[Federal Register Volume 67, Number 178 (Friday, September 13, 2002)]
[Notices]
[Pages 58058-58060]
From the Federal Register Online via the Government Printing Office [www.gpo.gov]
[FR Doc No: 02-23387]


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DEPARTMENT OF HEALTH AND HUMAN SERVICES

Food and Drug Administration

[Docket No. 98D-1146]


``Draft Guidance for Industry: Evaluating the Safety of 
Antimicrobial New Animal Drugs With Regard to Their Microbiological 
Effects on Bacteria of Human Health Concern;'' Availability

AGENCY: Food and Drug Administration, HHS.

ACTION: Notice.

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SUMMARY: The Food and Drug Administration is announcing the 
availability of a draft guidance document ( 152) entitled 
``Guidance for Industry: Evaluating the Safety of Antimicrobial New 
Animal Drugs with Regard to Their Microbiological Effects on Bacteria 
of Human Health Concern.'' This draft guidance document discusses a 
recommended approach for assessing the safety of antimicrobial new 
animal drugs with regard to their microbiological effects on bacteria 
of human health concern.

DATES: Submit written or electronic comments on agency guidance by 
November 27, 2002 to ensure their adequate consideration in preparation 
of the final document. General comments on agency guidance documents 
are welcome at any time.
    Written comments on the information collection requirements must be 
received by November 12, 2002.

ADDRESSES: Submit written requests for single copies of the draft 
guidance document to the Communications Staff (HFV-12), Center for 
Veterinary Medicine, Food and Drug Administration, 7519 Standish Pl., 
Rockville, MD 20855. Send one self-addressed adhesive label to assist 
that office in processing your requests.
    Submit written comments on the draft guidance document to the 
Dockets Management Branch (HFA-305), Food and Drug Administration, 5630 
Fishers Lane, rm. 1061, Rockville, MD 20852. Submit electronic comments 
to http:///www.fda.gov/dockets/ecomments. Comments should be identified 
with the full title of the draft guidance document and the docket 
number found in the heading of this document. See the SUPPLEMENTARY 
INFORMATION section for electronic access to the draft guidance 
document.
    Submit written comments on the collection of information 
requirements to the Dockets Management Branch (see previous paragraph). 
Comments should be identified with the docket number found in brackets 
in the heading of this document.

FOR FURTHER INFORMATION CONTACT: William T. Flynn, Center for 
Veterinary Medicine (HFV-2), 7519 Standish Pl., Rockville, MD 20855, 
301-827-4514, e-mail: wflynn@cvm.fda.gov.

SUPPLEMENTARY INFORMATION:

I. Background

    Antimicrobial drugs have been used since the mid-20th century to 
control and cure infectious diseases in humans. Since their discovery, 
these drugs have prevented millions of deaths worldwide by killing 
harmful bacteria or inhibiting their growth. Since the 1950s, when 
their use in animal production became widespread, antimicrobial drugs 
have helped to ensure animal health and have helped to provide an 
abundant and affordable supply of meat, milk, and eggs.
    However, soon after antimicrobial drugs became widely used, 
scientists noted the phenomenon of antimicrobial resistance. Use of 
antimicrobial drugs leads to antimicrobial resistance because, when an 
antimicrobial drug is used to treat an infection, the bacteria most 
sensitive to the drug die or their growth is inhibited. Those bacteria 
that have, or acquire, the ability to resist the antimicrobial drug 
survive and eventually replace the more drug-sensitive bacteria.
    Additionally, bacteria can become resistant indirectly when 
resistance traits are passed from other bacteria by mechanisms that 
allow the exchange of their genetic material. In this way, resistance 
can be transferred from nonpathogenic bacteria to bacteria that are 
pathogenic to humans.

[[Page 58059]]

    In recent years, national and international health organizations 
have considered evidence that use of antimicrobial drugs in food-
producing animals could lead to the emergence of antimicrobial drug-
resistant bacteria that are pathogenic to humans. For instance, 
Salmonella and Campylobacter can exist in the digestive tract of food-
producing animals without causing illness, but these same bacteria, 
when ingested by humans eating meat, milk, or eggs, can cause severe 
food-borne illness. FDA's main concern is that use of antimicrobial 
drugs in food-producing animals may lead to the emergence of bacterial 
pathogens that are resistant to drugs used to treat human illness, 
potentially making human illnesses more difficult to treat.
    Since the 1970s, FDA has evaluated the effects of antimicrobial 
drug products on enteric bacteria of food-producing animals in 
determining whether certain feed uses of an antimicrobial drug are safe 
under section 512 of the Federal Food, Drug, and Cosmetic Act (21 
U.S.C. 360b). FDA also published in the Federal Register of December 
17, 1999 (64 FR 70715), a final guidance entitled ``Consideration of 
the Human Health Impact of the Microbial Effects of Antimicrobial New 
Animal Drugs Intended for Use in Food-Producing Animals (Guidance 
 78). This guidance stated FDA's intention to consider the 
potential human health impact of the microbiological effects associated 
with all uses of all classes of antimicrobial new animal drugs intended 
for use in food-producing animals. Guidance  78 discussed the 
impact of antimicrobial drug use on the rate and extent of resistance 
emergence and on the quantity of bacteria in animals that are 
pathogenic to humans.
    In January 1999, FDA announced the availability of a discussion 
document entitled ``Proposed Framework for Evaluating and Assuring the 
Human Safety of the Microbial Effects of Antimicrobial New Animal Drugs 
Intended for Use in Food-Producing Animals'' (framework document) (64 
FR 887, January 6, 1999). The framework document laid out possible 
strategies for managing the potential risks associated with use of 
antimicrobial drugs in food-producing animals.
    The current draft guidance document outlines a risk analysis 
methodology as a process for evaluating antimicrobial resistance 
concerns as part of the pre-approval safety evaluation of a new animal 
drug. If the new animal drug sponsor elects to use this risk analysis 
methodology, it may use this guidance and the methodology described to 
conduct a qualitative risk assessment to help evaluate antimicrobial 
resistance concerns as part of an overall preapproval safety evaluation 
of their proposed animal drug product. The sponsor of the new animal 
drug electing to use this methodology should complete the qualitative 
antimicrobial risk assessment and submit it to FDA for review. The 
antimicrobial risk assessment is intended to characterize the human 
health risk associated with the proposed use of a given antimicrobial 
drug in animals. FDA's purpose in this guidance is to ensure the safety 
of animal drugs used in food-producing animals and to evaluate the 
human health impact of their intended use.

II. Significance of Guidance

    This level 1 draft guidance is being issued consistent with FDA's 
good guidance practices regulation (21 CFR 10.115). The draft guidance 
represents the agency's current thinking about the safety of new animal 
drugs, with regard to their microbiological effects on bacteria of 
human health concern. The document does not create or confer any rights 
for or on any person and will not operate to bind FDA or the public. 
Alternative methods may be used as long as they satisfy the 
requirements of the applicable statutes and regulations.

III. Paperwork Reduction Act of 1995

    Under the Paperwork Reduction Act of 1995 (the PRA) (44 U.S.C. 
3501-3520), Federal agencies must obtain approval from the Office of 
Management and Budget (OMB) for each collection of information they 
conduct or sponsor. ``Collection of information'' is defined in 44 
U.S.C. 3502(3) and 5 CFR 1320.3 and includes agency requests or 
requirements that members of the public submit reports, keep records, 
or provide information to a third party. Section 3506(c)(2)(A) of the 
PRA (44 U.S.C. 3506(c)(2)(A)) requires Federal agencies to provide a 
60-day notice in the Federal Register concerning each proposed 
collection of information before submitting the collection to OMB for 
approval. To comply with this requirement, FDA is publishing a notice 
of the proposed collection of information set forth in this document.
    With respect to the following collection of information, FDA 
invites comments on: (1) Whether the proposed collection of information 
is necessary for the proper performance of FDA's functions, including 
whether the information will have practical utility; (2) the accuracy 
of FDA's estimate of the burden of the proposed collection of 
information, including the validity of the methodology and assumptions 
used; (3) ways to enhance the quality, utility, and clarity of the 
information to be collected; and (4) ways to minimize the burden of the 
collection of information on respondents, including through the use of 
automated collection techniques, when appropriate, and other forms of 
information technology.

Evaluating the Safety of Antimicrobial New Animal Drugs With Regard to 
Their Microbiological Effects on Bacteria of Human Health Concern

    This draft guidance document discusses a recommended approach for 
assessing the antimicrobial resistance concerns as part of the overall 
preapproval safety evaluation of new animal drugs, focusing on the 
microbiological effects on bacteria of human health concern. In 
particular, the guidance describes a methodology sponsors of 
antimicrobial new animal drug applications for food-producing animals 
may use to complete a qualitative antimicrobial resistance risk 
assessment. This risk assessment should be submitted to FDA for the 
purposes of evaluating the safety of the new animal drug to human 
health. The guidance document outlines a process for integrating 
relevant information into an overall estimate of risk and discusses 
possible risk management strategies.
    Table 1 of this document represents the estimated burden of meeting 
the new reporting requests. The burden estimates for these information 
collection requests are based on information provided by the Office of 
New Animal Drug Evaluation, Center for Veterinary Medicine. The 
guidance document describes the type of information that should be 
collected by the drug sponsor when completing the antimicrobial 
resistance risk assessment. FDA will use the risk assessment and 
supporting information to evaluate the safety of original (21 CFR 
514.1) or supplemental (21 CFR 514.8) new animal drug applications 
(NADAs) for antimicrobial drugs intended for use in food-producing 
animals.
    FDA estimates the burden of this collection of information as 
follows:

[[Page 58060]]



                                   Table 1.--Estimated Annual Reporting Burden
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                                                                  Annual
                                                      No. of    Frequency      Total Annual       Hours    Total
        21 CFR 514.1(b)(8) and 514.8(a)(2)         Respondents      of     [chyph]Responses\1\     per     Hours
                                                                 Response                       Response
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Hazard Identification (initial scoping of issues--        5           1               5             30      150
 relevant bacteria, resistance determinants, food
 products; preliminary data gathering)
----------------------------------------------------------------------------------------------------------------
Release Assessment (literature review; review of          5           1               5          1,000    5,000
 research reports; data development; compilation,
 and presentation)
----------------------------------------------------------------------------------------------------------------
Exposure Assessment (identifying and extracting           5           1               5              8       40
 consumption data; estimating probability of
 contamination on food product)
----------------------------------------------------------------------------------------------------------------
Consequence Assessment (review ranking of human           5           1               5              4       20
 drug importance table)
----------------------------------------------------------------------------------------------------------------
Risk Estimation (integration of risk components;          5           1               5             12       60
 development of potential arguments as basis for
 overall risk estimate)
----------------------------------------------------------------------------------------------------------------
Risk Management (discussion of appropriate risk           5           1               5             30      150
 management activities)
----------------------------------------------------------------------------------------------------------------
Total Burden                                       ...........  .........  ...................  ........  5,420
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\1\There are no capital costs associated with this collection of information.
\2\ FDA estimates that on an annual basis an average of five NADAs (including original applications and major
  supplements) would be subject to information collection under this guidance. This estimate is based on a
  review of the number of major NADA approvals that occurred between October 1997 and October 2001. During that
  4-year period, an average of five antimicrobial NADAs (including original and major supplements) were approved
  in food-producing animals per year. This estimate excludes NADAs for antimicrobial drug combinations, generic
  drug applications (ANADAs), and certain supplemental NADAs.

IV. Comments

    This draft guidance document is being distributed for comment 
purposes only and is not intended for implementation at this time. 
Interested persons may submit to the Dockets Management Branch (see 
ADDRESSES) written comments regarding this draft guidance document. 
Submit written comments by [see DATES] to ensure adequate consideration 
in preparation of the final document. Two copies of any comments are to 
be submitted, except that individuals may submit one copy. Comments are 
to be identified with the docket number found in brackets in the 
heading of this document.
    Written comments concerning the information collection requirements 
must be received to the Dockets Management Branch by see (DATES). A 
copy of the document and received comments are available for public 
examination in the Documents Management Branch between 9 a.m. and 4 
p.m., Monday through Friday.
    Also in this issue of the Federal Register, FDA is publishing a 
notice of meeting to discuss this guidance.

V. Electronic Access

    Electronic comments may be submitted on the Internet at http://www/
fda/gov/dockets/ecomments. Once on this Internet site, select 98D-1146 
``Evaluating the Safety of Antimicrobial New Animal Drugs with Regard 
to Their Microbiological Effects on Bacteria of Human Health Concern'' 
and follow the directions. A copy of this document may be obtained on 
the Internet from the CVM home page at http://www.fda.gov/cvm.

    Dated: September 9, 2002.
Margaret M. Dotzel,
Associate Commissioner for Policy.
[FR Doc. 02-23387 Filed 9-10-02; 4:37 pm]
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