[Federal Register: November 18, 1998 (Volume 63, Number 222)]

[Notices]

[Page 64094-64096]

From the Federal Register Online via GPO Access [wais.access.gpo.gov]

[DOCID:fr18no98-104]

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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SUMMARY: The Food and Drug Administration (FDA) is announcing the availability of a draft guidance entitled ``Guidance for Industry: Evaluation of the Human Health Impact of the Microbial Effects of Antimicrobial New Animal Drugs Intended for Use in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 This draft guidance announces that FDA now believes it is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ADDRESSES: Submit written requests for single copies of this draft
guidance to the Communications Staff (HFV-12), Center for Veterinary Medicine(CVM), Food and Drug Administration, 7500 Standish Pl., Rockville, MD 20855.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 inprocessing 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 Comments should be identified with the full title of the draft guidance and the docket number found in brackets in the heading of this document. See the SUPPLEMENTARY INFORMATION section of this document for electronic access to the draft guidance.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Therefore, FDA is announcing the availability of a draft guidance entitled ``Guidance for Industry: Evaluation of the Human Health Impact of the Microbial Effects of Antimicrobial New Animal Drugs Intended for Use in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's Home Page.

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.

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]

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