December 15, 2003


 FDA guidance on antimicrobials aims to prevent resistance

Agency outlines detailed approach to evaluating animal drugs' microbiologic effects on bacteria and human health

Posted Dec. 1, 2003

The Food and Drug Administration has released a guidance document that outlines a comprehensive, evidence-based approach for assessing the likelihood that an antimicrobial drug used to treat a food animal may cause an antimicrobial resistance problem in humans consuming meat and byproducts from that animal. The FDA issued the document to help drug sponsors understand the agency's process of evaluating whether a product proposed for approval can be used safely and effectively.

The FDA encourages sponsors to use the guidance when they seek approval of an antimicrobial for use in food-producing animals, but the document is not a regulation. Sponsors may still use other methods to establish a drug's safety, as long as they comply with statutory and regulatory requirements. The FDA has also previously indicated that it considers the risk of antimicrobial resistance when evaluating drug safety, and sponsors must submit information to prove safety before a drug is approved. The new guideline just more precisely details a process for providing these data.

"Because of the perceived or real risk of antimicrobial resistance in humans associated with the use of antimicrobials in food animals, it was absolutely critical that a science- and risk-based process be established to assess and appropriately manage the potential risks," said Dr. Lyle Vogel, director of the AVMA Scientific Activities Division. "This is important for food safety as well as the public's perception of food safety."

Dr. Tom Burkgren, executive director of the American Association of Swine Veterinarians, agrees. "Research and development of antimicrobials for food animals has been in limbo, due to the uncertainty of the FDA's approval process," he said. "Companies would naturally be unwilling to risk a lot of money on a product that might never be approved for food animals."

Dr. Burkgren says only time will tell what impact Guidance for Industry #152 will have on food animal practitioners. "If the application of 152 is balanced and judicious, then we may see some progress in new approvals and in keeping the approvals that have been used for years," he said. On the other hand, a heavy-handed application of the guidelines could limit treatment options, he continued.

Dr. Vogel is also reserving judgment. "We don't know if the new requirements will further restrict the availability of new antimicrobials to prevent and treat diseases in food animals, or if the publication will open the gates and result in approval of new antimicrobials that have been held up in the pipeline waiting for publication of GFI#152," Dr. Vogel said.

He points out that the sponsors of new animal drug applications for antimicrobials are now required to furnish a considerable amount of additional information with the application for approval. "Will it be possible, or economical, for the sponsor to obtain the (additional) information?" Dr. Vogel pondered. "And if an approval is granted, will the risk management methods that are implemented be so restrictive that it is not economical to market the antimicrobial?" Most agree that it is too soon to tell.

Drug sponsors who choose to use the guidance will prepare a hazard characterization of the drug and then submit this to the FDA for review. This will include drug-specific data, such as biochemical properties, bacterial resistance information, and data gaps and areas of emerging science that may be relevant to the microbial food safety assessment. The FDA will review the hazard characterization and then tell the sponsor whether a risk assessment is needed and the areas they need to focus on.

The risk assessment has three parts. The first part, the release assessment, determines the probability that resistant bacteria are present in food-producing animals as a consequence of a drug's use. The second part, the exposure estimate, gauges the likelihood that humans will ingest the bacteria in question from the food commodity. Part three, the consequence assessment, weighs the chances that human exposure to the resistant bacteria will result in adverse human health consequences, such as increasing the duration of an illness, loss of therapeutic options, or treatment failure.

The FDA will consider all three assessment processes, integrating them to determine the overall human health risk of using an antimicrobial in an animal. The agency could approve the drug for use in food animals, or approve the drug but under specific use restrictions. If assessments show that the risks are substantial, the FDA could also deny the application for marketing authorization.

While it may be several years before the effect of the guidance is known, some hope the guidance will help thwart bills that are in Congress. In June, Sen. Edward M. Kennedy (D-MA) and Rep. Sherrod Brown (D-OH) introduced bills that would ban, in two years, the use of antimicrobials used in human medicine for nontherapeutic purposes in food animals. This would include routine uses to prevent diseases in livestock and other common uses. According to a study in the August issue of the Journal of Antimicrobial Chemotherapy, however, removal of growth-promoting antimicrobials in some European countries has substantially increased animal disease and the use in animals of antimicrobials that are important in human medicine. In addition, these bans have not greatly affected the prevalence of resistant enterococcal infection in humans.

"I hope that the implementation of GFI #152 will demonstrate that the bills are not needed, because the objective of the bills—to safeguard important antimicrobials for human use—will be met through a science- and risk-based process," Dr. Vogel said.

For more information on Guidance for Industry #152, "Evaluating the Safety of Antimicrobial New Animal Drugs with Regard to their Microbiological Effects on Bacteria of Human Health Concern," visit