Federal Register / Vol. 86, No. 180 / Tuesday, September 21, 2021 / Rules and Regulations 52401 

Name of Product/Data/Publication/Information/Service 

Current fee New fee 

NOAA National Center for Environmental Information 

Provision of Global Nighttime VIIRS day/night band data in HDF5 format ............................................................ 29,975.00 (*) 

Provision of regional data from the VIIRS instrument on a daily basis .................................................................. 14,720.00 (*) 

* Indicates a product no longer offered. 

[FR Doc. 2021–20194 Filed 9–20–21; 8:45 am] 

BILLING CODE 3510–HR–P 

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. 

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, 

charli.long-medrano@fda.hhs.gov. 

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, PRAStaff@fda.hhs.gov. 

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: 

• The scope and definitions; 

• who may initiate proceedings to 

establish an import tolerance; 

• contents of a submission requesting 

establishment of an import tolerance; 

• sources of data and information 

supporting the safety of a proposed 

import tolerance; 

• Agency procedures for 

establishment, amendment, or 

revocation of an import tolerance; 

• public disclosure of import 

tolerance-related actions (actions under 

consideration, establishment, 

amendment, or revocation); and 

• environmental impact assessment 

of import tolerance-related actions. 

In addition, conforming amendments 

are being made in §§ 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 

§ 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. 


lotter on DSK11XQN23PROD with RULES1
52402 Federal Register / Vol. 86, No. 180 / Tuesday, September 21, 2021 / Rules and Regulations 

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] 

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 

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, animalderived 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 § 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. 


lotter on DSK11XQN23PROD with RULES1
Federal Register / Vol. 86, No. 180 / Tuesday, September 21, 2021 / Rules and Regulations 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 (§ 510.201 (21 CFR 

510.201)); to define certain relevant 

terms (§ 510.202 (21 CFR 510.202)); to 

establish who may initiate proceedings 

to establish or amend an import 

tolerance (§ 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 (§ 510.205 (21 CFR 510.205)); 

and to describe the review of 

information to establish or amend an 

import tolerance (§ 510.206 (21 CFR 

510.206)). Provisions describing when 

and how information relating to import 

tolerances will be publicly disclosed, 

previously in proposed § 510.205, are 

now described and organized in 

redesignated § 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 § 510.209 (21 CFR 

510.209). Procedures for revocation of 

an import tolerance are described in 

redesignated § 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 §§ 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 foodproducing 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 FDAapproved 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: 


lotter on DSK11XQN23PROD with RULES1
52404 Federal Register / Vol. 86, No. 180 / Tuesday, September 21, 2021 / Rules and Regulations 

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 nontherapeutic 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 

§ 510.205, now § 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 


lotter on DSK11XQN23PROD with RULES1
Federal Register / Vol. 86, No. 180 / Tuesday, September 21, 2021 / Rules and Regulations 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 § 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 

ESGHelpDEsk@fda.hhs.gov for help 

with the ESG or cvmesubmitter@

fda.hhs.gov 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 immunecompromised 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-safetyguidances). 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 (mg/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 

§§ 500.80 through 500.92 (21 CFR part 

500, subpart E, Regulation of 

Carcinogenic Compounds Used in FoodProducing Animals). Any regulatory 

method for ascertaining the marker 

residue in the target tissue will be made 

publicly available pursuant to 

§ 510.207(b) of the final rule. We have 

revised §§ 510.205(e) and 510.207(b) of 

the final rule and made conforming 

changes to §§ 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 


lotter on DSK11XQN23PROD with RULES1
52406 Federal Register / Vol. 86, No. 180 / Tuesday, September 21, 2021 / Rules and Regulations 

1Available at: https://www.fda.gov/media/69949/ 

download. 

2Available at: https://www.fda.gov/regulatoryinformation/search-fda-guidance-documents/cvmgfi-159-vich-gl36-studies-evaluate-safety-residuesveterinary-drugs-human-food-general-approach. 

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 animalderived 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 animalderived food products are safe for 

human consumption. 

(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 foodproducing 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 

§ 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 


lotter on DSK11XQN23PROD with RULES1
Federal Register / Vol. 86, No. 180 / Tuesday, September 21, 2021 / Rules and Regulations 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

Category Primary 

estimate 

Low 

estimate 

High 

estimate 

Units 

Notes Year 

dollars 

Discount 

rate 

(%) 

Period 

covered 

(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 $millions/year .......... .................. .................. .................. .................. 7 ..................

.................. .................. .................. .................. 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. 


lotter on DSK11XQN23PROD with RULES1
52408 Federal Register / Vol. 86, No. 180 / Tuesday, September 21, 2021 / Rules and Regulations 

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-fdaregulations. 

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, animalderived 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 animalderived 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 § 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 

§ 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 §§ 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 § 510.205(f) and the 

information required to be submitted in 

a withdrawal of a request is set forth in 

§ 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 § 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

21 CFR Section; activity Number of 

respondents 

Number of 

responses per 

respondent 

Total annual 

responses 

Average 

burden per 

response 

Total hours 

510.205(e)(1) through (8); contents of request ................... 2 1 2 1 2 

510.205(a) through (e); request to establish an import tolerance based on permanent Codex MRL 2 ..................... 2 1 2 50 100 

510.205(a) through (e); request to establish an import tolerance not based on permanent Codex MRL 2 ............... 1 1 1 80 80 

510.205(f), request to amend an import tolerance .............. 1 1 1 32 32 

510.205(g), withdrawal of a request .................................... 1 1 1 1 1 


lotter on DSK11XQN23PROD with RULES1
Federal Register / Vol. 86, No. 180 / Tuesday, September 21, 2021 / Rules and Regulations 52409 

TABLE 3—ESTIMATED ANNUAL REPORTING BURDEN 1—Continued 

21 CFR Section; activity Number of 

respondents 

Number of 

responses per 

respondent 

Total annual 

responses 

Average 

burden per 

response 

Total hours 

Total .............................................................................. ........................ ........................ ........................ ........................ 215 

1There are no capital costs or operating and maintenance costs associated with this collection of information. 

2A 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 

■ 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. 

■ 2. In § 10.25, revise paragraph (a)(1) to 

read as follows: 

§ 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 

§ 71.1, for a food additive petition in 

§ 171.1 or § 571.1, for a new drug 

application in § 314.50, for a request to 

establish or amend an import tolerance 


lotter on DSK11XQN23PROD with RULES1
52410 Federal Register / Vol. 86, No. 180 / Tuesday, September 21, 2021 / Rules and Regulations 

in § 510.205, for a new animal drug 

application in § 514.1, or 

* * * * * 

PART 20—PUBLIC INFORMATION 

■ 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, 300u300u-5, 300aa-1. 

■ 4. In § 20.100, add paragraph (c)(47) to 

read as follows: 

§ 20.100 Applicability; cross-reference to 

other regulations. 

* * * * * 

(c) * * * 

(47) Requests to establish or amend 

import tolerances, in § 510.205 of this 

chapter. 

PART 25—ENVIRONMENTAL IMPACT 

CONSIDERATIONS 

■ 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. 

■ 6. In § 25.20, add paragraph (q) to read 

as follows: 

§ 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 

■ 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. 

■ 8. In § 500.80, in paragraph (a), add a 

new fourth sentence; and revise 

paragraph (c) to read as follows: 

§ 500.80 Scope of this subpart. 

(a) * * * The requirements of this 

subpart shall also apply to a request for 

an import tolerance under § 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 §§ 510.201 through 

510.213 of this chapter (Subpart C— 

Import Tolerances for Residues of 

Unapproved New Animal Drugs in 

Food). 

* * * * * 

■ 9. In § 500.82(b), revise the definition 

of ‘‘Sponsor’’ to read as follows: 

§ 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 § 510.205 of this 

chapter. 

* * * * * 

■ 10. In § 500.88, add paragraph (d) to 

read as follows: 

§ 500.88 Regulatory method. 

* * * * * 

(d) If the sponsor initially submitted 

a request for an import tolerance under 

§ 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 § 510.207(b) of this chapter. 

■ 11. In § 500.92, revise paragraph (a) to 

read as follows: 

§ 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 

■ 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. 

■ 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 

§ 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. 

§ 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. 

§ 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 

§ 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 § 10.25(b) of this 

chapter. 

§ 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 


lotter on DSK11XQN23PROD with RULES1
Federal Register / Vol. 86, No. 180 / Tuesday, September 21, 2021 / Rules and Regulations 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 § 25.40 of this chapter; and 

(8) Any information required under 

§§ 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 § 510.207(a) 

of this chapter has been made publicly 

available. 

§ 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. 

§ 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 §§ 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 § 20.61 of this chapter. 

§ 510.209 Establishment, denial, or 

amendment of an import tolerance. 

(a) If an import tolerance is 

established or amended, the 


lotter on DSK11XQN23PROD with RULES1
52412 Federal Register / Vol. 86, No. 180 / Tuesday, September 21, 2021 / Rules and Regulations 

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 § 510.210(a)(1) 

or (a)(2) is applicable at that time. 

§ 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 § 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 § 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 

§ 10.30 of this chapter. 

§ 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 

§ 10.20 of this chapter and in the form 

specified in § 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 § 510.205 or to revoke 

an import tolerance under § 510.210 and 

§ 10.25 of this chapter. 

§ 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 § 10.20 of 

this chapter and in the form specified in 

§ 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 

DEPARTMENT OF LABOR 

Wage and Hour Division 

29 CFR Part 791 

RIN 1235–AA37 

Rescission of Joint Employer Status 

Under the Fair Labor Standards Act 

Rule: Delay of Effective Date 

AGENCY: Wage and Hour Division 

(WHD), Department of Labor (DOL). 

ACTION: Final rule; delay of effective 

date. 

SUMMARY: This action delays until 

October 5, 2021, the effective date of the 

rule titled ‘‘Rescission of Joint Employer 

Status Under the Fair Labor Standards 

Act Rule,’’ published in the Federal 

Register on July 30, 2021, to conform to 

the effective date requirements of the 

Congressional Review Act. 

DATES: The effective date of the rule 

published at 86 FR 40939 on July 30, 

2021, is delayed to October 5, 2021. 

FOR FURTHER INFORMATION CONTACT: 

Amy DeBisschop, Division of 

Regulations, Legislation, and 

Interpretation, Wage and Hour Division, 

U.S. Department of Labor, Room S– 

3502, 200 Constitution Avenue NW, 

Washington, DC 20210; telephone: (202) 

693–0406 (this is not a toll-free 

number). Copies of this final rule may 

be obtained in alternative formats (Rich 

Text Format (RTF) or text format (txt), 

a thumb drive, an MP3 file, large print, 

braille, audiotape, compact disc, or 

other accessible format), upon request, 

by calling (202) 693–0675 (this is not a 

toll-free number). TTY/TDD callers may 

dial toll-free 1–877–889–5627 to obtain 

information or request materials in 

alternative formats. 

Questions of interpretation and/or 

enforcement of the agency’s regulations 

may be directed to the nearest WHD 

district office. Locate the nearest office 

by calling WHD’s toll-free help line at 

(866) 4US–WAGE ((866) 487–9243) 

between 8 a.m. and 5 p.m. in your local 

time zone, or logging onto WHD’s 

website for a nationwide listing of WHD 

district and area offices at http://

www.dol.gov/whd/america2.htm. 

SUPPLEMENTARY INFORMATION: On July 

30, 2021, the Department published a 

final rule titled ‘‘Rescission of Joint 

Employer Status Under the Fair Labor 

Standards Act Rule’’ (Joint Employer 

Rescission Final Rule) to rescind the 

final rule titled ‘‘Joint Employer Status 

Under the Fair Labor Standards Act,’’ 

which had been published on January 

16, 2020. 86 FR 40939 (July 30, 2021). 

The effective date set forth in the Joint 

Employer Rescission Final Rule is 

September 28, 2021, 60 days after 

publication. 

Pursuant to the Congressional Review 

Act (CRA), the Department submitted 

the required report and information on 

the Joint Employer Rescission Final 

Rule to each House of the Congress and 

the Comptroller General. 5 U.S.C. 

801(a)(1)(A)–(B). The Department has 

been informed that the Senate did not 

receive the submission until August 6, 

2021. The Office of Information and 

Regulatory Affairs (OIRA) designated 

the Joint Employer Rescission Final 

Rule as a major rule, as defined by 5 

U.S.C. 804(2). Accordingly, in order to 

conform to the effective date 

requirements of the CRA, the 

Department in this final rule is 

extending the effective date of the Joint 

Employer Rescission Final Rule to 

October 5, 2021, 60 days after the Senate 

received the Department’s submission. 5 

U.S.C. 801(a)(3). 

Section 553(b)(3)(B) of the 

Administrative Procedure Act (APA) 


lotter on DSK11XQN23PROD with RULES1