[Federal Register Volume 86, Number 180 (Tuesday, September 21, 2021)]
[Rules and Regulations]
[Pages 52401-52412]
From the Federal Register Online via the Government Publishing Office [www.gpo.gov]
[FR Doc No: 2021-19967]


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DEPARTMENT OF HEALTH AND HUMAN SERVICES

Food and Drug Administration

21 CFR Parts 10, 20, 25, 500, 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: Final rule.

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SUMMARY: The Food and Drug Administration (FDA, the Agency, we) is 
issuing a final rule that establishes procedures by which we may 
establish, amend, or revoke tolerances for residues of new animal drugs 
in any edible portion of any animal imported into the United States 
(import tolerances). These import tolerances provide a basis for the 
legal marketing of such animal-derived food.

DATES: This rule is effective January 19, 2022. Submit written comments 
(including recommendations) on information collection issues under the 
Paperwork Reduction Act of 1995 (PRA) by October 21, 2021 (see section 
IX, the ``Paperwork Reduction Act of 1995'' section of this document).

ADDRESSES: To ensure that comments on the information collection are 
received, the Office of Management and Budget (OMB) recommends that 
written comments be submitted to https://www.reginfo.gov/public/do/PRAMain. Find this particular information collection by selecting 
``Currently under Review--Open for Public Comments'' or by using the 
search function. All comments should be identified with the OMB control 
number 0910-NEW. Also include the FDA docket number found in brackets 
in the heading of this document.

FOR FURTHER INFORMATION CONTACT: 
    With regard to the final rule: Charli Long-Medrano, Center for 
Veterinary Medicine (HFV-150), Food and Drug Administration, 7500 
Standish Pl., Rockville, MD 20855, 240-402-0850, <a href="/cdn-cgi/l/email-protection#89eae1e8fbe5e0a7e5e6e7eea4e4ecedfbe8e7e6c9efede8a7e1e1faa7eee6ff"><span class="__cf_email__" data-cfemail="3b58535a495752155754555c16565e5f495a55547b5d5f5a15535348155c544d">[email protected]</span></a>.
    With regard to the information collection: JonnaLynn Capezzuto, 
Office of Operations, Food and Drug Administration, Three White Flint 
North, 10A-12M, 11601 Landsdown St., North Bethesda, MD 20852, 301-796-
3794, <a href="/cdn-cgi/l/email-protection#247476657750454242644240450a4c4c570a434b52"><span class="__cf_email__" data-cfemail="c9999b889abda8afaf89afada8e7a1a1bae7aea6bf">[email protected]</span></a>.

SUPPLEMENTARY INFORMATION:

Table of Contents

I. Executive Summary
    A. Purpose of the Final Rule
    B. Summary of the Major Provisions of the Final Rule
    C. Legal Authority
    D. Costs and Benefits
II. Table of Abbreviations/Commonly Used Acronyms in This Document
III. Background
    A. History and Scope of This Rulemaking
    B. General Overview of the Final Rule
IV. Legal Authority
V. Comments on the Proposed Rule and FDA Response
    A. General Comments on the Proposed Rule and FDA Response
    B. Comments on Information To Support Establishment of an Import 
Tolerance and FDA Response
    C. Comments on Environmental Review and FDA Response
VI. Effective Date
VII. Economic Analysis of Impacts
VIII. Analysis of Environmental Impact
IX. Paperwork Reduction Act of 1995
X. Federalism
XI. Consultation and Coordination With Indian Tribal Governments

I. Executive Summary

A. Purpose of the Final Rule

    This rule codifies procedures and food safety criteria by which 
tolerances for residues of unapproved new animal drugs in any edible 
portion of any animal imported into the United States (import 
tolerances) may be established or amended. These import tolerances 
provide a basis for the legal marketing of such animal-derived food. 
The regulation also specifies procedures by which import tolerances may 
be revoked.

B. Summary of the Major Provisions of the Final Rule

    This final rule codifies procedures and food safety criteria 
pertaining to the establishment, amendment, and revocation of import 
tolerances in new subpart C of part 510 of the Code of Federal 
Regulations (21 CFR part 510). Major provisions include:
    <bullet> The scope and definitions;
    <bullet> who may initiate proceedings to establish an import 
tolerance;
    <bullet> contents of a submission requesting establishment of an 
import tolerance;
    <bullet> sources of data and information supporting the safety of a 
proposed import tolerance;
    <bullet> Agency procedures for establishment, amendment, or 
revocation of an import tolerance;
    <bullet> public disclosure of import tolerance-related actions 
(actions under consideration, establishment, amendment, or revocation); 
and
    <bullet> environmental impact assessment of import tolerance-
related actions.

In addition, conforming amendments are being made in Sec. Sec.  10.25, 
20.100, 25.20, 500.80, 500.82, 500.88, and 500.92 (21 CFR 10.25, 
20.100, 25.20, 500.80, 500.82, 500.88, and 500.92). A technical 
amendment is being made in Sec.  10.25 (21 CFR 10.25) to include food 
additive petitions under 21 CFR 571.1 in the non-exhaustive list of 
petitions specified in FDA regulations.
    The procedures and food safety criteria in the final rule are 
fundamentally the same as in the proposed rule; however, the final rule 
has been minimally reorganized to clarify that import tolerances 
established at the Commissioner's initiative follow the same procedures 
as those established at the request of an interested person. We have 
also made nonsubstantive wording changes for clarity.

C. Legal Authority

    Our authority for issuing this final rule is provided by the new 
animal drug provisions of the Federal Food, Drug, and Cosmetic Act 
(FD&C Act) by which we establish tolerances for residues of new animal 
drugs and under provisions of the FD&C Act that give the Agency general 
rulemaking authority to issue regulations for the efficient enforcement 
of the FD&C Act.

[[Page 52402]]

D. Costs and Benefits

1. Costs of the Final Rule
    All entities affected by this final rule will incur the one-time 
cost for reading and understanding this rule. Based on the small number 
of firms that we estimate could request an import tolerance per year, 
only about five firms would need to read and understand this rule over 
the next 10 years. The total costs for reading and understanding the 
rule range from around $530 to around $660. Table 1 includes a summary 
of these costs.

                         Table 1--One-Time Costs for Reading and Understanding the Rule
                                                 [2020 Dollars]
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                                                                        Low           Medium           High
----------------------------------------------------------------------------------------------------------------
Reading time (hours)............................................            0.75            0.85               1
Wage ($ per hour)...............................................         $140.30         $140.30         $140.30
Affected entities...............................................               5               5               5
Number of people reading per entity.............................               1               1               1
                                                                 -----------------------------------------------
    Total cost..................................................            $530            $585            $660
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2. Benefits of the Final Rule
    The procedures codified herein clarify the import tolerance 
submission process for the establishment, amendment, and revocation of 
these tolerances. This should result in improving the efficiency of the 
program for both industry and government. However, we lack data to 
quantify these efficiency gains.

II. Table of Abbreviations/Commonly Used Acronyms in This Document

------------------------------------------------------------------------
              Abbreviation                        What it means
------------------------------------------------------------------------
ADAA...................................  Animal Drug Availability Act of
                                          1996.
ADI....................................  Acceptable Daily Intake.
CFR....................................  Code of Federal Regulations.
CNADA..................................  Application for Conditional
                                          Approval of a New Animal Drug.
Codex MRL..............................  MRL established by the Codex
                                          Alimentarius Committee.
CVM....................................  Center for Veterinary Medicine.
FAO....................................  Food and Agriculture
                                          Organization of the United
                                          Nations.
FDA....................................  U.S. Food and Drug
                                          Administration.
FD&C Act...............................  Federal Food, Drug, and
                                          Cosmetic Act.
GMP....................................  Good Manufacturing Process.
GFI....................................  Guidance for Industry.
JECFA..................................  Joint FAO/WHO Expert Committee
                                          on Food Additives.
JMPR...................................  Joint FAO/WHO Meeting on
                                          Pesticide Residues.
MRL....................................  Maximum Residue Limit.
NADA...................................  New Animal Drug Application.
US.....................................  United States.
VICH...................................  International Cooperation on
                                          Harmonisation of Technical
                                          Requirements for Registration
                                          of Veterinary Medicinal
                                          Products.
WHO....................................  World Health Organization of
                                          the United Nations.
------------------------------------------------------------------------

III. Background

A. History and Scope of This Rulemaking

    In 1996, the President signed into law the Animal Drug Availability 
Act of 1996 (ADAA) (Pub. L. 104-250), which amended the FD&C Act (21 
U.S.C. 360b(a)) to authorize the establishment of import tolerances 
that would provide a basis for the legal marketing of imported animal-
derived food containing residues of new animal drugs neither approved 
nor conditionally approved in the United States (unapproved new animal 
drugs).
    Without an import tolerance, any amount of residue of an unapproved 
new animal drug in imported, animal-derived food would cause that 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 (21 U.S.C. 360b). 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)). It remains unlawful to import animal-derived 
food containing a residue of an unapproved new animal drug, unless an 
import tolerance has been established for such drug and any residue of 
the new animal drug in the imported animal-derived food does not exceed 
that import tolerance. These regulations establish procedures under 
which the Agency will establish, amend, or revoke import tolerances for 
residues of unapproved new animal drugs.
    The ADAA also specified that in establishing import tolerances, FDA 
must rely on data sufficient to demonstrate that a proposed tolerance 
is safe based on similar food safety criteria used to establish a 
tolerance under a new animal drug application (NADA). For establishment 
of import tolerances, food safety data can be submitted by the drug 
manufacturer or be available from a relevant international organization 
such as the Codex Alimentarius Commission, provided such data are not 
inconsistent with criteria used to establish a tolerance for new animal 
drugs in NADAs.
    The regulations make it clear that the Commissioner may start a 
review process to establish, amend, or revoke an import tolerance on 
his or her own initiative under Sec.  10.25(b). These regulations also 
establish when import tolerance-related actions (actions resulting in 
establishment, amendment, or revocation) and their basis will be 
publicly disclosed.

[[Page 52403]]

B. General Overview of the Final Rule

    In issuing this rule, the Agency finalizes the provisions in the 
January 2012 proposed rule (77 FR 3653, January 25, 2012). This final 
rule reflects revisions the Agency made after considering all comments 
received.
    This final rule amends part 510 by adding sections to establish the 
scope of new subpart C (Sec.  510.201 (21 CFR 510.201)); to define 
certain relevant terms (Sec.  510.202 (21 CFR 510.202)); to establish 
who may initiate proceedings to establish or amend an import tolerance 
(Sec.  510.203 (21 CFR 510.203)); to describe the content, options for 
submission, and administration of a request to establish or amend an 
import tolerance (Sec.  510.205 (21 CFR 510.205)); and to describe the 
review of information to establish or amend an import tolerance (Sec.  
510.206 (21 CFR 510.206)). Provisions describing when and how 
information relating to import tolerances will be publicly disclosed, 
previously in proposed Sec.  510.205, are now described and organized 
in redesignated Sec.  510.207 (21 CFR 510.207). Procedures that FDA 
follows in establishment, denial of a request for establishment, and 
amendment of an import tolerance are described in redesignated Sec.  
510.209 (21 CFR 510.209). Procedures for revocation of an import 
tolerance are described in redesignated Sec.  510.210 (21 CFR 510.210). 
Procedures for requesting reconsideration or administrative stay of a 
decision to establish, amend, or revoke an import tolerance are 
specified in redesignated Sec. Sec.  510.212 and 510.213 (21 CFR 
510.212 and 510.213), respectively.

IV. Legal Authority

    We are issuing these regulations under the legal authority provided 
by section 512(a)(6) of the FD&C Act (21 U.S.C. 360b(a)(6)) relating to 
the establishment of import tolerances for unapproved new animal drugs 
and under section 701(a) of the FD&C Act (21 U.S.C. 371(a)), which 
gives FDA general rulemaking authority to issue regulations for the 
efficient enforcement of the FD&C Act.

V. Comments on the Proposed Rule and FDA Response

    We received 17 comments on the proposed import tolerance rule by 
the close of the comment period, each commenting on one or more aspects 
of the proposed rule. We received comments from a wide array of members 
of the public, including trade organizations, academia, public advocacy 
groups, consumers, and government agencies. The comments addressed 
numerous provisions of the proposed rule, including our specific 
requests for comments set forth in the proposed rule. Some comments 
addressed issues that are outside of the scope of this rule. Because 
such comments were beyond the scope of this rule, we do not include a 
discussion of them here.

A. General Comments on the Proposed Rule and FDA Response

    (Comment 1) Several comments expressed concern that establishment 
of import tolerances for unapproved new animal drugs is unfair to 
domestic producers who cannot legally use these drugs, thereby putting 
them at a competitive disadvantage.
    (Response 1) The ADAA amended the FD&C Act to permit FDA to 
establish a tolerance for residues of a new animal drug in any edible 
portion of any animal imported into the United States when the intended 
use of the new animal drug is not approved for use in the United 
States. The legislative history notes there may be appropriate 
instances (e.g., the disease treated does not exist in the United 
States) in which food-producing animals in other countries are treated 
with animal drugs that are not approved in the United States. Thus, 
Congress enacted this provision to provide a legal means by which food 
that may contain residues of these drugs may be imported into the 
United States. Under the FD&C Act, lawful use of the same animal drug 
in the United States requires that the new animal drug be approved or 
conditionally approved by FDA. This requires additional information and 
data from the sponsor to establish, among other things, that the drug 
is effective for its intended use and safe for the animals receiving 
the drug.
    (Comment 2) One comment states that establishing import tolerances 
would result in an increase in the volume of contaminated seafood into 
the United States.
    (Response 2) FDA notes that one consequence of establishing an 
import tolerance may be an increase in imported edible tissues from 
food-producing animals treated with the drug that is the subject of an 
import tolerance. However, these imported tissues will not be permitted 
entry if they contain residues above the import tolerance, the maximum 
concentration of residues of the new animal drug in the edible tissues 
that is determined to be safe for human consumers.
    (Comment 3) A few comments express concern that import tolerances 
risk exposing U.S. consumers to unsafe tissue residues.
    (Response 3) Section 512(a)(6) of the FD&C Act requires that the 
Agency rely on human food safety criteria similar to those used to 
establish tolerances for approved new animal drugs when establishing 
import tolerances. The human food safety criteria and review processes 
resulting in establishment of tolerances for domestically approved new 
animal drugs and for import tolerances for unapproved new animal drugs 
are fundamentally the same. Whether the Agency is establishing an 
import tolerance or a tolerance in the course of approving or 
conditionally approving a new animal drug, we require data and 
information to demonstrate that the residues of the new animal drug in 
the edible products of treated animals are safe for human consumers. 
Imported tissues will not be allowed entry into the United States if 
they contain residues above the import tolerance.
    (Comment 4) One comment states that the rule should include a 
requirement that the country in which the unapproved new animal drug is 
legally used have an equivalent animal drug regulatory program. In 
addition, a few comments recommend requiring that the requester submit: 
A record of the foreign country's approval actions and the approved 
uses of the new animal drug in other countries; information on 
alternative treatments or competing new animal drugs and an explanation 
of why the use of an unapproved new animal drug is necessary in light 
of alternatives; and an affidavit that there are no FDA-approved new 
animal drugs to treat the disease or condition for which the unapproved 
new animal drug is indicated. The comments also recommend that the 
requester be required to comply with the requirement to report adverse 
drug events and that food containing such new animal drug residues 
originate from a country that has approved the drug and is actively 
monitoring its use.
    (Response 4) We disagree. Under the FD&C Act, to establish an 
import tolerance, FDA only must consider information related to the 
human food safety of the unapproved new animal drug that is the subject 
of the import tolerance. The data sufficient to demonstrate that 
residues of the unapproved new animal drug that is the subject of a 
proposed import tolerance are safe is based on similar food safety 
criteria used to establish tolerances for new animal drugs approved in 
the United States. That is, the human food safety standard for 
domestically approved new animal drugs and new animal drugs for which 
an import tolerance is established is the same:

[[Page 52404]]

Reasonable certainty of no harm. The data that may be considered 
include data submitted to appropriate regulatory authorities in any 
country where the new animal drug is lawfully used and data available 
from an appropriate international organization, to the extent such data 
are not inconsistent with the criteria used to establish a tolerance 
for applications for new animal drugs in the United States.
    The FD&C Act does not require the Agency to consider the use of the 
drug in other countries (including the disease(s) for which the 
unapproved new animal drug is indicated and whether there are approved 
drugs or alternative treatments available), or that the country(ies) 
where the drug is approved have an equivalent regulatory program (e.g., 
any post-approval monitoring). In addition, the FD&C Act does not 
impose adverse drug event reporting requirements for the establishment 
of import tolerances. Once an import tolerance is established, imported 
animal-derived food that contains residues of the unapproved new animal 
drug may enter the United States if those residues are below the import 
tolerance. There is no requirement that the imported food originate 
from a country that has approved the drug.
    (Comment 5) Two comments state that U.S. consumers should be 
informed at the point of sale or through product labeling that imported 
edible tissues from food-producing animals may contain residues of new 
animal drugs that are not approved for use in the United States.
    (Response 5) FDA does not agree that such public disclosure is 
needed to address the safety of residues from drugs for which import 
tolerances are established. The purpose of the legislation was to 
ensure that any edible portion of any animal imported into the United 
States is safe so long as such residues are below the established 
import tolerance.
    (Comment 6) One comment states that establishing import tolerances 
undermines the new animal drug approval process. The commenter further 
states that FDA's estimate that an import tolerance review will require 
100 hours of a mid-level FDA employee's time is evidence that the 
import tolerance review will be less stringent.
    (Response 6) We disagree that establishment of import tolerances 
undermines the new animal drug approval process. Congress recognized 
that there may be appropriate instances in which food-producing animals 
in other countries are treated with animal drugs that are not approved 
in the United States. For example, the disease being treated does not 
exist in the United States, or the particular animal industry either 
may not exist in the United States or is very small, resulting in a 
limited or nonexistent market for the drug in the United States. Nor do 
we agree that our estimate that an import tolerance review will 
generally require 100 hours of a mid-level FDA employee's time is 
evidence that import tolerance review is less stringent than review of 
proposed tolerances as part of a new animal drug application. The human 
food safety standard for domestically approved drugs and drugs for 
which an import tolerance is established is the same: Reasonable 
certainty of no harm. Whether a person is requesting that the Agency 
establish an import tolerance or approve an NADA, the requester or 
sponsor, respectively, 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 for human consumption. In our 
experience, it requires about 100 hours of a mid-level FDA employee's 
time to review this evidence, whether submitted under a new animal drug 
application or a request to establish an import tolerance.
    (Comment 7) One comment states that tolerances should only be 
considered for an unapproved animal drug that is used solely for 
therapeutic purposes, asserting that the ADAA was intended to establish 
import tolerances for situations where a drug is used for treating 
diseases and conditions that do not occur in the United States.
    (Response 7) We disagree. The plain language of the statute does 
not limit the establishment of import tolerances to new animal drugs 
intended to be used solely for therapeutic purposes. Generally, the 
reason an animal drug developer does not seek approval of the new 
animal drug in the United States (with attendant tolerances) is because 
the particular animal-rearing industry may not exist in the United 
States at a scale to justify the expense of seeking FDA approval. In 
some cases, the new animal drug may be used for non-therapeutic 
purposes.

B. Comments on Information To Support Establishment of an Import 
Tolerance and FDA Response

    (Comment 8) One comment notes that the phrase ``some assurance that 
the drugs are manufactured under GMP conditions,'' a comment provided 
by a Veterinary Medicine Advisory Committee during a public meeting 
held on this topic in January 2002, and discussed in the preamble to 
the proposed rule, seems to go beyond the scope of what is necessary to 
ensure public safety and should be interpreted with broad flexibility.
    (Response 8) We agree. As noted previously, section 512(a)(6) of 
the FD&C Act provides that FDA shall rely on data sufficient to 
demonstrate that a proposed tolerance is safe based on similar food 
safety criteria used to establish tolerances for NADAs filed under 
section 512(b)(1) of the FD&C Act. Section 512(a)(6) of the FD&C Act 
does not require the Agency to consider other requirements, such as an 
assurance of good manufacturing processes (GMPs), applicable to the new 
animal drug approval process in determining whether the Agency should 
grant a request to establish an import tolerance.
    (Comment 9) Two comments assert that conditions of use of 
unapproved animal drugs do not need to be considered in establishing 
import tolerances so long as residues in imported tissues are below the 
import tolerance.
    (Response 9) We disagree. Information about the conditions of use 
of the new animal drug must be considered when deciding to establish or 
amend an import tolerance so that the relevance of the submitted human 
food safety data, particularly tissue residues that may result from the 
lawful dosing regimen, can be determined. The tissue residue 
concentration is affected by the dosing regimen, i.e., the dose level 
and duration for which the animal is treated. Knowing that the new 
animal drug tissue concentrations reported in the human food safety 
studies are the result of animals dosed under the same conditions of 
use as described in the request provides FDA with assurance that the 
residue data are an appropriate basis to make decisions regarding 
whether to establish or amend an import tolerance.
    (Comment 10) One comment expressed concern that proposed Sec.  
510.205, now Sec.  510.205(e)(5), which provides that a request for an 
import tolerance may include other human food safety information as 
deemed necessary by the Commissioner, is too broad, and that the 
possibility of ad hoc requirements may serve to curtail the initiation 
of requests or frustrate the efforts of those who do submit import 
tolerance requests.
    (Response 10) The Agency does not intend to use this provision to 
require more human food safety information than is necessary to assess 
whether residues of unapproved new animal drugs in edible tissues of 
treated animals are safe for human

[[Page 52405]]

consumption. The Agency will use similar criteria as for the approval 
of NADAs in making its determinations, including any other information 
the Commissioner deems necessary to assure safe and effective use. See 
section 512(d)(1)(D) of the FD&C Act. Similarly, the Agency must ensure 
that a request for a particular import tolerance includes all the 
relevant information needed to make an appropriate human food safety 
determination. For example, the requester may not have submitted enough 
information for FDA to adequately assess the toxicity of the new animal 
drug or the requester may not have provided enough detail about the 
proposed analytical method. The information requested will not be ad 
hoc because it must be relevant to the criteria and review standards 
for human food safety, which are the same for approval of new animal 
drugs and establishment of import tolerances.
    (Comment 11) One comment asks whether the Agency employs analysts 
to verify the accuracy of translations of materials submitted in a 
foreign language.
    (Response 11) The Agency will rely on the requester's assertion 
that it is submitting a complete and accurate translation of any 
materials submitted in a foreign language. As provided for in 18 U.S.C. 
1001, any person, in any matter within the jurisdiction of the Agency, 
who knowingly and willfully falsifies, conceals, or covers up by any 
trick, scheme, or device a material fact; makes any materially false, 
fictitious, or fraudulent statement or representation; or makes or uses 
any false writing or document knowing the same to contain any 
materially false, fictitious, or fraudulent statement or entry, may be 
subject to criminal fines or imprisonment.
    (Comment 12) One comment requests that electronic submission of 
import tolerance request dossiers be an option. There should be no need 
for paper submissions.
    (Response 12) We agree that electronic submission of import 
tolerance requests should be an option and are providing for electronic 
submission of requests in Sec.  510.105(b) of this final rule. At 
present, the Center for Veterinary Medicine (CVM) Office of New Animal 
Drug Evaluation (ONADE) can receive and process electronic submissions 
for import tolerance files. Submissions to CVM can be made after first 
registering with FDA's Electronic Submissions Gateway (ESG) and CVM's 
Electronic Submission System. Additional information and a user guide 
on eSubmitter can be obtained at either the ``CVM eSubmitter Resource 
Center'' website or the ``Getting Started with eSubmitter'' website. 
Contact <a href="/cdn-cgi/l/email-protection#145147535c7178645051677f547270753a7c7c673a737b62"><span class="__cf_email__" data-cfemail="561305111e333a261213253d16303237783e3e2578313920">[email protected]</span></a> for help with the ESG or 
<a href="/cdn-cgi/l/email-protection#6201140f071117000f0b16160710220406034c0a0a114c050d14"><span class="__cf_email__" data-cfemail="7516031810060017181c01011007351311145b1d1d065b121a03">[email protected]</span></a> for help using CVM's eSubmitter tool.
    (Comment 13) Several comments question how FDA will evaluate an 
established acceptable daily intake (ADI), especially considering 
different food consumption patterns of different countries. Comments 
also question whether FDA considers subpopulations, such as children 
and immune-compromised people who may be particularly sensitive to the 
effects of exposure to drug residues. Comments express concerns that 
safety standards are being loosened and unsafe residues will be allowed 
in foods.
    (Response 13) The ADI established for residues of an unapproved new 
animal drug in edible tissues of food-producing animals that is used in 
evaluating an import tolerance request is based on the same toxicity 
data and information as is used to establish an ADI for a domestically 
approved new animal drug and is evaluated using the same standards and 
methodology that is used for a domestic drug approval. The toxicity 
data that FDA uses to determine the ADI are described in guidances 
available on our website (https://www.fda.gov/animal-veterinary/guidance-industry/human-food-safety-guidances). The guidances for 
toxicology studies are documents that are internationally harmonized 
through the International Cooperation on Harmonisation of Technical 
Requirements for Registration of Veterinary Medicinal Products (VICH) 
Expert Working Groups. The ADI, expressed in a micrograms or milligrams 
of the new animal drug per kilogram of body weight per day ([micro]g/kg 
bw/day or mg/kg bw/day), is the amount of drug residue that can be 
consumed on a daily basis for up to a lifetime without adverse effects 
or harm to the health of a consumer.
    The ADI is meant to be applied to a general population, including 
sensitive subpopulations. The ADI determination uses conservative 
procedures to ensure that the final value is protective of a general 
population, such as application of a safety factor to account for human 
variability in sensitivity to the toxicity of the new animal drug, and 
tests for specific subpopulations if needed (asthmatic persons, 
allergic persons, etc.). Additionally, the application of the ADI to 
safe concentrations of the drug residues in edible tissues uses a lower 
average human body weight (60 kg) and conservative estimates of food 
consumption, such as a high milk consumption factor of 1.5 liter per 
day. Therefore, the Agency believes using the same methodology to 
calculate ADI for import tolerances as U.S.-approved animal drugs is 
appropriate.
    (Comment 14) One comment states that the rule should explicitly 
prohibit the setting of import tolerances for residues of new animal 
drugs that induce cancer when ingested by humans or animals.
    (Response 14) We disagree that the rule should explicitly prohibit 
the Agency from considering new animal drugs of carcinogenic concern 
(new animal drugs that induce cancer when ingested by people or 
animals). Section 512(a)(6) of the FD&C Act provides FDA the authority 
to consider requests to establish import tolerances using food safety 
criteria similar to those that are applied to the approval of new 
animal drugs. Under section 512(d)(1)(I) of the FD&C Act, the Agency 
may approve NADAs for drugs of carcinogenic concern as long as the 
compound does not adversely affect the animals and no residue of a 
carcinogenic compound will be found in food produced from those 
animals. Pursuant to section 512(a)(6) of the FD&C Act, FDA will 
consider requests for import tolerances for animal drugs of 
carcinogenic concern using similar food safety criteria as it would for 
a new animal drug application for approval. Thus, if FDA determines 
that a new animal drug for which an import tolerance request has been 
submitted is a new animal drug of carcinogenic concern, the requester 
will be directed to comply with the ``no residue'' requirements of 
Sec. Sec.  500.80 through 500.92 (21 CFR part 500, subpart E, 
Regulation of Carcinogenic Compounds Used in Food-Producing Animals). 
Any regulatory method for ascertaining the marker residue in the target 
tissue will be made publicly available pursuant to Sec.  510.207(b) of 
the final rule. We have revised Sec. Sec.  510.205(e) and 510.207(b) of 
the final rule and made conforming changes to Sec. Sec.  500.80, 
500.82, 500.88, and 500.92 to clarify the process for evaluating a new 
animal drug of carcinogenic concern under these circumstances.
    (Comment 15) One comment states that the rule should specifically 
prohibit the setting of import tolerances for antimicrobial animal 
drugs that are in the same classes as drugs used in human medicine.
    (Response 15) We disagree. Rather than declining to establish 
import tolerances for residues of antimicrobial new animal drugs that 
are in the same classes as drugs used in human medicine, we intend to 
apply the same

[[Page 52406]]

human food safety standard (reasonable certainty of no harm) as we 
apply to all new animal drugs, including antimicrobial new animal 
drugs, seeking approval under an NADA or application for conditional 
approval of a new animal drug (CNADA). For requests for import 
tolerances for antimicrobials, FDA evaluates the impacts on human 
health, including the potential transmission of antimicrobial resistant 
bacteria of human health concern through the consumption of animal-
derived food products. To assess these impacts, FDA recommends 
conducting the qualitative risk assessment described in Guidance for 
Industry (GFI) #152 entitled ``Evaluating the Safety of Antimicrobial 
New Animal Drugs with Regard to Their Microbiological Effects on 
Bacteria of Human Health Concern,'' October 23, 2003.\1\ In addition, 
we recommend that requesters address the step-wise approach outlined in 
GFI #159 (VICH GL36), ``Studies to Evaluate the Safety of Residues of 
Veterinary Drugs in Human Food: General Approach to Establish a 
Microbiological ADI,'' March 5, 2013,\2\ to assure the Agency that any 
impacts of antimicrobial new animal drug residues on the intestinal 
flora of human consumers are minimal. By addressing these important 
human food safety endpoints for antimicrobial new animal drugs, 
requesters will be able to assure the Agency that the imported animal-
derived food products are safe for human consumption.
---------------------------------------------------------------------------

    \1\ Available at: https://www.fda.gov/media/69949/download.
    \2\ Available at: https://www.fda.gov/regulatory-information/search-fda-guidance-documents/cvm-gfi-159-vich-gl36-studies-evaluate-safety-residues-veterinary-drugs-human-food-general-approach.
---------------------------------------------------------------------------

    (Comment 16) A comment stated that the rule should specifically 
prohibit the setting of import tolerances for veterinary drugs that 
have extralabel use restrictions in the United States or that are 
banned from use in domestic livestock enterprises (including 
aquaculture).
    (Response 16) As noted previously, whether a person is requesting 
the Agency establish an import tolerance or approve an NADA, the 
requester or sponsor, respectively, 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 for human consumption. If 
the requester can satisfy the human food safety requirements, the 
Agency may establish an import tolerance for a food-producing species 
for which there is no extralabel use restriction, even if an extralabel 
use prohibition exists for other food-producing species.
    (Comment 17) One comment requests that the requirement that the 
unapproved animal drug be registered (lawfully used) in another country 
should be revised to allow a request for an import tolerance to 
simultaneously progress with registration of the drug in foreign 
countries.
    (Response 17) The statute gives us discretion to ``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.'' As we noted in the preamble to 
the proposed rule, the Agency has interpreted this statutory language 
to mean that we may establish an import tolerance for a new animal drug 
that is not approved or conditionally approved in the United States but 
that is lawfully used in another country. Thus, foreign lawful use in 
at least one country must occur before a request to establish an import 
tolerance is submitted to the Agency.
    (Comment 18) One comment requests that FDA revise the evidentiary 
standard for revocation of an import tolerance to be ``evidence to show 
a reasonable basis from which serious questions may be inferred about 
the ultimate safety of the unapproved new animal drug residue and any 
substance that may be formed as a result of the unapproved new animal 
drug's use.'' The comment raises the concern that the proposed rule 
appears to require consumers to bring conclusive evidence to obtain a 
review of the import tolerance.
    (Response 18) We disagree. The standard for revoking an import 
tolerance is provided for in section 512(a)(6) of the FD&C Act, which 
states that the Agency may revoke an import tolerance ``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 final rule reflects this standard in 
Sec.  510.210(a). An import tolerance can be revoked upon petition or 
by the initiative of the Commissioner.

C. Comments on Environmental Review and FDA Response

    (Comment 19) In the preamble to the proposed rule, the Agency 
requested 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. FDA received two comments 
indicating that available information shows that FDA's establishment of 
import tolerances should present no appreciable risk to the environment 
from either the consumption or disposal of edible tissues containing 
residues of animal drugs. Two comments support creation by FDA of a 
categorical exclusion from the requirement to prepare an environmental 
assessment (EA) for an import tolerance request. For example, one 
comment presents evidence why risks to the environment should not be 
significant, showing calculations and summarizing information 
indicating that residues in certain media (e.g., wastewater, soil) 
would be below threshold criteria already established by FDA in 
guidance documents or in existing categorical exclusions for other 
actions. Thus, the basis for establishing a new categorical exclusion 
for import tolerances is already in place.
    (Response 19) We agree with the comments' assessment of the low 
risk of significant environmental impacts from either the consumption 
or disposal of edible tissues containing residues of animal drugs. 
Since the 2012 proposed rule, we have reviewed EAs for several import 
tolerance requests for new animal drugs used in both aquatic and 
terrestrial environments (aquatic: Azamethiphos and lufenuron in 
salmonids, benzocaine in Atlantic salmon and rainbow trout, and 
emamectin and teflubenzuron in Atlantic salmon; terrestrial: Monensin 
and monepantel in sheep; see https://www.fda.gov/AnimalVeterinary/Products/ImportExports/ucm315830.htm). Regardless of the environment in 
which the drugs were used, each EA described the introduction of drug 
residues into the domestic environment as being through the consumption 
of food resulting in: (1) Excreta entering sewage treatment facilities 
and (2) waste of edible tissues disposed of in landfills. Each EA 
resulted in a finding by the Agency of no significant environmental 
impact; thus, for each import tolerance action a finding of no 
significant impact was prepared.
    In response to comments that FDA create a categorical exclusion 
from the requirement to prepare an EA for an action on an import 
tolerance, the Agency is considering proposing a new categorical 
exclusion specific to establishment, amendment, or revocation of an 
import tolerance. This would require review by the White House Council 
on Environmental Quality, as well as additional rulemaking with public 
notice and comment. The Agency is currently evaluating available 
information to

[[Page 52407]]

determine if this category of actions would individually or 
cumulatively result in significant effects on the environment and will 
proceed as appropriate.
    (Comment 20) One comment notes that establishment of an import 
tolerance should also have no appreciable environmental effect outside 
the United States. If the new animal drug is not expected to have 
significant environmental impacts in the country where it is registered 
for use, it is hard to imagine a situation where movement of residues 
to another country or into the global commons, such as the open ocean, 
would present a significant environmental risk.
    (Response 20) We agree with the comment's assessment of the low 
risk of significant environmental effects abroad of residues of new 
animal drugs appropriately registered in the country they are used 
based on our experience to date. An analysis of effects abroad is not 
currently required in the EA for establishment of an import tolerance; 
however, when necessary, such an analysis will be completed by the 
Agency.

VI. Effective Date

    The rule is effective January 19, 2022.

VII. Economic Analysis of Impacts

    We have examined the impacts of the final 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 us 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). We 
believe that this final rule is not a significant regulatory action as 
defined by Executive Order 12866.
    The Regulatory Flexibility Act requires us to analyze regulatory 
options that would minimize any significant impact of a rule on small 
entities. Because the final rule will simply codify the procedures that 
are currently used for the import tolerance program, we certify that 
the final rule will not have a significant economic impact on a 
substantial number of small entities.
    The Unfunded Mandates Reform Act of 1995 (section 202(a)) requires 
us to prepare a written statement, which includes an assessment of 
anticipated costs and benefits, before issuing ``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 $158 
million, using the most current (2020) Implicit Price Deflator for the 
Gross Domestic Product. This final rule would not result in an 
expenditure in any year that meets or exceeds this amount.
Summary of Cost and Benefits
    Firms are currently able to request that we establish or amend an 
import tolerance. The final rule will not change the current procedures 
for these requests. Thus, we include only the incremental costs of 
reading and understanding the final rule on import tolerance 
procedures.
    In table 2, FDA provides the Regulatory Information Service Center 
and Office of Information and Regulatory Affairs Consolidated 
Information Center accounting information.

                                                  Table 2--Economic Data: Costs and Benefits Statement
--------------------------------------------------------------------------------------------------------------------------------------------------------
                                                                                             Units
                                                                             ------------------------------------
                Category                    Primary       Low        High                               Period                     Notes
                                           estimate    estimate    estimate      Year      Discount     covered
                                                                                dollars    rate (%)     (years)
--------------------------------------------------------------------------------------------------------------------------------------------------------
Benefits:
    Annualized, Monetized $millions/year  ..........  ..........  ..........  ..........           7  ..........  ......................................
                                          ..........  ..........  ..........  ..........           3  ..........  ......................................
    Annualized Quantified...............  ..........  ..........  ..........  ..........           7  ..........  ......................................
                                          ..........  ..........  ..........  ..........           3  ..........  ......................................
                                         ---------------------------------------------------------------------------------------------------------------
    Qualitative.........................  Codifying current practices of the
                                          import tolerance program could
                                          improve the efficiency of the
                                          program.
--------------------------------------------------------------------------------------------------------------------------------------------------------
Costs:
    Annualized, Monetized $millions/year    <$0.0001    <$0.0001    <$0.0001        2020           7          10  ......................................
                                            <$0.0001    <$0.0001    <$0.0001        2020           3          10  ......................................
    Annualized..........................  ..........  ..........  ..........  ..........           7  ..........  ......................................
    Quantified..........................  ..........  ..........  ..........  ..........           3  ..........  ......................................
    Qualitative.........................  ..........  ..........  ..........  ..........  ..........  ..........  ......................................
--------------------------------------------------------------------------------------------------------------------------------------------------------
Transfers:
    Federal Annualized Monetized          ..........  ..........  ..........  ..........           7  ..........
     $millions/year.
                                          ..........  ..........  ..........  ..........           3  ..........
                                         ---------------------------------------------------------------------------------------------------------------
    From/To.............................  From:
                                          To:
                                         ---------------------------------------------------------------------------------------------------------------
    Other...............................  ..........  ..........  ..........  ..........           7  ..........  ......................................
    Annualized, Monetized $millions/year  ..........  ..........  ..........  ..........           3  ..........  ......................................
                                         ---------------------------------------------------------------------------------------------------------------
    From/To.............................  From:
                                          To:
--------------------------------------------------------------------------------------------------------------------------------------------------------
Effects:
    State, Local or Tribal Government: No Effect........................................................................................................
    Small Business: The final rule will not have a significant impact on a substantial number of small entities that manufacture unapproved drugs that
     are the subject of an import tolerance request..
    Wages: No effect....................................................................................................................................
    Growth: No effect...................................................................................................................................
--------------------------------------------------------------------------------------------------------------------------------------------------------


[[Page 52408]]

    We have developed a comprehensive Economic Analysis of Impacts that 
assesses the impacts of the final rule. The full analysis of economic 
impacts is available in the docket for this final rule (FDA-2001-N-
0075) and at https://www.fda.gov/about-fda/reports/economic-impact-analyses-fda-regulations.

VIII. Analysis of 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.

IX. Paperwork Reduction Act of 1995

    This final rule contains information collection provisions that are 
subject to review by OMB under the PRA (44 U.S.C. 3501-3521). The 
title, description, and respondent description of the information 
collection provisions are shown in the following paragraphs 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.
    Title: Reporting Requirements to Establish, Amend, or Revoke an 
Import Tolerance (21 CFR 510.205)
    Description: The FD&C Act, as amended by the ADAA, authorizes the 
establishment and revocation of tolerances for unapproved new animal 
drugs where edible portions of animals imported into the United States 
may contain residues of such drugs (import tolerances) (section 
512(a)(6) of the FD&C Act). Import tolerances provide a basis for the 
legal marketing of imported animal-derived food containing residues of 
new animal drugs neither approved nor conditionally approved in the 
United States (unapproved new animal drugs). Without an import 
tolerance, any amount of residue of an unapproved new animal drug in 
imported, animal-derived food would cause that food to be adulterated 
under section 402(a)(2)(C)(ii) of the FD&C Act 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)). It remains unlawful to import animal-derived 
food containing a residue of an unapproved new animal drug, unless an 
import tolerance has been established for such drug and any residue of 
the new animal drug in the imported animal-derived food does not exceed 
that import tolerance.
    This final rule amends our regulations in part 510 to establish new 
information collection provisions regarding requests to establish, 
amend, or revoke import tolerances for residues of unapproved new 
animal drugs in food. This final rule establishes procedures by which a 
person may make such requests, as well as procedures for 
reconsideration of action or an administrative stay of action to 
establish, amend, or revoke an import tolerance. The regulations make 
it clear that the Commissioner may start a review process to establish, 
amend, or revoke an import tolerance on his or her own initiative under 
Sec.  10.25(b). These regulations also establish when import tolerance-
related actions (actions resulting in establishment, amendment, or 
revocation) and their basis will be publicly disclosed.
    The information required to be submitted in a request to establish 
an import tolerance is set forth in Sec.  510.205(e). The request must 
identify the drug; describe the conditions of use; describe the 
proposed import tolerance(s) for residues of the new animal drug; 
provide human food safety information to support the proposed import 
tolerance(s); provide other human food safety information as deemed 
necessary by the Commissioner; describe 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; include an 
environmental assessment; and provide any information required under 
Sec. Sec.  500.80 through 500.92, where applicable. The information 
required to be submitted in a request to amend an import tolerance is 
set forth in Sec.  510.205(f) and the information required to be 
submitted in a withdrawal of a request is set forth in Sec.  
510.205(g).
    The information submitted to us in a request to establish, amend, 
or revoke import tolerances is necessary to allow us to establish 
import tolerances that would provide a basis for the legal marketing of 
imported animal-derived food containing residues of new animal drugs 
neither approved nor conditionally approved in the United States 
(unapproved new animal drugs). We will use the information collected 
through the import tolerances procedure to complete our evaluation.
    Comments regarding the information collection topics solicited in 
the proposed rule are discussed in the preamble in section V. See, in 
particular, comments 4, 9, 10, 12, 18, and 19. None of the comments 
suggested we modify the estimated annual burden associated with the 
information collection. However, we have revised the analysis of the 
information collection provisions to accurately reflect the final rule. 
We added a row to table 3 to report the new burden of Sec.  510.205(g) 
(withdrawal of a request), and we removed a row from table 3 to reflect 
that the collections of information in our procedural regulations at 21 
CFR part 10 (in particular, 21 CFR 10.20, 10.30, 10.33, and 10.35) 
already are approved under OMB control number 0910-0191.
    Description of Respondents: Respondents to the collection of 
information are: manufacturers of the unapproved new animal drug that 
is the subject of the request, foreign producers who use the unapproved 
new animal drug and their trade associations, and importers of animal-
derived food bearing or containing residues of the unapproved new 
animal drug.
    We estimate the burden of this information collection as follows:

                                 Table 3--Estimated Annual Reporting Burden \1\
----------------------------------------------------------------------------------------------------------------
                                                     Number of
    21 CFR Section; activity         Number of     responses per   Total annual   Average burden    Total hours
                                    respondents     respondent       responses     per response
----------------------------------------------------------------------------------------------------------------
510.205(e)(1) through (8);                     2               1               2               1               2
 contents of request............
510.205(a) through (e); request                2               1               2              50             100
 to establish an import
 tolerance based on permanent
 Codex MRL \2\..................
510.205(a) through (e); request                1               1               1              80              80
 to establish an import
 tolerance not based on
 permanent Codex MRL \2\........
510.205(f), request to amend an                1               1               1              32              32
 import tolerance...............
510.205(g), withdrawal of a                    1               1               1               1               1
 request........................

[[Page 52409]]

 
    Total.......................  ..............  ..............  ..............  ..............             215
----------------------------------------------------------------------------------------------------------------
\1\ There are no capital costs or operating and maintenance costs associated with this collection of
  information.
\2\ A Codex MRL is a permanent maximum residue limit (MRL) that has been established by the Codex Alimentarius
  Committee.

    We base our estimate of the number of respondents and number of 
responses per respondent in table 3 on our experience since the passage 
of the ADAA and the number of actual requests received. We base our 
estimate of the average burden per response on our experience with the 
human food safety technical section of an NADA, as discussed previously 
in this document.
    A request to establish or amend an import tolerance must include 
human food safety data and other information. The information submitted 
is similar to that submitted to establish a tolerance under an NADA. 
The collection of information required for submission of NADAs has been 
reviewed under the PRA. 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 3 for the preparation of a 
request to establish or amend an import tolerance not based on a 
permanent Codex MRL, approximately 80 hours. We believe a request to 
establish or amend an import tolerance based on a permanent Codex MRL 
will be less burdensome, approximately 50 hours. 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.
    If there is a permanent Codex MRL for a new animal drug, the final 
rule requires the requester to provide the permanent Codex MRL and 
monographs and reports from the Joint FAO/World Health Organization of 
the United Nations (WHO) Expert Committee on Food Additives (JECFA) 
and/or the Joint FAO/WHO Meeting on Pesticide Residues (JMPR) that 
support the development of the Codex MRL.
    If there is not a permanent Codex MRL, or upon notification by FDA, 
the final rule requires the requester to 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 in which the new animal drug is lawfully used. 
We may regard a request 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.
    The information collection provisions of this final rule have been 
submitted to OMB for review as required by section 3507(d) of the PRA. 
Before the effective date of this final rule, FDA will publish a notice 
in the Federal Register announcing OMB's decision to approve, modify, 
or disapprove the information collection provisions in this final rule. 
An Agency may not conduct or sponsor, and a person is not required to 
respond to, a collection of information unless it displays a currently 
valid OMB control number.

X. Federalism

    We have analyzed this final rule in accordance with the principles 
set forth in Executive Order 13132. FDA has determined that the rule 
does 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, we conclude that the 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.

XI. Consultation and Coordination With Indian Tribal Governments

    We have analyzed this rule in accordance with the principles set 
forth in Executive Order 13175. We have determined that the rule does 
not contain policies that have substantial direct effects on one or 
more Indian Tribes, on the relationship between the Federal Government 
and Indian Tribes, or on the distribution of power and responsibilities 
between the Federal Government and Indian Tribes. Accordingly, we 
conclude that the rule does not contain policies that have tribal 
implications as defined in the Executive Order and, consequently, a 
tribal summary impact statement is not required.

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 500

    Animal drugs, Animal feeds, Cancer, Labeling, Packaging and 
containers, Polychlorinated biphenyls (PCBs).

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, 21 CFR 
parts 10, 20, 25, 500, and 510 are amended as follows:

PART 10--ADMINISTRATIVE PRACTICES AND PROCEDURES

0
1. The authority citation for 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.

0
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, for a food 
additive petition in Sec.  171.1 or Sec.  571.1, for a new drug 
application in Sec.  314.50, for a request to establish or amend an 
import tolerance

[[Page 52410]]

in Sec.  510.205, for a new animal drug application in Sec.  514.1, or
* * * * *

PART 20--PUBLIC INFORMATION

0
3. The authority citation for 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.

0
4. In Sec.  20.100, add paragraph (c)(47) to read as follows:


Sec.  20.100   Applicability; cross-reference to other regulations.

* * * * *
    (c) * * *
    (47) Requests to establish or amend import tolerances, in Sec.  
510.205 of this chapter.

PART 25--ENVIRONMENTAL IMPACT CONSIDERATIONS

0
5. The authority citation for 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.

0
6. In Sec.  25.20, add paragraph (q) to read as follows:


Sec.  25.20  Actions requiring preparation of an environmental 
assessment.

* * * * *
    (q) Establishment, amendment, or revocation of an import tolerance 
in accordance with subpart C of part 510 of this chapter.

PART 500--GENERAL

0
7. The authority citation for part 500 continues to read as follows:

    Authority: 21 U.S.C. 321, 331, 342, 343, 348, 351, 352, 353, 
360b, 371, 379e.

0
8. In Sec.  500.80, in paragraph (a), add a new fourth sentence; and 
revise paragraph (c) to read as follows:


Sec.  500.80   Scope of this subpart.

    (a) * * * The requirements of this subpart shall also apply to a 
request for an import tolerance under Sec.  510.205 of this chapter. * 
* *
* * * * *
    (c) If FDA concludes on the basis of the threshold assessment or at 
a later time during the approval process or during the review of a 
request for an import tolerance that the data show that the sponsored 
compound and its metabolites should not be subject to this subpart, FDA 
will continue to consider the compound for approval under the general 
safety provisions of the Federal Food, Drug, and Cosmetic Act for risks 
other than cancer or continue its review of the import tolerance 
request under the provisions of Sec. Sec.  510.201 through 510.213 of 
this chapter (Subpart C--Import Tolerances for Residues of Unapproved 
New Animal Drugs in Food).
* * * * *

0
9. In Sec.  500.82(b), revise the definition of ``Sponsor'' to read as 
follows:


Sec.  500.82   Definitions.

* * * * *
    (b) * * *
    Sponsor means the person or organization proposing or holding an 
approval by FDA for the use of a sponsored compound or the person 
initiating a request for an import tolerance under Sec.  510.205 of 
this chapter.
* * * * *

0
10. In Sec.  500.88, add paragraph (d) to read as follows:


Sec.  500.88   Regulatory method.

* * * * *
    (d) If the sponsor initially submitted a request for an import 
tolerance under Sec.  510.205 of this chapter, FDA will make the 
complete regulatory method for ascertaining the marker residue in the 
target tissue publicly available pursuant to Sec.  510.207(b) of this 
chapter.

0
11. In Sec.  500.92, revise paragraph (a) to read as follows:


Sec.  500.92   Implementation.

    (a) This subpart E applies to all new animal drug applications, 
food additive petitions, color additive petitions, and requests for 
import tolerances concerning any compound intended for use in food-
producing animals (including supplemental applications and amendments 
to petitions).
* * * * *

PART 510--NEW ANIMAL DRUGS

0
12. The authority citation for part 510 continues to read as follows:

    Authority:  21 U.S.C. 321, 331, 351, 352, 353, 360b, 371, 379e.

0
13. Add subpart C to read as follows:
Subpart C--Import Tolerances for Residues of Unapproved New Animal 
Drugs in Food
Sec.
510.201 Scope.
510.202 Definitions.
510.203 Initiation of a proceeding to establish or amend an import 
tolerance.
510.205 Content and administration of a request.
510.206 Review of information supporting actions to establish or 
amend an import tolerance.
510.207 Disclosure of information submitted in a request.
510.209 Establishment, denial, or amendment of an import tolerance.
510.210 Revocation of an import tolerance.
510.212 Administrative reconsideration of action.
510.213 Administrative stay of action.

Subpart C--Import Tolerances for Residues of Unapproved New Animal 
Drugs in Food


Sec.  510.201   Scope.

    This subpart 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.  510.202  Definitions.

    The following definitions of terms apply when used in this subpart:
    CNADA means an application for conditional approval of a new animal 
drug submitted under section 571 of the Federal Food, Drug, and 
Cosmetic Act, and includes all amendments and permissible supplements.
    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.
    NADA means a new animal drug application submitted under section 
512 of the Federal Food, Drug, and Cosmetic Act, including all 
amendments and permissible supplements, for approval of a new animal 
drug.
    Request means a request to establish or amend an import tolerance.


Sec.  510.203   Initiation of a proceeding to establish or amend an 
import tolerance.

    (a) Any interested person may request that the Commissioner 
establish or amend an import tolerance. Such a request must be in the 
form specified in Sec.  510.205 of this chapter.
    (b) The Commissioner may initiate a proceeding to establish or 
amend an import tolerance on his or her own initiative pursuant to 
Sec.  10.25(b) of this chapter.


Sec.  510.205  Content and administration of a request.

    (a) Pertinent information previously submitted to and currently 
retained in the files of the Food and Drug Administration (FDA) may be 
incorporated in, and will be considered as part of, a request on the 
basis of specific reference to such information. If

[[Page 52411]]

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.
    (b) Requests shall be submitted and addressed to the Document 
Control Unit (HFV-199), Center for Veterinary Medicine, Food and Drug 
Administration, 7500 Standish Pl., Rockville, MD 20855. Requests may be 
submitted in an electronic format as authorized by FDA. See FDA's 
Electronic Submissions Gateway website: https://www.fda.gov/industry/electronic-submissions-gateway.
    (c) Any material submitted in a foreign language shall be 
accompanied by a complete and accurate English translation. 
Translations of literature printed in a language other than English 
shall be accompanied by copies of the original publication.
    (d) 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 maintaining a place 
of business within the United States.
    (e) The request must 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 residues of the new animal 
drug;
    (4) Human food safety information to support the proposed import 
tolerance(s) in either of the following forms:
    (i) 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.
    (ii) 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;
    (5) Other human food safety information as deemed necessary by the 
Commissioner;
    (6) 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;
    (7) An environmental assessment under Sec.  25.40 of this chapter; 
and
    (8) Any information required under Sec. Sec.  500.80 through 500.92 
of this chapter (Subpart E, Regulation of Carcinogenic Compounds Used 
in Food-Producing Animals), where applicable.
    (f) 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.
    (g) The requester may withdraw the request at any time before the 
notification provided for in Sec.  510.207(a) of this chapter has been 
made publicly available.


Sec.  510.206  Review of information supporting actions to establish or 
amend an import tolerance.

    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.


Sec.  510.207  Disclosure of information submitted in a request.

    (a) 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.
    (b) Any 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. If FDA determines that the new 
animal drug referred to in the request is a new animal drug that 
induces cancer when ingested by people or animals, and the requester 
complies with the requirements of Sec. Sec.  500.80 through 500.92 of 
this chapter (Subpart E, Regulation of Carcinogenic Compounds Used in 
Food-Producing Animals), the regulatory method for ascertaining the 
marker residue in the target tissue will be made publicly available. 
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.


Sec.  510.209   Establishment, denial, or amendment of an import 
tolerance.

    (a) If an import tolerance is established or amended, the

[[Page 52412]]

Commissioner will provide public notification of the action, which will 
be effective from the date of public notification. A copy of the 
notification will be sent to any requestor at the time the information 
is made available to the public.
    (b) 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.
    (c) A tolerance established in an approved NADA or conditionally 
approved CNADA will supersede an existing import tolerance. In the 
event the conditionally approved CNADA is not renewed or is withdrawn, 
or such drug does not achieve 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.  510.210(a)(1) or (a)(2) is applicable at that time.


Sec.  510.210  Revocation of 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 if:
    (1) Scientific evidence shows an import tolerance to be unsafe; or
    (2) Information demonstrates that the use of a new animal drug 
under actual use conditions results in food being imported into the 
United States with residues exceeding the import tolerance.
    (b) The Commissioner will provide public notification under Sec.  
510.207(b) that will specify the basis for the decision 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.


Sec.  510.212  Administrative reconsideration of action.

    (a) The Commissioner may at any time, on his or her own initiative 
or on the petition of an interested person under part 10 of this 
chapter, reconsider part or all of a decision to establish, not 
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 petition for reconsideration 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 petition for 
reconsideration.
    (c) An interested person who wishes to rely on information not 
included in the administrative record shall submit either a petition to 
amend an import tolerance under Sec.  510.205 or to revoke an import 
tolerance under Sec.  510.210 and Sec.  10.25 of this chapter.


Sec.  510.213   Administrative stay of action.

    (a) The Commissioner may at any time, on his or her own initiative 
or on the request of an interested person under part 10 of this 
chapter, stay or extend the effective date of a decision to establish, 
not 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: September 10, 2021.
Janet Woodcock,
Acting Commissioner of Food and Drugs.
[FR Doc. 2021-19967 Filed 9-20-21; 8:45 am]
BILLING CODE 4164-01-P


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