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 of such drug, even though such drug or animal feed containing such drug when used in another dosage, or another method or duration of administration or application, or different condition, is not a new animal drug.
(j)
(k) The term
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 for such preparations should bear a clear warning that either:
(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
(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 transfer this resistance, and the development of sensitivity to antibiotics in humans, unauthorized and unsafe residues of antibiotics cannot be permitted in food obtained from treated animals.
(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
(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 should be directed to the Director, Center for Veterinary Medicine, Food and Drug Administration, 7500 Standish Pl., Rockville, MD 20855.
(a) On receiving notification that an application submitted pursuant to § 514.1 of this chapter for a new animal drug is approved, the applicant shall establish and maintain such records and make such reports as are specified in this section to facilitate a determination as to whether there may be grounds for suspending or withdrawing approval of the application or whether any applicable regulation should be amended or repealed. The applicant shall maintain adequately organized and indexed files containing full reports of information pertinent to the safety or effectiveness of the new animal drug that have not previously been submitted as part of his application for the drug and which are received or otherwise obtained by him from any source, as follows:
(1) Unpublished reports of clinical or other animal experience, studies, investigations, and tests conducted by the applicant or reported to him by any person involving the new animal drug that is the subject of the application or any related drugs. An adequate summary and bibliography of reports in the scientific literature would ordinarily suffice. (The application must identify at the time of each report submission, each drug he considers related to the subject drug.)
(2) Experience, investigations, studies, or tests involving the chemical or physical properties or any other properties of the new animal drug, such as its behavior or properties in relation to microorganisms, including both the effects of the drug on microorganisms and the effect of microorganisms on the drug.
(3) For information required by this section, adequate identification of its source, when known, including the name and post office address of the person who furnishes such information.
(4) Copies of all mailing pieces and other labeling, and, if it is a prescription new animal drug or a veterinary feed directive drug, all advertising other than that contained in the application used in promoting the drug, and copies of the currently used package labeling that gives full information for use of the drug whether or not such labeling is contained in the application.
(5) Information concerning the quantity of the new animal drug distributed in a manner and form that facilitates estimates of the incidence of any adverse effects reported to be associated with the use of the drug. This does not require disclosure of financial, pricing, or sales data.
(6) Information concerning any previously unreported changes from the conditions described in an application conforming to the conditions of § 514.8(a)(5) of this chapter.
(b) The applicant shall submit to the Food and Drug Administration copies of the records and reports described in paragraph (a) of this section, except routine assay and control records, appropriately identified with the new animal drug application(s) to which they relate, as follows:
(1) Immediately upon receipt by the applicant, complete records or reports covering information of the following kinds:
(i) Information concerning a mixup in the new animal drug or its labeling with another article.
(ii) Information concerning any bacteriological or significant physical or other change or deterioration in the new animal 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.
(2) As soon as possible, and in any event within 15 working days of its receipt by the applicant, complete records of reports concerning any information of the following kinds:
(i) Information concerning any unexpected side effects, injury, toxicity, or sensitivity reaction or any unexpected incidence or severity thereof associated with clinical use, 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.
(ii) Information concerning any unusual failure of the new animal drug to exhibit its expected pharmacological activities.
(3) When mailing pieces, any other labeling, and advertising are devised for promotion of the new animal drug, specimens shall be submitted at the time of initial dissemination of such labeling and at the time of initial publication of any advertisement for a prescription drug. Mailing pieces and labeling designed to contain samples of a drug shall be complete except for the omission of the drug.
(4) All the kinds of information described in paragraph (a) of this section,
(i) At intervals within 6 months beginning with the date of approval of the new animal drug application during the first year following such date, and at yearly intervals thereafter.
(ii) Whenever an applicant is required to submit reports under the provisions of paragraph (b)(4)(i) of this section with respect to more than one approved application for preparations containing the same new animal drug so that the same item(s) of information is (are) required to be reported for more than one application, he may elect to submit as a part of the report for one such application all the information common to such applications in lieu of reporting separately and repetitively on each. The applicant shall state when this is done and identify all the new animal drug applications for which the reports are submitted.
(iii) The submitted copies of records and reports shall include all the required information that was received or otherwise obtained by the applicant during the designated intervals.
(5) On written order of the Commissioner, within the time stated in such order or agreed to by the applicant and the Commissioner, any designated records or reports containing the kinds of information described in this section shall be submitted.
(c) The applicant shall, upon request of any properly authorized officer or employee of the Department at reasonable times, permit such officers to have access to and copy and verify any records and reports established and maintained under the provisions of this section.
(d) If the Food and Drug Administration finds 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 the provisions of this section, or that the applicant has refused to permit access to or copying of, or verification of such records or reports, the Commissioner shall give the applicant notice and opportunity for a hearing on the question of whether to withdraw the approval of the application, as provided in § 514.200 of this chapter.
(e) Upon written request of the applicant stating reasonable grounds therefor, the Commissioner will make available any information in possession of the Food and Drug Administration of the kinds the applicant is required to maintain under the provisions of this section, except information readily available to the applicant from other sources or information which the Commissioner concludes is confidential.
(f) The
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) 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.
(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.
(a) The information described in § 510.300, except that described in paragraphs (b) (1) and (2) of that section, shall be submitted appropriately identified with the new animal drug application(s) to which they relate in duplicate on Form FD-2301 “Transmittal of Periodic Reports and Promotional Material for New Animal Drugs.”
(b) All adverse experiences with new animal drugs as described in § 510.300(b)(2) or § 510.301(b) whether or not related to a required periodic report submitted on a Form FD-2301, shall be reported on Form FD-1932 “Adverse Drug Reaction” (except as provided in paragraph (c) of this section). Reports of adverse drug experiences may be submitted initially in the form of a written communication, but any such communication shall be followed promptly (but not necessarily within the prescribed 15 working days) by a completed Form FD-1932. A separate “Adverse Drug Reaction” form should be submitted for each patient where feasible.
(c) In lieu of Form FD-1932 the holder of an approved new animal drug application may submit:
(1) A computerized report if the information contained therein and the sequence in which it is presented are equivalent to that required by Form FD-1932 and the report is submitted in duplicate. Such reports will require initial approval by the Food and Drug Administration prior to use; and
(2) Copies of reports of reactions appearing in the published scientific literature may be submitted.
(d) Forms FD-1932 and FD-2301, with instructions for their use, may be obtained from the Food and Drug Administration, Department of Health and Human Services, Center for Veterinary Medicine, 7500 Standish Pl., Rockville, MD 20855.
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 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 may be followed by dystocia, fetal death, retained placenta, and metritis. Additionally, corticosteroids used in dogs, rabbits, and rodents during pregnancy have produced cleft palate in offspring. Use in dogs has resulted in other congenital anomalies, including deformed forelegs, phocomelia, and anasarca. Drugs subject to this section are required to carry the veterinary prescription legend and are subject to the labeling requirements of § 201.105 of this chapter.
(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) For the purpose of this section, free-choice administration of animal drugs in feeds involves feeds that are placed in feeding or grazing areas and are not intended to be consumed fully at a single feeding or to constitute the entire diet of the animal. Such methods of administering drugs include, but are not limited to, medicated blocks (agglomerated feed compressed or rendered into a solid mass and cohesive enough to hold its form), mineral mixes, and liquid feed tank supplements (“lick tank” supplements) containing one or more animal drugs. The manufacture of medicated free-choice feeds is subject to the current good manufacturing practice regulations for medicated feeds.
(b) The Food and Drug Administration has concluded that there are questions about the safety and effectiveness of drugs when administered in free-choice feeds. Therefore, such methods of administration cause the drugs so administered to be new animal drugs, for which approved new animal drug applications (NADA's) are required. (See § 510.3(i)). In addition, the exemption from the requirement of an approved medicated feed application provided in § 558.4 of this chapter does not apply to any free-choice medicated feed.
(c) An NADA or supplemental NADA for products for free-choice feeding submitted for approval under section 512(b) of the act shall provide for:
(1) The manufacture of a finished product for the free-choice administration of a new animal drug. Such an approval will not provide a basis upon which an application can be approved under section 512(m) of the act; or
(2) The manufacture of a Type A medicated article for use in the subsequent manufacture of a free-choice medicated feed. The approved NADA will provide a basis upon which an application can be approved under section 512(m) of the act. Data for a specific free-choice product may, if desired, be generated and submitted to the Food and Drug Administration by the manufacturer of the free-choice feed in the form of a master file which can be referenced in the NADA or supplemental NADA submitted by the new animal drug sponsor.
(d) Approval of the NADA or supplemental NADA submitted under paragraph (c) of this section will be reflected in a regulation in part 558 of this chapter published under section 512(i) of the act. The regulation will either state the formulation of the approved free-choice product or specify the specific free-choice administration products in which the drug is approved for use. If the approval is for a Type A medicated article, the regulation in part 558 of this chapter will indicate that each use of the Type A medicated article in a free-choice product must be the subject of an approved supplemental NADA.
(e) An application submitted under section 512(m) of the act to provide for manufacture of a specific free-choice feed from an approved Type A medicated article will be approved if, in addition to the information required by the medicated feed application, it includes a reference to the exact formula of the product to be manufactured as follows:
(1) The formula is the same as the one published in the new animal drug regulations; or
(2) The data in a master file have been referenced in an NADA or supplemental NADA; and
(3) Use of the Type A medicated article in the specific formulation has been approved on the basis that:
(i) The formula is the same as the one for which acceptable data have been submitted in a master file by the medicated feed applicant; or
(ii) The medicated feed applicant has written authority to reference a master file that has acceptable data for the formula in question.
Animal feeds that bear or contain penicillin, chlortetracycline, feed grade zinc bacitracin, and bacitracin methylene disalicylate, with or without added suitable nutritive ingredients are exempt from the certification requirements of section 512 of the act provided they are the subject of and in compliance with regulations for their use in this subchapter E, part 558 of this chapter, or any one of the paragraphs of this section:
(a) Where indicated in paragraph (b) of this section it is manufactured with or without one, but only one, of the following ingredients in a quantity, by weight of feed, as hereinafter indicated:
(1) Arsanilic acid: Not less than 0.005 percent and not more than 0.01 percent.
(2) Sodium arsanilate: Not less than 0.005 percent and not more than 0.01 percent.
(3) 3-Nitro-4-hydroxyphenylarsonic acid: Not less than 0.0025 percent and not more than 0.0075 percent except in chicken or turkey feed which shall contain not less than 0.0025 percent and not more than 0.005 percent.
(b) It is intended for use in any one of the following conditions set forth in this paragraph:
(1) It is intended for use solely in the treatment of chronic respiratory disease (air-sac infection), infectious sinusitis, and blue comb (nonspecific infectious enteritis) in poultry and/or bacterial swine enteritis; its labeling bears adequate directions and warnings for such use; and it contains, per ton of
(2) It is intended for use solely in the treatment of chronic respiratory disease (air-sac infection) and infectious sinusitis in poultry; its labeling bears adequate directions and warnings for such use; and it contains not less than 0.1 percent para-aminobenzoic acid or the sodium or potassium salt or para-aminobenzoic acid.
(3)-(29) [Reserved]
(c) It is intended for use as follows:
(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