[Docket No. 93DÄ0398]

Proposed Guideline Regarding Microbiological Testing for Antimicrobial
Food-Animal Drugs; Availability

AGENCY: Food and Drug Administration, HHS.

ACTION: Notice.

SUMMARY: The Food and Drug Administration (FDA) is announcing the availability
of a proposed guideline entitled "Microbiological Testing of Antimicrobial
Drug Residues in Food'' prepared by the Center for Veterinary Medicine (CVM)
regarding the tests required for food-animal antimicrobial drug products to
establish their human-food safety. This proposed guideline provides criteria
for determining which antimicrobials will require supplemental testing, and
recommends test procedures that are necessary to ensure that antimicrobial
residues will not cause intestinal microflora perturbations in the consumer.

DATES: Submit written comments by April 6, 1994.

ADDRESSES: Submit written requests for single copies of the proposed guideline
to the Communications and Education Branch (HFVÄ12), Center for Veterinary
Medicine, Food and Drug Administration, 7500 Standish Pl., Rockville, MD
20855, 301Ä594Ä1755, or the contact person (address below). Send two
self-addressed adhesive labels to assist that office in processing your
requests. Submit written comments on the proposed guideline to the Dockets
Management Branch (HFAÄ305), Food and Drug Administration, rm. 1Ä23, 12420
Parklawn Dr., Rockville, MD 20857. Requests and comments should be identified
with the docket number found in brackets in the heading of this document. A
copy of the proposed guideline and received comments are available for public
examination in the Dockets Management Branch between 9 a.m. and 4 p.m., Monday
through Friday.

FOR FURTHER INFORMATION CONTACT: Haydee Fernandez, Center for Veterinary
Medicine (HFVÄ154), Food and Drug Administration, 7500 Standish Pl.,
Rockville, MD 20855, 301Ä594Ä1684.

SUPPLEMENTARY INFORMATION: FDA is announcing the availability of a proposed
guideline entitled "Microbiological Testing of Antimicrobial Drug Residues in
Food'' regarding required testing for food-animal antimicrobial drug products.
In evaluating new animal drug applications (NADA's) the agency must determine,
among other factors, the safety of the intended use of the drug, including the
cumulative effect on man or animal required by section 512(d)(2)(B) of the
Federal Food, Drug, and Cosmetic Act (the act) (21 U.S.C. 360b(d)(2)(B)). The
proposed guideline provides criteria that will be used to determine which
antimicrobial drugs will require supplemental testing to ensure that
antimicrobial residues will not cause intestinal microflora perturbations in
the consumer exposed to antimicrobial residues.

 It is well known that therapeutic doses of antibiotics can cause adverse
effects on the intestinal microflora ecology. In most cases the lowest dose at
which these perturbations occur have not been determined; however, CVM
believes that the ecology of the human intestinal microflora should not be
disturbed by the residues of antimicrobials used in food-animals.

 In June 1992, CVM sponsored a symposium on the Microbiological Significance
of Drug Residues in Food to evaluate scientific expertise in this area.
Information discussed at the symposium reaffirmed CVM's conclusion that the
residue antimicrobial activity is a valid endpoint for establishing residue
tolerances for antimicrobial animal drugs.

 CVM proposes establishing two categories for antimicrobial drugs: (1) "New
Animal Antimicrobial Drugs Requiring Additional Human Food Safety
Microbiological Testing'' and (2) "New Animal Antimicrobial Drugs Exempt from
Additional Human Food Safety Microbiological Testing.'' To qualify for
exemption from additional microbiological testing, the antimicrobial drug must
have either: (1) "Very low'' residue levels, (2) residues with limited
antimicrobial activity, or (3) no adverse effects on intestinal microflora at
approved dosages. Antimicrobial drugs will require additional testing in cases
where a safe residue concentration retains antimicrobial activity in humans at
residue exposure levels greater than 1 part per million in the total diet.

 CVM requests comments regarding how the proposed guideline should relate the
effects of low doses of antibiotics observed in model systems to potential
adverse biological effects in humans. In addition, information is requested on
the appropriate endpoints for monitoring the effects of the different classes
of antibiotics.

 Interested persons may, on or before April 6, 1994, submit to the Dockets
Management Branch (address above) written comments on the proposed guideline.
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. The proposed guideline and received
comments may be seen in the office above between 9 a.m. and 4 p.m., Monday
through Friday.

Dated: December 28, 1993.

William K. Hubbard,

Acting Deputy Commissioner for Policy.

[FR Doc. 94Ä114 Filed 1Ä5Ä94; 8:45 am]

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