-hydroxy-4-methyl-coumarin bis(2-chloroethyl) phosphate) in the edible tissues of cattle.
A tolerance is established for negligible residues of hydrocortisone (as hydrocortisone sodium succinate or hydrocortisone acetate) in milk at 10 parts per billion.
A tolerance of zero is established for residues of hygromycin B in or on eggs and the uncooked edible tissues of swine and poultry.
(a)
(b)
(i)
(ii)
(iii)
(iv)
(v)
(2)
(i)
(ii)
(a)
(b)
(a)
(b)
(2)
(ii)
(3)
(ii)
(4)
(5)
A tolerance of 0.1 part per million is established for negligible residues of levamisole hydrochloride in the edible tissues of cattle, sheep, and swine.
(a)
(b)
(c)
A tolerance is established for residues of maduramicin ammonium in chickens as follows:
(a) A tolerance for maduramicin ammonium (marker residue) in chickens is 0.38 parts per million in fat (target tissue). A tolerance refers to the concentration of marker residues in the target tissue used to monitor for total drug residues in the target animals.
(b) The safe concentrations for total maduramicin ammonium residues in uncooked edible chicken tissues are: 0.24 parts per million in muscle; 0.72 parts per million in liver; 0.48 parts per million in skin; and 0.48 parts per million in fat. A safe concentration refers to the total residue concentration considered safe in edible tissues.
A tolerance of 25 parts per billion is established for residues of the parent compound, melengestrol acetate, in fat of cattle.
A tolerance of zero is established for residues of methylparaben in milk from dairy animals.
A tolerance is established for negligible residues of methylprednisolone in milk at 10 parts per billion.
A tolerance of 0.02 part per million is established for negligible residues of metoserpate hydrochloride (methyl-
(a)
(b)
(1)
(ii)
(iii)
(2)
(ii) [Reserved]
(3)
(c)
A tolerance of 0.7 part per million is established for
(a)
(b)
(ii)
(iii)
(iv)
(2)
(ii)
(iii)
(c)
(a)
(b)
(2) [Reserved]
(a)
(b)
(1)
(2)
(3)
A tolerance of 0.1 part per million is established for negligible residues of nequinate in the uncooked edible tissues of chickens.
A tolerance of 4 parts per million is established for residues of nicarbazin in uncooked chicken muscle, liver, skin, and kidney.
Tolerances for residues of novobiocin are established at 0.1 part per million in milk from dairy animals and 1 part per million in the uncooked edible tissues of cattle, chickens, turkeys, and ducks.
A tolerance of zero is established for residues of nystatin in or on eggs and the uncooked edible tissues of swine and poultry.
Tolerances are established for negligible residues of oleandomycin in uncooked edible tissues of chickens, turkeys, and swine at 0.15 part per million.
(a) [Reserved]
(b)
(a)
(b)
(1) 2 parts per million (ppm) in muscle.
(2) 6 ppm in liver.
(3) 12 ppm in fat and kidney.
(4) 0.3 ppm in milk.
Tolerances are established for residues of penicillin and the salts of penicillin in food as follows:
(a) 0.05 part per million (negligible residue) in the uncooked edible tissues of cattle.
(b) Zero in the uncooked edible tissues of chickens, pheasants, quail, swine, and sheep; in eggs; and in milk or in any processed food in which such milk has been used.
(c) 0.01 part per million in the uncooked edible tissues of turkeys.
A tolerance of 0.1 part per million piperazine base is established for edible tissues of poultry and swine.
(a)
(b)
(ii)
(iii)
(2) [Reserved]
A tolerance of zero is established for residues of prednisolone in milk from dairy animals.
A tolerance of zero is established for residues of prednisone in milk from dairy animals.
No residues of progesterone are permitted in excess of the following increments above the concentrations of progesterone naturally present in untreated animals:
(a) In uncooked edible tissues of steers and calves:
(1) 3 parts per billion for muscle.
(2) 12 parts per billion for fat.
(3) 9 parts per billion for kidney.
(4) 6 parts per billion for liver.
(b) In uncooked edible tissues of lambs:
(1) 3 parts per billion for muscle.
(2) 15 parts per billion for fat, kidney, and liver.
A tolerance of zero is established for residues of propylparaben in milk from dairy animals.
Tolerances are established for residues of pyrantel tartrate in edible tissues of swine as follows:
(a) 10 parts per million in liver and kidney.
(b) 1 part per million in muscle.
(a)
(b)
(ii)
(2)
(ii)
Tolerances are established for residues of robenidine hydrochloride in edible tissues of chickens as follows:
(a) 0.2 part per million in skin and fat.
(b) 0.1 part per million (negligible residue) in edible tissues other than skin and fat.
A tolerance of zero is established for residues of salicylic acid in milk from dairy animals.
(a)
(b) [Reserved]
(a)
(b)
(2) [Reserved]
(a)
(b)
(c)
Tolerances are established for residues of streptomycin in uncooked, edible tissues of chickens, swine, and calves of 2.0 parts per million (ppm) in kidney and 0.5 ppm in other tissues.
Tolerances for residues of sulfabromomethazine sodium in food are established as follows:
(a) In the uncooked edible tissues of cattle at 0.1 part per million (negligible residue).
(b) In milk at 0.01 part per million (negligible residue).
A tolerance of zero is established for residues of sodium sulfachloropyrazine monohydrate in the uncooked edible tissues of chickens.
A tolerance of 0.1 part per million is established for negligible residues of sulfachlorpyridazine in uncooked edible tissues of calves and swine.
(a) [Reserved]
(b)
(2) A tolerance of 0.01 ppm is established for negligible residues of sulfadimethoxine in milk.
Tolerances for residues of sulfaethoxypyridazine in food are established as follows:
(a) Zero in the uncooked edible tissues of swine and in milk.
(b) 0.1 part per million (negligible residue) in uncooked edible tissues of cattle.
A tolerance of zero is established for residues of sulfamerazine (N
A tolerance of 0.1 part per million is established for negligible residues of sulfamethazine in the uncooked edible tissues of chickens, turkeys, cattle, and swine.
A tolerance of zero is established for residues of sulfanitran (acetyl(
A tolerance of 0.1 part per million is established for negligible residues of sulfaquinoxaline in the uncooked edible tissues of chickens, turkeys, calves, and cattle.
A tolerance of 0.1 part per million is established for negligible residues of sulfathiazole in the uncooked edible tissues of swine.
A tolerance of zero is established for residues of sulfomyxin (N-sulfomethyl-polymyxin B sodium salt) in uncooked edible tissues from chickens and turkeys.
No residues of testosterone, resulting from the use of testosterone propionate, are permitted in excess of the following increments above the concentrations of testosterone naturally present in untreated animals:
(a) In uncooked edible tissues of heifers:
(1) 0.64 part per billion in muscle.
(2) 2.6 parts per billion in fat.
(3) 1.9 parts per billion in kidney.
(4) 1.3 parts per billion in liver.
(b) [Reserved]
(a)
(b)
Tolerances are established at 0.1 part per million for negligible residues of thiabendazole in uncooked edible tissues of cattle, goats, sheep, pheasants, and swine, and at 0.05 part per million for negligible residues in milk.
(a)
(b)
(ii)
(2)
(ii)
(3)
(ii)
A tolerance of 0.6 part per million is established for 8-
(a)
(b)
Tolerances are established for residues of tylosin in edible products of animals as follows:
(a) In chickens and turkeys: 0.2 part per million (negligible residue) in uncooked fat, muscle, liver, and kidney.
(b) In cattle: 0.2 part per million (negligible residue) in uncooked fat, muscle, liver, and kidney.
(c) In swine: 0.2 part per million (negligible residue) in uncooked fat, muscle, liver, and kidney.
(d) In milk: 0.05 part per million (negligible residue).
(e) In eggs: 0.2 part per million (negligible residue).
A tolerance of 200 parts per billion (ppb) is established for residues of tripelennamine in uncooked edible tissues of cattle and 20 ppb in milk.
(a)
(b)
(ii) [Reserved]
(2)
(ii) [Reserved]
(c)
(a)
(b)
(2)
(a)
(b)
(1)
(2)
(c)
(a)
(b)
(ii) [Reserved]
(2) [Reserved]
Tolerances are established for residues of zoalene (3,5-dinitro-
(a) In edible tissues of chickens:
(1) 6 parts per million in uncooked liver and kidney.
(2) 3 parts per million in uncooked muscle tissue.
(3) 2 parts per million in uncooked fat.
(b) In edible tissues of turkeys: 3 parts per million in uncooked muscle tissue and liver.
21 U.S.C. 360b, 371.
(a) Regulations in this part provide for approved uses of drugs and combinations of drugs in animal feeds. Approved combinations of such drugs are specifically identified or incorporated by cross-reference. Unless specifically provided for by the regulations, a combination of two or more drugs is not approved.
(b) The following definitions apply to terms used in this part:
(1) New animal drugs approved for use in animal feed are placed in two categories as follows:
(i) Category I—These drugs require no withdrawal period at the lowest use level in each species for which they are approved.
(ii) Category II—These drugs require a withdrawal period at the lowest use level for at least one species for which they are approved, or are regulated on a “no-residue” basis or with a zero tolerance because of a carcinogenic concern regardless of whether a withdrawal period is required, or are a veterinary feed directive drug.
(2) A “Type A medicated article” is intended solely for use in the manufacture of another Type A medicated article or a Type B or Type C medicated feed. It consists of a new animal drug(s), with or without carrier (e.g., calcium carbonate, rice hull, corn, gluten) with or without inactive ingredients. The manufacture of a Type A medicated article requires an application approved under § 514.105 of this chapter or an index listing granted under § 516.151 of this chapter.
(3) A “Type B medicated feed” is intended solely for the manufacture of other medicated feeds (Type B or Type C). It contains a substantial quantity of nutrients including vitamins and/or minerals and/or other nutritional ingredients in an amount not less than 25 percent of the weight. It is manufactured by diluting a Type A medicated article or another Type B medicated feed. The maximum concentration of animal drug(s) in a Type B medicated feed is 200 times the highest continuous use level for Category I drugs and 100 times the highest continuous use level for Category II drugs. The term “highest continuous use level” means the highest dosage at which the drug is approved for continuous use (14 days or more), or, if the drug is not approved for continuous use, it means the highest level used for disease prevention or control. If the drug is approved for multiple species at different use levels, the highest approved level of use would govern under this definition. The manufacture of a Type B medicated feed from a Category II, Type A medicated article requires a medicated feed mill license application approved under § 515.20 of this chapter.
(4) A “Type C medicated feed” is intended as the complete feed for the animal or may be fed “top dressed” (added on top of usual ration) on or offered “free-choice” (e.g., supplement) in conjunction with other animal feed. It contains a substantial quantity of nutrients including vitamins, minerals, and/or other nutritional ingredients. It is manufactured by diluting a Type A medicated article or a Type B medicated feed. A Type C medicated feed may be further diluted to produce another Type C medicated feed. The manufacture of a Type C medicated feed from a Category II, Type A medicated article requires a medicated feed mill license application approved under § 515.20 of this chapter.
(5) A Type B or Type C medicated feed manufactured from a drug component (bulk or “drum-run” (dried crude fermentation product)) requires an application approved under § 514.105 of this chapter or an index listing granted under § 516.151 of this chapter.
(6) A “veterinary feed directive (VFD) drug” is a new animal drug approved under section 512(b) of the Federal Food, Drug, and Cosmetic Act (the act) or listed in the index under section 572 of the act for use in or on animal feed. Use of a VFD drug must be under the professional supervision of a licensed veterinarian.
(7) A “veterinary feed directive” is a written statement issued by a licensed veterinarian in the course of the veterinarian's professional practice that orders the use of a VFD drug in or on an animal feed. This written statement authorizes the client (the owner of the animal or animals or other caretaker)
(8) A “medicated feed” means a Type B medicated feed as defined in paragraph (b)(3) of this section or a Type C medicated feed as defined in paragraph (b)(4) of this section.
(9) For the purposes of this part, a “distributor” means any person who distributes a medicated feed containing a VFD drug to another distributor or to the client-recipient of the VFD.
(10) An “animal production facility” is a location where animals are raised for any purpose, but does not include the specific location where medicated feed is made.
(11) An “acknowledgment letter” is a written communication provided to a distributor by a consignee who is not the ultimate user of medicated feed containing a VFD drug. An acknowledgment letter affirms that the consignee will not ship such medicated animal feed to an animal production facility that does not have a VFD, and will not ship such feed to another distributor without receiving a similar written acknowledgment letter.
(a) A feed manufacturing facility must possess a medicated feed mill license in order to manufacture a Type B or Type C medicated feed from a Category II, Type A medicated article.
(b) The manufacture of the following types of feed are exempt from the required license, unless otherwise specified:
(1) Type B or Type C medicated feed using Category I, Type A medicated articles or Category I, Type B or Type C medicated feeds; and
(2) Type B or Type C medicated feed using Category II, Type B or Type C medicated feeds.
(c) The use of Type B and Type C medicated feeds shall also conform to the conditions of use provided for in subpart B of this part and in § 558.15 of this chapter.
(d) This paragraph identifies each drug by category, the maximum level of drug in Type B medicated feeds, and the assay limits for the drug in Type A medicated articles and Type B and Type C medicated feeds, as follows:
(e) When drugs from both categories are in combination, the Category II requirements will apply to the combination drug product.
For
(a)
(1) Type B feed that is intended for further manufacture of other medicated feeds (§ 558.3(b)(3)) or:
(2) Type C feed that is intended for the following:
(i) Further manufacture of another Type C feed, or
(ii) Top-dressing (adding on top of the usual ration) (§ 558.3(b)(4)).
(b)
(c)
(1) An original NADA,
(2) A supplemental NADA, or
(3) An abbreviated NADA.
(d)
(1) Data, or a reference to data in a master file (MF), that shows the relevant ranges of conditions under which the drug will be chemically stable in liquid feed under field use conditions; and
(2) Data, or a reference to data in an MF, that shows that the drug is physically stable in liquid feed under field conditions; or
(3) Feed labeling with recirculation or agitation directions as follows:
(i) For liquid feeds stored in recirculating tank systems: Recirculate immediately prior to use for not less than 10 minutes, moving not less than 1 percent of the tank contents per minute from the bottom of the tank to the top. Recirculate daily as described even when not used.
(ii) For liquid feeds stored in mechanical, air, or other agitation-type tank systems: Agitate immediately prior to use for not less than 10 minutes, creating a turbulence at the bottom of the tank that is visible at the top. Agitate daily as described even when not used.
(e)
(1) Directly in the NADA,
(2) By a sponsor, or
(3) To an MF that a sponsor may then reference in its NADA with written consent of the MF holder.
(f)
(1) The formula and/or specifications of the liquid medicated feed, where the owner of this information requests such publication; and/or
(2) A statement that the approval has been granted for a proprietary formula and/or specifications.
(g)
(1) All liquid medicated feeds that contain a Category II drug, and
(2) Liquid medicated feeds that contain a Category I drug and use a proprietary formula and/or specifications.
(h)
(i)
(2) To obtain a waiver, you must submit a letter requesting a waiver to the Office of New Animal Drug Evaluation (HFV-100), Center for Veterinary Medicine, Food and Drug Administration, 7500 Standish Pl., Rockville, MD 20855.
(3) The letter must include a copy of the product label; a description of the formulation; and information to establish that the physical, chemical, or other properties of the new animal
(j)
(a) What conditions must I meet if I am a veterinarian issuing a veterinary feed directive (VFD)?
(1) You must be appropriately licensed.
(2) You must issue a VFD only within the confines of a valid veterinarian-client-patient relationship (see definition at § 530.3(i) of this chapter).
(3) You must complete the VFD in writing and sign it or it will be invalid.
(4) You must include all of the following information in the VFD or it will be invalid:
(i) You and your client's name, address and telephone and, if the VFD is faxed, facsimile number.
(ii) Identification and number of animals to be treated/fed the medicated feed, including identification of the species of animals, and the location of the animals.
(iii) Date of treatment, and, if different, date of prescribing the VFD drug.
(iv) Approved or index listed indications for use.
(v) Name of the animal drug.
(vi) Level of animal drug in the feed, and the amount of feed required to treat the animals in paragraph (a)(4)(ii) of this section.
(vii) Feeding instructions with the withdrawal time.
(viii) Any special instructions and cautionary statements necessary for use of the drug in conformance with the approval.
(ix) Expiration date of the VFD.
(x) Number of refills (reorders) if necessary and permitted by the approval.
(xi) Your license number and the name of the State issuing the license.
(xii) The statement: “Extra-label use, (i.e., use of this VFD feed in a manner other than as provided for in the VFD drug approval) is strictly prohibited.”
(xiii) Any other information required by the VFD drug approval regulation.
(5) You must produce the VFD in triplicate.
(6) You must issue a VFD only for the approved or indexed conditions and indications for use of the VFD drug.
(b) What must I do with the VFD if I am a veterinarian?
(1) You must give the original VFD to the feed distributor (directly or through the client).
(2) You must keep one copy of the VFD.
(3) You must give the client a copy of the VFD.
(4) You may send a VFD to the client or distributor by facsimile or other electronic means provided you assure that the distributor receives the original signed VFD within 5 working days of receipt of the facsimile or other electronic order.
(5) You may not transmit a VFD by telephone.
(c) What are the VFD recordkeeping requirements?
(1) The VFD feed distributor must keep the VFD original for 2 years from the date of issuance. The veterinarian and the client must keep their copies for the same period of time.
(2) All involved parties must make the VFD available for inspection and copying by FDA.
(3) All involved parties (the VFD feed distributor, the veterinarian, and the client) must keep VFD's transmitted by facsimile or other electronic means for a period of 2 years from date of issuance.
(4) All involved parties must have a copy of the VFD before distribution of a VFD feed to the ultimate user.
(d) What are the notification requirements if I am a distributor of animal feed containing a VFD drug?
(1) You must notify FDA only once, by letter, that you intend to distribute animal feed containing a VFD drug.
(i) The notification letter must include the complete name and address of each business site from which distribution will occur.
(ii) A responsible person from your firm must sign and date the notification letter.
(iii) You must submit the notification letter to the Center for Veterinary Medicine, Division of Animal Feeds (HFV-220), 7500 Standish Pl., Rockville, MD 20855, prior to beginning your first distribution.
(iv) You must notify the Center for Veterinary Medicine at the above address within 30 days of any change in name or business address.
(2) If you are a distributor who ships an animal feed containing a VFD drug to another consignee-distributor in the absence of a valid VFD, you must obtain an “acknowledgment letter,” as defined in § 558.3(b)(11), from the consignee-distributor. The letter must include a statement affirming that the consignee-distributor has complied with “distributor notification” requirements of paragraph (d)(1) of this section.
(e) What are the additional recordkeeping requirements if I am a distributor?
(1) You must keep records of receipt and distribution of all medicated animal feed containing a VFD drug.
(2) You must keep these records for 2 years from date of receipt and distribution.
(3) You must make records available for inspection and copying by FDA.
(f) What cautionary statements are required for VFD drugs and animal feeds containing VFD drugs? All labeling and advertising must prominently and conspicuously display the following cautionary statement: “Caution: Federal law limits this drug to use under the professional supervision of a licensed veterinarian. Animal feed bearing or containing this veterinary feed directive drug shall be fed to animals only by or upon a lawful veterinary feed directive issued by a licensed veterinarian in the course of the veterinarian's professional practice.”
(a) The Commissioner of Food and Drugs will propose to revoke currently approved subtherapeutic (increased rate of gain, disease prevention. etc.) uses in animal feed of antibiotic and sulfonamide drugs whether granted by approval of new animal drug applications, master files and/or antibiotic or food additive regulations, by no later than April 20, 1975, or the nitrofuran drugs by no later than September 5, 1975, unless data are submitted which resolve conclusively the issues concerning their safety to man and animals and their effectiveness under specific criteria established by the Food and Drug Administration based on the guidelines included in the report of the FDA task force on the use of antibiotics in animal feeds. All persons or firms previously marketing identical, related, or similar products except the nitrofuran drugs not the subject of an approved new animal drug application must submit a new animal drug application by July 19, 1973, or by December 4, 1973, in the case of nitrofuran drugs, if marketing is to continue during the interim. New animal drug entities with antibacterial activity not previously marketed, now pending approval or submitted for approval prior to, on, or following the effective date of this publication, shall satisfy such criteria prior to approval.
(b) Any person interested in developing data which will support retaining approval for such uses of such antibiotic, nitrofuran, and sulfonamide drugs pursuant to section 512(l) of the Federal Food, Drug, and Cosmetic Act shall submit to the Commissioner the following:
(1) By July 19, 1973, records and reports of completed, ongoing, or planned studies, including protocols, on the tetracyclines, streptomycin, dihydrostreptomycin, penicillin, and the sulfonamides; for all other antibiotics by October 17, 1973; and for the nitrofuran drugs by March 4, 1974. The Food and Drug Administration encourages sponsors to consult with the Center for Veterinary Medicine on protocol design and plans for future studies.
(2) By April 20, 1974, data from completed studies on the tetracyclines, streptomycin, dihydrostreptomycin, the sulfonamides, and penicillin assessing the effect of the subtherapeutic use of the drug in feed on the salmonella
(3) By April 20, 1975, data satisfying all other specified criteria for safety and effectiveness, including the effect on the salmonella reservoir for any antibiotic or sulfonamide drugs and by September 5, 1975, for the nitrofuran drugs, approved for subtherapeutic use in animal feeds. Drug efficacy data shall be submitted for any feed-use combination product containing such drug and any feed-use single ingredient antibiotic, nitrofuran, or sulfonamide not reviewed by the National Academy of Sciences—National Research Council, Drug Efficacy Study covering drugs marketed between 1938 and 1962.
(4) Progress reports on studies underway every January 1 and July 1 until completion.
(c) Failure on the part of any sponsor to comply with any of the provisions of paragraph (b) of this section for any of the antibacterial drugs included in paragraph (b)(1) of this section, or interim results indicating a health hazard, will be considered as grounds for immediately proceeding to withdraw approval of that drug for use in animal feeds under section 512(l) of the act in the case of failure to submit required records and reports and under section 512(e) where new information shows that such drug is not shown to be safe.
(d) Criteria based upon the guidelines laid down by the task force may be obtained from the Food and Drug Administration, Center for Veterinary Medicine, 7500 Standish Pl., Rockville, MD 20855.
(e) Reports as specified in this section shall be submitted to: Food and Drug Administration, Center for Veterinary Medicine, Office of New Animal Drug Evaluation (HFV-100), 7500 Standish Pl., Rockville, MD 20855.
(f) Following the completion of the requirements of paragraphs (a) and (b) of this section and the studies provided for therein:
(1) Those antibiotic, nitrofuran, and sulfonamide drugs which fail to meet the prescribed criteria for subtherapeutic uses but which are found to be effective for the therapeutic purposes will be permitted in feed only for high-level, short-term therapeutic use and only by or on the order of a licensed veterinarian.
(2) Animal feeds containing antibacterial drugs permitted to remain in use for subtherapeutic purposes shall be labeled to include a statement of the quantity of such drugs.
(g) The submission of applications and data required by paragraphs (a) and (b) of this section is not required for the continued manufacture of any Type A medicated article which is produced solely from a Type A article that is in compliance with the requirements of this section:
(1) The following antibacterial Type A articles manufactured by the designated sponsors are eligible for interim marketing based on their compliance with the requirements of this section:
(2) The following is a list of drug combinations permitted when prepared from antibacterial Type A articles listed in paragraph (g)(1) of this section. Drug combinations listed in subpart B of this part name their sponsors and are incorporated herein by reference since they are safe and effective by contemporary standards, or such sponsors have been notified of any additional safety or efficacy data required on an individual basis:
(a)
(1) 50 percent aklomide.
(2) 20 percent sulfanitran and 25 percent aklomide.
(3) 25 percent aklomide, 20 percent sulfanitran, and 5 percent roxarsone.
(4) 50 percent aklomide and 10 percent roxarsone.
(b)
(c)
(1)
(i)
(ii)
(2)
(i)
(ii)
(3)
(i)
(ii)
(4)
(i)
(ii)
(a)
(b)
(c)
(d)
(i)
(
(
(ii)
(
(
(2)
(3)
(i)
(ii)
(iii)
For
(a)
(1) 25 percent amprolium and 8 percent ethopabate or 5 percent amprolium and 1.6 percent ethopabate;
(2) 25 percent amprolium and 0.8 percent ethopabate or 5 percent amprolium and 0.16 percent ethopabate.
(3) 25 percent amprolium and 0.8 percent ethopabate.
(b)
(1) No. 050604 for products described in paragraph (a) of this section.
(2) No. 016592 for product described in paragraph (a)(3) of this section.
(c)
(d)
(e)
(2) [Reserved]
For
(a)
(1) 000986 for 75 grams apramycin (as apramycin sulfate) per pound for use as in paragraph (d)(1) of this section.
(2) [Reserved]
(b) [Reserved]
(c)
(d)
(ii)
(iii)
(2) [Reserved]
(a)
(b)
(c)
(i)
(ii)
(iii)
(2) Arsanilate sodium may be used in accordance with the provisions of this section in the combinations provided as follows:
(i) Amprolium in accordance with § 558.55.
(ii) Zoalene in accordance with § 558.680.
(a)
(1) To 015565: 20, 50, and 100 percent for use as in the table in paragraph (c)(1), entry (ii), item 1; entry (ii), item 2; entry (iv); entry (vi); and entry (vii) of this section.
(2) To 015565: 20 percent for use as in paragraph (c)(1), entry (i); entry (ii), item 3 of this section.
(3) To 061133: 90 grams per pound arsanilic acid and 4.6 grams per pound erythromycin equivalents as erythromycin thiocyanate for use as in paragraph (c)(1), entry (iii); 90 grams per pound arsanilic acid and 9.25 grams per pound erythromycin equivalents as erythromycin thiocyanate for use as in paragraph (c)(1), entry (v).
(b)
(c)
(2) Arsanilic acid may be used in accordance with the provisions of this section in the combinations provided as follows:
(i) Amprolium in accordance with § 558.55.
(ii) Amprolium and ethopabate in accordance with § 558.58.
(iii) Bacitracin zinc in accordance with § 558.78.
(iv) Bacitracin and zoalene in accordance with § 558.680.
(v) Zoalene in accordance with § 558.680.
(a)
(b)
(c)
(d)
(2) It is used as bacitracin methylene disalicylate in feed for animals as follows:
(i)
(
(
(ii)
(
(
(3) Bacitracin methylene disalicylate may also be used with:
(i) Amprolium as in § 558.55.
(ii) Amprolium and ethopabate as in § 558.58.
(iii) Carbarsone (not USP) as in § 558.120.
(iv) Decoquinate alone and with roxarsone as in § 558.195.
(v) Diclazuril alone and with roxarsone as in § 558.198.
(vi) Fenbendazole as in § 558.258.
(vii) Halofuginone hydrobromide alone and with roxarsone as in § 558.265.
(viii) Hygromycin B as in § 588.274.
(ix) Ivermectin as in § 558.300.
(x) Lasalocid sodium alone and with roxarsone as in § 558.311.
(xi) Monensin alone and with roxarsone as in § 588.355.
(xii) Narasin alone and with roxarsone as in § 558.363.
(xiii) Nicarbazin alone or with narasin or roxarsone or with narasin and roxarsone as in § 558.366.
(xiv) Nitarsone as in § 558.369.
(xv) Robenidine alone and with roxarsone as in § 558.515.
(xvi) Salinomycin alone and with roxarsone as in § 558.550.
(xvii) Semduramicin alone and with roxarsone as in § 558.555.
(xviii) Zoalene alone and with arsanilic acid or roxarsone as in § 558.680.
For
(a)
(b)
(c)
(d)
(2) It is used in feed for growing cattle at 35 to 70 milligrams per head per day as follows:
(i) To aid in stimulating growth and improving feed efficiency.
(ii) For increased rate of weight gain and improved feed efficiency; see sponsor 046573.
(3) It may be used as approved in combination with:
(i) Amprolium alone and with roxarsone as in § 558.55.
(ii) Amprolium and ethopabate alone and with roxarsone as in § 558.58.
(iii) Carbarsone as in § 558.120.
(iv) Clopidol alone and with roxarsone as in § 558.175.
(v) Decoquinate alone and with roxarsone as in § 558.195.
(vi) Hygromycin B alone and with penicillin as in § 558.274.
(vii) Lasalocid sodium alone or with roxarsone as in § 558.311.
(viii) Monensin alone and with roxarsone as in § 558.355.
(ix) Naracin as in § 558.363.
(x) Nitarsone as in § 558.369.
(xi) Robenidine as in § 558.515.
(xii) Salinomycin alone and with roxarsone as in § 558.550.
(xiii) Zoalene alone and with arsanilic acid or roxarsone as in § 558.680.
For
(a)
(1) To 016592: 2, 4, and 10 grams for use as in paragraphs (d)(1), (d)(2), (d)(3), and (d)(4) of this section.
(2) To 016592: 0.4 gram for use as in paragraph (d)(2) of this section.
(3) [Reserved]
(4) To Nos. 016968, 017790, and 021930: 0.4 and 2 grams for use as in paragraph (d)(2) and 2 grams for use as in paragraph (d)(3) of this section.
(5) To 016592: 10 grams to make 40 to 800 grams per ton Type B feed for use as in paragraph (d)(4) of this section.
(b)
(2) The expiration date for the liquid Type B feed is 8 weeks after date of manufacture. The expiration date for the dry Type C feed made from the liquid Type B feed is 1 week after date of manufacture.
(c) [Reserved]
(d)
(i)
(
(
(ii) [Reserved]
(2)
(i)
(
(
(ii)
(
(
(3)
(i)
(
(
(ii)
(
(
(4)
(
(
(ii)
(
(
(iii) Used as a free-choice Type C medicated loose mineral feed for pasture cattle (slaughter, stocker, and feeder cattle, and dairy and beef replacement heifers) as follows:
(
(
(
(
(iv) Use free-choice Type C medicated feeds for pasture cattle (slaughter, stocker, and feeder cattle, and dairy and beef replacement heifers) as follows:
(
(
(
(5) Bambermycins may also be used in combination with:
(i) Amprolium alone or with roxarsone as in § 558.55.
(ii) Amprolium and ethopabate alone or with roxarsone as in § 558.58.
(iii) Diclazuril as in § 558.198.
(iv) Halofuginone as in § 558.265.
(v) Lasalocid alone or with roxarsone as in § 558.311.
(vi) Monensin alone or with roxarsone as in § 558.355.
(vii) Narasin alone or with nicarbazin or roxarsone as in § 558.363.
(viii) Nicarbazin as in § 558.366.
(ix) Salinomycin alone or with roxarsone as in § 558.550.
(x) Zoalene alone or with roxarsone as in § 558.680.
For
(a)
(b)
(c)
(d)
(1)
(i)
(ii)
(2)
(i)
(ii)
(3)
(i)
(ii)
(4)
(i)
(ii)
(a)
(2) 25 percent carbarsone and 5 grams per pound bacitracin (as bacitracin methylene disalicylate) to 046573 in § 510.600(c) of this chapter.
(b)
(c) [Reserved]
(d)
(i)
(
(
(ii)
(
(
(iii)
(
(
(iv)
(
(
(2) Carbarsone (not U.S.P.) may be used in accordance with the provisions of this section in the combinations provided as follows:
(i) Zoalene in accordance with § 558.680.
(ii) Amprolium as in § 558.55.
(a)
(b)
(1) Nos. 046573, 048164, and 066104: 50 to 100 grams per pound (g/lb) of Type A medicated article.
(2) No. 021930: 50 g/lb of Type A medicated article.
(c)
(d)
(2) Manufacture for use in free-choice feeds as in paragraph (e)(4)(iii) of this section must conform to § 510.455 of this chapter.
(3) When manufactured for use as in paragraph (e)(5)(iv) of this section, include on labeling the warning: “Psittacosis, avian chlamydiosis, or ornithosis is a reportable communicable disease, transmissible between wild and domestic birds, other animals, and
(e) Conditions of use—(1)
(2)
(3)
(4)
(5)
(6) It is used as a free-choice, loose mineral Type C feed as follows:
(i)
(ii)
(iii)
(iv)
(v)
(7)
(i) Amprolium in accordance with § 558.55.
(ii) Amprolium plus ethopabate in accordance with § 558.58.
(iii) Bacitracin methylene disalicylate in accordance with § 558.76.
(iv) Clopidol in accordance with § 558.175.
(v) Decoquinate in accordance with § 558.195.
(vi) Hygromycin B in accordance with § 558.274.
(vii) Laidlomycin in accordance with § 558.305.
(viii) Lasalocid in accordance with § 558.311.
(ix) Monensin in accordance with § 558.355.
(x) Robenidine hydrochloride in accordance with § 558.515.
(xi) Roxarsone in accordance with § 558.530.
(xii) Salinomycin alone or with roxarsone in accordance with § 558.550.
(xiii) Tiamulin in accordance with § 558.600.
(xiv) Zoalene in accordance with § 558.680.
For
(a)
(b)
(c) It is used in feed for beef cattle as follows:
(1)
(2)
(3)
(a)
(2) 40 grams of chlortetracycline per pound, 8.8 percent of sulfamethazine, and penicillin procaine equivalent in activity to 20 grams of penicillin per pound to 046573 and 048164 in § 510.600(c) of this chapter.
(b)
(2) The antibiotic activities are expressed in terms of the appropriate antibiotic standards.
(3) Type C medicated feed contains in each ton, 100 grams of chlortetracycline, 50 grams of penicillin as procaine penicillin, and 100 grams of sulfamethazine.
(c)
(d)
(2) Withdraw 15 days prior to slaughter.
(a)
(2) 40 grams of chlortetracycline hydrochloride, 8.8 percent (40 grams) sulfathiazole and procaine penicillin equivalent in activity to 20 grams of penicillin per pound to No. 046573 in § 510.600(c) of this chapter.
(b)
(2) The antibiotic activities are expressed in terms of the appropriate antibiotic standards.
(c)
(d)
(1)
(2)
(3)
(a)
(b)
(c) [Reserved]
(d)
(a)
(b)
(1) No. 000859 for use of Type A medicated articles containing 1.12, 2.0, 11.2, or 50 percent coumaphos as in paragraphs (e)(2) and (e)(3) of this section.
(2) No. 017800 for use of Type A medicated articles containing 11.2 percent coumaphos as in paragraph (e)(1) of this section.
(3) No. 051311 for use of Type A medicated articles containing 1.12 percent coumaphos as in paragraph (e)(1) of this section.
(c)
(d)
(e)
(ii)
(iii)
(2)
(ii)
(iii)
(3)
(ii)
(iii)
(a)
(b)
(c)
(d)
(2) Type A medicated articles may be used to manufacture dry or liquid Type B cattle (including veal calf), sheep, and goat feeds as in paragraphs (e)(2) and (e)(3) of this section.
(3) Type C cattle feeds may be manufactured from decoquinate liquid Type B feeds having a pH between 5.0 to 6.5 and containing a suspending agent to maintain a viscosity of not less than 500 centipoises.
(e)
(1)
(2)
(3)
(a)
(b)
(c)
(d)
(2)
(a)
(b)
(2) Dichlorvos is a cholinesterase inhibitor. Do not use this product in animals simultaneously or within a few days before or after treatment with or exposure to cholinesterase-inhibiting drugs, pesticides, or chemicals. If human or animal poisoning should occur, immediately consult a physician or a veterinarian. Atropine is antidotal.
(3) Labeling for Type A articles and Type B feeds must include a statement that containers or materials used in packaging such Type A articles and Type B feeds are not to be reused and all such packaging materials must be destroyed after the product has been used.
(c)
(d)
(1)
(i)
(ii)
(2)
(i)
(ii)
(3)
(i)
(ii)
(a)
(b)
(A)
(B)
(ii)
(A)
(B)
(2) [Reserved]
(a)
(2) 5 and 10 percent to 061623 for use in paragraphs (d)(1)(i) and (ii) of this section.
(b)
(c)
(d)
(2) In feed for feedlot beef cattle at 37 milligrams per head per day as an aid in stimulating growth and improving feed efficiency.
(3) Erythromycin thiocyanate may be used in accordance with the provisions of this section in the combinations provided as follows:
(i) Amprolium in accordance with § 558.55.
(ii) Amprolium and ethopabate in accordance with § 558.58.
(iii) Arsanilic acid in accordance with § 558.62.
(iv) Zoalene in accordance with § 558.680.
(a)
(b)
(c)
(d)
(1)
(i)
(ii)
(2)
(i)
(ii)
(a)
(b)
(c)
(d)
(e)
(2)
(3)
(ii)
(4)
(5)
(a)
(1) 40 grams per kilogram for use as in paragraph (e)(1) of this section.
(2) 500 grams per kilogram for use as in paragraphs (e)(2) and (e)(3) of this section.
(b)
(c)
(2) The expiration date of veterinary feed directives (VFDs) for florfenicol medicated feeds:
(i) For catfish and freshwater-reared salmonids, must not exceed 15 days from the date of issuance;
(ii) For swine must not exceed 90 days from the date of issuance.
(3) VFDs for florfenicol shall not be refilled.
(d)
(e)
(2)
(a)
(b)
(c)
(d)
(i)
(A)
(B)
(ii)
(A)
(B)
(iii)
(A)
(B)
(iv)
(A)
(B)
(v)
(A)
(B)
(vi)
(A)
(B)
(vii)
(A)
(B)
(viii)
(A)
(B)
(2) It is used in feed for turkeys as follows:
(i)
(A)
(B)
(ii)
(A)
(B)
(iii)
(A)
(B)
(3) It is used in feed for replacement cage laying chickens and replacement broiler breeder chickens as follows:
(i)
(A)
(B)
(ii)
(A)
(B)
(a)
(2) 2.4 grams per pound to Nos. 043733 and 051311 in § 510.600(c) of this chapter for use in swine feed as in paragraph (c)(1)(ii) of this section.
(3) [Reserved]
(4) 0.6 gram per pound to 017790 and 043733 in § 510.600(c) of this chapter for use in chickens as in paragraph (c)(1)(i) of this section and in swine as in paragraph (c)(1)(ii) of this section.
(5)-(6) [Reserved]
(7) 2.4 grams per pound to 021930 in § 510.600(c) of this chapter for use in chickens as in paragraph (c)(1)(i) and in swine as in paragraph (c)(1)(ii) of this section.
(8) 0.6 and 1.6 grams per pound granted to 046573 in § 510.600(c) of this chapter for use in chickens as in paragraph (c)(1)(i) and in swine as in paragraph (c)(1)(ii) of this section.
(b)
(c)
(2) Hygromycin B may also be used in combination with:
(i) Amprolium in accordance with § 558.55.
(ii) Zoalene in accordance with § 558.680.
For
(a)
(b)
(c)
(ii)
(2)
(ii)
(iii)
(a)
(b)
(c)
(d)
(e)
(a)
(b)
(c)
(d)
(i) For liquid feeds stored in recirculating tank systems: Recirculate immediately prior to use for no less than 10 minutes, moving not less than 1 percent of the tank contents per minute from the bottom of the tank to the top. Recirculate daily as described even when not used.
(ii) For liquid feeds stored in mechanical, air, or other agitation type tank systems: Agitate immediately prior to use for not less than 10 minutes, creating a turbulence at the bottom of the tank that is visible at the top. Agitate daily as described even when not used.
(2) The expiration date for the liquid Type B feed is 21 days after date of manufacture. The expiration date for the dry Type C feed made from the liquid Type B feed is 7 days after date of manufacture.
(3) Labeling for all Type B feeds (liquid and dry) and Type C feeds containing laidlomycin shall bear the following statements:
(i) Do not allow horses or other equines access to feeds containing laidlomycin propionate potassium.
(ii) The safety of laidlomycin propionate potassium in unapproved species has not been established.
(iii) Not for use in animals intended for breeding.
(e)
(a)
(b)
(1) 3.0, 3.3, 3.8, 4.0, 4.3, 4.4, 5.0, 5.1, 5.5, 5.7, 6.0, 6.3, 6.7, 7.2, 7.5, 8.0, 8.3, 10.0, 12.5, 15, 20, and 50 percent activity to No. 046573 for use as in paragraphs (e)(1) (i), (ii), (iii), (iv), and (x) of this section.
(2) 15 percent activity to No. 066104 as provided by No. 046573 for use as in paragraph (e)(1)(v) of this section.
(3) 15, 20, 33.1, and 50 percent activity to No. 046573 for use in cattle feeds as in paragraphs (e)(1)(vi), (vii), (ix), (xi), (xii), and (xv) of this section, and for use in sheep as in paragraph (e)(1)(viii) of this section.
(4) 15 percent activity to No. 046573 for use in Type C rabbit feeds as in paragraph (e)(1)(xvi) of this section and for use in ruminant free-choice Type C feeds as in paragraphs (e)(2), (e)(3), and (e)(4) of this section.
(5) 15 and 20 percent activity to Nos. 017800 and 021930 for use in free-choice mineral feeds for cattle as in paragraph (e)(1)(xviii) of this section.
(6) 20 percent activity as a liquid Type A article to No. 046573 for use in cattle feeds as in paragraphs (e)(1)(vi), (e)(1)(vii), (e)(1)(ix), (e)(1)(xi), (e)(1)(xii), and (e)(3) of this section, and for use in sheep feeds as in paragraph (e)(1)(viii) of this section.
(7) 20 percent activity to No. 046573 for use as follows:
(i) Chukar partridges as in paragraph (e)(1)(xiii).
(ii) Turkeys as in paragraph (e)(1)(xiv).
(iii) Rabbits as in paragraph (e)(1)(xvi).
(8) [Reserved]
(9) 15 percent activity to No. 068287 for use in free-choice protein blocks for cattle as in paragraphs (e)(1)(xix) of this section.
(c)
(d)
(i) For liquid feeds stored in recirculating tank systems: Recirculate immediately prior to use for no less than 10 minutes, moving not less than 1 percent of the tank contents per minute from the bottom of the tank to the top. Recirculate daily as described even when not used.
(ii) For liquid feeds stored in mechanical, air, or other agitation-type tank systems: Agitate immediately prior to use for not less than 10 minutes, creating a turbulence at the bottom of the tank that is visible at the top. Agitate daily as described even when not used.
(2) A physically stable lasalocid liquid feed will not be subject to the requirements for mixing directions prescribed in paragraph (d)(1) of this section provided it has a pH of 4.0 to 8.0 and contains a suspending agent(s) sufficient to maintain a viscosity of not less than 300 centipoises per second for 3 months.
(3) If a manufacturer is unable to meet the requirements of paragraph (d)(1) or (d)(2) of this section, the manufacturer may secure approval of a positionally stable liquid feed by:
(i) Either filing a new animal drug application for the product or establishing a master file containing data to support the stability of its product;
(ii) Authorizing the agency to reference and rely upon the data in the master file to support approval of a supplemental new animal drug application to establish physical stability; and
(iii) Requesting the sponsor of an approved new animal drug application to file a supplement to provide for use of its lasalocid Type A article in the manufacture of the liquid feed specified in the appropriate master file. If the data demonstrate the stability of the liquid feed described in the master file, the supplemental new animal drug application will be approved. The approval will provide a basis for the individual liquid feed manufacturer to manufacture under a medicated feed license the liquid mediated feed described in the master file. A manufacturer who seeks to market a physically unstable lasalocid liquid feed with mixing directions different from the standard directions established in paragraph (d)(1) of this section may also follow this procedure.
(4) If adequate information is submitted to show that a particular liquid feed containing lasalocid is stable outside the pH of 4.0 to 8.0, the pH restriction described in paragraphs (d)(1) and (d)(2) of this section may be waived.
(5) Required label statements:
(i) For liquid Type B feed (cattle and sheep): Mix thoroughly with grain and/or roughage prior to feeding. Feeding undiluted, mixing errors, or inadequate mixing (recirculation or agitation) may result in an excess lasalocid concentration which could be fatal to cattle and sheep. Do not allow horses or other equines access to Type A articles or Type B feeds containing lasalocid as ingestion may be fatal. Safety of lasalocid for use in unapproved species has not been established.
(ii) For Type A articles or Type B feeds (cattle and sheep): Feeding undiluted or mixing errors may result in an excess lasalocid concentration which could be fatal to cattle and sheep. Do not allow horses or other equines access to Type A articles or Type B feeds containing lasalocid as ingestion may be fatal. Safety of lasalocid for use in unapproved species has not been established.
(iii) For Type A articles, Type B or Type C feeds (cattle): A withdrawal period has not been established for this product in preruminating calves. Do not use in calves to be processed for veal.
(6) Lasalocid Type A medicated articles containing lasalocid dried fermentation residue are for use in cattle and sheep feed only.
(7) Each use in a free-choice Type C cattle feed as in paragraphs (e)(1)(xii) and (e)(1)(xviii) of this section must be the subject of an approved NADA or supplemental NADA as provided in § 510.455 of this chapter.
(e)(1)
(2) It is used as a free-choice mineral Type C feed as follows:
(i)
(ii)
(iii)
(iv)
(v)
(3) It is used as a ruminant free-choice liquid Type C feed as follows:
(i)
(ii)
(iii)
(iv)
(v)
(4) It is used as a free-choice, loose mineral Type C feed as follows:
(i)
(ii)
(iii)
(iv)
(v)
(5)
(i) Melengestrol acetate alone or in combination with tylosin in accordance with § 558.342.
(ii) [Reserved]
For
(a)
(b)
(c)
(1)
(ii)
(iii)
(2)
(ii)
(iii)
(a)
(1) No. 000009 for 20 and 50 grams per pound.
(2)-(4) [Reserved]
(5) No. 043733 for 8 and 20 grams per pound.
(6)-(12) [Reserved]
(13) No. 051311 for 2.5 and 8 grams per pound.
(14)-(15) [Reserved]
(b)
(c)
(2) Labeling of Type A medicated articles and Type B and Type C medicated feeds containing lincomycin intended for use in swine shall bear the following directions: “CAUTION: Occasionally, swine fed lincomycin may within the first 2 days after the onset of treatment develop diarrhea and/or swelling of the anus. On rare occasions, some pigs may show reddening of the skin and irritable behavior. These conditions have been self-correcting within 5 to 8 days without discontinuing the lincomycin treatment.”
(3) Labeling of Type A medicated articles and single-ingredient Type B and Type C medicated feeds containing lincomycin intended for use in swine shall bear the following directions:
(i) No. 000009: “CAUTION: The effects of lincomycin on swine reproductive performance, pregnancy, and lactation have not been determined. Not for use in swine intended for breeding when lincomycin is fed at 20 grams per ton of complete feed.”
(ii) Nos. 043733 and 051311: “CAUTION: Not to be fed to swine that weigh more than 250 lb.”
(d)
(2)
(3) Lincomycin may also be used in combination with:
(i) Amprolium and ethopabate or amprolium and ethopabate with roxarsone in accordance with § 558.58.
(ii) Clopidol in accordance with § 558.175.
(iii) Decoquinate in accordance with § 558.195.
(iv) Fenbendazole as provided in § 558.258.
(v) Halofuginone in accordance with § 558.265.
(vi) Ivermectin as in § 558.300.
(vii) Lasalocid alone or with roxarsone in accordance with § 558.311.
(viii) Monensin alone or with roxarsone in accordance with § 558.355.
(ix) Nicarbazin alone or with narasin or roxarsone as in § 558.366.
(x) Pyrantel as in § 558.485.
(xi) Robenidine in accordance with § 558.515.
(xii) Roxarsone in accordance with § 558.530.
(xiii) Salinomycin with or without roxarsone as in § 558.550.
(xiv) Zoalene in accordance with § 558.680.
For
(a)
(b)
(c)
(i)
(ii)
(2) [Reserved]
(a)
(2) Liquid Type A medicated article containing 500 mg melengestrol acetate per pound.
(b)
(1) No. 000009 for use of products described in paragraph (a) of this section.
(2) No. 021641 for use of product described in paragraph (a)(2) of this section.
(c)
(d)
(i) For liquid feeds stored in recirculating tank systems: Recirculate immediately prior to use for no less than 10 minutes, moving not less than 1 percent of the tank contents per minute from the bottom of the tank to the top. Recirculate daily as described even when not used.
(ii) For liquid feeds stored in mechanical, air, or other agitation type tank systems: Agitate immediately prior to use for not less than 10 minutes, creating a turbulence at the bottom of the tank that is visible at the top. Agitate daily as described even when not used.
(2) A physically stable melengestrol acetate liquid Type B or C feed will not be subject to the requirements for mixing directions prescribed in paragraphs (c)(1) of this section provided it has a pH of 4.0 to 8.0 and contains a suspending agent(s) sufficient to maintain a viscosity of not less than 300 centipoises per second for 3 months.
(3) Combination Type B or C medicated feeds containing lasalocid must be labeled in accordance with § 558.311(d)(5) of this chapter.
(4) Liquid combination Type B or C medicated feeds containing melengestrol acetate and lasalocid must be manufactured in accordance with § 558.311(d) of this chapter.
(5) Combination Type B or C medicated feeds containing monensin must be labeled in accordance with § 558.355(d) of this chapter.
(6) Liquid combination Type B or C medicated feeds containing melengestrol acetate and monensin must be manufactured in accordance with § 558.355(f)(3)(i) of this chapter.
(7) Liquid combination Type B or C medicated feeds containing melengestrol acetate and tylosin must be manufactured in accordance with § 558.625(c) of this chapter.
(8) Liquid melengestrol acetate may not be mixed with oxytetracycline in a common liquid feed supplement.
(e)
(2) Melengestrol may also be used with ractopamine alone or in combination as in § 558.500 of this chapter.
For
(a)
(b)
(2)
(3)
(a)
(b)
(1) To No. 000986: 36.3 (for export only), 44, 45, 60, or 90.7 grams per pound for use as in paragraphs (f)(1)(i) and (f)(4) of this section.
(2) To 000986: 110 grams per lb., paragraphs (f)(1) (i), (iii), (iv), (v), (ix), and (x).
(3) To 000986: 44 grams per lb. with 18 grams per lb. of roxarsone, 110 grams per lb. with 45 grams per lb. of roxarsone, paragraph (f)(1)(ii).
(4) To No. 000986: 45, 60, or 90.7 grams per pound for use as in paragraph (f)(2) of this section.
(5) To 066104: 45 and 60 grams per pound, as monensin sodium provided by No. 000986, paragraphs (f)(1)(xiii), (xx), and (xxi) of this section.
(6) To No. 000986: 45, 60, or 90.7 grams per pound for use as in paragraph (f)(5) of this section.
(7) To 000986: 20, 30, 45, 60, 80, and 90.7 grams per pound, as monensin sodium, paragraph (f)(3) of this section.
(8) To 046573: 45 and 60 grams per pound, as monensin sodium provided by No. 000986, paragraph (f)(1)(xiv) of this section.
(9) To 046573: 45 and 60 grams per pound, as monensin sodium provided by No. 000986, paragraphs (f)(1)(xv) and (xvi) of this section.
(10) To 016592: 45 and 60 grams per pound, as monensin sodium, paragraph (f)(1)(xvii) of this section.
(11) To 046573: 45 and 60 grams per pound, as monensin sodium provided by No. 000986, paragraphs (f)(1)(xiv), (xviii), (xix), (xxiii), (xxiv), (xxv), (xxvi), and (xxvii) of this section.
(12) To 066104: 45 and 60 grams per pound, as monensin sodium provided by No. 000986, paragraph (f)(1)(xxii) of this section.
(13) To 021930: 60 and 80 grams per pound, paragraph (f)(3)(v) of this section.
(14) To 000986: 60, 80, and 90.7 grams per pound, as monensin sodium, paragraph (f)(6) of this section.
(c) [Reserved]
(d)
(2) - (3) [Reserved]
(4) Liquid Type B feeds shall bear an expiration date of 8 weeks after its date of manufacture.
(5) All Type A medicated articles containing monensin shall bear the following warning statement: When mixing and handling monensin Type A medicated articles, use protective clothing, impervious gloves, and a dust mask. Operators should wash thoroughly with soap and water after handling. If accidental eye contact occurs, immediately rinse thoroughly with water.
(6) All formulations containing monensin shall bear the following caution statement: Do not allow horses or other equines access to feed containing monensin. Ingestion of monensin by horses has been fatal.
(7) Type A medicated articles containing monensin intended for use in cattle and goats shall bear, in addition to the caution statement in paragraph (d)(6) of this section, the following statements:
(i) Monensin medicated cattle and goat feeds are safe for use in cattle and goats only. Consumption by unapproved species may result in toxic reactions.
(ii) Feeding undiluted or mixing errors resulting in high concentrations of monensin has been fatal to cattle and could be fatal to goats.
(iii) Must be thoroughly mixed in feeds before use.
(iv) Do not feed undiluted.
(v) Do not exceed the levels of monensin recommended in the feeding directions, as reduced average daily gains may result.
(vi) Do not feed to lactating goats.
(vii) If feed refusals containing monensin are fed to other groups of cattle, the concentration of monensin in the refusals and amount of refusals fed should be taken into consideration to prevent monensin overdosing.
(viii) A withdrawal period has not been established for this product in pre-ruminating calves. Do not use in calves to be processed for veal.
(ix) You may notice the following: Reduced voluntary feed intake in dairy cows fed monensin. This reduction increases with higher doses of monensin fed. Rule out monensin as the cause of reduced feed intake before attributing to other causes such as illness, feed management, or the environment. Reduced milk fat percentage in dairy cows fed monensin. This reduction increases with higher doses of monensin fed. Increased incidence of cystic ovaries and metritis in dairy cows fed monensin. Reduced conception rates, increased services per animal, and extended days open and corresponding calving intervals in dairy cows fed monensin. Have a comprehensive and
(x) Inadequate mixing (recirculation or agitation) of monensin liquid Type B or Type C medicated feeds has resulted in increased monensin concentration which has been fatal to cattle and could be fatal to goats.
(8) Type A medicated articles containing monensin intended for use in chickens, turkeys, and quail shall bear the following statements:
(i) Do not allow horses, other equines, mature turkeys, or guinea fowl access to feed containing monensin. Ingestion of monensin by horses and guinea fowl has been fatal.
(ii) Must be thoroughly mixed in feeds before use.
(iii) Do not feed undiluted.
(iv) Do not feed to laying chickens.
(v) Do not feed to chickens over 16 weeks of age.
(vi) For replacement chickens intended for use as cage layers only.
(vii) Some strains of turkey coccidia may be monensin tolerant or resistant. Monensin may interfere with development of immunity to turkey coccidiosis.
(viii) In the absence of coccidiosis in broiler chickens the use of monensin with no withdrawal period may limit feed intake resulting in reduced weight gain.
(9) Type B feeds containing monensin shall bear the statements specified in the following paragraphs of this section when intended for use in:
(i)
(ii)
(iii)
(iv)
(v)
(vi)
(10) Type C feeds containing monensin shall bear the statements specified in the following paragraphs of this section when intended for use in:
(i)
(ii)
(iii)
(iv)
(v)
(vi)
(11) Type B and Type C liquid feeds requiring recirculation or agitation that contain monensin and are intended for use in cattle (including dairy cows) and goats shall bear the caution statement specified in paragraph (d)(7)(x) of this section.
(12) Mixing directions for liquid feeds requiring recirculation or agitation:
(i) For liquid feeds stored in recirculating tank systems: Recirculate immediately prior to use for not less than 10 minutes, moving not less than 1 percent of the tank contents per minute from the bottom of the tank to the top. Recirculate daily as described even when not used.
(ii) For liquid feeds stored in mechanical, air, or other agitation-type tank systems: Agitate immediately prior to use for not less than 10 minutes, creating a turbulence at the bottom of the tank that is visible at the top. Agitate daily as described even when not used.
(e)
(f)
(1)
(
(
(ii)
(
(
(iii)
(
(
(iv)
(
(
(v)
(
(
(vi)
(
(
(vii)
(
(
(viii)
(
(
(ix)
(
(
(x)
(
(
(xi)
(
(
(xii)
(
(
(xiii)
(
(
(xiv)
(
(
(xv)
(
(
(xvi)
(
(
(xvii)
(
(
(xviii)
(
(
(xix)
(
(
(xx)
(
(
(xxi)
(
(
(xxii)
(
(
(xxiii)
(
(
(xxiv)
(xxv)
(
(
(xxvi)
(
(
(xxvii)
(
(
(xxviii)
(
(
(xxix)
(
(
(xxx)
(
(
(2)
(
(
(ii)
(
(
(iii)
(
(
(iv)
(
(
(v)
(
(
(vi)
(
(
(3)
(
(
(
(
(
(
(ii)
(
(
(iii)
(
(
(iv) [Reserved]
(v)
(
(
(vi)
(
(
(vii)
(
(
(ix)
(
(
(x)
(
(
(
(xi)
(
(
(xii)
(
(
(xiii)
(A)
(B)
(xiv)
(A)
(B)
(4)
(i)(
(ii)
(
(
(iii)
(
(
(iv)
(v)
(
(
(vi)
(
(
(vii)
(
(
(iv)
(
(
(5)
(ii)
(iii)
(6)
(
(
(
(
(
(
(ii) [Reserved]
(7) Monensin may also be used in combination with:
(i) Decoquinate alone or with tylosin as in § 558.195.
(ii) Melengestrol acetate alone or with tylosin as in § 558.342.
(iii) Ractopamine alone or in combination as in § 558.500.
(iv) Zilpaterol alone or in combination as in § 558.665.
For
(a)
(b)
(c)
(2) Consult your veterinarian before using in severely debilitated animals and for assistance in the diagnosis, treatment, and control of parasitism.
(d)
(2)
(ii)
(3)
(a)
(1) To 000986: 36, 45, 54, 72, and 90 grams per pound, paragraph (d)(1)(i) of this section.
(2) To 000986: 36, 45, 54, 72, and 90 grams per pound, with 10, 20, 50, and 80 percent roxarsone, paragraph (d)(1)(ii) of this section.
(3) To 000986: 36 grams per pound, with 36 grams per pound nicarbazin, paragraph (d)(1)(iii) of this section.
(4) To 016592: 36, 45, 54, 72, and 90 grams per pound, with 2 and 10 grams per pound bambermycins, paragraph (d)(1)(iv) of this section.
(5) To 016592: 45 grams per pound, with 4 and 10 grams per pound bambermycins, and 45.4, 90, and 227 grams per pound roxarsone, paragraph (d)(1)(vii) of this section.
(6) To 046573: 45 grams per pound with 10, 25, 30, 40, 50, 60, or 75 grams per pound bacitracin methylene disalicylate and 45.4, 90, or 227 grams per pound roxarsone, paragraphs (d)(1)(viii) and (d)(1)(ix) of this section.
(7) To 046573: 36, 45, 54, 72, or 90 grams per pound, with 10, 25, 40, or 50 grams per pound bacitracin zinc, paragraph (d)(1)(x) of this section.
(b)
(c) [Reserved]
(d)
(1)
(A)
(B)
(ii)
(A)
(B)
(iii)
(A)
(B)
(iv)
(A)
(B)
(v)
(A)
(B)
(vi)
(A)
(B)
(vii)
(A)
(B)
(viii)
(A)
(B)
(ix)
(A)
(B)
(x)
(A)
(B)
(xi)
(A)
(B)
(2) Narasin may also be used for broilers in combination with:
(i) Nicarbazin with lincomycin as in § 558.366.
(ii) Nicarbazin and bacitracin methylene disalicylate as in § 558.366.
(iii) Bacitracin methylene disalicylate, nicarbazin, and roxarsone as in § 558.366.
(iv) Nicarbazin and roxarsone as in § 558.366.
For
(a)
(b)
(c) [Reserved]
(d)
(a)
(b)
(c)
(d)
(1)
(ii)
(iii)
(2)
(ii)
(iii)
(a)
(b)
(c)
(d)
(a)
(b)
(c) [Reserved]
(d)
(1)
(ii)
(iii)
(2)
(ii)
(iii)
(a)
(b)
(c)
(1)
(i)
(ii)
(2)
(i)
(ii)
(a)
(b)
(c)
(1)
(
(
(ii)
(
(
(2)
(
(
(ii)
(
(
(iii)
(
(
(3)
(ii)
(iii)
(4)
(ii)
(iii)
(a)
(b)
(c)
(1)
(i)
(ii)
(2)
(i)
(ii)
(a)
(b)
(c)
(d)
(1)
(ii)
(2)
(ii)
(a)
(1) 10, 20, 30, 50, 100, and 200 grams per pound to No. 066104 in § 510.600(c) of this chapter.
(2) 50, 100, and 200 grams per pound to No. 048164 in § 510.600(c) of this chapter.
(b)
(2) The articles in paragraph (a)(1) of this section contain an amount of mono-alkyl (C
(3) 50-, 100-, and 200-gram per pound articles in paragraph (a)(2) of this section contain oxytetracycline dihydrate expressed in terms of an equivalent amount of oxytetracycline hydrochloride. Another 100-gram per pound article in paragraph (a)(2) of this section contains oxytetracycline hydrochloride.
(c)
(d)
(2)
(3)
(4)
(5)
(6) Oxytetracycline may be used in accordance with the provisions of this section in the combinations as follows:
(i) Carbadox as in § 558.115.
(ii) Lasalocid as in § 558.311.
(iii) Melengestrol acetate as in § 558.342.
(iv) Robenidine hydrochloride as in § 558.515.
(v) Salinomycin as in § 558.550.
(a)
(b)
(c)
(d)
(2)
(3)
(4)
(a)
(b)
(c) Related tolerances. See § 556.510 of this chapter.
(d)
(2) Penicillin may be used in accordance with the provisions of this section in the combinations provided as follows:
(i) Amprolium in accordance with § 558.55.
(ii) Amprolium plus ethopatbate in accordance with § 558.58.
(iii) Hygromycin B in accordance with § 558.274.
(iv) Nicarbazin alone or with roxarsone as in § 558.366.
(v) Roxarsone and zoalene in accordance with § 558.680.
(vi) Zoalene in accordance with § 558.680.
(a)
(2) Liquid Type A medicated articles: 99.5 percent to 000069 in § 510.600(c) of this chapter.
(b)
(2) Poloxalene dry Type A article and liquid Type A article must be thoroughly blended and evenly distributed in feed prior to use. This may be accomplished by adding the Type A article to a small quantity of feed, mixing thoroughly, then adding this mixture to the remaining feed and again mixing thoroughly. Dosage is 1 gram of poloxalene per 100 pounds of body weight daily and continued during exposure to bloat producing conditions. If bloating conditions are severe, the dose is doubled. Treatment should be started 2 to 3 days before exposure to bloat-producing conditions. Repeat dosage if animals are exposed to bloat-producing conditions more than 12 hours after the last treatment. Do not exceed the higher dosage levels in any 24-hour period.
(a)
(b)
(2) For control of legume (alfalfa, clover) bloat in cattle grazing of prebloom legumes, use 10.00 grams of poloxalene per pound of liquid Type C feed (2.2 percent weight/weight). Each animal must consume 0.15 pound of Type C feed per 100 pounds of body weight daily for adequate protection. If consumption exceeds 0.2 pound of Type C feed per 100 pounds of body weight daily, cattle should be changed to a Type C feed containing 7.5 grams of poloxalene per pound.
(3) Poloxalene liquid Type A article must be thoroughly blended and evenly distributed into a liquid Type C feed and offered to cattle in a covered liquid Type C feed feeder with lick wheels. The formula for the liquid Type C feed, on a weight/weight basis, is as follows: Ammonium polyphosphate 2.66 percent, phosphoric acid (75 percent) 3.37 percent, sulfuric acid 1.00 percent, water 10.00 percent, and molasses sufficient to make 100.00 percent, vitamins A and D and/or trace minerals may be added. One free-turning lick wheel per 25 head of cattle must be provided.
(4) The medicated liquid Type C feed must be introduced at least 2 to 5 days before legume consumption to accustom the cattle to the medicated liquid Type C feed and to lick wheel feedings. If the medicated liquid wheel Type C feed feeding is interrupted, this 2- to 5-day introductory feeding should be repeated.
(a)
(b)
(1) No. 066104: 9.6, 19.2, 48, and 80 grams per pound for use as in paragraph (e)(1) of this section.
(2) [Reserved]
(3) Nos. 010439, 011490, 011749, 016968, 021930, 017790, 043733, and 049685: 9.6 and 19.2 grams per pound for use as in paragraphs (e)(1)(i) through (e)(1)(iii) of this section.
(4) [Reserved]
(5) No. 051311: 19.2 and 48 grams per pound for use as in paragraphs (e)(1)(i) through (e)(1)(iii) of this section.
(6) Nos. 034936 and 046987: 9.6 and 19.2 grams per pound for use as in paragraphs (e)(1)(i) and (e)(1)(ii) of this section.
(7) Nos. 000069 and 017135: 48 grams per pound for use as in paragraph (e)(2) of this section.
(c)
(d)
(2) Do not mix in Type B or Type C medicated feeds containing bentonite.
(e)
(1)
(A)
(B)
(ii)
(A)
(B)
(iii)
(A)
(B)
(iv)
(A)
(B)
(v)
(A)
(B)
(vi)
(A)
(B)
(vii)
(A)
(B)
(viii)
(A)
(B)
(ix)
(A)
(B)
(x)
(A)
(B)
(xi)
(A)
(B)
(xii)
(A)
(B)
(C)
(2)
(A)
(B)
(ii) [Reserved]
For
(a)
(b)
(c)
(d)
(i) Ractopamine may increase the number of injured and/or fatigued pigs during marketing.
(ii) “Not for use in breeding swine.”
(iii) No increased benefit has been shown when ractopamine concentrations in the diet are greater than 4.5 g/ton.
(2) Tylosin in combinations as tylosin phosphate.
(3) Ractopamine liquid Type B cattle feeds may be manufactured from dry ractopamine Type A articles. The liquid Type B feeds must be maintained at a pH of 4.5 to 7.5 or, if in combination with monensin and/or tylosin, at a pH of 4.5 to 6.0. Mixing directions for liquid Type B feeds requiring recirculation or agitation: Recirculate immediately prior to use for not less than 10 minutes, moving not less than 1 percent of the tank contents per minute from the bottom of the tank to the top. Recirculate daily as described even when not used.
(e)
(2)
(a)
(b)
(c)
(d)
For
(a)
(b)
(1) No. 046573 for use of 10, 20, and 50 percent Type A medicated articles as in paragraph (d)(1)(i) of this section.
(2) No. 046573 for use of 10, 20, 50, and 80 percent Type A medicated articles as in paragraphs (d)(1) through (d)(3) of this section.
(c)
(d)
(2)
(3)
(4)
(i) Aklomide as in § 558.35.
(ii) Amprolium as in § 558.55.
(iii) Amprolium and ethopabate as in § 558.58.
(iv) Bacitracin methylene disalicylate as in § 558.76.
(v) Bacitracin zinc as in § 558.78.
(vi) Bambermycins and bambermycins plus certain anticoccidials as in § 558.95.
(vii) Chlortetracycline as in § 558.128.
(viii) Clopidol as in § 558.175.
(ix) Decoquinate alone or in combination as in § 558.195.
(x) Diclazuril alone or in combination as in § 558.198.
(xi) Halofuginone alone or in combination as in § 558.265.
(xii) Lasalocid alone or in combination as in § 558.311.
(xiii) Monensin alone or in combination as in § 558.355.
(xiv) Narasin alone or in combination as in § 558.363.
(xv) Nequinate as in § 558.365.
(xvi) Nicarbazin alone or in combination as in § 558.366.
(xvii) Nitromide and sulfanitran as in § 558.376.
(xviii) Penicillin and zoalene as in § 558.680.
(xix) Robenidine hydrochloride as in § 558.515.
(xx) Salinomycin alone or in combination as in § 558.550.
(xxi) Semduramicin alone or in combination as in § 558.555.
(xxii) Sulfadimethoxine, ormetoprim as in § 558.575.
(xxiii) Zoalene alone or in combination as in § 558.680.
For
(a)
(b)
(1) No. 046573 for use as in paragraph (d) of this section.
(2) No. 016592 for use as in paragraphs (d)(1)(i), (d)(1)(iii) through (d)(1)(xvi), (d)(1)(xxiii) and (d)(1)(xxiv), (d)(2)(i), (d)(3)(i), and (d)(4) of this section.
(3) No. 048164 for use as in paragraphs (d)(1)(xv) and (d)(1)(xvi) of this section.
(c) [Reserved]
(d)
(i)(
(
(
(ii)(
(
(
(iii)(
(
(
(iv)(
(
(
(v)(
(
(
(vi)(
(
(
(vii)(
(
(
(viii)(
(
(
(ix)(
(
(
(x)(
(
(
(xi)(
(
(
(xii) (
(
(
(xiii)(
(
(
(xiv)(
(
(
(xv)(
(
(
(xvi)(
(
(
(xvii)(A)
(B)
(C)
(xviii)(A)
(B)
(C)
(xix)(A)
(B)
(C)
(xx)(A)
(B)
(C)
(xxi)(A)
(B)
(C)
(xxii)
(A)
(B)
(xxiii)
(
(
(xxiv)
(
(
(2)
(
(
(ii) [Reserved]
(3)
(i)(A)
(B)
(C)
(ii)
(A)
(B)
(iii)
(A)
(B)
(iv)(A)
(B)
(C)
(v)
(A)
(B)
(vi)(A)
(B)
(C)
(vii)
(A)
(B)
(4)
(i)
(
(
(ii) [Reserved]
For
(a)
(1) 22.7 grams (g) per pound (lb) (50 g/kilogram (kg)) semduramicin (as semduramicin sodium).
(2) 22.7 g/lb (50 g/kg) semduramicin (as semduramicin sodium biomass).
(b)
(c)
(d)
(e)
(a)
(1) 25 percent sufadimethoxine and 15 percent ormetoprim to 046573 for use for poultry as in paragraphs (d)(1), (d)(2), (d)(3), (d)(4), and (d)(7) of this section.
(2) 25 percent sulfadimethoxine and 5 percent ormetoprim to No. 015331 for use for fish as in paragraphs (d)(5) and (d)(6) of this section.
(b)
(c) [Reserved]
(d)
(1)
(
(
(ii)
(
(
(2)
(ii)
(iii)
(3)
(ii)
(iii)
(4)
(
(
(ii)
(
(
(5)
(ii)
(iii)
(6)
(ii)
(iii)
(7)
(ii)
(iii)
(a)
(b)
(c)
(1)
(ii)
(iii)
(2)
(ii)
(iii)
(a)
(b)
(c)
(1)
(2)
(3)
(a)
(b)
(c)
(2) [Reserved]
(d)
(1)
(
(
(ii)
(
(
(iii)
(
(
(2)
(
(
(ii)
(
(
(3)
(
(
(ii) [Reserved]
(4)
$(
$(
(ii)
(
$(
(a)
(b)
(c)
(d)
(2) Not for use in swine weighing over 250 pounds.
(3) Use as sole source of tiamulin.
(e)
(2) [Reserved]
(a)
(b)
(c)
(d)
(1)
(
(
(ii)
(
(
(2)
(ii)
(iii)
(3)
(ii)
(iii)
(4)
(ii)
(iii)
(5)
(ii)
(iii)
(a)
(b)
(c)
(2) The expiration date of VFDs for tilmicosin must not exceed 90 days from the time of issuance. VFDs for tilmicosin shall not be refilled.
(3) Do not use in Type B or Type C medicated feeds containing bentonite.
(d)
(e)
(1)
(2)
(3)
(a)
(b)
(1) To 000986: 10, 40, 100 grams per pound, paragraphs (f)(1) (i) through (vi) of this section.
(2) [Reserved]
(3) To 043733: 20 and 40 grams per pound, paragraphs (f)(1)(i) through (vi) of this section.
(4) [Reserved]
(5) To No. 051311: 0.4, 0.8, 1, and 8 grams per pound, paragraph (f)(1)(vi)(
(6)-(7) [Reserved]
(8) To 035369: 4 and 10 grams per pound, paragraph (f)(1)(vi)(
(9) [Reserved]
(10) To 021930: 0.4, 0.8, and 1.6 grams per pound, paragraph (f)(1)(vi)(
(11) [Reserved]
(12) To 021930: 2 grams per pound, paragraph (f)(1)(vi)(
(13) [Reserved]
(14) To 016968: 1, 2, 4, 8, and 10 grams per pound, paragraphs (f)(1) (i), (iii), (iv), and (vi) of this section; 20, 25, 40, and 100 grams per pound, paragraphs (f)(1) (i) through (vi) of this section.
(15)-(24) [Reserved]
(25) To 066104: 4, 8, and 10 grams per pound, paragraph (f)(1)(vi)(
(26)-(32) [Reserved]
(33) To 034936: 0.8 and 2 grams per pound, paragraph (f)(1)(vi)(
(34) [Reserved]
(35) To 039741: 2 and 10 grams per pound, paragraph (f)(1)(vi)(
(36)-(37) [Reserved]
(38) To 053740: 1 gram per pound, paragraph (f)(1)(vi)(
(39) To 061623: 10 grams per pound, paragraph (f)(1)(vi)(
(40) To 035955: 10 grams per pound, paragraph (f)(1)(vi)(
(41) [Reserved]
(42) To 010439: 0.4, 0.5, and 2 grams per pound, paragraph (f)(1)(vi) (
(43)-(44) [Reserved]
(45) To 017139: 4 and 10 grams per pound, paragraph (f)(1)(vi)(
(46)-(47) [Reserved]
(48) To 017790: 5, 10, 20, and 40 grams per pound, paragraphs (f)(1) (i) through (vi) of this section.
(49)-(53) [Reserved]
(54) To 046573: 5, 10, 20, and 40 grams per pound, paragraphs (f)(1) (i) through (vi) of this section.
(55)-(56) [Reserved]
(57) To 028459: 0.4 and 10 grams per pound; paragraph (f)(1)(vi)(
(58)-(62) [Reserved]
(63) To 046987: 5, 10, 20, and 40 grams per pound, paragraphs (f)(1) (i) through (vi) of this section.
(64)-(65) [Reserved]
(66) To 024174: 5, 10, 20, and 40 grams per pound, paragraphs (f)(1) (i) through (vi) of this section.
(67) To 027190: 2 grams per pound; paragraph (f)(1)(vi)(
(68)-(76) [Reserved]
(77) To 050639: 5, 10, 20, and 40 grams per pound, paragraphs (f)(1) (i) through (vi) of this section.
(78) To 050972: 0.36, 0.4, 0.72, and 0.8 gram per pound, paragraph (f)(1)(vi)(
(79) [Reserved]
(80) To 049685: 5, 10, 20, and 40 grams per pound, paragraphs (f)(1) (i) through (vi) of this section.
(81)-(82) [Reserved]
(83) To 046573: 5-, 10-, 20-, and 40-grams per pound, paragraphs (f)(1) (i) through (vi) of this section.
(84) [Reserved]
(85) To 047126: 10, 40, and 100 grams per pound, paragraphs (f)(1) (i) through (vi) of this section.
(86)-(88) [Reserved]
(89) To 048164: 5, 10, 20, and 40 grams per pound, paragraph (f)(1) (i) through (vi) of this section.
(c)
(i) For liquid feeds stored in recirculating tank systems: Recirculate immediately prior to use for not less than 10 minutes, moving not less than 1 percent of the tank contents per minute from the bottom of the tank to the top. Recirculate daily as described even when not used.
(ii) For liquid feeds stored in mechanical, air, or other agitation-type tank systems: Agitate immediately prior to use for not less than 10 minutes, creating a turbulence at the bottom of the tank that is visible at the top. Agitate daily as described even when not used.
(2) Tylosin liquid Type B medicated feeds used to make Type C medicated feeds for cattle may be manufactured from tylosin Type A medicated articles according to the following mixing directions:
(i) Presolubilize tylosin in 50 percent urea for approximately 1 hour prior to adding any feed components or other active ingredients.
(ii) Maintain a pH between 4.5 and 6.0.
(3) Tylosin liquid Type B medicated feeds must bear an expiration date of 8 weeks after the date of manufacture.
(d) [Reserved]
(e)
(f)
(i)
(
(
(ii)
(
(
(iii)
(
(
(iv)
(
(
(v)
(
(
(vi)
(
(
(
(
(
(
(
(
(
(
(
(vi) Pyrantel tartrate in accordance with § 558.485.
(
(
(
(2) Tylosin may also be used in combination with:
(i) Decoquinate and monensin as in § 558.195.
(ii) Hygromycin B as in § 558.274.
(iii) Melengestrol acetate alone or in combination with certain ionophores as in § 558.342.
(iv) Monensin as in § 558.355.
(v) Narasin as in § 558.363.
(vi) Pyrantel tartrate as in § 558.485.
(vii) Ractopamine alone or in combination as in § 558.500.
(viii) Salinomycin as in § 558.550.
(ix) Zilpaterol alone or in combination as in § 558.665.
For
(a) [Reserved]
(b)
(1) To 000986: 40 grams per pound each, paragraph (f)(2)(i).
(2) To 000986: 10 grams per pound each, paragraph (f)(2)(i).
(3)-(4) [Reserved]
(5) To No. 051311: 40 grams per pound each, paragraph (f)(2)(ii) of this section.
(6) To 017139: 4, 10, or 20 grams per pound each, paragraph (f)(2)(ii) of this section.
(7) To 021930: 2 grams per pound each, paragraph (f)(2)(i) of this section; 5, 10, 20, or 40 grams per pound each, paragraph (f)(2)(ii) of this section.
(8) [Reserved]
(9) [Reserved]
(10) To 000986, 010439, 011749, 016968, 024174, 030841, 034936, 035098, 043733, 046573, 046987, 048164, and 051359: 5, 10, 20, or 40 grams per pound each, paragraph (f)(2)(ii) of this section.
(c)-(d) [Reserved]
(e)
(f)
(1)
(2)
(ii) Maintaining weight gains and feed efficiency in the presence of atrophic rhinitis; lowering the incidence and severity of
(3)
For
(a)
(2) 2.2 percent activity (10 grams per pound) to 046573, 016968, and 017790 in § 510.600(c) of this chapter for use as in paragraphs (d)(1)(iv) and (d)(1)(v) of this section.
(b)
(c)
(2) Dilute Type A article with at least 10 pounds of a feed ingredient prior to final mixing in 1 ton of Type C feed.
(d)
(i) 100 grams per ton for 2 weeks, for treatment of swine dysentery in nonbreeding swine over 120 pounds.
(ii) 100 grams per ton for 2 weeks, 50 grams per ton thereafter, for treatment and control of swine dysentery in swine up to 120 pounds.
(iii) 25 grams per ton, as an aid in control of dysentery in swine up to 120 pounds. For use in animals or on premises with a history of swine dysentery but where symptoms have not yet occurred.
(iv) 10 grams per ton from weaning up to 120 pounds for increased rate of weight gain and improved feed efficiency, followed by 5 grams per ton to market weight for increased rate of weight gain and improved feed efficiency. For continuous use from weaning to market weight.
(v) 10 grams per ton from weaning up to 120 pounds for increased rate of weight gain and improved feed efficiency, followed by 5 to 10 grams per ton to market weight for increased rate of weight gain. For continuous use from weaning to market weight.
(2)
(i) 5 to 15 grams per ton for increased rate of weight gain, for use in broiler chickens, not for use in layers.
(ii) 5 grams per ton for increased rate of weight gain and improved feed efficiency in broiler chickens, not for use in layers.
(iii) 20 grams per ton for prevention of necrotic enteritis caused by
(iv) 10 to 20 grams per ton for increased rate of weight gain and improved feed efficiency in growing turkeys.
(3)
(i) 16.0 to 22.5 grams per ton to provide 100 to 340 milligrams per head per day for increased rate of weight gain.
(ii) 13.5 to 16.0 grams per ton to provide 85 to 240 milligrams per head per day for reduction of incidence of liver abscesses.
(iii) 11.0 to 16.0 grams per ton to provide 70 to 240 milligrams per head per day for improved feed efficiency.
(iv) Feed continuously as sole ration to cattle fed in confinement for slaughter. Not for use in animals intended for breeding.
(4) Virginiamycin may be used in combination with:
(i) Amprolium and ethopabate as in § 558.58.
(ii) Diclazuril as in § 558.198.
(iii) Halofuginone as in § 558.265.
(iv) Lasalocid as in § 558.311.
(v) Monensin alone or with roxarsone as in § 558.355.
(vi) Salinomycin alone or with roxarsone as in § 558.550.
(vii) Semduramicin alone or with roxarsone as in § 558.555.
For
(a)
(b)
(c)
(d)
(i) Do not allow horses or other equines access to feed containing zilpaterol.
(ii) Not for use in animals intended for breeding.
(iii) Do not use in veal calves.
(2) Type B Liquid Feeds can be manufactured containing 68 to 680 g zilpaterol hydrochloride/ton. The liquid Type B feeds must be maintained at a pH of 3.8 to 7.5. For liquid feeds stored in recirculating tank systems: Recirculate immediately prior to use for not less than 10 minutes, moving not less than 1 percent of the tank contents per minute from the bottom of the tank to the top. Recirculate daily as described even when not used. For liquid feeds stored in mechanical, air or other agitation-type tank systems: Agitate immediately prior to use for not less than 10 minutes, creating a turbulence at the bottom of the tank that is visible at the top. Agitate daily as described even when not used.
(e)
(a)
(b)
(c)
(d)
(2) Zoalene may also be used in combination with roxarsone as in § 558.530.
21 U.S.C. 321, 341, 342, 346a, 348, 371.
(a)
(b)
(c)
(d) As used in this part, the term
(e)
(f)
(g) The word
(h)
(i)
(1) The probable consumption of the substance and of any substance formed in or on food because of its use;
(2) The cumulative effect of the substance in the diet, taking into account any chemically or pharmacologically related substance or substances in such diet;
(3) Safety factors which, in the opinion of experts qualified by scientific training and experience to evaluate the safety of food and food ingredients, are generally recognized as appropriate.
(j) The term
(k)
(l)
(m)
(a) Over the years the Food and Drug Administration has given informal written opinions to inquirers as to the safety of articles intended for use as components of, or in contact with, food. Prior to the enactment of the Food Additives Amendment of 1958 (Pub. L. 85-929, Sept. 6, 1958), these opinions were given pursuant to section 402(a)(1) of the Federal Food, Drug, and Cosmetic Act, which reads in part: “A food shall be deemed to be adulterated if it bears or contains any poisonous or deleterious substance which may render it injurious to health”.
(b) Since enactment of the Food Additives Amendment, the Food and Drug Administration has advised such inquirers that an article:
(1) Is a food additive within the meaning of section 201(s) of the act; or
(2) Is generally recognized as safe (GRAS); or
(3) Has prior sanction or approval under that amendment; or
(4) Is not a food additive under the conditions of intended use.
(c) In the interest of the public health, such articles which have been considered in the past by the Food and Drug Administration to be safe under the provisions of section 402(a)(1), or to be generally recognized as safe for their intended use, or to have prior sanction or approval, or not to be food additives under the conditions of intended use, must be reexamined in the light of current scientific information and current principles for evaluating the safety of food additives if their use is to be continued.
(d) Because of the time span involved, copies of many of the letters in which the Food and Drug Administration has expressed an informal opinion concerning the status of such articles may no longer be in the file of the Food and Drug Administration. In the absence of information concerning the names and uses made of all the articles referred to in such letters, their safety of use cannot be reexamined. For this reason all food additive status opinions of the kind described in paragraph (c) of this section given by the Food and Drug Administration are hereby revoked.
(e) The prior opinions of the kind described in paragraph (c) of this section will be replaced by qualified and current opinions if the recipient of each such letter forwards a copy of each to the Department of Health and Human Services, Food and Drug Administration, Center for Veterinary Medicine, Office of Surveillance and Compliance (HFV-200), 7500 Standish Pl., Rockville, MD 20855, along with a copy of his letter of inquiry, on or before July 23, 1970.
(f) This section does not apply to food additive status opinion letters pertaining to articles that were considered by the Food and Drug Administration
Regulations providing for the use of food packaging materials as prior sanctioned in part 181 of this chapter are incorporated in Subchapter E as applicable to packaging materials used for animal feed and pet food.
Regulations providing for the use of food packaging materials in parts 174 through 179 of this chapter are incorporated in Subchapter E as applicable to packaging materials used for animal feed and pet food.
(a) The Commissioner upon his own initiative may propose the issuance of a regulation prescribing, with respect to any particular use of a food additive, the conditions under which such additive may be safely used. Notice of such proposal shall be published in the
(b) Action upon a proposal made by the Commissioner shall proceed as provided in part 10 of this chapter.
A food additive or food containing a food additive intended for investigational use by qualified experts shall be exempt from the requirements of section 409 of the act under the following conditions:
(a) If intended for investigational use in vitro or in laboratory research animals, it bears a label which states prominently, in addition to the other information required by the act, the warning:
(b) If intended for use in animals other than laboratory research animals and if the edible products of the animals are to be marketed as food, permission for the marketing of the edible products as food has been requested by the sponsor, and authorization has been granted by the Food and Drug Administration in accordance with § 511.1 of this chapter or by the Department of Agriculture in accordance with 9 CFR 309.17, and it bears a label which states prominently, in addition to the other information required by the act, the warning:
Edible products of investigational animals are not to be used for food unless authorization has been granted by the U.S. Food and Drug Administration or by the U.S. Department of Agriculture.
(c) If intended for nonclinical laboratory studies in food-producing animals, the study is conducted in compliance with the regulations set forth in part 58 of this chapter.
(a) Food additives that cause similar or related pharmacological effects will be regarded as a class, and in the absence of evidence to the contrary, as having additive toxic effects and will be considered as related food additives.
(b) Tolerances established for such related food additives may limit the amount of a common component that may be present, or may limit the amount of biological activity (such as cholinesterase inhibition) that may be present or may limit the total amount
(c) Where food additives from two or more chemicals in the same class are present in or on a food, the tolerance for the total of such additives shall be the same as that for the additive having the lowest numerical tolerance in this class, unless there are available methods that permit quantitative determination of the amount of each food additive present or unless it is shown that a higher tolerance is reasonably required for the combined additives to accomplish the physical or technical effect for which such combined additives are intended and that the higher tolerance will be safe.
(d) Where residues from two or more additives in the same class are present in or on a food and there are available methods that permit quantitative determination of each residue, the quantity of combined residues that are within the tolerance may be determined as follows:
(1) Determine the quantity of each residue present.
(2) Divide the quantity of each residue by the tolerance that would apply if it occurred alone, and multiply by 100 to determine the percentage of the permitted amount of residue present.
(3) Add the percentages so obtained for all residues present.
(4) The sum of the percentages shall not exceed 100 percent.
When pesticide chemical residues occur in processed foods due to the use of raw agricultural commodities that bore or contained a pesticide chemical in conformity with an exemption granted or a tolerance prescribed under section 408 of the act, the processed food will not be regarded as adulterated so long as good manufacturing practice has been followed in removing any residue from the raw agricultural commodity in the processing (such as by peeling or washing) and so long as the concentration of the residue in the processed food when ready to eat is not greater than the tolerance prescribed for the raw agricultural commodity. But when the concentration of residue in the processed food when ready to eat is higher than the tolerance prescribed for the raw agricultural commodity, the processed food is adulterated unless the higher concentration is permitted by a tolerance obtained under section 409 of the act. For example, if fruit bearing a residue of 7 parts per million of DDT permitted on the raw agricultural commodity is dried and a residue in excess of 7 parts per million of DDT results on the dried fruit, the dehydrated fruit is adulterated unless the higher tolerance for DDT is authorized by the regulations in this part. Food that is itself ready to eat, and which contains a higher residue than allowed for the raw agricultural commodity, may not be legalized by blending or mixing with other foods to reduce the residue in the mixed food below the tolerance prescribed for the raw agricultural commodity.
(a) In reaching a decision on any petition filed under section 409 of the act, the Commissioner will give full consideration to the specific biological properties of the compound and the adequacy of the methods employed to demonstrate safety for the proposed use, and the Commissioner will be guided by the principles and procedures for establishing the safety of food additives stated in current publications of the National Academy of Sciences-National Research Council. A petition will not be denied, however, by reason of the petitioner's having followed procedures other than those outlined in the publications of the National Academy of Sciences-National Research Council if, from available evidence, the Commissioner finds that the procedures used give results as reliable as, or more reliable than, those reasonably to be expected from the use of the outlined procedures. In reaching a decision, the Commissioner will give due weight to the anticipated levels and patterns of consumption of the additive specified or reasonably inferable. For the purposes of this section, the principles for evaluating safety of additives set forth in the above-mentioned publications will apply to any substance
(b) Upon written request describing the proposed use of an additive and the proposed experiments to determine its safety, the Commissioner will advise a person who wishes to establish the safety of a food additive whether he believes the experiments planned will yield data adequate for an evaluation of the safety of the additive.
(a) General recognition of safety may be based only on the views of experts qualified by scientific training and experience to evaluate the safety of substances directly or indirectly added to food. The basis of such views may be either (1) scientific procedures or (2) in the case of a substance used in food prior to January 1, 1958, through experience based on common use in food. General recognition of safety requires common knowledge about the substance throughout the scientific community knowledgeable about the safety of substances directly or indirectly added to food.
(b) General recognition of safety based upon scientific procedures shall require the same quantity and quality of scientific evidence as is required to obtain approval of a food additive regulation for the ingredient. General recognition of safety through scientific procedures shall ordinarily be based upon published studies which may be corroborated by unpublished studies and other data and information.
(c) General recognition of safety through experience based on common use in food prior to January 1, 1958, may be determined without the quantity or quality of scientific procedures required for approval of a food additive regulation. General recognition of safety through experience based on common use in food prior to January 1, 1958, shall ordinarily be based upon generally available data and information. An ingredient not in common use in food prior to January 1, 1958, may achieve general recognition of safety only through scientific procedures.
(d) The food ingredients listed as GRAS in part 582 of this chapter do not include all substances that are generally recognized as safe for their intended use in food. Because of the large number of substances the intended use of which results or may reasonably be expected to result, directly or indirectly, in their becoming a component or otherwise affecting the characteristics of food, it is impracticable to list all such substances that are GRAS. A food ingredient of natural biological origin that has been widely consumed for its nutrient properties in the United States prior to January 1, 1958, without known detrimental effects, which is subject only to conventional processing as practiced prior to January 1, 1958, and for which no known safety hazard exists, will ordinarily be regarded as GRAS without specific inclusion in part 582 of this chapter.
(e) A food ingredient that is not GRAS or subject to a prior sanction requires a food additive regulation promulgated under section 409 of the act before it may be directly or indirectly added to food.
(f) A food ingredient that is listed as GRAS in part 582 of this chapter shall be regarded as GRAS only if, in addition to all the requirements in the applicable regulation, it also meets all of the following requirements:
(1) It complies with any applicable specifications, or in the absence of such specifications, shall be of a purity suitable for its intended use.
(2) It performs an appropriate function in the food or food-contact article in which it is used.
(3) It is used at a level no higher than necessary to achieve its intended purpose in that food or, if used as a component of a food-contact article, at a level no higher than necessary to achieve its intended purpose in that article.
(g) New information may at any time require reconsideration of the GRAS status of a food ingredient. Any change in status shall be accomplished pursuant to § 570.38.
(h) If a substance is affirmed as GRAS pursuant to § 570.35 and listed in a regulation with no limitation other than good manufacturing practice, it
(i) If an ingredient is affirmed as GRAS pursuant to § 570.35 and listed in a regulation with specific limitation(s), it may be used in food only within such limitation(s) (including the category of food(s), the functional use(s) of the ingredient, and the level(s) of use). Any use of such and ingredient not in full compliance with each such established limitation shall require a food additive regulation.
(j) Pursuant to § 570.35, a food ingredient may be affirmed as GRAS and listed in a regulation for a specific use(s) without a general evaluation of use of the ingredient. In addition to the use(s) specified in the regulation, other uses of such an ingredient may also be GRAS. Any affirmation of GRAS status for a specific use(s), without a general evaluation of use of the ingredient, is subject to reconsideration upon such evaluation.
(a) The Commissioner, either on his initiative or on the petition of an interested person, may affirm the GRAS status of substances that directly or indirectly become components of food.
(b)(1) If the Commissioner proposes on his own initiative that a substance is entitled to affirmation as GRAS, he will place all of the data and information on which he relies on public file in the office of the Division of Dockets Management and will publish in the
(2) The
(3) The Commissioner will evaluate all comments received. If he concludes that there is convincing evidence that the substance is GRAS as defined in § 570.3(k), he will publish a notice in the
(4) If, after evaluation of the comments, the Commissioner concludes that there is a lack of convincing evidence that the substance is GRAS and that it should be considered a food additive subject to section 409 of the act, he shall publish a notice thereof in the
(c)(1) Persons seeking the affirmation of GRAS status of substances as provided for in § 570.30(e), except those subject to the NAS-NRC GRAS list survey (36 FR 20546), shall submit a petition for GRAS affirmation pursuant to part 10 of this chapter. Such petition shall contain information to establish that the GRAS criteria as set forth in § 570.30(b) have been met, in the following form:
(i) Description of the substance, including:
(
(
(
(
(
(
(
(
(ii) Use of the substance, including:
(
(
(
(iii) Methods for detecting the substance in food, including:
(
(
(iv) Information to establish the safety and functionality of the substance in food. Published scientific literature, evidence that the substance is identical to a GRAS counterpart of natural biological origin, and other data may be submitted to support safety. Any adverse information or consumer complaints shall be included. Complete bibliographic references shall be provided where a copy of the article is not provided.
(v) A statement signed by the person responsible for the petition that to the best of his knowledge it is a representative and balanced submission that includes unfavorable information, as well as favorable information, known to him pertinent to the evaluation of the safety and functionality of the substance.
(vi) If nonclinical laboratory studies are involved, additional information and data submitted in support of filed petitions shall include, with respect to each nonclinical study, either a statement that the study was conducted in compliance with the requirements set forth in part 58 of this chapter, or, if the study was not conducted in compliance with such regulations, a brief statement of the reason for the noncompliance.
(vii) [Reserved]
(viii) A claim for categorical exclusion under § 25.30 or 25.32 of this chapter or an environmental assessment under § 25.40 of this chapter.
(2) Within 30 days after the date of filing the petition, the Commissioner will place the petition on public file in the Division of Dockets Management and will publish a notice of filing in the
(3) The notice of filing in the
(4) The Commissioner will evaluate the petition and all available information including all comments received. If the petition and such information provide convincing evidence that the substance is GRAS as defined in § 570.3, he will publish an order in the
(5) If, after evaluation of the petition and all available information, the Commissioner concludes that there is a lack of convincing evidence that the substance is GRAS and that it should be considered a food additive subject to section 409 of the act, he shall publish a notice thereof in the
(6) The notice of filing in the
(a) The Commissioner may, in accordance with § 570.35 (b)(4) or (c)(5),
(b)(1) The Commissioner, on his own initiative or on the petition of any interested person, pursuant to part 10 of this chapter, may issue a notice in the
(2) The
(3) The Commissioner will evaluate all comments received. If he concludes that there is a lack of convincing evidence that the substance is GRAS or is otherwise exempt from the definition of a food additive in section 201(s) of the act, he will publish a notice thereof in the
(c) A
(1) It may promulgate a food additive regulation governing use of the additive.
(2) It may promulgate an interim food additive regulation governing use of the additive.
(3) It may require discontinuation of the use of the additive.
(4) It may adopt any combination of the above three approaches for different uses or levels of use of the additive.
(d) If the Commissioner of Food and Drugs is aware of any prior sanction for use of the substance, he will concurrently propose a separate regulation covering such use of the ingredient under this subchapter E. If the Commissioner is unaware of any such applicable prior sanction, the proposed regulation will so state and will require any person who intends to assert or rely on such sanction to submit proof of its existence. Any regulation promulgated pursuant to this section constitutes a determination that excluded uses would result in adulteration of the food in violation of section 402 of the act, and the failure of any person to come forward with proof of such an applicable prior sanction in response to the proposal will constitute a waiver of the right to assert or rely on such sanction at any later time. The notice will also constitute a proposal to establish a regulation under this subchapter E., incorporating the same provisions, in the event that such a regulation is determined to be appropriate as a result of submission of proof of such an applicable prior sanction in response to the proposal.
21 U.S.C. 321, 342, 348, 371; 42 U.S.C. 241.
(a) Petitions to be filed with the Commissioner under the provisions of section 409(b) of the act shall be submitted in triplicate. If any part of the material submitted is in a foreign language, it shall be accompanied by an accurate and complete English translation. The petition shall state petitioner's post office address to which published notices or orders issued or objections filed pursuant to section 409 of the act may be sent.
(b) Pertinent information may be incorporated in, and will be considered as part of, a petition on the basis of specific reference to such information submitted to and retained in the files of the Food and Drug Administration. However, any reference to unpublished information furnished by a person other than the applicant will not be considered unless use of such information is authorized in a written statement signed by the person who submitted it. Any reference to published information offered in support of a food-additive petition should be accompanied by reprints or photostatic copies of such references.
(c) Petitions shall include the following data and be submitted in the following form:
Attached hereto, in triplicate, and constituting a part of this petition, are the following:
A. The name and all pertinent information concerning the food additive, including chemical identity and composition of the food additive, its physical, chemical, and biological properties, and specifications prescribing the minimum content of the desired component(s) and identifying and limiting the reaction byproducts and other impurities. Where such information is not available, a statement as to the reasons why it is not should be submitted.
When the chemical identity and composition of the food additive is not known, the petition shall contain information in sufficient detail to permit evaluation regarding the method of manufacture and the analytical controls used during the various stages of manufacturing, processing, or packing of the food additive which are relied upon to establish that it is a substance of reproducible composition. Alternative methods and controls and variations in methods and controls within reasonable limits that do not affect the characteristics of the substance or the reliability of the controls may be specified.
If the food additive is a mixture of chemicals, the petition shall supply a list of all substances used in the synthesis, extraction, or other method of preparation, regardless of whether they undergo chemical change in the process. Each substance should be identified by its common English name and complete chemical name, using structural formulas when necessary for specific identification. If any proprietary preparation is used as a component, the proprietary name should be followed by a complete quantitative statement of composition. Reasonable alternatives for any listed substance may be specified.
If the petitioner does not himself perform all the manufacturing, processing, and packing operations for a food additive, the petition shall identify each person who will perform a part of such operations and designate the part.
The petition shall include stability data, and, if the data indicate that it is needed to ensure the identity, strength, quality, or purity of the additive, the expiration date that will be employed.
B. The amount of the food additive proposed for use and the purposes for which it is proposed, together with all directions, recommendations, and suggestions regarding the proposed use, as well as specimens of the labeling proposed for the food additive and any labeling that will be required by applicable provisions of the Federal Food, Drug, and Cosmetic Act on the finished food by reason of the use of the food additive. If the additive results or may reasonably be expected to result from the use of packaging material, the petitioner shall show how this may occur
(Typewritten or other draft-labeling copy will be accepted for consideration of the petition, provided a statement is made that final printed labeling identical in content to the draft copy will be submitted as soon as available and prior to the marketing of the food additive.
If the food additive is one for which a tolerance limitation is required to assure its safety, the level of use proposed should be no higher than the amount reasonably required to accomplish the intended physical or other technical effect, even though the safety data may support a higher tolerance.)
C. Data establishing that the food additive will have the intended physical or other technical effect or that it may reasonably be expected to become a component, or to affect the characteristics, directly or indirectly, of food and the amount necessary to accomplish this. These data should include information in sufficient detail to permit evaluation with control data.
D. A description of practicable methods to determine the amount of the food additive in the raw, processed, and/or finished food and of any substance formed in or on such food because of its use. The test proposed shall be one that can be used for food-control purposes and that can be applied with consistent results by any properly equipped and trained laboratory personnel.
E. Full reports of investigations made with respect to the safety of the food additive.
(A petition may be regarded as incomplete unless it includes full reports of adequate tests reasonably applicable to show whether or not the food additive will be safe for its intended use. The reports ordinarily should include detailed data derived from appropriate animal and other biological experiments in which the methods used and the results obtained are clearly set forth. The petition shall not omit without explanation any reports of investigations that would bias an evaluation of the safety of the food additive.)
F. Proposed tolerances for the food additive, if tolerances are required in order to ensure its safety. A petitioner may include a proposed regulation.
G. If submitting petition to modify an existing regulation issued pursuant to section 409(c)(1)(A) of the act, full information on each proposed change that is to be made in the original regulation must be submitted. The petition may omit statements made in the original petition concerning which no change is proposed. A supplemental petition must be submitted for any change beyond the variations provided for in the original petition and the regulation issued on the basis of the original petition.
H. The petitioner is required to submit either a claim for categorical exclusion under § 25.30 or § 25.32 of this chapter or an environmental assessment under § 25.40 of this chapter.
Yours very truly,
Petitioner ____
By ____
(d) The petitioner will be notified of the date on which his petition is filed, and an incomplete petition, or one that has not been submitted in triplicate, will usually be retained but not filed as a petition under section 409 of the act. The petitioner will be notified in what respects his petition is incomplete.
(e) The petition must be signed by the petitioner or by his attorney or agent, or (if a corporation) by an authorized official.
(f) The data specified under the several lettered headings should be submitted on separate sheets or sets of sheets, suitably identified. If such data have already been submitted with an earlier application, the present petition may incorporate it by specific reference to the earlier. If part of the data have been submitted by the manufacturer of the food additive as a master file, the petitioner may refer to the master file if and to the extent he obtains the manufacturer's written permission to do so. The manufacturer may authorize specific reference to the data without disclosure to the petitioner. Nothing herein shall prevent reference to published data.
(g) A petition shall be retained but shall not be filed if any of the data prescribed by section 409(b) of the act are lacking or are not set forth so as to be readily understood.
(h)(1) The following data and information in a food additive petition are available for public disclosure, unless extraordinary circumstances are shown, after the notice of filing of the petition is published in the
(i) All safety and functionality data and information submitted with or incorporated by reference in the petition.
(ii) A protocol for a test or study, unless it is shown to fall within the exemption established for trade secrets and confidential commercial information in § 20.61 of this chapter.
(iii) Adverse reaction reports, product experience reports, consumer complaints, and other similar data and information, after deletion of:
(
(
(iv) A list of all ingredients contained in a food additive, whether or not it is in descending order of predominance. A particular ingredient or group of ingredients shall be deleted from any such list prior to public disclosure if it is shown to fall within the exemption established in § 20.61 of this chapter, and a notation shall be made that any such ingredient list is incomplete.
(v) An assay method or other analytical method, unless it serves no regulatory or compliance purpose and is shown to fall within the exemption established in § 20.61 of this chapter.
(2) The following data and information in a food additive petition are not available for public disclosure unless they have been previously disclosed to the public as defined in § 20.81 of this chapter or they relate to a product or ingredient that has been abandoned and they no longer represent a trade secret or confidential commercial or financial information as defined in § 20.61 of this chapter:
(i) Manufacturing methods or processes, including quality control procedures.
(ii) Production, sales, distribution, and similar data and information, except that any compilation of such data and information aggregated and prepared in a way that does not reveal data or information which is not available for public disclosure under this provision is available for public disclosure.
(iii) Quantitative or semiquantitative formulas.
(3) All correspondence and written summaries of oral discussions relating to a food additive petition are available for public disclosure in accordance with the provisions of part 20 of this chapter when the food additive regulation is published in the
(4) For purposes of this regulation, safety and functionality data include all studies and tests of a food additive on animals and humans and all studies and tests on a food additive for identity, stability, purity, potency, performance, and usefulness.
(i)(1) Within 15 days after receipt, the Commissioner will notify the petitioner of acceptance or nonacceptance of a petition, and if not accepted the reasons therefor. If accepted, the date of the notification letter sent to petitioner becomes the date of filing for the purposes of section 409(b)(5) of the act. If the petitioner desires, he may supplement a deficient petition after being notified regarding deficiencies. If the supplementary material or explanation of the petition is deemed acceptable, petitioner shall be notified. The date of such notification becomes the date of filing. If the petitioner does not wish to supplement or explain the petition and requests in writing that it be filed as submitted, the petition shall be filed and the petitioner so notified. The date of such notification becomes the date of filing.
(2) The Commissioner will publish in the
(j) The Commissioner may request a full description of the methods used in, and the facilities and controls used for, the production of the food additive, or a sample of the food additive, articles used as components thereof, or of the food in which the additive is proposed
(k) If nonclinical laboratory studies are involved, petitions filed with the Commissioner under section 409(b) of the act shall include, with respect to each study, either a statement that the study was conducted in compliance with the requirements set forth in part 58 of this chapter, or, if the study was not conducted in compliance with such regulations, a brief statement of the reason for the noncompliance.
After a petition has been filed, the petitioner may submit additional information or data in support thereof. In such cases, if the Commissioner determines that the additional information or data amounts to a substantive amendment, the petition as amended will be given a new filing date, and the time limitation will begin to run anew. If nonclinical laboratory studies are involved, additional information and data submitted in support of filed petitions shall include, with respect to each such study, either a statement that the study was conducted in compliance with the requirements set forth in part 58 of this chapter, or, if the study was not conducted in compliance with such regulations, a brief statement of the reason or the noncompliance.
(a) In some cases the Commissioner will notify the petitioner that the petition, while technically complete, is inadequate to justify the establishment of a regulation or the regulation requested by petitioner. This may be due to the fact that the data are not sufficiently clear or complete. In such cases, the petitioner may withdraw the petition pending its clarification or the obtaining of additional data. This withdrawal will be without prejudice to a future filing. Upon refiling, the time limitation will begin to run anew from the date of refiling.
(b) At any time before the order provided for in § 571.100(a) has been forwarded to the
(a) The Commissioner will forward for publication in the
(b) If the Commissioner determines that additional time is needed to study and investigate the petition, he shall by written notice to the petitioner extend the 90-day period for not more than 180 days after the filing of the petition.
A regulation published in accordance with § 571.100(a) shall become effective upon publication in the
Objections and hearings relating to food additive regulations under section 409(c), (d), or (h) of the act shall be governed by part 12 of this chapter.
Food additives intended for use as an ingredient in food for animals that are raised for food production and that have the potential to contaminate human food with residues whose consumption could present a risk of cancer to people must satisfy the requirements of subpart E of part 500 of this chapter.
(a) The Commissioner, on his own initiative or on the petition of any interested person, pursuant to part 10 of this chapter, may propose the issuance of a regulation amending or repealing a regulation pertaining to a food additive or granting or repealing an exception for such additive.
(b) Any such petition shall include an assertion of facts, supported by data, showing that new information exists with respect to the food additive or that new uses have been developed or old uses abandoned, that new data are available as to toxicity of the chemical, or that experience with the existing regulation or exemption may justify its amendment or repeal. New data shall be furnished in the form specified in § 571.1 for submitting petitions.
21 U.S.C. 321, 342, 348.
Acrylamide-acrylic acid resin (hydrolized polyacrylamide), only for the purposes of this section as described below, may be safely used in accordance with the following prescribed conditions:
(a) The additive is produced by polymerization of acrylamide with partial hydrolysis, or by copolymerization of acrylamide and acrylic acid with the greater part of the polymer being composed of acrylamide units.
(b) The additive meets the following specifications:
(1) A minimum molecular weight of 3 million.
(2) Viscosity range: 3,000 to 6,000 centipoises at 77 °F in a 1 percent aqueous solution as determined by LVF Brookfield Viscometer or equivalent using a number 6 spindle at 20 r.p.m.
(3) Residual acrylamide: Not more than 0.05 percent.
(c) It is used as a thickener and suspending agent in nonmedicated aqueous suspensions intended for addition to animal feeds.
The food additive aminoglycoside 3′-phosphotransferase II may be safely used in the development of genetically modified cotton, oilseed rape, and tomatoes in accordance with the following prescribed conditions:
(a) The food additive is the enzyme aminoglycoside 3′-phosphotransferase II (CAS Reg. No. 58943-39-8) which catalyzes the phosphorylation of certain aminoglycoside antibiotics, including kanamycin, neomycin, and gentamicin.
(b) Aminoglycoside 3′-phosphotransferase II is encoded by the
(c) The level of the additive does not exceed the amount reasonably required for selection of plant cells carrying the
The food additive ammoniated cottonseed meal may be safely used in accordance with the following conditions:
(a) The food additive is the product obtained by the treatment of cottonseed meal with anhydrous ammonia until a pressure of 50 pounds per square inch gauge is reached.
(b) It is used or intended for use in the feed of ruminants as a source of protein and/or as a source of nonprotein nitrogen in an amount not to exceed 20 percent of the total ration.
(c) To assure safe use, the label and labeling of the additive and of any feed additive supplement, concentrate, or premix prepared therefrom shall bear, in addition to the other information required by the act, the following:
(1) The name of the additive.
(2) The maximum percentage of equivalent crude protein from the nonprotein nitrogen.
(3) Directions for use to provide not more than 20 percent of the additive in the total ration.
(4) A statement:
(i) That not more than one-third of the total protein in the feed should come from nonprotein nitrogen sources.
(ii) That the additive is not to be given to debilitated or starved animals.
(iii) “Warning—This feed should be used only in accordance with directions furnished on the label.”
The food additive ammoniated rice hulls may be safely used in accordance with the following prescribed conditions:
(a) The food additive is the product obtained by the treatment of ground rice hulls with monocalcium phosphate and anhydrous ammonia at a temperature of 350 °F and a pressure of 175 pounds per square inch.
(b) It is used or intended for use in the feed of beef cattle as a source of crude fiber and as the sole source of nonprotein nitrogen in an amount not to exceed 20 percent of the total ration.
(c) To assure safe use of the additive, the label and labeling of the additive and of any feed additive supplement, feed additive concentrate, or feed additive premix prepared therefrom, shall contain, in addition to other information required by the act, the following:
(1) The name of the additive.
(2) The maximum percentage of equivalent crude protein from the nonprotein nitrogen.
(3) Directions for use to provide not more than 20 percent of the additive in the total ration, and a prominent statement: “Warning—This feed should be used only in accordance with the directions furnished on the label.”
(a) The food additive anhydrous ammonia is applied directly to corn plant material and thoroughly blended prior to ensiling. It is used or intended for use as a source of nonprotein nitrogen in cattle feed in accordance with paragraphs (a)(1), (2), or (3) as follows:
(1)(i) The food additive anhydrous ammonia is applied as a component of an aqueous premix containing 16 to 17 percent ammonia, with molasses, minerals, and not less than 83 percent crude protein. The premix is a source of nonprotein nitrogen and minerals.
(ii) In addition to the requirements of paragraph (b) of this section, the labeling shall bear an expiration date of not more than 10 weeks after date of manufacture; a statement that additional protein should not be fed to lactating dairy cows producing less than 32 pounds of milk per day nor beef cattle consuming less than 1 percent of body weight daily in shelled corn; and a warning not to use additional trace mineral supplementation with treated silage.
(2)(i) The food additive anhydrous ammonia is applied directly to corn plant material for use in dairy or beef cattle rations.
(ii) The anhydrous ammonia is applied at a rate not to exceed the equivalent of 0.35 percent of the corn plant material.
(iii) It is applied to corn plant material containing 30 to 35 percent dry matter.
(iv) It is applied so that 75 to 85 percent of the additive is liquid at ambient pressure.
(3)(i) The food additive anhydrous ammonia is applied after being diluted to a 15 to 30 percent aqueous ammonia solution (by weight).
(ii) The anhydrous ammonia solution is applied at a rate not to exceed anhydrous ammonia equivalent to 0.3 percent of the corn plant material.
(iii) It is applied to corn plant material containing 28 to 38 percent dry matter.
(iv) The silage treated with aqueous ammonia is to be fed to dairy cattle only.
(b) Its labeling shall bear, in addition to the other requirements of the act, the name of the additive, the concentration of ammonia, the maximum percentage of equivalent crude protein from nonprotein nitrogen, and directions for use consistent with this section.
(a)
(b)
(c)
(1) In poultry and swine feed in an amount not to exceed 5 percent by weight of the feed.
(2) In feed concentrates for cattle in an amount not to exceed 10 percent by weight of the concentrate.
(d)
(1) The name of the additive, condensed animal protein hydrolysate.
(2) Adequate directions for use including maximum quantities permitted for each species and a guaranteed analysis of the additive.
The food additive feed grade biuret may be safely used in ruminant feed in accordance with the following prescribed conditions:
(a) The food additive is the product resulting from the controlled pyrolysis of urea conforming to the following specifications:
(b) It is used in ruminant feeds as a source of nonprotein nitrogen.
(c) To assure safe use of the additive:
(1) The label and labeling of the additive and that of any feed additive supplement, feed additive concentrate, feed additive premix, or complete feed prepared therefrom shall contain, in addition to other information required by the act, the following:
(i) The name of the additive.
(ii) The maximum percentage of equivalent crude protein from nonprotein nitrogen.
(2) The label shall recommend that the diet be balanced to provide adequate nutrients when equivalent crude protein from all forms of nonprotein nitrogen exceed one-third of the total crude protein in the total daily ration.
The food additive 1,3-butylene glycol (1,3-butanediol) may be safely used in accordance with the following prescribed conditions:
(a) It complies with the specifications in § 173.220(a) of this chapter.
(b) It is intended for use in swine feed as a source of energy.
(c) It is to be thoroughly mixed into feed at levels not to exceed 9 percent of the dry matter of the total ration.
(d) 1,3-Butylene glycol should be mixed in feed with equipment adapted for the addition of liquids, and the feed should be mixed not less than 5 minutes after its addition.
The food additive calcium periodate may be safely used in accordance with the following prescribed conditions:
(a) The additive is produced by reacting calcium iodate with calcium hydroxide or calcium oxide to form a substance consisting of not less than 60 percent by weight of penta calcium orthoperiodate containing 28 to 31 percent by weight of iodine.
(b) It is used or intended for use in salt for livestock as a source of iodine.
Calcium silicate, including synthetic calcium silicate, may be safely used as an anticaking agent in animal feed, provided that the amount of calcium silicate does not exceed 2 percent.
Feed-grade calcium stearate and sodium stearate may be safely used in an animal feed in accordance with the following prescribed conditions:
(a) Feed-grade calcium stearate and sodium stearate are the calcium or sodium salts of a fatty acid mixture that is predominately stearic acid. Associated fatty acids, including palmitic acid and minor amounts of lauric, myristic, pentadecanoic, margaric, arachidic, and other fatty acids may be contained in the mixture, but such associated fatty acids in aggregate do not exceed 35 percent by weight of the mixture. The fatty acids may be derived from feed-grade fats or oils.
(b) The additives meet the following specifications:
(1) Unsaponifiable matter does not exceed 2 percent.
(2) They are free of chick-edema factor.
(c) The additives are manufactured so that in aqueous solution they are exposed for 1 hour or longer to temperature in excess of 180 °F.
(d) They are used as anticaking agents in animal feeds in accordance with current good manufacturing practices.
Choline xanthate may be safely used as a component of animal feed as an added source of choline to supplement the diets of poultry, ruminants, and swine in accordance with good feeding practice.
(a) The additive is the seed meal of
(b) The additive conforms to the following percent-by-weight specifications: moisture, not more than 11 percent; oil, not more than 4 percent; crude protein, not less than 24 percent; crude fiber, not more than 26 percent; glucosinolate calculated as epi-progoitrin, not more than 4 percent; goitrin, not more than 0.1 percent; nitrile calculated as 1-cyano-2-hydroxy-3-butene, not more than 1.4 percent. At least 50 percent of the nitrogen shall be soluble in 0.5
(c) The additive is used or intended for use in the feed of feedlot cattle as a source of protein in an amount not to exceed 4.2 percent of the total ration.
The food additive diammonium phosphate may be safely used in ruminant feed in accordance with the following prescribed conditions:
(a) The food additive is the product resulting from the neutralization of feeding-phosphoric-acid or defluorinated wet-process phosphoric acid with anhydrous ammonia. It contains not less than 106.25 percent equivalent crude protein (nitrogen × 6.25) and 20 percent phosphorus. It contains not more than the following:
(b) It is used in ruminant feeds as a source of phosphorus and nitrogen in an amount that supplies not more than 2 percent of equivalent crude protein in the total daily ration.
(c) To assure safe use of the additive, the label and labeling of the additive and that of any feed additive supplement, feed additive concentrate, feed additive premix, or complete feed prepared therefrom shall contain, in addition to other information required by the act, the following:
(1) The name of the additive.
(2) The maximum percentage of equivalent crude protein from the nonprotein nitrogen.
(3) If the feed additive premix, feed additive concentrate, or feed additive supplement contains more than 2 percent equivalent crude protein from diammonium phosphate, adequate directions for use and a prominent statement, “Warning—This feed should be used only in accordance with directions furnished on the label.”
(a)
(b)
(c)
The food additive disodium EDTA (disodium ethylenediaminetetraace- tate) may be safely used in animal feeds, in accordance with the following prescribed conditions:
(a) The food additive contains a minimum of 99 percent disodium ethylenediaminetetraacetate dihydrate (C
(b) It is used to solubilize trace minerals in aqueous solutions, which are then added to animal feeds.
(c) It is used or intended for use in an amount not to exceed 240 parts per million of the additive in finished feed.
(d) To assure safe use of the additive the label and labeling shall bear:
(1) The name of the additive; and
(2) Adequate mixing directions to ensure that the chelated trace-mineral mix is uniformly blended throughout the feed.
Ethoxyquin (1,2-dihydro-6-ethoxy-2,2,4-trimethylquinoline) may be safely used in animal feeds, when incorporated therein in accordance with the following prescribed conditions.
(a) It is intended for use only: (1) As a chemical preservative for retarding oxidation of carotene, xanthophylls, and vitamins A and E in animal feed and fish food and, (2) as an aid in preventing the development of organic peroxides in canned pet food.
(b) The maximum quantity of the additive permitted to be used and to remain in or on the treated article shall not exceed 150 parts per million.
(c) To assure safe use of the additive, the label and labeling of the food additive container and that of any intermediate premixes prepared therefrom shall contain, in addition to other information required by the act:
(1) The name of the additive, ethoxyquin.
(2) A statement of the concentration or strength contained therein.
(3) Adequate use directions to provide for a finished article with the proper concentration of the additive as provided in paragraph (b) of this section, whether or not intermediate premixes are to be used.
(d) The label of any animal feed containing the additive shall, in addition to the other information required by the act, bear the statement “Ethoxyquin, a preservative” or “Ethoxyquin added to retard the oxidative destruction of carotene, xanthophylls, and vitamins A and E.”
Ethoxyquin (1,2-dihydro-6-ethoxy-2,2,4-trimethylquinoline) may be safely used in the dehydrated forage crops listed in paragraph (a) of this section when incorporated therein in accordance with the conditions prescribed in this section:
(a) It may be added to dehydrated forage prepared from:
(b) Such additive is used only as a chemical preservative for the purpose of retarding oxidative destruction of naturally occurring carotenes and vitamin E in the forage crops.
(c) It is added to the dehydrated forage crops in an oil mixture containing
(d) The maximum quantity of the additive permitted to be used and to remain in or on the dehydrated forage crop shall not exceed 150 parts per million.
(e) To assure the safe use of the additive, the label of the market package shall contain, in addition to other information required by the act:
(1) The name of the additive as specified in this section.
(2) Directions for the incorporation of the additive in the forage crops, as specified in paragraph (c) of this section, with the directive that only suitable animal or suitable vegetable oils are to be used in the oil mix.
(f) The label of any dehydrated forage crops treated with the additive or the label of an animal-feed supplement containing such treated forage crops, shall, in addition to other information required by the act, bear the following statements:
(1) “Ethoxyquin, a preservative,” or “Ethoxyquin added to retard the oxidative destruction of carotene and vitamin E.”
(2) The statement “For use in animal feed only.”
The food additive ethyl cellulose may be safely used in animal feed in accordance with the following prescribed conditions:
(a) The food additive is a cellulose ether containing ethoxy (OC
(b) It is used or intended for use as a binder or filler in dry vitamin preparations to be incorporated into animal feed.
The food additive ethylene dichloride may be safely used in the manufacture of animal feeds in accordance with the following prescribed conditions:
(a) It is used as a solvent in the extraction processing of animal byproducts for use in animal feeds.
(b) The maximum quantity of the additive permitted to remain in or on the extracted byproducts shall not exceed 300 parts per million.
(c) The extracted animal byproduct is added as a source of protein to a total ration at levels consistent with good feeding practices, but in no event at levels exceeding 13 percent of the total ration.
(a)
(b)
(c)
(d)
(2) The maximum level of use of fermented ammoniated condensed whey and equivalent crude protein from all other added forms of nonprotein nitrogen shall not exceed 30 percent of the dietary crude protein.
(3) The additive may be used as follows:
(i) Mixed with grain, roughage, or grain and roughage prior to feeding.
(ii) As a component of free-choice liquid feeds, used to supplement the diets of cattle fed other sources of nutrients, fermented ammoniated condensed whey shall not exceed 80 percent of the free-choice liquid feed.
(e)
(1) The name of the additive.
(2) The maximum percentage of equivalent crude protein from nonprotein nitrogen.
(3) Adequate directions for use in accordance with the provisions in paragraph (d) of this section.
The food additive formaldehyde may be safely used in the manufacture of animal feeds in accordance with the following conditions:
(a) The additive is used, or intended for use, to improve the handling characteristics of fat by producing a dry, free-flowing product, as follows:
(1) For animal fat in combination with certain oilseed meals, as a component of dry, nonpelletted feeds for beef and nonlactating dairy cattle.
(i) An aqueous blend of soybean and sunflower meals in a ratio of 3:1, respectively, is mixed with animal fat such that the oilseed meals and animal fat are in a ratio of 3:2. The feed ingredients are those defined by the “Official Publication” of the Association of American Feed Control Officials, Inc., 2003 ed., pp. 303, 308, and 309, which is incorporated by reference. The Director of the Office of the Federal Register approves this incorporation by reference in accordance with 5 U.S.C. 552(a) and 1 CFR part 51. You may obtain copies from the Assistant Secretary-Treasurer, Association of American Feed Control Officials Inc., P.O. Box 478, Oxford, IN 47971, or you may examine a copy at the Division of Dockets Management, Food and Drug Administration, 5630 Fishers Lane, rm. 1061, Rockville, MD 20852, or at the National Archives and Records Administration (NARA). For information on the availability of this material at NARA, call 202-741-6030, or go to:
(ii) Formaldehyde (37 percent solution) is added to the mixture at a level of 4 percent of the dry matter weight of the oilseed meals and animal fat. This mixture, upon drying, contains not more than 1 percent formaldehyde and not more than 12 percent moisture.
(iii) To assure the safe use of the additive, in addition to the other information required by the Federal Food, Drug, and Cosmetic Act (the act), the label and labeling of the dried mixture shall bear:
(A) The name of the additive.
(B) Adequate directions for use providing that the feed as consumed does not contain more than 25 percent of the mixture.
(2) For soybean and canola seeds and/or meals to which there may be added vegetable oil as a component of dry, nonpelleted feeds for beef and dairy cattle, including lactating dairy cattle.
(i) An aqueous blend of oilseed and/or meals, with or without added vegetable oil, in a ratio such that, on a dry matter basis, the final protein level will be 25 to 35 percent and the fat content will be 20 to 45 percent. The feed ingredients are those defined by the “Official Publication” of the Association of American Feed Control Officials, Inc., 2003 ed., pp. 301, 307, 308, and 309, which is incorporated by reference. The Director of the Office of the Federal Register approves this incorporation by reference in accordance with 5 U.S.C. 552(a) and 1 CFR part 51. You may obtain copies from the Assistant Secretary-Treasurer, Association of American Feed Control Officials Inc., P.O. Box 478, Oxford, IN 47971, or you may examine a copy at the Division of Dockets Management, Food and Drug Administration, 5630 Fishers lane, rm. 1061, Rockville, MD 20852, or at the National Archives and Records Administration (NARA). For information on the availability of this material at NARA, call 202-741-6030, or go to:
(ii) Formaldehyde (37 percent solution) is added to the mixture at a level of 2.7 percent of the dry matter weight basis of the oilseeds and/or meals and the vegetable oil. This mixture, upon drying, contains not more than 0.5 percent formaldehyde and not more than 12 percent moisture.
(iii) To assure the safe use of the additive, in addition to the other information required by the act, the label and labeling of the dried mixture shall bear:
(A) The name of the additive.
(B) The statement, “This supplement is not to exceed 12.5% of the total ration. Dietary calcium and magnesium levels should be considered when supplementing the diet with fat.”
(C) The minimum and maximum levels of crude fat must be guaranteed and
(b)(1) The food additive is formaldehyde (CAS No. 50-00-0; 37 percent aqueous solution). It is used at a rate of 5.4 pounds (2.5 kilograms) per ton of animal feed or feed ingredient. It is an antimicrobial agent used to maintain complete animal feeds or feed ingredients
(2) To assure safe use of the additive, in addition to the other information required by the Act, the label and labeling shall contain:
(i) The name of the additive.
(ii) A statement that formaldehyde solution which has been stored below 40 °F or allowed to freeze should not be applied to complete animal feeds or feed ingredients.
(iii) Adequate directions for use including a statement that formaldehyde should be uniformly sprayed on and thoroughly mixed into the complete animal feeds or feed ingredients and that the complete animal feeds or feed ingredients so treated shall be labeled as containing formaldehyde. The label must prominently display the statement: “Treated with formaldehyde to maintain feed
(iv) The labeling for feed or feed ingredients to which formaldehyde has been added under the provisions of paragraph (b)(1) of this section is required to carry the following statement: “Treated with formaldehyde to maintain feed
(3) To assure safe use of the additive, in addition to the other information required by the Act, the label and labeling shall contain:
(i) Appropriate warnings and safety precautions concerning formaldehyde.
(ii) Statements identifying formaldehyde as a poison with potentials for adverse respiratory effects.
(iii) Information about emergency aid in case of accidental inhalation.
(iv) Statements reflecting requirements of applicable sections of the Superfund Amendments and Reauthorization Act (SARA), and the Occupational Safety and Health Administration's (OSHA) human safety guidance regulations.
(v) Contact address and phone number for reporting adverse reactions or to request a copy of the Materials Safety Data Sheet (MSDS).
Formic acid may be safely used as a preservative in hay crop silage in an amount not to exceed 2.25 percent of the silage on a dry weight basis or 0.45 percent when direct-cut. The top foot of silage stored should not contain formic acid and silage should not be fed to livestock within 4 weeks of treatment.
Condensed, extracted glutamic acid fermentation product may be safely used in animal feed under the following conditions:
(a) The additive is a concentrated mixture of the liquor remaining from the extraction of glutamic acid, combined with the cells of
(b) It is used or intended for use as follows:
(1) In poultry feed as a source of protein in an amount not to exceed 5 percent of the total ration.
(2) In cattle feed as a source of protein in an amount not to exceed 10 percent of the feed.
(c) In order to assure safe use, the label and labeling of the additive shall bear, in addition to the other information required by the Act, the following:
(1) The name of the additive.
(2) A statement of the concentration of the additive contained in any mixture.
(3) Adequate directions for use.
Hemicellulose extract may be safely used in animal feed when incorporated therein in accordance with the following conditions:
(a) The additive is produced from the aqueous extract obtained by the treatment of wood with water at elevated
(b) The additive may be used in a liquid or dry state with the liquid product containing not less than 55 percent carbohydrate and the dry product containing not less than 84 percent carbohydrate.
(c) The additive is used as a source of metabolizable energy in animal feed in accordance with good manufacturing and feeding practices.
(a)
(b)
(c)
(d)
(e)
(1) The name of the additive.
(2) Adequate directions for use in accordance with the provisions in paragraph (d) of this section.
(a)
(b)
(c)
(d)
(1) The name of the additive, hydrolyzed leather meal.
(2) Adequate directions to provide finished feeds complying with paragraph (c) of this section.
Iron ammonium citrate may be safely used in animal feed in accordance with the following prescribed conditions:
(a) The additive is the chemical green ferric ammonium citrate.
(b) The additive is used or intended for use as an anticaking agent in salt for animal consumption so that the level of iron ammonium citrate does not exceed 25 parts per million (0.0025 percent) in the finished salt.
(c) To assure safe use of the additive the label or labeling of the additive shall bear, in addition to the other information required by the Act:
(1) The name of the additive.
(2) Adequate directions to provide a final product that complies with the limitations prescribed in paragraph (b) of this section.
Iron-choline citrate complex made by reacting approximately equimolecular quantities of ferric hydroxide, choline, and citric acid may be safely used as a source of iron in animal feed.
Lignin sulfonates may be safely used in animal feeds in accordance with the following prescribed conditions:
(a) For the purpose of this section, the food additive is either one, or a combination of, the ammonium, calcium, magnesium, or sodium salts of the extract of spent sulfite liquor derived from the sulfite digestion of wood or of abaca (
(b) It is used or intended for use in an amount calculated on a dry weight basis, as follows:
(1) As a pelleting aid in the liquid or dry form in an amount not to exceed 4 percent of the finished pellets.
(2) As a binding aid in the liquid form in the flaking of feed grains in an amount not to exceed 4 percent of the flaked grain.
(3) As a surfactant in molasses used in feeds, as liquid lignin sulfonate, in an amount not to exceed 11 percent of the molasses.
(4) As a source of metabolizable energy, in the liquid or dry form, in an amount not to exceed 4 percent of the finished feed.
The food additive, menadione dimethylpyrimidinol bisulfite, may be safely used in accordance with the following conditions:
(a) The additive is the 2-hydroxy-4,6-dimethylpyrimidinol salt of menadione (C
(b) The additive is used or intended for use as a nutritional supplement for the prevention of vitamin K deficiency as follows:
(1) In chicken and turkey feed at a level not to exceed 2 grams per ton of complete feed.
(2) In the feed of growing and finishing swine at a level not to exceed 10 grams per ton of feed.
(c) To assure safe use, the label and labeling of the additive shall bear adequate directions for use.
The food additive may be safely used as follows:
(a) The additive is 1,2,3,4-tetrahydro-2-methyl-1,4-dioxo-2-naphthalene sulfonic acid with 3-pyridine carboxylic acid amine (CAS No. 73581-79-0).
(b) The additive is used or intended for use as a nutritional supplement for both the prevention of vitamin K deficiency and as a source of supplemental niacin as follows:
(1) In chicken and turkey feeds at a level not to exceed 2 grams per ton of complete feed.
(2) In growing and finishing swine feeds at a level not to exceed 10 grams per ton of complete feed.
(c) To assure safe use, the label and labeling of the additive shall bear adequate directions for use.
The food additive methyl esters of higher fatty acids may be safely used in animal feeds in accordance with the following prescribed conditions:
(a) The food additive is manufactured by reaction of methyl alcohol with feed-grade fats or oils and consists of not less than 70 percent methyl esters of the following straight-chain monocarboxylic acids: Docosahexanoic acid, eicosapentanoic acid, linoleic acid, myristic acid, oleic acid, palmitic acid, palmitoleic acid, and stearic acid, and lesser amounts of the associated acid esters.
(b) The food additive meets the following specifications:
(1) Free methyl alcohol not to exceed 150 parts per million.
(2) Unsaponifiable matter not to exceed 2 percent.
(3) It is free of chick-edema factor or other factors toxic to chicks, as evidenced during the bioassay method for determining the chick-edema factor as prescribed in paragraph (b)(4)(ii) of this section.
(4) For the purposes of this section:
(i) Unsaponifiable matter shall be determined by the method described in Section 28.081, “Unsaponifiable Residue (20)—Official Final Action” of the “Official Methods of Analysis of the Association of Official Analytical Chemists,” 13th Ed., 1980, p. 451, which is incorporated by reference. Copies are available from the AOAC INTERNATIONAL, 481 North Frederick Ave., suite 500, Gaithersburg, MD 20877, or at the National Archives and Records Administration (NARA). For information on the availability of this material at NARA, call 202-741-6030, or go to:
(ii) The chick-edema factor bioassay method described under “26. Oils, Fats,
(iii) “Other factors toxic to chicks” referred to in paragraph (b)(3) of this section shall be determined during the course of the bioassay test described in paragraph (b)(4)(ii) of this section, on the basis of chick deaths or other abnormalities not attributable to chick-edema factor or to the experimental conditions of the test.
(c) It is used or intended for use as a supplementary source of fat for animal feed.
(d) To assure safe use of the additive, in addition to the other information required by the act:
(1) The label and labeling of the additive, and any feed additive supplement, feed additive concentrate, feed additive premix, or complete feed prepared therefrom shall bear:
(i) The name of the additive.
(ii) The designation “feed grade” in juxtaposition with the name and equally as prominent.
(2) The label or labeling of the additive and any feed additive supplement, feed additive concentrate, feed additive premix, or complete feed prepared therefrom shall bear adequate directions for use.
Methyl glucoside-coconut oil ester may be safely used in accordance with the following conditions:
(a) The additive meets the specifications prescribed in § 172.816 of this chapter.
(b) It is used as a surfactant in molasses intended for use in animal feed at a level not to exceed 320 parts per million.
Mineral oil may be safely used in animal feed, subject to the provisions of this section.
(a) Mineral oil, for the purpose of this section, is that complying with the definition and specifications contained in § 172.878 (a) and (b) or in § 178.3620(b)(1) (i) and (ii) of this chapter.
(b) It is used in animal feeds for the following purposes:
(1) To reduce dustiness of feeds or mineral supplements.
(2) To serve as a lubricant in the preparation of pellets, cubes, or blocks and to improve resistance to moisture of such pellets, cubes, or blocks.
(3) To prevent the segregation of trace minerals in mineralized salt.
(4) To serve as a diluent carrier in the manufacture of feed grade biuret in accordance with good manufacturing practice.
(5) For the removal of water from substances intended as ingredients of animal feed.
(c) The quantity of mineral oil used in animal feed shall not exceed 3.0 percent in mineral supplements, nor shall it exceed 0.06 percent of the total ration when present in feed or feed concentrates.
The food additive natamycin (CAS No. 7681-93-8) may be safely used in broiler chicken feeds in accordance with the following specifications:
(a) The additive is a stereoisomer of 22-[(3-amino-3,6,dideoxy-β-D-mannopyranosyl)oxy]-1,3,26-trihydroxy-12-methyl-10-oxo-6,11,28-trioxatricyclo[22.3.1.0
(b) The additive shall conform to U.S.P. specifications.
(c) The additive (as part of a premix composed of calcium carbonate, natamycin, and lactose) is used for retarding the growth of
(d) Each pound (454 grams (g)) of the premix shall contain 434 (g) of calcium carbonate, 10 g of natamycin activity, and 10 g of lactose. The premix shall be mixed into broiler chicken feed at the rate of 1 pound (0.454 kilograms (kg)) per ton (908 kg) of feed to provide natamycin at a level of 11 parts per million (ppm). The premix shall be thoroughly mixed into the dry components of the broiler chicken feed before adding the liquid components. Broiler feeds to which the natamycin premix is added shall be used within 4 weeks of addition of the premix.
(e) To assure the safe use of the additive, the label or labeling of the additive shall bear, in addition to other information required by the Federal Food, Drug, and Cosmetic Act, the following:
(1) The name and CAS number of the additive, and its purpose.
(2) A listing of ingredients consisting of calcium carbonate, the additive, and lactose and their proportions in the premix as prescribed under paragraph (d) of this section.
(3) Adequate directions for use to ensure a broiler chicken feed that is in compliance with the limitations prescribed in paragraph (d) of this section.
(4) An appropriate cautionary statement: “Caution: Store in a tightly-closed, light-resistant container in a cool, dry place.”
(5) An expiration date of 1 year from the date of manufacture.
(6) A contact address and telephone number for reporting adverse reactions experienced by users, or to request a copy of the Material Safety Data Sheet for natamycin.
Sodium nitrite may be safely used in canned pet food containing meat and fish in accordance with the following prescribed conditions:
(a) It is used or intended for use alone as a preservative and color fixative in canned pet food containing fish, meat, and fish and meat byproducts so that the level of sodium nitrite does not exceed 20 parts per million.
(b) To assure safe use of the additive, in addition to the other information required by the act:
(1) The label of the additive shall bear:
(i) The name of the additive.
(ii) A statement of the concentration of the additive in any mixture.
(2) The label or labeling shall bear adequate directions to provide a final product that complies with the limitations prescribed in paragraph (a) of this section.
Petrolatum may be safely used in or on animal feed, subject to the following prescribed conditions:
(a) Petrolatum complies with the specifications set forth in the U.S. Pharmacopeia XVI for white petrolatum or in The National Formulary XII for yellow petrolatum.
(b) Petrolatum meets the following ultraviolet absorbance limits when subjected to the analytical procedure described in § 172.886(b) of this chapter.
Ultraviolet absorbance per centimeter path length:
(c) It is used in animal feed for the following purposes:
(1) To reduce dustiness of feeds or mineral supplements.
(2) To serve as a lubricant in the preparation of pellets, cubes, or blocks, and to improve resistance to moisture of such pellets, cubes, or blocks.
(d) The quantity of petrolatum present in animal feeds from the uses specified in paragraph (c) of this section shall not exceed 3 percent in mineral supplements nor shall it exceed 0.06 percent of the total ration when present in feed or feed concentrates.
(e) When used in combination with technical white mineral oil for the uses described in paragraph (c) of this section, the total quantity of combined petrolatum and technical white mineral oil shall not exceed the limits prescribed in paragraph (d) of this section.
(f) Petrolatum may contain any antioxidant permitted in food by regulations issued in accordance with section 409 of the act, in an amount not greater than that required to produce its intended effect.
Odorless light petroleum hydrocarbons complying with § 172.884(a) and (b) of this chapter may be safely used in an amount not in excess of that required as a component of insecticide formulations used in compliance with regulations issued in this part.
(a)
(b)
(1) Crude protein, not less than 60 percent.
(2) Crude fat, not less than 2 percent.
(3) Crude fiber, not more than 2 percent.
(4) Ash, not more than 13 percent.
(5) Moisture, not more than 6 percent.
(c)
The food additive poloxalene may be safely used in accordance with the following prescribed conditions:
(a) The additive consists of polyoxy-propylene-polyoxyethylene glycol non-ionic block polymer meeting the following specifications:
(1) Molecular weight range: 2,850-3,150.
(2) Hydroxyl number: 35.7-39.4.
(3) Cloud point (10 percent solution): 42 °C-46 °C.
(4) Structural formula:
(b) In feed as a surfactant for the flaking of feed grains when added to liquid grain conditioner in an amount
(c) The label and labeling shall bear, in addition to the other information required by the Act:
(1) The name of the additive.
(2) Adequate directions and warnings for use.
(a)
(b)
(2) The polyethylene is designed in a pellet form in a configuration presenting maximum angular surface having the following dimensions in centimeters:
(c)
(d)
(1) The name of the additive “polyethylene roughage replacement.”
(2) Adequate directions for use which shall provide for the administration of one-half pound of polyethylene pellets per head per day for 6 successive days. All natural roughage should be removed for a minimum of 12 hours prior to administration of polyethylene roughage replacement. Roughage replacement must be adequately mixed in the ration for uniform distribution.
(a) The food additive polyethylene glycol (400) mono- and dioleate meets the following specifications: Saponification number, 80-88; acid number, 5.0 maximum; and average molecular weight range, 640-680.
(b) It is used as a processing aid in the production of animal feeds when present as a result of its addition to molasses in an amount not to exceed 250 parts per million of the molasses.
The food additive polyoxyethylene glycol (400) mono- and dioleates may be safely used as an emulsifier in calf-milk replacer formulations.
The food additive polysorbate 60 (polyoxyethylene (20) sorbitan monostearate) may be safely used in animal feeds in accordance with the following prescribed conditions:
(a) It is used alone or in combination with sorbitan monostearate as an emulsifier in mineral premixes and dietary supplements for animal feeds.
(b) It is used as an emulsifier in milk-replacer formulations for calves.
The food additive polysorbate 80 (polyoxyethylene (20) sorbitan monooleate) may be safely used as an emulsifier in milk-replacer formulations for calves.
The food additive poly(2-vinylpyridine-co-styrene) may be safely used as nutrient protectant in feed for beef cattle and dairy cattle and replacement dairy heifers when used in accordance with the following conditions:
(a) The additive meets the following specifications:
(b) The additive is used in the manufacture of rumen-stable, abomasum-dispersible nutrient(s) for beef cattle and dairy cattle and replacement dairy heifers such that the maximum use of the additive from all sources does not exceed 5.1 grams per head per day. The
(1)
(2)
(c)
(1) The name of the additive.
(2) A statement of the concentration of poly(2-vinylpyridine-co-styrene) in any product or mixture.
(3) Adequate directions for the use of the rumen-stable, abomasum-dispersible nutrient(s) products.
(4) The following statement: “Warning: Maximum use of poly(2-vinylpyridine-co-styrene) from all sources is not to exceed 5.1 grams per head per day.”
Normal propyl alcohol may be safely used in feeds and feed supplements for cattle as a source of metabolizable energy. It is incorporated in the feed or feed supplement in an amount which provides not more than 54.5 grams of the additive per head per day.
Pyrophyllite (aluminum silicate monohydrate) may be safely used as the sole anticaking aid, blending agent, pelleting aid, or carrier in animal feed when incorporated therein in an amount not to exceed 2 percent in complete animal feed.
(a)
(b)
(1) Ammonium salts:
(2) Calcium salts:
(c)
(d)
(1) The name of the additive.
(2) Adequate directions for use, including statements expressing maximum use levels. For ammonium salts of volatile fatty acids, the statements:
(a) Public Law 103-354 enacted October 13, 1994 (the 1994 Act), states that FDA shall not implement or enforce the final rule issued on September 13, 1993 (58 FR 47962), in which FDA stayed the 1987 amendments and any modification of such rule issued after enactment of the 1994 Act; unless the Commissioner of Food and Drugs makes a determination that:
(1) Selenium additives are not essential at levels authorized in the absence of such final rule, to maintain animal nutrition and protect animal health;
(2) selenium at such levels is not safe to the animals consuming the additive;
(3) selenium at such levels is not safe to individuals consuming edible portions of animals that receive the additive;
(4) selenium at such levels does not achieve its intended effect of promoting normal growth and reproduction of livestock and poultry; and
(5) the manufacture and use of selenium at such levels cannot reasonably be controlled by adherence to current good manufacturing practice requirements.
(6) Paragraphs (b) through (g) of this section provide the currently acceptable levels of selenium supplementation.
(b) The food additive selenium is a nutrient administered in animal feed as sodium selenite or sodium selenate or in a controlled-release sodium selenite bolus, as provided in paragraphs (f) and (g) of this section, or as selenium yeast, as provided in paragraph (h) of this section.
(c) It is added to feed as follows:
(1) In complete feed for chickens, swine, turkeys, sheep, cattle, and ducks at a level not to exceed 0.3 part per million.
(2) In feed supplements for limit feeding as follows:
(i)
(ii)
(3) In salt-mineral mixtures for free-choice feeding as follows:
(i)
(ii)
(d) The additive shall be incorporated into feed as follows:
(1) It shall be incorporated into each ton of complete feed by adding no less than 1 pound of a premix containing no more than 272.4 milligrams of added selenium per pound.
(2) It shall be incorporated into each ton of salt-mineral mixture for sheep or beef cattle from a premix containing no more than 4.5 grams of added selenium per pound.
(e) The premix manufacturer shall follow good manufacturing practices in the production of selenium premixes. Inventory, production, and distribution records must provide a complete and accurate history of product production. Production controls must assure products to be what they are purported and labeled. Production controls shall include analysis sufficient to adequately monitor quality.
(f) The label or labeling of any selenium premix shall bear adequate directions and cautions for use including this statement: “Caution: Follow label directions. The addition to feed of higher levels of this premix containing selenium is not permitted.”
(g) The additive is orally administered to beef and dairy cattle as an osmotically controlled, constant release bolus containing sodium selenite. Each bolus contains 360 milligrams of selenium as sodium selenite, and delivers 3 milligrams of selenium per day for 120 days. To ensure safe use of the additive:
(1) The osmotically controlled, constant release bolus is for use only in
(2) Only one bolus containing 360 milligrams of selenium as sodium selenite is administered orally to each animal in 120 days.
(3) The labeling shall bear the following: “This bolus delivers the maximum daily allowable amount of selenium and shall be the sole source of supplementation. Do not use in areas containing excess selenium. Do not rebolus within 4 months.”
(h) Selenium yeast is a dried, non-viable yeast (
(1) Selenium, as selenium yeast, is added to feed as follows:
(i) In complete feed for chickens, turkeys, swine, beef cattle, and dairy cattle at a level not to exceed 0.3 part per million.
(ii) In feed supplements for limit feeding for beef cattle at a level not to exceed an intake of 3 milligrams per head per day.
(iii) In salt-mineral mixtures for free-choice feeding for beef cattle up to 120 parts per million in a mixture for free-choice feeding at a rate not to exceed an intake of 3 milligrams per head per day.
(2) Guaranteed organic selenium content from selenium yeast must be declared on the selenium yeast product label.
(3) The additive, as selenium yeast, shall be incorporated into feed as follows:
(i) It shall be incorporated into each ton of complete feed by adding no less than 1 pound of a premix containing no more than 272.4 milligrams of added selenium per pound.
(ii) It shall be incorporated into each ton of salt-mineral mixture for beef cattle from a premix containing no more than 4.5 grams of added selenium per pound.
(4) Usage of this additive must conform to the requirements of paragraphs (e) and (f) of this section.
At 58 FR 47973, Sept. 13, 1993, the amendments to § 573.920 that were published at 52 FR 10887, Apr. 6, 1987; 52 FR 21001, June 4, 1987; and 54 FR 14214, Apr. 10, 1989 were stayed until further notice. At 59 FR 45973, Sept. 6, 1994, the stay was confirmed.
The food additive silicon dioxide may be safely used in animal feed in accordance with the following conditions:
(a) The food additive is manufactured by vapor phase hydrolysis or by other means whereby the particle size is such as to accomplish the intended effect.
(b) It is used or intended for use in feed components as an anticaking agent, and/or grinding aid, as follows:
(c) It is used in feed as an anticaking agent in an amount not to exceed that reasonably required to accomplish its intended effect and in no case in an amount to exceed 2 percent by weight of the finished feed.
The food additive sorbitan monostearate may be safely used alone or in combination with polysorbate 60 as an emulsifier in mineral premixes and dietary supplements for animal feeds.
The food additive taurine (2-amino-ethanesulfonic acid) may be safely used in feed in accordance with the following prescribed conditions:
(a) It is used as a nutritional supplement in the feed of growing chickens.
(b) It is added to complete feeds so that the total taurine content does not exceed 0.054 percent of the feed.
(c) To assure safe use of the additive, the label and labeling shall bear in addition to the other information required by the Act:
(1) The name of the additive.
(2) The quantity of the additive contained therein.
(3) Adequate directions for use.
The food additive verxite may be safely used in animal feed in accordance with the following prescribed conditions:
(a) The additive is a magnesium-aluminum-iron silicate conforming to one of the following:
(1)(i) Verxite granules: The additive contains a minimum of 98 percent of hydrobiotite; it is thermally expanded and has a bulk density of from 5 to 9 pounds per cubic foot.
(ii) It is used or intended for use:
(
(
(2)(i) Verxite flakes: The additive contains a minimum of 98 percent of hydrobiotite; it has a bulk density of from 20 to 30 pounds per cubic foot.
(ii) It is used or intended for use as an anticaking or blending agent in ruminant feeds in an amount not to exceed that necessary to accomplish its intended effect and in no case to exceed 1 percent by weight of the final feed for ruminants.
(3)(i) Verxite grits: The additive contains a minimum of 80 percent of hydrobiotite; it has a bulk density of from 40 to 50 pounds per cubic foot.
(ii) It is used or intended for use as a partial roughage replacement in ruminant feeds in an amount not to exceed that necessary to accomplish its intended effect and in no case to exceed 1 percent by weight of the final feed.
(b) To assure safe use of the additive, the label of any feed additive supplement, feed additive concentrate, feed additive premix, or complete feed prepared therefrom shall bear, in addition to the other information required by the Act, the name of the additive (verxite granules, verxite flakes, or verxite grits), adequate directions for use, and, when the additive is present in excess of 1 percent, a statement of the quantity of the additive contained therein and the term “nonnutritive” in juxtaposition therewith.
The food additive xanthan gum may be safely used in animal feed as follows:
(a) The food additive is xanthan gum as defined in § 172.695 of this chapter and meets all of the specifications thereof.
(b) It is used or intended for use as a stabilizer, emulsifier, thickener, suspending agent, or bodying agent in animal feed as follows:
(1) In calf milk replacers at a maximum use level of 0.1 percent, as fed.
(2) In liquid feed supplements for ruminant animals at a maximum use level of 0.25 percent (5 pounds per ton).
(c) To assure safe use of the additive:
(1) The label of its container shall bear, in addition to other information required by the act, the name of the additive.
(2) The label or labeling of the additive container shall bear adequate directions for use.
Yellow prussiate of soda (sodium ferrocyanide decahydrate: Na
21 U.S.C. 321, 342, 343, 348, 371.
Regulations providing for irradiation in the production, processing, and handling of food in part 179 of this chapter are incorporated in subchapter E as applicable to use in the production, processing, handling, and labeling of animal feed and pet food, except where specifically provided for in this part.
Ionizing radiation for treatment of complete diets for animals may be safely used under the following conditions:
(a)
(1) Gamma rays for sealed units of the radionuclides cobalt-60 or cesium-137.
(2) Electrons generated from machine sources at energy levels not to exceed 10 million electron volts.
(b)
(2) If an irradiated feed ingredient is less than 5 percent of the final product, the final product can be irradiated without being considered to be re-irradiated.
Ionizing radiation for the treatment of complete poultry diets and poultry feed ingredients may be safely used as follows:
(a)
(b)
(c)
(1) Minimum dose 2.0 kiloGrays (kGy) (0.2 megarad (Mrad)); maximum dose 25 kGy (2.5 megarads Mrad). The absorbed dose of irradiation is to be based on initial concentration of salmonella using the relationship that 1.0 kGy (0.1 Mrad) reduces salmonella concentration by one log cycle (one decimal reduction).
(2) Feeds treated by irradiation should be formulated to account for nutritional loss.
(3) If an irradiated feed ingredient is less than 5 percent of the final product, the final product can be irradiated without being considered to be reirradiated.
21 U.S.C. 321, 342, 348, 371.
(a) It is impracticable to list all substances that are generally recognized as safe for their intended use. However, by way of illustration, the Commissioner regards such common food ingredients as salt, pepper, sugar, vinegar, baking powder, and monosodium glutamate as safe for their intended use. The lists in subparts B through H of this part include additional substances that, when used for the purposes indicated, in accordance with good manufacturing or feeding practice, are regarded by the Commissioner as generally recognized as safe for such uses.
(b) For the purposes of this section, good manufacturing or feeding practice shall be defined to include the following restrictions:
(1) The quantity of a substance added to animal food does not exceed the amount reasonably required to accomplish its intended physical, nutritional, or other technical effect in food; and
(2) The quantity of a substance that becomes a component of animal food as a result of its use in the manufacturing, processing, or packaging of food, and which is not intended to accomplish any physical or other technical effect in the food itself, shall be reduced to the extent reasonably possible.
(3) The substance is of appropriate grade and is prepared and handled as a food ingredient. Upon request the Commissioner will offer an opinion, based on specifications and intended use, as to whether or not a particular grade or lot of the substance is of suitable purity for use in food and would generally be regarded as safe for the purpose intended, by experts qualified to evaluate its safety.
(c) The inclusion of substances in the list of nutrients does not constitute a finding on the part of the Department that the substance is useful as a supplement to the diet for animals.
(d) Substances that are generally recognized as safe for their intended use within the meaning of section 409 of the Act are listed in subparts B through H of this part. When the status of a substance has been reevaluated and affirmed as GRAS or deleted from subparts B through H of this part, an appropriate explanation will be noted, e.g., “affirmed as GRAS,” “food additive regulation,” “interim food additive regulation,” or “prohibited from use in food,” with a reference to the appropriate new regulation. Such notation will apply only to the specific use covered by the review, e.g., direct animal food use and/or indirect animal food use and/or animal feed use and will not affect its status for other uses not specified in the referenced regulation, pending a specific review of such other uses.
Spices and other natural seasonings and flavorings that are generally recognized as safe for their intended use, within the meaning of section 409 of the act, are as follows:
Essential oils, oleoresins (solvent-free), and natural extractives (including distillates) that are generally recognized as safe for their intended use, within the meaning of section 409 of the act, are as follows:
Natural substances used in conjunction with spices and other natural seasonings and flavorings that are generally recognized as safe for their intended use, within the meaning of section 409 of the act, are as follows:
Natural extractives (solvent-free) used in conjunction with spices, seasonings, and flavorings that are generally recognized as safe for their intended use, within the meaning of section 409 of the act, are as follows:
Certain other spices, seasonings, essential oils, oleoresins, and natural extracts that are generally recognized as safe for their intended use, within the meaning of section 409 of the act, are as follows:
Synthetic flavoring substances and adjuvants that are generally recognized as safe for their intended use, within the meaning of section 409 of the act, are as follows:
These substances added to animal feeds as nutritional dietary supplements are generally recognized as safe when added at levels consistent with good feeding practice.
Adjuvants, identified and used in accordance with 40 CFR 180.1001(c) and (d), which are added to pesticide use dilutions by a grower or applicator prior to application to the raw agricultural commodity, are exempt from the requirement of tolerances under section 409 of the act.
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21 U.S.C. 321, 342, 348, 371.
The feed additive ethyl alcohol containing ethyl acetate meets the requirement of 27 CFR 21.62, being not less than 92.5 percent ethyl alcohol, each 100 gallons having had added the equivalent of 4.25 gallons of 100 percent ethyl acetate. It is used in accordance with good feeding practices in ruminant feed supplements as a source of added energy.
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(i) Amorphous fumed hydrophobic silica: Not less than 99.0 percent silicon dioxide after ignition. Not more than 3 ppm arsenic. Not more than 0.003 percent heavy metals (as lead). Not more than 10 ppm lead. Not more than 2.5 percent loss on drying. Not more than 2 percent loss on ignition after drying. Not more than 1 percent insoluble substances. Not more than 50 parts per million dichlorodimethylsilane.
(ii) Precipated hydrophobic silica: Not less than 94.0 percent silicon dioxide after ignition. Not more than 3 ppm arsenic. Not more than 0.003 percent heavy metals (as lead). Not more than 10 ppm lead. Not more than 7 percent loss on drying. Not more than 8.5 percent loss on ignition after drying. Not more than 5 percent soluble ionizable salts (as sodium sulfate). Not more than 1 percent insoluble substances. Not more than 50 parts per million dichlorodimethylsilane.
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(2) The product must comply with the following specifications:
(i) Not less than 94.0 percent 25-hydroxyvitamin D
(ii) Not more than 1 percent of any individual sterol.
(iii) Not more than 5 percent water.
(iv) Not more than 20 parts per million (ppm) lead.
(v) Not more than 20 ppm aluminum.
(vi) Not more than 1.0 percent solvents and non-detectable levels of 2', 4', 5', 7'-tetraiodofluorescin.
(3) Product labeling shall bear the following:
(i) A statement to indicate that the maximum use level of 25-hydroxyvitamin D
(ii) Adequate use directions to ensure that 25-hydroxyvitamin D
(iii) An expiration date on all premix labeling.
(iv) A statement on all premix labeling (feed and drinking water forms) that 25-hydroxyvitamin D
21 U.S.C. 321, 342, 343, 348, 371.
(a) The substances listed in this part have been prohibited from use in animal food or feed by the Food and Drug Administration because of a determination that they present a potential risk to the public health or have not been shown by adequate scientific data to be safe for use in such food or feed. Use of any of these substances in violation of this part causes the animal food or feed involved to be adulterated and in violation of the Act.
(b) This part includes only a partial list of substances prohibited from use in animal food or feed; it is for easy reference purposes and is not a complete list of substances that may not
(c) The Food and Drug Administration either on its own initiative or on behalf of any interested person who has submitted a petition, may publish a proposal to establish, amend, or repeal a regulation under this part on the basis of new scientific evaluation or information. Any such petition shall include an adequate scientific basis to support the petition, shall be the form set forth in § 571.1 of this chapter, and will be published in the
The Food and Drug Administration has determined that gentian violet has not been shown by adequate scientific data to be safe for use in animal feed. Use of gentian violet in animal feed causes the feed to be adulterated and in violation of the Federal Food, Drug, and Cosmetic Act (the act), in the absence of a regulation providing for its safe use as a food additive under section 409 of the act, unless it is subject to an effective notice of claimed investigational exemption for a food additive under § 570.17 of this chapter, or unless the substance is intended for use as a new animal drug and is subject to an approved application under section 512 of the act, or an index listing under section 572 of the act, or an effective notice of claimed investigational exemption for a new animal drug under part 511 of this chapter or § 516.125 of this chapter.
The Food and Drug Administration has determined that propylene glycol in or on cat food has not been shown by adequate scientific data to be safe for use. Use of propylene glycol in or on cat food causes the feed to be adulterated and in violation of the Federal Food, Drug, and Cosmetic Act (the act), in the absence of a regulation providing for its safe use as a food additive under section 409 of the act, unless it is subject to an effective notice of claimed investigational exemption for a food additive under § 570.17 of this chapter, or unless the substance is intended for use as a new animal drug and is subject to an approved application under section 512 of the act or an effective notice of claimed investigational exemption for a new animal drug under part 511 of this chapter.
(a)
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(c)
(i) Label the materials as follows: “Do not feed to cattle or other ruminants”; and
(ii) Maintain records sufficient to track the materials throughout their receipt, processing, and distribution, and make the copies available for inspection and copying by the Food and Drug Administration.
(2) Renderers described in paragraph (c)(1) of this section will be exempted from the requirements of paragraphs (c)(1)(i) and (c)(1)(ii) of this section if they:
(i) Use exclusively a manufacturing method that has been validated by the Food and Drug Administration to deactivate the agent that causes transmissible spongiform encephalopathy (TSE) and whose design has been made available to the public;
(ii) Use routinely a test method that has been validated by the Food and Drug Administration to detect the presence of the agent that causes TSE's and whose design has been made available to the public. Renderers whose products test positive for agents that cause TSE's must comply with paragraphs (c)(1)(i) and (c)(1)(ii) of this section. Records of the test results shall be made available for inspection by the Food and Drug Administration; or
(iii) Use exclusively a method for controlling the manufacturing process that minimizes the risk of the TSE agent entering the product and whose design has been made available to the public and validated by the Food and Drug Administration.
(3) Renderers described in paragraph (c)(1) of this section will be exempted from the requirements of paragraph (c)(1)(ii) of this section if they use a permanent method, approved by FDA, to make a mark indicating that the product contains or may contain protein derived from mammalian tissue. If the marking is by the use of an agent that cannot be detected on visual inspection, the renderer must use an agent whose presence can be detected by a method that has been validated by the Food and Drug Administration and whose design has been made available to the public.
(d)
(2) Protein blenders, feed manufacturers, and distributors, shall be exempt from paragraphs (d)(1) of this section if they:
(i) Purchase animal products from renderers that certified compliance with paragraph (c)(2) of this section or purchase such materials from parties that certify that the materials were purchased from renderers that certified compliance with paragraph (c)(2) of this section; or
(ii) Comply with the requirements of paragraph (c)(2) of this section where appropriate.
(3) Protein blenders, feed manufacturers, and distributors, shall be exempt from paragraph (c)(1)(ii) of this section if they:
(i) Purchase animal protein products that are marked in accordance with paragraph (c)(3) of this section or purchase such materials from renderers that certified compliance with paragraph (c)(3) of this section, or purchase such materials from parties that certify that the materials were purchased from renderers that certified compliance with paragraph (c)(3) of this section; or
(ii) Comply with the requirements of paragraph (c)(3) of this section where appropriate.
(4) Pet food products that are sold or are intended for sale at retail and feeds for nonruminant laboratory animals are exempt from the labeling requirements in paragraphs (c) and (d) of this section. However, if the pet food products or feeds for nonruminant laboratory animals are sold or are intended for sale as distressed or salvage items, then such products shall be labeled in accordance with paragraph (c) or (d) of this section, as appropriate.
(5) Copies of certifications as described in paragraphs (d)(2) and (d)(3) of this section, shall be made available for inspection and copying by the Food and Drug Administration.
(e)
(i) Comply with paragraphs (c)(1) or (d)(1) of this section as appropriate except that the labeling requirement shall apply only to products that contain or may contain protein derived from mammalian tissues or feeds containing such products;
(ii) In the case of a renderer, obtain nonmammalian or pure porcine or pure equine materials only from single-species slaughter facilities;
(iii) Provide for measures to avoid commingling or cross-contamination;
(A) Maintain separate equipment or facilities for the manufacture, processing, or blending of such materials; or
(B) Use clean-out procedures or other means adequate to prevent carry-over of products that contain or may contain protein derived from mammalian tissues into animal protein or feeds that may be used for ruminants; and
(iv) Maintain written procedures specifying the clean-out procedures or other means, and specifying the procedures for separating products that contain or may contain protein derived from mammalian tissue from all other protein products from the time of receipt until the time of shipment.
(2) Renderers, blenders, feed manufacturers, and distributors will be exempted from applicable requirements of paragraph (e)(1) of this section, if they meet the criteria for exemption under paragraphs (c)(2) or (c)(3) of this section, and (d)(2) or (d)(3) of this section.
(f)
(g)
(2) Animal protein products, and feeds containing such products, that are not in compliance with the labeling requirements of paragraphs (c) through (f) of this section will be deemed misbranded under section 403(a)(1) or 403(f) of the act.
(h)
(2) Written procedures required by this section shall be made available for inspection and copying by the Food and Drug Administration.
At 62 FR 30976, June 5, 1997, § 589.2000 was added. Paragraph (e)(1)(iv) of this section contains information collection and recordkeeping requirements and will not become effective until approval has been given by the Office of Management and Budget.
A list of CFR titles, subtitles, chapters, subchapters and parts and an alphabetical list of agencies publishing in the CFR are included in the CFR Index and Finding Aids volume to the Code of Federal Regulations which is published separately and revised annually.
Material Approved for Incorporation by Reference
Table of CFR Titles and Chapters
Alphabetical List of Agencies Appearing in the CFR
List of CFR Sections Affected
The Director of the Federal Register has approved under 5 U.S.C. 552(a) and 1 CFR Part 51 the incorporation by reference of the following publications. This list contains only those incorporations by reference effective as of the revision date of this volume. Incorporations by reference found within a regulation are effective upon the effective date of that regulation. For more information on incorporation by reference, see the preliminary pages of this volume.
All changes in this volume of the Code of Federal Regulations that were made by documents published in the
For the period before January 1, 2001, see the “List of CFR Sections Affected, 1949-1963, 1964-1972, 1973-1985, and 1986-2000” published in 11 separate volumes.