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U.S. Department of Health and Human Services

Animal & Veterinary

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CVM Plans To Modify Guidance On Microbiological Safety Of Drug Residues In Food

March 3, 2000

In January 1996, CVM made available a guidance document entitled "Microbiological Testing of Antimicrobial Drug Residues in Food" (Guidance for Industry #52.) This guidance document describes when antimicrobial drugs would be exempt from additional microbiological testing and when additional testing would be required. According to this guidance document, a maximum acceptable daily intake (ADI) of 1.5 mg of microbiologically active residues per person per day is established for antimicrobial drug residues. This threshold ADI was based on the best information available at that time and was believed to produce no adverse effects on the human intestinal microflora of the consumer.

In a workshop sponsored by FDA on September 20 and 21, 1999, in Rockville, Maryland, information from two FDA-funded research contracts was presented on the effect of low doses of different classes of antimicrobials on several microbiological endpoints of the human intestinal microflora. The purpose of these studies was to determine effects of antimicrobials in two types of model systems that could be used, once properly validated, for regulatory purposes. The model systems studied were an in vitro model (continuous flow one-chambered chemostat) and an in vivo model [human flora associated (HFA) mice]. Both systems were inoculated with human intestinal microflora.

From reviewing the data generated by these contracts, workshop participants concluded that the threshold ADI established by CVM is not appropriate for all classes of antimicrobials. Microbiological endpoints that could be of public health concern are affected to different degrees by different classes of antimicrobials. Research performed with the fluoroquinolone drug ciprofloxacin showed that low levels of this drug, even dose levels equivalent to the traditional threshold ADI of 1.5 mg/person/day, altered the ecology of the intestinal microflora in both of the model systems. The microbiological endpoints most adversely affected were the development of resistant strains, disruption of the barrier effect, and changes in bacterial populations.

Based on this information, the Center plans to modify its current Guidance No. 52, and in the near future plans to publish in the Federal Register a notice of availability for comment of a modified guidance document. The Center will implement this modified guidance in accordance with the Agency's good guidance practices. This guidance might be further revised to reflect agreement with the International Cooperation on Harmonisation of Technical Requirements for Registration of Veterinary Medicinal Products (VICH) guidance for antimicrobial residues in food.

Until such time as CVM implements a revised guidance document on this issue, sponsors of new antimicrobial drug applications should contact the Center concerning microbiological testing for approval of their products. Sponsors may contact Dr. Haydée Fernández at (301) 827-6981 or Dr. Mark Robinson at (301) 827-5258.


Contact FDA

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Issued by: FDA, Center for Veterinary Medicine

Communications Staff, HFV-12

7519 Standish Place

Rockville, MD 20855