[Federal Register Volume 77, Number 16 (Wednesday, January 25, 2012)]
[Proposed Rules]
[Pages 3653-3664]
From the Federal Register Online via the Government Publishing Office [www.gpo.gov]
[FR Doc No: 2012-1430]
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DEPARTMENT OF HEALTH AND HUMAN SERVICES
Food and Drug Administration
21 CFR Parts 10, 20, 25, and 510
[Docket No. FDA-2001-N-0075 (formerly Docket No. 2001N-0284)]
RIN 0910-AF78
Import Tolerances for Residues of Unapproved New Animal Drugs in
Food
AGENCY: Food and Drug Administration, HHS.
ACTION: Proposed rule.
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SUMMARY: The Food and Drug Administration (FDA) is proposing to
establish procedures by which a person may request that the Agency
establish or amend tolerances for unapproved new animal drugs where
edible portions of animals imported into the United States may contain
residues of such drugs (import tolerances), as well as procedures to
revoke an existing import tolerance. Such import tolerances provide a
basis for legally marketing food of animal origin that is imported into
the United States and contains residues of unapproved new animal drugs.
DATES: Submit either electronic or written comments on the proposed
rule by April 24, 2012. Submit comments on information collection
issues under the Paperwork Reduction Act of 1995 by February 24, 2012,
(see the ``Paperwork Reduction Act of 1995'' section of this document).
ADDRESSES: You may submit comments, identified by Docket No. FDA-2001-
N-0075 and RIN 0910-AF78, by any of the following methods, except that
comments on information collection issues under the Paperwork Reduction
Act of 1995 must be submitted to the Office of Regulatory Affairs,
Office of Management and Budget (OMB) (see the ``Paperwork Reduction
Act of 1995'' section of this document).
Electronic Submissions
Submit electronic comments in the following way:
Federal eRulemaking Portal: http://www.regulations.gov.
Follow the instructions for submitting comments.
Written Submissions
Submit written submissions in the following ways:
Fax: (301) 827-6870.
Mail/Hand delivery/Courier (for paperor CD-ROM
submissions): Division of Dockets Management (HFA-305), Food and Drug
Administration, 5630 Fishers Lane, rm. 1061, Rockville, MD 20852.
Instructions: All submissions received must include the Agency
name, Docket No. FDA-2001-N-0075, and RIN 0910-AF78 for this
rulemaking. All comments received may be posted without change to
http://www.regulations.gov, including any personal information
provided. For additional information on submitting comments, see the
``Comments'' heading of the SUPPLEMENTARY INFORMATION section of this
document.
Docket: For access to the docket to read background documents or
comments received, go to http://www.regulations.gov and insert the
docket number, found in brackets in the heading of this document, into
the ``Search'' box and follow the prompts and/or go to the Division of
Dockets Management, 5630 Fishers Lane, rm. 1061, Rockville, MD 20852.
FOR FURTHER INFORMATION CONTACT: Scott Melton, Center for Veterinary
Medicine (HFV-232), Food and Drug Administration, 7519 Standish Pl.,
Rockville, MD 20855, (240) 276-8666, email: [email protected].
SUPPLEMENTARY INFORMATION:
I. Background
A. Legislative and Rulemaking Background
The President signed into law the Animal Drug Availability Act of
1996 (ADAA) on October 9, 1996. Section 4 of the ADAA amended section
512(a) of the Federal Food, Drug, and Cosmetic Act (the FD&C Act) (21
U.S.C. 360b(a)) by adding the following: ``(6) For purposes of section
402(a)(2)(D) (now section 402(a)(2)(C)(ii) as a result of the Food
Quality Protection Act), a use or intended use of a new animal drug
shall not be deemed unsafe under this section if the Secretary
establishes a tolerance for such drug (import tolerance) and any edible
portion of any animal imported into the United States does not contain
residues exceeding such tolerance. In establishing such tolerance, the
Secretary shall rely on data sufficient to demonstrate that a proposed
tolerance is safe based on similar food safety criteria used by the
Secretary to establish tolerances for applications for new animal drugs
filed under subsection (b)(1). The Secretary may consider and rely on
data submitted by the drug manufacturer, including data submitted to
appropriate regulatory authorities in any country where the new animal
drug is lawfully used or data available from a relevant international
organization, to the extent such data are not inconsistent with the
criteria used by the Secretary
[[Page 3654]]
to establish a tolerance for applications for new animal drugs filed
under subsection (b)(1). For purposes of this paragraph, `relevant
international organization' means the Codex Alimentarius Commission or
other international organization deemed appropriate by the Secretary.
The Secretary may, under procedures specified by regulation, revoke a
tolerance established under this paragraph if information demonstrates
that the use of the new animal drug under actual use conditions results
in food being imported into the United States with residues exceeding
the tolerance or if scientific evidence shows the tolerance to be
unsafe.'' \1\
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\1\ The Secretary of Health and Human Services (the Secretary)
has delegated to the Commissioner of Food and Drugs (the
Commissioner) the functions vested in the Secretary under the FD&C
Act and therefore, the authority under section 512(a)(6) of the FD&C
Act is exercised by the Commissioner.
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A residue is any compound present in edible tissues that results
from the use of a drug, and includes the drug, its metabolites, and any
other substance formed in or on food because of the drug's use (title
21 of the Code of Federal Regulations Sec. 530.3(f) (21 CFR
530.3(f))).
Any amount of residue in imported, animal-derived food from a new
animal drug not approved or conditionally approved in the United States
and for which no import tolerance exists, even a level of residue
considered safe by a country where the new animal drug is lawfully
used, would cause the imported, animal-derived food to be adulterated
under section 402(a)(2)(C)(ii) of the FD&C Act (21 U.S.C.
342(a)(2)(C)(ii)) because the drug would be deemed unsafe under section
512 of the FD&C Act. Such food could be denied entry into the United
States under section 801(a)(3) of the FD&C Act (21 U.S.C. 381(a)(3)).
Thus, it is unlawful to import animal-derived food that bears or
contains residues of a new animal drug that is not approved or
conditionally approved in the United States, unless a tolerance has
been established for the residues of that new animal drug in imported,
animal-derived food (import tolerance) and the residue of the new
animal drug in the imported, animal-derived food does not exceed the
import tolerance. It should be noted that the establishment of an
import tolerance for an unapproved new animal drug does not provide for
the lawful use of the drug in the United States, and such use would
cause the drug to be deemed unsafe within the meaning of section 512 of
the FD&C Act and adulterated within the meaning of section 501(a)(5) of
the FD&C Act (21 U.S.C. 351(a)(5)).
This import tolerance proposed regulation, if finalized, will be
FDA's last action to fully implement the ADAA. This proposed regulation
describes procedures by which a person could request that the Agency
establish or amend an import tolerance for a new animal drug not
approved or conditionally approved for use in the United States. This
proposed regulation would also establish procedures to revoke an
existing import tolerance as provided in section 512(a)(6) of the FD&C
Act. This regulation does not preclude the Commissioner from
establishing or amending an import tolerance on his or her own
initiative under Sec. 10.25(b) (21 CFR 10.25(b)).
Public and Advisory Committee Input Prior To Rulemaking
In the Federal Register of August 10, 2001 (66 FR 42167), the
Agency published an advance notice of proposed rulemaking (ANPRM) to
discuss issues pertaining to the development of regulations regarding
import tolerances. FDA solicited comments on four specific issues and
for any other issues relating to import tolerances. In January 2002,
FDA's Center for Veterinary Medicine (CVM, the Center) held a public
meeting with the Veterinary Medicine Advisory Committee (VMAC) to
discuss import tolerances. The Center presented the four specific
issues that were included in the previously published ANPRM. These
questions, as well as a summary of VMAC's responses and public comments
to the ANPRM, follow:
Issue 1: Approaches the Agency Could Use To Find a Safe Import
Tolerance
There are different approaches the Agency could use to find a safe
import tolerance. It could look at toxicity and residue data and build
in a conservative safety factor. Alternatively, it could also review
conditions of use such as good agricultural practices, route of
administration, and dose, which may result in a different safety factor
or factors. Additionally, it could consider manufacturing information
such as that required for a domestic application, which also could
result in a different safety factor or factors. Which approach is
preferable?
The consensus of VMAC was that import tolerances should be based on
a food safety approach similar to that currently employed by FDA to
establish tolerances for new animal drugs for which applications are
filed under section 512(b)(1) of the FD&C Act. The committee noted that
there should be some assurance that drugs covered by import tolerances
are manufactured under good manufacturing practices (GMP)-like
conditions.
Comments received from the public on this issue were similar to the
comments that were received from VMAC.
Issue 2: Analytical Techniques
Only the drug marker residue for the drug substance, not the
product formulation or the sponsor of the import tolerance, can be
determined by the type of analytical method that is typically used to
assay imports. Are there analytical techniques or other approaches that
would allow the Agency to determine whether a residue is due to use of
the drug product for which the tolerance is approved?
The consensus of VMAC was that they were not aware of a practical
methodology to accomplish this task.
Issue 3: Agency Disclosure to the Public
Should the Agency disclose to the public that it is
considering an import tolerance for a new animal drug?
If so, when (e.g., upon request, upon filing)?
How should the Agency do so (e.g., Federal Register,
Internet)?
How much detail should the Agency provide, keeping in mind
that it cannot disclose trade secrets or confidential commercial
information?
The consensus of VMAC was that FDA should do an initial review of
each request to establish or amend an import tolerance to determine the
completeness of the submission package. If the requester's package is
complete, then the public should be made aware that the Agency is
considering establishing the requested import tolerance. This public
notification should occur via publication in the Federal Register, the
CVM Web site and other avenues, as appropriate. This notification
should occur in a timely manner in order to allow for adequate public
feedback and consideration of public concerns prior to a decision on
the establishment of an import tolerance.
Public comments on this issue included suggestions that requests to
establish import tolerances should be disclosed to the public early in
the process. Commenters also indicated that submitted data should have
the same confidentiality protections as that provided to data submitted
as part of a new animal drug application (NADA). Most commenters felt
that a Freedom of Information (FOI) summary should be made publicly
available following establishment of the import tolerance.
[[Page 3655]]
Issue 4: Import Tolerances Effect on the Environment
FDA is considering amending the regulations at 21 CFR 25.33 to
allow a categorical exclusion for import tolerances under the National
Environmental Policy Act, if there is information that shows that
establishing import tolerances does not have a significant effect on
the environment. The Agency is seeking information on whether import
tolerances will have a significant effect on the environment.
The consensus of VMAC was that they could not think of any instance
relative to residues within animal-derived food products that would
have a significant environmental impact.
Other public comments on this issue included that categorical
exclusion from the requirement to submit an environmental assessment
would be appropriate for import tolerances on a case-by-case basis, if
no extraordinary circumstances exist.
Issue 5: Please Comment on Any Other Aspects of Import Tolerances You
Wish To Raise
There were no additional comments from VMAC.
Other public comments on this issue included that FDA should not
establish an import tolerance for a new animal drug not allowed to be
used in food animals in the United States or prohibited in the United
States from extra-label use in food producing animals. Another comment
suggested that an import tolerance for an unapproved new animal drug
should apply to domestically-produced animal-derived food. Some
commenters questioned whether the Agency would have the resources for
residue testing.
B. Current Process for Establishing New Animal Drug Tolerances
1. Overview of the Approval Process for NADAs Submitted Under Section
512(b)(1) of the FD&C Act
Before FDA can approve an NADA submitted under section 512(b)(1) of
the FD&C Act, the Agency must, among other things, determine that there
is substantial evidence that the new animal drug will have the effect
it purports or is represented to have under the conditions of use
prescribed, recommended, or suggested in the proposed labeling, and
that the NADA contains full reports of investigations including
adequate tests by all methods reasonably applicable to show whether the
new animal drug is safe for use under the conditions prescribed,
recommended, or suggested in the proposed labeling (21 U.S.C.
360b(d)(1)(A) and (d)(1)(E)). In addition, for new animal drugs
intended for use in food-producing animals, in determining whether a
new animal drug is safe for use under the conditions prescribed,
recommended, or suggested in the proposed labeling, FDA must consider,
among other factors, the probable consumption of such drug by humans
due to its presence in or on animal-derived food and the effect of such
drug on humans (21 U.S.C. 360b(d)(2)). As a part of that determination,
FDA may set tolerances for new animal drug residues that occur in the
food (21 U.S.C. 360b(d)(1)(F)).
2. Human Food Safety Data Requirements To Establish New Animal Drug
Tolerances
The human food safety requirements for approval of an NADA are
broadly described in 21 CFR part 500, subpart E and in 21 CFR
514.1(a)(7) and (a)(8). The sponsor of a new animal drug is required to
furnish FDA with evidence demonstrating that the residues of the new
animal drug in the edible products of treated animals are safe. FDA has
developed a number of guidance documents, which are available on the
FDA Web site (http://www.fda.gov/AnimalVeterinary/GuidanceComplianceEnforcement/GuidanceforIndustry/ucm123817.htm), to
inform sponsors of the scientific data FDA believes could provide an
acceptable basis for determining the human food safety of a new animal
drug.
Human food safety data are generated by conducting studies to
assess the nature and quantity of residues in foods derived from
animals treated with a new animal drug. The human food safety studies
fall into three general categories: Toxicity studies; residue chemistry
studies; and, for antimicrobial new animal drugs, microbial safety
studies.
The toxicity studies are designed to evaluate the oral toxicity of
a new animal drug to humans, who may be exposed to the drug through the
consumption of food derived from animals treated with the new animal
drug. The goal of the toxicity studies is to determine an acceptable
daily intake (ADI). The ADI is used to calculate the amount of total
residues permitted in each edible tissue, also known as the safe
concentration.
The residue chemistry studies are designed to determine the
concentration of drug residue actually appearing at the time of
slaughter of the target animal in the edible tissues of that animal
species as a result of treatment with the proposed new animal drug.
Data from studies that investigate the metabolism of the veterinary
drug are used to establish a relationship between the residue selected
for assay (marker residue) and the concentration of the total residue
in the target tissue. These residue chemistry data are used to
calculate the tolerance. Tolerances are the maximum concentration of a
new animal drug residue that can legally remain in an edible tissue
from animals treated with the new animal drug. When a tolerance is
assigned for an approved or conditionally approved new animal drug, a
practicable regulatory analytical method is also established to
quantify and confirm residues of the new animal drug to monitor the
safety of the food supply.
For antimicrobial new animal drugs, typically data are generated
that support the conduct of a qualitative risk assessment that
addresses the release, exposure, and consequence of the effects of the
new animal drug on the development of resistant bacteria in or on the
target animal and the potential impact on human health.
C. International Harmonization of Food Safety Standards
FDA works toward international harmonization of food safety
standards, including food safety controls such as veterinary drug
tolerances.
Under the proposed regulation, FDA intends to harmonize its import
tolerances with the Maximum Residue Limits (MRLs) established by the
Codex Alimentarius Commission of the Joint Food and Agriculture
Organization (FAO)/World Health Organization (WHO) Food Standards
Program (Codex MRL), provided that the Codex Alimentarius Commission
has established a permanent Codex MRL and that the Agency has
sufficient information to make a determination that the permanent Codex
MRL will protect the U.S. public health and will meet the standards of
the FD&C Act. If the Codex Alimentarius Commission has established a
permanent Codex MRL for a new animal drug, the Agency would allow the
submission of human food safety information in the form of monographs
and reports from the Joint FAO/WHO Meeting on Pesticide Residues (JMPR)
and/or the Joint Expert Committee on Food Additives of the FAO and the
WHO (JECFA) to support the requested import tolerance. The JMPR and/or
JECFA monographs and reports provide an evaluation of human food safety
data; these data are then used to derive the ADI and the recommended
MRL. If FDA review of the committee reports and monographs raises
additional scientific concerns that merit more detailed review, the
Agency
[[Page 3656]]
proposes to require submission of the complete toxicology and residue
chemistry study reports, including the underlying data.
If the Codex Alimentarius Commission has not established a
permanent Codex MRL for a new animal drug, the Agency proposes to
require submission of the complete toxicology and residue chemistry
study reports, including the underlying data. In addition, in the
absence of a permanent Codex MRL, the Agency proposes that the
requester should provide full reports of investigations made with
respect to the human food safety of the new animal drug, including data
submitted to the appropriate regulatory authority in any country where
the new animal drug is lawfully used.
II. Summary of the Proposed Rule
A. Scope (Proposed Sec. 510.201)
Proposed Sec. 510.201 establishes and restricts proposed subpart C
to procedures by which the Agency may establish, amend, or revoke an
import tolerance for residues of a new animal drug not approved or
conditionally approved for use in the United States but lawfully used
in other countries and present in imported, animal-derived food and
food products, as well as procedures to reconsider or stay actions
regarding an import tolerance. Under section 512(a)(6) of the FD&C Act,
the Secretary may consider and rely on data submitted to appropriate
regulatory authorities in any country where the new animal drug is
lawfully used. In addition, the Secretary may use data available from a
relevant international organization to the extent such data are not
inconsistent with the criteria used to establish a tolerance for new
animal drug applications submitted under section 512(b)(1) of the FD&C
Act. For purposes of section 512(a)(6) of the FD&C Act, ``relevant
international organization'' means the Codex Alimentarius Commission or
other international organization deemed appropriate by the Secretary.
When evaluating the residue of a new animal drug as part of the
determination of a tolerance, FDA considers the conditions of use
including dose, duration, and formulation. The conditions of use can
affect the uptake, metabolism, and distribution of the residues in the
treated food animal and therefore, are a critical component of the
human food safety evaluation for a tolerance of a domestic new animal
drug as part of a new animal drug approval. Similarly, the Codex
Alimentarius requires that a veterinary drug under evaluation for an
MRL be approved in at least one member country in order to assure that
the conditions of use are available as part of the scientific
evaluation. FDA believes that it would also be important that the
evaluation for a tolerance for residues of a new animal drug in
imported food consider conditions of use. Consequently, FDA believes
that the new animal drug under evaluation must be lawfully used in at
least one country in a manner consistent with the conditions of use
that cause the residues in the imported food, and that the information
resulting from this lawful use be made available to FDA as part of the
evaluation for an import tolerance.
B. Definitions (Proposed Sec. 510.203)
Proposed Sec. 510.203 contains definitions for the terms import
tolerance and request. The proposed definition of import tolerance (``a
tolerance for a residue of a new animal drug not approved or
conditionally approved for use in the United States, but present in any
imported edible portion of any animal'') is derived from the statutory
language, which provides that a use or intended use of a new animal
drug shall not be deemed unsafe under section 512 of the FD&C Act, ``if
the Secretary establishes a tolerance for such drug and any edible
portion of any animal imported into the United States does not contain
residues exceeding such tolerance.'' 21 U.S.C. 360b(a)(6). The proposed
definition for request (``a request to establish or amend an import
tolerance'') sets forth the meaning of the term, as it is used in
proposed subpart C.
C. Requests To Establish or Amend an Import Tolerance (Proposed Sec.
510.205)
1. Initiation of a Request To Establish or Amend an Import Tolerance
(Proposed Sec. 510.205(a))
Proposed Sec. 510.205(a) provides that any person could request
that the Commissioner establish or amend an import tolerance and that
such a request would have to be in the form specified in proposed Sec.
510.205, which is described in this section of the document. Proposed
Sec. 510.205(a) also provides that the Commissioner could initiate a
proceeding to establish or amend an import tolerance on his or her own
initiative under 21 CFR 10.25(b).
2. Content and Administration of a Request (Proposed Sec. 510.205(b))
Under this proposed section, a request to establish or amend an
import tolerance would have to include the following information: (1)
The established name and all pertinent information concerning the new
animal drug, including chemical identity and composition of the new
animal drug, and its physical, chemical, and biological properties; (2)
the conditions of use for the new animal drug, including the route of
administration and dosage, together with all labeling, directions, and
recommendations regarding the uses in countries in which the new animal
drug is lawfully used; (3) the proposed import tolerance(s) for the new
animal drug; (4) human food safety information to support the proposed
import tolerance(s); and (5) a complete description of a practicable
validated method for measuring the residue level in imported edible
portions of any animal treated with the new animal drug.
The contents of the request would have to include data sufficient
to demonstrate that a proposed tolerance is safe based on similar human
food safety criteria used by the Commissioner to establish tolerances
for applications for new animal drugs filed under section 512(b)(1) of
the FD&C Act. Consistent with section 512(a)(6) of the FD&C Act,
information to support the establishment of an import tolerance for a
new animal drug could include data submitted by the drug manufacturer,
including data submitted to appropriate regulatory authorities in any
country where the new animal drug is lawfully used, or data available
from a relevant international organization, such as the Codex
Alimentarius Commission, to the extent such data are not inconsistent
with the criteria used by the Commissioner to establish a tolerance for
applications for new animal drugs filed under section 512(b)(1) of the
FD&C Act.
Under the proposed rule, human food safety information to support
the proposed import tolerance could be submitted in two possible forms.
First, if a permanent Codex MRL has been established, the requester
would provide the permanent Codex MRL and monographs and reports from
the JECFA and/or monographs and reports from the JMPR that support the
development of the permanent Codex MRL. FDA could request additional
information as needed. If no permanent Codex MRL has been established,
or upon notification by FDA, the requester would have to provide full
reports of investigations made with respect to the human food safety of
the new animal drug.
Should full reports be required by the rule or requested by FDA, a
request to establish or amend an import tolerance could be regarded as
incomplete unless it includes full reports of adequate tests,
[[Page 3657]]
by all methods reasonably applicable, to show whether or not any edible
portion of any animal receiving the new animal drug would be safe for
human consumption. The reports would have to include detailed data
derived from appropriate animal and other biological experiments in
which the methods used and the results obtained are clearly set forth.
Under the proposed rule, the request would have to include either a
statement that all such reports have been submitted or an explanation
of why such reports were not submitted. With respect to each
nonclinical laboratory study contained in the request, the requestor
would have to submit either a statement that the study was conducted in
compliance with the good laboratory practice regulations set forth in
21 CFR part 58, or, if the study was not conducted in compliance with
such regulations, a brief statement of the reason for the
noncompliance, and an explanation of how the noncompliance may have
impacted the study.
Furthermore, a request to establish or amend an import tolerance
would have to include any other information that could be deemed
necessary by the Commissioner to address particular human food safety
concerns that may be associated with certain new animal drugs or
classes of new animal drugs. For example, for certain antimicrobial new
animal drugs, the Agency could consider information regarding
antimicrobial resistance concerns in making its determination that a
proposed import tolerance is safe.
A request to establish or amend an import tolerance would also have
to include information on where the new animal drug is lawfully used.
Such information includes the conditions of use for the new animal
drug, including the route of administration and dosage; labeling;
directions; and recommendations. When an import tolerance is
established, it would be available to any importer into the United
States of the same food product(s) containing the unapproved drug
product that is subject to the import tolerance.
The request would also have to include a complete description of a
practicable validated method for measuring the residue level of the new
animal drug in the imported edible product derived from animals treated
with the new animal drug. The availability of such a method is
important for monitoring compliance with the import tolerance.
Under this proposed rule, if finalized, a requester would be
required to submit an environmental assessment, as described in 21 CFR
25.40, to facilitate the Agency's assessment of potential environmental
impacts under the National Environmental Policy Act; Executive Order
12114, ``Environmental Effects Abroad of Major Federal Actions,'' of
January 4, 1979 (44 FR 1957, January 9, 1979); and 21 CFR 25.60. As
previously discussed in this document, the Agency solicited comments on
the issue of whether import tolerances will have a significant effect
on the environment in the August 2001 ANPRM and January 2002 VMAC.
Although categorical exclusions are not addressed in this proposed
rule, the Agency is still considering the comments received in response
to the August 2001 ANPRM and January 2002 VMAC. If, in the future, the
Agency determines it to be appropriate, FDA will consult with the
Council on Environmental Quality (CEQ) regarding the establishment of
categorical exclusions for certain import tolerance requests. FDA
reiterates its previous requests for comments and supporting
information relevant to the issue of whether import tolerances will
have a significant effect on the environment in the United States or
abroad.
Proposed Sec. 501.205(b) provides that requests for an import
tolerance would have to be submitted to FDA in triplicate. By prior
arrangement, requests could be submitted in an electronic format.
Pertinent information previously submitted to and currently
retained in the files of FDA could be incorporated in, and would be
considered as part of, a request to establish or amend an import
tolerance on the basis of specific reference to such information. If
the requester refers to any nonpublic information other than its own,
the requester would have to obtain a written right of reference to that
nonpublic information and submit such right of reference with the
request. Any reference to published information would have to be
accompanied by reprints or copies of such references. If a part of the
material submitted is in a foreign language, it would have to be
accompanied by a complete and accurate English translation.
Translations of literature printed in a foreign language would have to
be accompanied by copies of the original publication.
Furthermore, the request would have to be dated and signed by the
requester or by his or her authorized representative. If the requester
or such authorized representative does not reside or have a place of
business within the United States, the requester would also have to
furnish the name and post office address of, and the request would have
to be countersigned by, an authorized attorney, agent, or official
residing or maintaining a place of business within the United States.
A request to amend an established import tolerance would have to
contain information to support each proposed change. The request could
omit statements made in the original request for which no change is
proposed.
The requester could withdraw a request to establish or amend an
import tolerance at any time before the notification provided for in
proposed Sec. 510.205(d)(2) has been made publicly available.
3. Review of Information Submitted in a Request (Proposed Sec.
510.205(c))
In establishing an import tolerance or amending an existing import
tolerance, the Commissioner would rely on data sufficient to
demonstrate that a proposed tolerance is safe based on similar human
food safety criteria used by the Commissioner to establish tolerances
for applications for new animal drugs filed under section 512(b)(1) of
the FD&C Act. In establishing or amending an import tolerance, the
Commissioner would give appropriate consideration to the residue
concentrations and conditions of use of the animal drug in the import
tolerance request.
4. Disclosure of Information Submitted in a Request (Proposed Sec.
510.205(d))
FDA intends to be as transparent as possible about requests to
establish, amend, or revoke import tolerances, as well as the basis for
establishing, amending, or revoking import tolerances. This
transparency is in response to the VMAC consensus that disclosure of
import tolerance requests be made to the public early in the review
process. The rule proposes that when a request to establish or amend an
import tolerance has been filed, this request would be made publicly
available. In addition, the decision to establish, amend, or revoke an
import tolerance would be made publicly available. A summary of the
basis for the decision would also be publicly released. All information
and safety data submitted with, or incorporated by reference in, the
request would be available for public disclosure, in accordance with
the provisions of part 20 (21 CFR part 20). Trade secrets and
confidential commercial or financial information would be exempted from
release under Sec. 20.61.
[[Page 3658]]
5. Establishment or Amendment of an Import Tolerance (Proposed Sec.
510.205(e))
The rule proposes that when a request to establish or amend an
import tolerance is granted, a copy of the public notification would be
sent to the requestor. Similarly, when a request to establish or amend
an import tolerance is denied, a copy of the notification of the denial
would be sent to the requestor as well as made publicly available,.
This proposed section also makes clear that if a tolerance is
established as part of an approval of a new animal drug application
under section 512(b)(1) of the FD&C Act (21 U.S.C. 360b(b)(1)), or
conditional approval under section 571 of the FD&C Act, (21 U.S.C.
360ccc), the approved new animal drug tolerance would supersede any
existing import tolerance for that new animal drug. A notification that
the existing import tolerance has been superseded by a tolerance for
that new animal drug would be made publicly available and a copy of
this notification would be sent to the requester.
In the event that the conditionally approved application for a new
animal drug is not renewed or is withdrawn, or such drug does not
achieve full approval under section 512 of the FD&C Act within 5 years
following the date of the conditional approval, the Agency would
reinstate the import tolerance and a notification would be made
available to the public, and copy of this public notification would be
sent to the original requestor.
D. Revoking an Import Tolerance (Proposed Sec. 510.207)
Proposed Sec. 510.207 specifies the procedures by which an
established tolerance for residues of an unapproved new animal drug in
food products of animal origin imported into the United States could be
revoked. Section 512(a)(6) of the FD&C Act authorizes this action if
information demonstrates that the use of the new animal drug under
actual use conditions results in food being imported into the United
States with residues exceeding the tolerance or if scientific evidence
shows the tolerance to be unsafe. The Commissioner, on his or her own
initiative or on the petition of an interested person, under part 10
(21 CFR part 10), could revoke an import tolerance. The grounds for
revocation of the import tolerance would be made publicly available.
E. Reconsideration of Action (Proposed Sec. 510.209)
Proposed Sec. 510.209 specifies the process for an interested
person to petition that the Commissioner reconsider a decision to
establish, amend, or revoke an import tolerance and also provides that
the Commissioner could reconsider a decision on his or her own
initiative. The section proposes that a petition for reconsideration of
such a decision would have to be filed with the Division of Dockets
Management under Sec. 10.20, and be in the form set out in Sec.
10.33. Under proposed Sec. 510.209, an interested person would have to
petition for reconsideration no later than 30 days after public
notification of the decision, although the Commissioner could, for good
cause, permit a petition to be filed more than 30 days after public
notification of the decision. The petition for reconsideration would
have to demonstrate that the Commissioner did not adequately consider
relevant information and views that are in the administrative record.
No new information could be included in a petition for reconsideration.
F. Administrative Stay of Action (Proposed Sec. 510.211)
Proposed Sec. 510.211 specifies the process for an interested
person to petition that the Commissioner stay or extend the effective
date of a decision to establish, amend, or revoke an import tolerance.
It also provides that the Commissioner, on his or her own initiative,
could stay or extend the effective date of a decision to establish,
amend, or revoke an import tolerance. The proposed section would
specify that a petition for a stay or for an extension of the effective
date of such a decision be filed with the Division of Dockets
Management in accordance with Sec. 10.20, and be in the form set out
in Sec. 10.35. Under proposed Sec. 510.211, an interested person
would have to petition the Commissioner stay or extend the effective
date of a decision with respect to establishing, amending, or revoking
an import tolerance no later than 30 days after the date of public
notification, although the Commissioner could, for good cause, permit a
petition to be filed more than 30 days after the date of public
notification of the decision.
III. Conforming Changes
FDA is proposing conforming changes to certain applicable sections
of the Code of Federal Regulations (CFR) that would add a reference to
the processes for establishing or amending import tolerances and
revoking such tolerances listed under section 512 of the FD&C Act. The
affected sections in title 21 of the CFR are:
Sec. 10.25 Initiation of administrative proceedings.
Sec. 20.100 Applicability; cross-reference to other
regulations.
Sec. 25.20 Actions requiring preparation of an
environmental assessment.
IV. Legal Authority
FDA is proposing this rule under the authority of section 512(a)(6)
of the FD&C Act, which states that ``a use or intended use of a new
animal drug shall not be deemed unsafe * * * if the Secretary
establishes a tolerance for such drug and any edible portion of any
animal imported into the United States does not contain residues
exceeding such tolerance.'' Furthermore, ``the Secretary may, under
procedures specified by regulation, revoke a tolerance established
under this paragraph if information demonstrates that the use of the
new animal drug under actual use conditions results in food being
imported into the United States with residues exceeding the tolerance
or if scientific evidence shows the tolerance to be unsafe.'' FDA is
also proposing these regulations under section 701(a) of the FD&C Act
(21 U.S.C. 371(a)), which authorizes the issuance of regulations for
the efficient enforcement of the FD&C Act.
V. Analysis of Impacts
A. Introduction
FDA has examined the impacts of the proposed rule under Executive
Order 12866, Executive Order 13563, the Regulatory Flexibility Act (5
U.S.C. 601-612), and the Unfunded Mandates Reform Act of 1995 (Pub. L.
104-4). Executive Orders 12866 and 13563 direct Agencies to assess all
costs and benefits of available regulatory alternatives and, when
regulation is necessary, to select regulatory approaches that maximize
net benefits (including potential economic, environmental, public
health and safety, and other advantages; distributive impacts; and
equity). The Agency believes that this proposed rule is not a
significant regulatory action as defined by Executive Order 12866.
The Regulatory Flexibility Act requires Agencies to analyze
regulatory options that would minimize any significant impact of a rule
on small entities. Because FDA anticipates most requests will rely on
data already gathered, analyzed, and summarized in publicly available
dossiers supporting a
[[Page 3659]]
permanent Codex MRL, and because FDA has received only two requests to
establish import tolerances since 1996, both from large manufacturers
of new animal drugs, the Agency proposes to certify that the final rule
will not have a significant economic impact on a substantial number of
small entities.
Section 202(a) of the Unfunded Mandates Reform Act of 1995 requires
that Agencies prepare a written statement, which includes an assessment
of anticipated costs and benefits, before proposing ``any rule that
includes any Federal mandate that may result in the expenditure by
state, local, and tribal governments, in the aggregate, or by the
private sector, of $100,000,000 or more (adjusted annually for
inflation) in any one year.'' The current threshold after adjustment
for inflation is $136 million, using the most current (2010) Implicit
Price Deflator for the Gross Domestic Product. FDA does not expect this
proposed rule to result in any 1-year expenditure that would meet or
exceed this amount.
B. The Proposed Rule
FDA is proposing procedures to establish or amend a tolerance for a
new animal drug that has not been approved or conditionally approved
for use in the United States where edible portions of animals imported
into the United States may contain residues of such drugs (import
tolerance), as well as procedures to revoke an existing import
tolerance. Import tolerances will provide a basis for legally marketing
food of animal origin that is imported into the United States
containing residues of unapproved new animal drugs. The proposed rule
sets forth the information that a requester would need to submit to
support the establishment or amendment of an import tolerance. This
information may include data submitted by the requester, including data
submitted to appropriate regulatory authorities in any country where
the new animal drug is used legally, or data available from a relevant
international organization such as the Codex Alimentarius Commission.
The proposed rule would also require that requests to establish or
amend an import tolerance include a practical validated method for
measuring the residue level of the new animal drug in the imported
edible product derived from animals treated with the new animal drug.
The proposed rule also allows for the public notification of requests
to establish or amend an import tolerance, information supporting such
requests, and for public notification when establishing, amending, or
revoking import tolerances. In addition, the proposed rule describes
procedures for revoking an existing import tolerance if scientific
evidence shows the tolerance to be unsafe or if information
demonstrates that use of the new animal drug under actual use
conditions results in food being imported into the United States with
residues exceeding the tolerance.
C. Need for the Proposed Rule
While interested parties may currently submit requests for the
establishment of import tolerances under the authority of the statutory
provision (21 U.S.C. 360b(a)(6)), this proposed rule, if finalized,
will provide a more efficient method for the submission of requests to
establish import tolerances since the regulation would set forth the
information required to be submitted in such a request. In addition,
under section 512(a)(6) of the FD&C Act, in order to be able to revoke
existing import tolerances, the Agency must specify, by regulation,
procedures to revoke an import tolerance. This proposed rule, if
finalized, would establish such procedures.
D. Benefits of the Proposed Rule
As stated previously in this document, this proposed rule, if
finalized, would set forth procedures by which interested parties may
submit requests for the establishment, amendment or revocation of an
import tolerance. In doing so, the proposed rule, if finalized, should
initially increase the number of requests to establish, amend, or
revoke an import tolerance the Agency would otherwise expect to
receive. Under the new procedures, FDA estimates that it will receive
2.2 requests to establish import tolerances per year. At this time FDA
does not expect the number of annual requests to increase any further
in future years. FDA currently does not have the data to estimate the
value of these import tolerances should they be established. FDA
assumes, however, that profits earned importing animal-derived food
containing allowable residues of unapproved new animal drugs that are
the subject of established import tolerances would be greater than the
marginal costs of requesting the establishment of such import
tolerances.
E. Costs of the Proposed Rule
1. Requesters
Those who choose to request the establishment, amendment, or
revocation of an import tolerance will voluntarily incur compliance
costs. These costs are expected to be composed of labor costs for
organizing the pertinent information that will be submitted with a
request to establish, amend, or revoke an import tolerance.
FDA expects to receive two requests annually to establish import
tolerances for unapproved new animal drugs for which a permanent Codex
MRL has been established. In these cases, FDA estimates that a
requester would expend about 50 hours to locate and review the
toxicology and residue chemistry reports from the Codex MRL dossier and
to prepare and submit the request to FDA. The median compliance officer
wage rate for the pharmaceutical industry (NAICS 325400--Pharmaceutical
and Medicine Manufacturing), adjusted 35 percent for benefits, is about
$42 per hour. The annual compliance cost for petitioners requesting the
establishment of an import tolerance for unapproved new animal drugs
with permanent Codex MRLs would be about $4,000 (2 requesters times 50
hours times $42 per hour), or about $2,100 per request.
FDA estimates that it would receive 0.2 requests annually to
establish import tolerances for unapproved new animal drugs for which a
permanent Codex MRL has not been established. FDA estimates that a
requester would expend about 80 hours to prepare such a request. Using
the same $42 per hour rate for wages and benefits, the cost to prepare
a request of this type would be about $3,300. Since FDA expects only
one of these requests every 5 years, the average annual cost would be
about $650.
Total annual industry costs for the 2.2 requests to establish an
import tolerance are estimated at about $4,800 (2 requests that cost
$2,100 each plus one request that costs $650).
Requests to revoke or amend an import tolerance are expected to be
extremely infrequent events. FDA believes that these requests are
likely to be submitted significantly less than even once every 5 years.
FDA recognizes that requesters may incur some administrative costs for
time spent in preparing a request to amend or revoke an import
tolerance. While FDA has not added such costs to the total compliance
cost estimates, due to the relative infrequency of these requests FDA
concludes that the annual cost for each of these types of requests
would be insignificant. Even in the rare year in which FDA receives one
of these requests, at an estimated burden of about 32 labor hours, the
marginal cost would amount to about $1,300. This would add about 28
percent to the very low annual costs of the proposed rule.
FDA projects the compliance costs of this rule to industry over a
10-year period at $42,400 using a 3 percent
[[Page 3660]]
discount rate, and at $36,300 using a 7 percent discount rate.
2. Government
FDA estimates that each request to establish, amend, or revoke an
import tolerance would require up to 100 hours of total time spent in
review and document preparation by mid-level FDA employees. Assuming a
GS-13, Step-1 hourly pay rate of about $43, with a 35 percent increase
for benefits, the 100 hours of labor for each review are estimated to
cost about $5,800. This equates to about $12,800 annually for the 2.2
reviews. Over a 10-year period, the administrative costs to the
Government are projected at $112,200 using a 3 percent discount rate,
and at $96,000 using a 7 percent discount rate.
F. Regulatory Alternatives
Section 4 of the ADAA, which provides for the establishment and
revocation of import tolerances, requires FDA to make determinations on
requests to establish, amend or revoke import tolerances based on human
food safety criteria similar to those used to establish tolerances for
new animal drug applications. FDA consulted VMAC at a public meeting in
2001 to discuss issues pertaining to the development of regulations
regarding import tolerances. The ADAA language and VMAC recommendations
provided a framework for the proposed import tolerance procedures that
did not allow for the development of alternative procedures significant
enough to have led FDA to estimate a substantially larger or smaller
number of annual requests to establish import tolerances than the 2.2
requests previously described.
G. Impacts on Small Entities
The Regulatory Flexibility Act requires Agencies to prepare a
regulatory flexibility analysis if a rule is expected to have a
significant economic impact on a substantial number of small entities.
Although the Agency believes it is very unlikely that significant
economic impacts would occur, the Agency cannot rule out this
possibility completely because of some uncertainty in the type or size
of entities that may request the establishment, amendment, or
revocation of import tolerances.
The Regulatory Flexibility Act requires a description of the small
entities that would be affected by the rule, and an estimate of the
number of small entities to which the rule would apply. FDA believes
that manufacturers of new animal drugs will make all or nearly all
requests to establish import tolerances. Manufacturers of new animal
drugs are classified in the North American Industrial Classification
System (NAICS) under industry code 325412--Pharmaceutical Preparation
Manufacturing. Census data in this category from 2007 show that 744
companies with 963 establishments manufacture pharmaceuticals in the
United States. FDA requests public comment on the probability that any
entities other than pharmaceutical manufacturers would request the
establishment, amendment, or revocation of an import tolerance.
The Small Business Administration defines those entities within
NAICS code 325412 as small entities if they employ less than 750
employees. Census data shows that 711 of the 963 establishments within
NAICS code 325412, or 74 percent, had less than 100 employees in 2007.
Available Census data from 2007 identifies the number of establishments
in NAICS code 325412 with 100 or more employees, but does not identify
those with 100 to 749 employees. The 2002 Census data, however,
indicates that up to 97 percent of all establishments in NAICS code
325412 have less than 750 employees. The existence of some multi-
establishment companies in this NAICS code would likely decrease the
number of companies that would meet the definition of a small entity.
Regardless, FDA acknowledges that it is likely that a substantial
number of pharmaceutical manufacturers would meet the criteria to be
considered small entities.
For those establishments with one to four employees and five to
nine employees, the average annual value of shipments ranges from
$825,000 to $3.37 million in 2002, the latest year for which value of
shipments for establishments differentiated by employee size is
available. For all establishments with 10 or more employees, it is much
greater. If a manufacturer composed of only one establishment of one to
four employees requested the establishment of one import tolerance for
an unapproved new animal drug that was not the subject of a permanent
Codex MRL, the one-time cost of this effort would represent about 0.40
percent of average annual revenues. If this manufacturer requested the
establishment of one import tolerance for an unapproved new animal drug
that was the subject of a permanent Codex MRL, the one-time cost of
this effort would represent about 0.25 percent of average annual
revenues. Those establishments with more than 10 employees would incur
compliance costs that represent significantly less than 0.1 percent of
average revenues from requesting the establishment of an import
tolerance for an unapproved new animal drug with or without a permanent
Codex MRL. Further, requests to amend or revoke an established import
tolerance, which the Agency expects to be submitted significantly less
frequently than once every 5 years, would result in compliance costs
that represent even smaller percentages of average annual revenues for
the establishment sizes listed previously in this document.
Accordingly, FDA believes that this proposed rule would not have a
significant impact on a substantial number of small entities.
VI. Paperwork Reduction Act of 1995
This proposed rule contains information collection requirements
that are subject to review by the Office of Management and Budget (OMB)
under the Paperwork Reduction Act of 1995 (44 U.S.C. 3501-3520). A
description of these requirements is given in table 1 of this document
with an estimate of the annual reporting burden. Included in the
estimate is the time for reviewing instructions, searching existing
data sources, gathering and maintaining the data needed, and completing
and reviewing each collection of information.
FDA invites comments on the following topics: (1) Whether the
proposed collection of information is necessary for the proper
performance of FDA's functions, including whether the information will
have practical utility; (2) the accuracy of FDA's estimate of the
burden of the proposed collection of information, including the
validity of the methodology and assumptions used; (3) ways to enhance
the quality, utility, and clarity of the information to be collected;
and (4) ways to minimize the burden of the collection of information on
respondents, including through the use of automated collection
techniques, when appropriate, and other forms of information
technology.
Title: Import Tolerances for Residues of Unapproved New Animal
Drugs in Food.
Description: FDA is proposing procedures by which a person may
request that the Agency establish or amend tolerances for unapproved
new animal drugs where edible portions of animals imported into the
United States may contain residues of such drugs (import tolerance).
The Agency is also proposing procedures to revoke an existing import
tolerance, as well as procedures for reconsideration of action or an
administrative stay of action to establish, amend, or revoke an import
tolerance. The ADAA amended the FD&C Act to authorize FDA to establish
and revoke import tolerances. Import
[[Page 3661]]
tolerances will provide a basis for legally marketing food of animal
origin that is imported into the United States and contains residues of
unapproved new animal drugs.
If there is a permanent Codex MRL for a new animal drug, the
proposed rule provides that the requester should provide, in addition
to the requirements outlined in proposed Sec. 510.205(b)(5)(i),
(b)(5)(ii), (b)(5)(iii), (b)(5)(v), and (b)(5)(vi), the permanent Codex
MRL and monographs and reports from the JECFA and/or the JMPR that
support the development of the Codex MRL.
If there is not a permanent Codex MRL, or upon notification by FDA,
the proposed rule provides that the requester should provide, in
addition to the requirements outlined in proposed Sec.
510.205(b)(5)(i), (b)(5)(ii), (b)(5)(iii), (b)(5)(v), and (b)(5)(vi),
full reports of investigations made with respect to the human food
safety of the new animal drug including data submitted to the
appropriate regulatory authority in any country where the new animal
drug is lawfully used. A request may be regarded as incomplete unless
it includes full reports of adequate tests by all methods reasonably
applicable to show whether or not food derived from animals receiving
the new animal drug will be safe for human consumption.
Description of Respondents: We anticipate that most requests to
establish or amend an import tolerance will come from the manufacturer
of the unapproved new animal drug at issue in the request. Requests may
also be submitted by trade associations of foreign producers who use
the unapproved new animal drug or by importers of animal-derived food
bearing or containing residues of the unapproved new animal drug. At
this time since the Agency has not established an appreciable number of
import tolerances, we are unable to estimate the number of requests to
revoke an established import tolerance we may receive.
Burden: Interested persons are required to submit human food safety
data and other information similar to that used to establish a
tolerance under an NADA. The collection of information required for
submission of NADAs has been reviewed under the Paperwork Reduction Act
of 1995. The Agency has proposed extension of this existing collection
most recently in 2007 (72 FR 37240, July 9, 2007). A proportion of the
time estimated in that proposed extension for the paperwork associated
with the human food safety technical section of an NADA was used to
estimate the time (hours per response) presented in table 1 of this
document for the preparation of a request to establish or amend an
import tolerance not based on a permanent Codex MRL. We believe a
request to establish or amend an import tolerance based on a permanent
Codex MRL will be less burdensome. Based on the Agency's experience
with establishing tolerances for approved new animal drugs, the Agency
believes that requests to revoke an import tolerance, as well as
petitions for reconsideration of an action or for an administrative
stay of an action will be infrequent occurrences.
Table 1--Estimated Annual Reporting Burden \1\
--------------------------------------------------------------------------------------------------------------------------------------------------------
Number of
21 CFR Section Number of responses per Total annual Average burden Total hours
respondents respondent responses per response
--------------------------------------------------------------------------------------------------------------------------------------------------------
510.205(b)(5)(i), (b)(5)(ii), and (b)(5)(iii)...................... 2.2 1 2.2 1 2.2
510.205(b)(5)(iv)(A) (request to establish an import tolerance 2 1 2 50 100
based on permanent Codex MRL).....................................
510.205(b)(5)(iv)(B) (request to establish an import tolerance not 0.2 1 0.2 80 16
based on permanent Codex MRL).....................................
510.205(b)(6) (request to amend an import tolerance)............... 0.1 1 0.1 32 3
510.207, 510.209, and 510.211 (request to revoke an import 0.1 1 0.1 10 1
tolerance, for reconsideration of an action or for administrative
stay of an action)................................................
--------------------------------------------------------------------------------------------------------------------------------------------------------
\1\ There are no capital costs or operating costs associated with this collection of information.
The number of respondents and number of responses per respondent
listed in table 1 of this document are an estimate based on the
Agency's experience since the passage of the ADAA and actual requests
received. The average burden per response is an estimate based on the
review of the human food safety technical section of an NADA as
discussed previously in this document. The number of respondents and
number of responses per respondent for Sec. Sec. 510.207, 510.209 and
510.211 are based on the expectation that such responses will occur
infrequently and that the Agency anticipates the average burden per
response will require much less time than a request to establish or
amend a tolerance.
In compliance with the Paperwork Reduction Act of 1995 (44 U.S.C.
3507(d)), the Agency has submitted the information collection
provisions of this proposed rule to OMB for review. Interested persons
are requested to fax comments regarding information collection to the
Office of Information and Regulatory Affairs, OMB. To ensure that
comments on information collection are received, OMB recommends that
written comments be faxed to the Office of Information and Regulatory
Affairs, OMB, Attn: FDA Desk Officer, fax: (202) 395-5806.
VII. Environmental Impact
The Agency has determined under 21 CFR 25.30(h) that this action is
of a type that does not individually or cumulatively have a significant
effect on the human environment. Therefore, neither an environmental
assessment nor environmental impact statement is required.
VIII. Federalism
FDA has analyzed this proposed rule in accordance with the
principles set forth in Executive Order 13132. FDA has determined that
the proposed rule, if finalized, would not contain policies that have
substantial direct effects on the States, on the relationship between
the National Government and the States, or on the distribution of power
and responsibilities among the various levels of government.
Accordingly, the Agency tentatively concludes that the proposed rule
does not contain policies that have federalism implications as defined
in the Executive order and, consequently, a federalism summary impact
statement is not required.
[[Page 3662]]
IX. Request for Comments
Interested persons may submit to the Division of Dockets Management
(see ADDRESSES) either electronic or written comments regarding this
document. It is only necessary to send one set of comments. Identify
comments with the docket number found in brackets in the heading of
this document. Received comments may be seen in the Division of Dockets
Management between 9 a.m. and 4 p.m., Monday through Friday.
List of Subjects
21 CFR Part 10
Administrative practice and procedure, News media.
21 CFR Part 20
Confidential business information, Courts, Freedom of information,
Government employees.
21 CFR Part 25
Environmental impact statements, Foreign relations, Reporting and
recordkeeping requirements.
21 CFR Part 510
Administrative practice and procedure, Animal drugs, Labeling,
Reporting and recordkeeping requirements.
Therefore, under the Federal Food, Drug, and Cosmetic Act and under
authority delegated to the Commissioner of Food and Drugs, it is
proposed that 21 CFR parts 10, 20, 25, and 510 be amended as follows:
PART 10--ADMINISTRATIVE PRACTICES AND PROCEDURES
1. The authority citation for 21 CFR part 10 continues to read as
follows:
Authority: 5 U.S.C. 551-558, 701-706; 15 U.S.C. 1451-1461; 21
U.S.C. 141-149, 321-397, 467f, 679, 821, 1034; 28 U.S.C. 2112; 42
U.S.C. 201, 262, 263b, 264.
2. In Sec. 10.25, revise paragraph (a)(1) to read as follows:
Sec. 10.25 Initiation of administrative proceedings.
* * * * *
(a) * * *
(1) In the form specified in other applicable FDA regulations,
e.g., the form for a color additive petition in Sec. 71.1 of this
chapter, for a food additive petition in Sec. Sec. 171.1 or 571.1 of
this chapter, for a new drug application in Sec. 314.50 of this
chapter, for a request to establish or amend an import tolerance in
Sec. 510.205 of this chapter, for a new animal drug application in
Sec. 514.1 of this chapter, or
* * * * *
PART 20--PUBLIC INFORMATION
3. The authority citation for 21 CFR part 20 continues to read as
follows:
Authority: 5 U.S.C. 552; 18 U.S.C. 1905; 19 U.S.C. 2531-2582; 21
U.S.C. 321-393, 1401-1403; 42 U.S.C. 241, 242, 242a, 242l, 242n,
243, 262, 263, 263b-263n, 264, 265, 300u-300u-5, 300aa-1.
4. In Sec. 20.100, add new paragraph (c)(45) to read as follows:
Sec. 20.100 Applicability; cross-reference to other regulations.
* * * * *
(c) * * *
(45) Requests to establish or amend import tolerances, in Sec.
510.205 of this chapter.
PART 25--ENVIRONMENTAL IMPACT CONSIDERATIONS
5. The authority citation for 21 CFR part 25 continues to read as
follows:
Authority: 21 U.S.C. 321-393; 42 U.S.C. 262, 263b-264; 42 U.S.C.
4321, 4332; 40 CFR parts 1500-1508; E.O. 11514, 35 FR 4247, 3 CFR,
1971 Comp., p. 531-533, as amended by E.O. 11991, 42 FR 26967, 3
CFR, 1978 Comp., p. 123-124 and E.O. 12114, 44 FR 1957, 3 CFR, 1980
Comp., p. 356-360.
6. In Sec. 25.20, add new paragraph (o) to read as follows:
Sec. 25.20 Actions requiring preparation of an environmental
assessment.
* * * * *
(o) Establishment, amendment, or revocation of an import tolerance
in accordance with subpart C of part 510 of this chapter.
PART 510--NEW ANIMAL DRUGS
7. The authority citation for 21 CFR part 510 continues to read as
follows:
Authority: 21 U.S.C. 321, 331, 351, 352, 353, 360b, 371, 379e.
8. Revise subpart C to read as follows:
Subpart C--Import Tolerances for Residues of Unapproved New Animal
Drugs in Food
Sec.
510.201 Scope.
510.203 Definitions.
510.205 Request to establish or amend an import tolerance.
510.207 Revoking an import tolerance.
510.209 Reconsideration of action.
510.211 Administrative stay of action.
Sec. 510.201 Scope.
This part applies to tolerances for residues of new animal drugs
not approved or conditionally approved for use in the United States,
but lawfully used in another country and present in imported animal-
derived food and food products.
Sec. 510.203 Definitions.
The following definitions of terms apply when used in this subpart:
Import tolerance means a tolerance for a residue of a new animal
drug not approved or conditionally approved for use in the United
States, but present in any imported edible portion of any animal.
Request means a request to establish or amend an import tolerance.
Sec. 510.205 Request to establish or amend an import tolerance.
(a) Initiation of a request. Any person may request that the
Commissioner of Food and Drugs (the Commissioner) establish or amend an
import tolerance. A request must be in the form specified in this
section. The Commissioner may also initiate a proceeding to establish
or amend an import tolerance on his or her own initiative under Sec.
10.25(b) of this chapter.
(b) Content and administration of a request. (1) Pertinent
information previously submitted to and currently retained in the files
of the Food and Drug Administration may be incorporated in, and will be
considered as part of, a request on the basis of specific reference to
such information. If the requester refers to any nonpublic information
other than its own, the requester shall obtain a written right of
reference to that nonpublic information and submit the right of
reference with the request. Any reference to published information
offered in support of a request should be accompanied by reprints or
copies of such references.
(2) Requests shall be submitted in triplicate and be addressed to
the Document Control Unit (HFV-199), Center for Veterinary Medicine,
Food and Drug Administration, 7500 Standish Pl., Rockville, MD 20855.
By prior arrangement, requests may be submitted in an electronic
format.
(3) If a part of the material submitted is in a foreign language,
it shall be accompanied by a complete and accurate English translation.
Translations of literature printed in a foreign language shall be
accompanied by copies of the original publication.
(4) The request must be dated and must be signed by the requester
or by his or her authorized attorney, agent, or official and shall
state the requester's correspondence address. If the requester or such
authorized representative does not reside or have a place of business
within the United States, the requester must also furnish the name and
post office address of, and the request must be countersigned by, an
authorized attorney, agent, or official residing or
[[Page 3663]]
maintaining a place of business within the United States.
(5) The request must include the following information:
(i) The established name and all pertinent information concerning
the new animal drug, including chemical identity and composition of the
new animal drug, and its physical, chemical, and biological properties;
(ii) The conditions of use for the new animal drug, including the
route of administration and dosage, together with all labeling,
directions, and recommendations regarding the uses in countries in
which the new animal drug is lawfully used;
(iii) The proposed import tolerance(s) for the new animal drug;
(iv) Human food safety information to support the proposed import
tolerance(s) in either of the following forms:
(A) If a permanent Maximum Residue Limit (MRL) has been established
by the Codex Alimentarius Committee (Codex MRL), the requester shall
provide the permanent Codex MRL and monographs and reports from the
Joint Expert Committee on Food Additives (JECFA) of the Food and
Agriculture Organization (FAO) and the World Health Organization (WHO)
of the United Nations and/or monographs and reports from the Joint FAO/
WHO Meeting on Pesticide Residues (JMPR) that support the development
of the permanent Codex MRL. FDA may request additional information as
needed.
(B) If no permanent Codex MRL has been established, or upon
notification by FDA, the requester must provide full reports of
investigations made with respect to the human food safety of the new
animal drug. A request may be regarded as incomplete unless it includes
full reports of adequate tests by all methods reasonably applicable to
show whether or not any imported edible portion of any animal receiving
the new animal drug will be safe for human consumption. The reports
must include detailed data derived from appropriate animal and other
biological experiments in which the methods used and the results
obtained are clearly set forth, including data submitted to the
appropriate regulatory authority in any country where the new animal
drug is lawfully used. The request must also include a statement that
all such reports have been submitted, or contain an explanation of why
such reports were not submitted. With respect to each nonclinical
laboratory study contained in the request, the requestor must submit
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, and
how this may have impacted the study;
(v) Other human food safety information as deemed necessary by the
Commissioner; and
(vi) A description of practicable methods for determining the
quantity, if any, of the new animal drug in or on food, and any
substance formed in or on food because of its use.
(6) A request to amend an established import tolerance must contain
information to support each proposed change. The request may omit
statements made in the original request for which no change is
proposed.
(7) The requester may withdraw the request at any time before the
notification provided for in paragraph (d)(3) of this section has been
made publicly available.
(c) Review of information submitted in a request. In establishing
or amending an import tolerance, the Commissioner shall rely on data
sufficient to demonstrate that a proposed tolerance is safe based on
similar food safety criteria used by the Commissioner to establish
tolerances for applications for new animal drugs filed under section
512(b)(1) of the Federal Food, Drug, and Cosmetic Act. In establishing
or amending an import tolerance, the Commissioner will give appropriate
consideration to the anticipated residue concentrations and conditions
of use of the new animal drug specified.
(d) Disclosure of information submitted in a request. (1) When a
request is determined to be complete for FDA's consideration, the
Commissioner will provide public notification of the request containing
the name of the requester and a brief description of the request in
general terms. A copy of the notification will be sent to the requester
at the time the information is made available to the public.
(2) A notification establishing, amending, or revoking an import
tolerance will be made publicly available. A summary of the basis for
the decision will be publicly released in accordance with the
provisions of part 20 of this chapter. All information and safety data
submitted with the request, or previously submitted information
incorporated in, and considered as part of, a request on the basis of
specific reference to such information, shall be available for public
disclosure, also in accordance with the provisions of part 20 of this
chapter. Trade secrets and confidential commercial or financial
information are exempted from release under Sec. 20.61 of this
chapter.
(e) Establishment or amendment of an import tolerance. (1) If a
request to establish or amend an import tolerance is granted, the
Commissioner will provide public notification establishing or amending
an import tolerance, which will be effective from the date of public
notification. A copy of the notification will be sent to the requestor
at the time the information is made available to the public.
(2) If a request to establish or amend an import tolerance is
denied, a notification of the denial will be made publicly available,
and a copy of the denial letter, including the reasons for such action,
will be sent to the requester.
(3) A tolerance established in an approved new animal drug
application submitted under section 512(b)(1) of the Federal Food,
Drug, and Cosmetic Act or a conditionally approved application for
conditional approval submitted under section 571 of the Federal Food,
Drug, and Cosmetic Act, will supersede an existing import tolerance and
a notification of such action will be made publicly available and a
copy of the notification will be sent to the requester. In the event
that the conditionally approved application for a new animal drug is
not renewed or is withdrawn, or such drug does not achieve full
approval under section 512 of the Federal Food, Drug, and Cosmetic Act
within 5 years following the date of the conditional approval, the
Agency will reinstate the import tolerance unless Sec. 510.207(a)(1)
or (a)(2) applies. A notification of such action will be made publicly
available and a copy of the notification will be sent to the original
requestor.
Sec. 510.207 Revoking an import tolerance.
(a) The Commissioner, on his or her own initiative or on the
petition of an interested person, under Sec. 10.25 of this chapter,
may revoke an import tolerance based upon:
(1) Scientific evidence showing an import tolerance to be unsafe;
or
(2) Information demonstrating that the use of a new animal drug
results in food being imported into the United States with residues
exceeding the import tolerance.
(b) The Commissioner will provide public notification under Sec.
510.205(d)(2) that will specify which of these grounds upon which he or
she is acting and will be effective at the time the information is made
available to the public.
(c) A petition for revocation must be submitted in the form
specified in Sec. 10.30 of this chapter.
[[Page 3664]]
Sec. 510.209 Reconsideration of action.
(a) The Commissioner, on his own initiative or on the petition of
an interested person under part 10 of this chapter, may at any time
reconsider part or all of a decision to establish, amend, or revoke an
import tolerance.
(b) A petition for reconsideration must be submitted in accordance
with Sec. 10.20 of this chapter and in the form specified in Sec.
10.33 of this chapter no later than 30 days after the date of public
notification of the decision involved. The Commissioner may, for good
cause, permit a petition to be filed more than 30 days after public
notification of the decision. The grounds must demonstrate that
relevant information contained in the administrative record was not
previously or not adequately considered by the Commissioner. No new
information may be included in a request for reconsideration. An
interested person who wishes to rely on information not included in the
administrative record shall submit either a request to amend an import
tolerance under Sec. 510.205 or a petition to revoke an import
tolerance under Sec. 510.207 and Sec. 10.25 of this chapter.
Sec. 510.211 Administrative stay of action.
(a) The Commissioner, on his or her own initiative or on the
request of an interested person under part 10 of this chapter, may at
any time stay or extend the effective date of a decision to establish,
amend, or revoke an import tolerance.
(b) A request for stay must be submitted in accordance with Sec.
10.20 of this chapter and in the form specified in Sec. 10.35 of this
chapter no later than 30 days after public notification of the decision
involved. The Commissioner may, for good cause, permit a petition to be
filed more than 30 days after public notification of the decision.
Dated: January 19, 2012.
Leslie Kux,
Acting Assistant Commissioner for Policy.
[FR Doc. 2012-1430 Filed 1-24-12; 8:45 am]
BILLING CODE 4160-01-P