[Federal Register Volume 63, Number 222 (Wednesday, November 18, 1998)]
[Notices]
[Pages 64094-64096]
From the Federal Register Online via the Government Printing Office [www.gpo.gov]
[FR Doc No: 98-30747]


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DEPARTMENT OF HEALTH AND HUMAN SERVICES

Food and Drug Administration
[Docket No. 98D-0969]


``Guidance for Industry: Evaluation of the Human Health Impact of 
the Microbial Effects of Antimicrobial New Animal Drugs Intended for 
Use in Food-Producing Animals''; Availability

AGENCY: Food and Drug Administration, HHS.

ACTION: Notice.

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SUMMARY: The Food and Drug Administration (FDA) is announcing the 
availability of a draft guidance entitled ``Guidance for Industry: 
Evaluation of the Human Health Impact of the Microbial Effects of 
Antimicrobial New Animal Drugs Intended for Use in Food-Producing 
Animals.'' This draft guidance announces that FDA now believes it is 
necessary to evaluate the human health impact of the microbial effects 
associated with all uses of all classes of antimicrobial new animal 
drugs intended for use in food-producing animals when approving such 
drugs.

DATES: Written comments should be submitted by December 18, 1998.

ADDRESSES: Submit written requests for single copies of this draft 
guidance to

[[Page 64095]]

the Communications Staff (HFV-12), Center for Veterinary Medicine 
(CVM), Food and Drug Administration, 7500 Standish Pl., Rockville, MD 
20855. Send one self-addressed adhesive label to assist the office in 
processing your requests.
    Submit written comments to the Dockets Management Branch (HFA-305), 
Food and Drug Administration, 5630 Fishers Lane, rm. 1061, Rockville MD 
20852. Comments should be identified with the full title of the draft 
guidance and the docket number found in brackets in the heading of this 
document. See the SUPPLEMENTARY INFORMATION section of this document 
for electronic access to the draft guidance.
FOR FURTHER INFORMATION CONTACT: Margaret A. Miller, Office of New 
Animal Drug Evaluation (HFV-100), Center for Veterinary Medicine, Food 
and Drug Administration, 7500 Standish Pl., Rockville, MD 20855, 301-
594-1620.

SUPPLEMENTARY INFORMATION:

I. Background

    FDA's ``Good Guidance Practices'' (GGP's) require the agency to 
publish, as Level 1 guidance, a change in interpretation or policy that 
is of more than a minor nature (62 FR 8961, February 27, 1997). 
Therefore, FDA is announcing the availability of a draft guidance 
entitled ``Guidance for Industry: Evaluation of the Human Health Impact 
of the Microbial Effects of Antimicrobial New Animal Drugs Intended for 
Use in Food-Producing Animals.'' The draft guidance describes the 
agency's current thinking on this subject.
    Since the 1970's, FDA has evaluated the effects of an antimicrobial 
drug product on enteric bacteria of food-producing animals in 
determining whether certain feed uses of an antimicrobial new animal 
drug are safe under section 512 of the Federal Food, Drug, and Cosmetic 
Act (the act) (21 U.S.C. 360b). Under section 512 of the act, an 
application for approval of a new animal drug must ``include adequate 
tests by all methods reasonably applicable to show whether or not such 
drug is safe for use * * *'' (21 U.S.C. 360b(d)(1)(A)) . Section 201(u) 
of the act (21 U.S.C. 321(u)) states that when ``safe' is used in 
section 512, the term ``has reference to the health of man or animal''. 
In addition, section 512(d)(2) of the act states that, when determining 
the safety of a new animal drug, the agency ``shall consider, among 
other relevant factors, (A) the probable consumption of such drug and 
of any substance formed in or on food because of the use of such drug, 
[and] (B) the cumulative effect on man * * * of such drug, taking into 
account any chemically or pharmacologically related substance * * *'' 
(21 U.S.C. 360b(d)(2)).
    In the past, FDA evaluated the human health impact of the microbial 
effects of only certain uses of antimicrobial new animal drugs in 
animal feeds (Ref. 1). However, based on scientific evidence referenced 
in the draft guidance, the agency now believes that sponsors of all 
antimicrobial new animal drugs intended for use in food-producing 
animals should provide information that will allow the agency to 
evaluate the human health impact of the intended use.
    To assess the human health impact, the following two separate, but 
related aspects, should be evaluated: (1) The quantity of resistant 
enteric bacteria formed in the animal's intestinal tract following 
exposure to the antimicrobial new animal drug (resistance) and (2) 
changes in the number of enteric bacteria in the animal's intestinal 
tract that can cause human illness (pathogen load). In some cases, a 
preapproval study or studies may be needed. FDA recognizes that there 
is no standardized protocol established for determining the human 
health impact of the microbial effect(s) of an antimicrobial product, 
and that one standard study is likely to be inappropriate for all 
intended uses.
    This draft guidance represents the agency's current thinking only 
about its authority under the act to consider the human health impact 
of the microbial effects associated with all uses of all classes of 
antimicrobial new animal drugs intended for use in food-producing 
animals. It does not provide technical guidance regarding the design of 
studies or types of information required to satisfy the requirements to 
demonstrate safety. The agency intends to solicit public comments on 
this issue at a meeting of the Veterinary Medicine Advisory Committee 
in Rockville, MD, on December 10 and 11, 1998, and possibly later at 
other public meetings that involve experts in public health.
    The draft document does not create or confer any rights for or on 
any person and does not operate to bind FDA or the public. An 
alternative approach may be used if such approach satisfies the 
requirement of the applicable statute, regulations, or both.
    References that are cited in the draft guidance have been placed on 
display in the Dockets Management Branch (address above), and may be 
seen by interested persons between 9 a.m. and 4 p.m., Monday through 
Friday.

II. Comment

     Interested persons may, on or before December 18, 1998, submit to 
the Dockets Management Branch (address above) written comments 
regarding this draft guidance. 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. A copy of the draft guidance and received comments 
may be seen in the office above between 9 a.m. and 4 p.m., Monday 
through Friday.

III. Electronic Access

    Persons with access to the Internet may obtain the draft guidance 
using the World Wide Web (WWW). For WWW access, connect to CVM at 
``http://www.fda.gov/cvm''.

IV. References

    The following references have been placed on display in the Dockets 
Management Branch (address above) and may be seen by interested persons 
between 9 a.m. and 4 p.m., Monday through Friday.
    1. U.S. Food and Drug Administration, ``Human Health Safety 
Criteria,'' Center for Veterinary Medicine, Guideline 18.
    2. Food and Drug Administration, ``Penicillin Use in Animal 
Feeds,'' 42 FR 43769-43793, August 30, 1977.
    3. Endtz, H., G. Ruiijs, et. al., ``Quinolone Resistance in 
Campylobacter Isolated From Man and Poultry Following the 
Introduction of Fluoroquinolones in Veterinary Medicine,'' Journal 
of Antimicrobial Chemotherapy, 27, 199-208, 1991.
    4. Aserkoff, B., and J. V. Bennett, ``Effect of Antibiotic 
Therapy in Acute Salmonellosis on the Fecal Excretion of 
Salmonella,''New England Journal of Medicine, 281, 636-640, 1969.
    5. Seyfarth, A. M., H. C. Wegener, and N. Frimodt-Moller, 
``Antimicrobial Resistance in Salmonella enterica subsp. enterica 
serovar typhimurium from Humans and Production Animals,'' Journal of 
Antimicrobial Chemotherapy, 40, 67-75, 1997.
    6. D'Aoust, J-Y., Salmonella Species, In: Food Microbiology 
Fundamentals and Frontiers, edited by Doyle, M. P., L. R. Beuchat, 
and T. J. Montville, ASM Press, Washington, DC, pp. 129-158, 1997.
    7. Nachamkin, I., Campylobacter jejuni, In: Food Microbiology 
Fundamentals and Frontiers, edited by Doyle, M. P., L. R. Beuchat, 
T. J. Montville, ASM Press, Washington, DC, pp. 159-170, 1997.
    8. Bates, J., J. Z. Jordens, and D. T. Griffiths, ``Farm Animals 
as a Putative Reservoir for Vancomycin-resistant Enterococcal 
Infection in Man,'' Journal of Antimicrobial Chemotherapy, 34, 507-
514, 1994.
    9. Department of Agriculture, Food Safety Inspection Service, 
``Pathogen Reduction; Hazard Analysis and Critical Control Point 
(HACCP) Systems; Final Rule,'' 61 FR 38805-38989, July 25, 1996.

[[Page 64096]]

    10. Department of Agriculture, ``Nationwide Beef Microbiological 
Baseline: Steers and Heifers,'' October 1992-September 1993; 
``Nationwide Broiler Chicken Microbiological Baseline,'' July 1994-
June 1995; and ``Nationwide Pork Microbiological Baseline: Market 
Hogs,'' April 1995-March 1996: Food Safety Inspection Service, Data 
Collection Programs, Microbiology Division.
    11. U.S. Food and Drug Administration, ``Microbiological Testing 
of Antimicrobial Drug Residues in Food,'' Center for Veterinary 
Medicine, Guideline 52.

    Dated: November 10, 1998.
William B. Schultz,
Deputy Commissioner for Policy.
[FR Doc. 98-30747 Filed 11-17-98; 8:45 am]
BILLING CODE 4160-01-F