FDA Proposal for Establishing Microbiological Acceptable Daily Intakes for Antimicrobial Residues

Abstract

For many years, the effect of very low levels of antimicrobials present as residues in food on the human intestinal microflora of the consumer has been a scientific concern both nationally and internationally. Prior to 1990, this issue had not been formally addressed by the Center for Veterinary Medicine (CVM). From the human food safety perspective, the evaluation of toxicological effects of drug residues did not include adverse effects on the human intestinal microflora. Following the 1992 symposium ‘Microbiological Significance of Drug Residues in Food’ co-sponsored by CVM and the Animal health Institute (AHI), CVM concluded that antimicrobial activity is a valid endpoint for establishing the tolerance for antimicrobial drugs and that ‘very low’ levels of antimicrobials would probably not perturb the intestinal microflora. In January of 1996, CVM published a guidance document entitled ‘Microbiological Testing of Antimicrobial Drug Residues in Food’ which established a threshold Acceptable Daily Intake (ADI) of 1.5 mg/person/day for additional human food safety microbiological testing for veterinary antimicrobial drugs. If a sponsor of a new animal drug is seeking an ADI higher than the threshold, additional microbiological testing would be required to prove that the residues of the drug in edible tissues would not perturb the ecology of the intestinal microflora. The Agency established the threshold based on the best available scientific information at the time, recognizing that the threshold would be re-evaluated once additional scientific information was obtained on the adequacy of this number for different classes of antimicrobials.