Veterinarians representing the American Association of Swine Veterinarians (AASV) met with Food and Drug Administration (FDA) officials on October 8 to discuss the agency’s proposed ban on the extralabel use of cephalosporins.
The FDA has issued an order effective November 30 that would ban the extralabel use of the cephalosporin class of antimicrobials in food-producing animals. This ban would not affect the approved uses as described on the label. Swine veterinarians, along with other veterinary groups, have expressed multiple concerns with the ban which prompted swine veterinarians to join the AASV leadership in a meeting at FDA headquarters in Rockville, Md.
The group met with Dr. Bernadette Dunham, Director of the FDA Center for Veterinary Medicine (CVM), and other CVM officials to discuss the agency’s rationale for issuing the order and to express the concerns of swine veterinarians. The CVM is responsible for the approval and regulation of veterinary antimicrobials. The Animal Medicinal Drug Use Clarification Act (AMDUCA) governs the extralabel use of antimicrobials and authorizes FDA to restrict such use if the agency determines it to be a threat to public health.
During discussions, the agency reiterated its support for the ban citing their interpretation of data collected through the National Antimicrobial Resistance Monitoring System (NARMS), results of published studies, and the findings of FDA investigations along with a healthy dose of precautionary principle. The regulators stated that they considered the cephalosporin class of antimicrobials to be similar to that of the fluoroquinolones with regards to the potential importance to human health. They indicated that they had considered banning the extralabel use of cephalosporins by generation rather than the entire class but determined that would be too cumbersome and was not well defined. The agency did, however, agree to review all comments received during the comment period and left the door open to possibly modifying the order based on the issues brought forth in the comments.
The AASV representatives explained the process swine veterinarians undertake to determine effective treatment regimens for the conditions affecting the food animals they treat. Emphasizing the importance of AMDUCA, they expressed concern regarding the lack of availability of approved products effective in the treatment of a number of conditions encountered on the farm and thus the need for extralabel use in some situations. The veterinarians described the collection and laboratory analysis of diagnostic samples used to establish a therapeutic protocol. They emphasized reliance on their training and understanding of pharmacokinetic properties to properly utilize antimicrobials in a responsible manner recognizing the public health concerns as well as the necessity to relieve animal suffering and disease.
The group also questioned the validity of the data used to support the proposed ban. There have long been questions regarding the design and interpretation of the NARMS project for instance. The NARMS data for pork indicates that the incidence of Salmonella is extremely low and found no cephalosporin resistance in Salmonella isolates from 2004 or 2005. Likewise, the data also found an extremely low incidence of cephalosporin resistant E. coli isolates in 2002 – 2005. In addition, a number of studies have identified the presence of cephalosporin resistance in animals having never received cephalosporins or, in some cases, any antimicrobials at all.
The veterinarians questioned why CVM considers the extralabel use of an approved product for non-labeled indications in the approved species at the approved dosage and route of administration to be a greater risk for the development of resistance than the approved labeled use. CVM’s response was that they do not have information regarding the pharmacokinetic profile and safety data for bacteria not approved on the label. It seems, however, that given the fact that antimicrobials affect all susceptible bacteria in the animal being treated whether or not that bacteria is on the approved label the more rational approach would be to use an approved product for the species being treated rather than a product labeled for a different species. We know much more information about the pharmacokinetics, tissue distribution and withdrawal times for products approved for use in a particular species.
The AASV is preparing comments in response to the proposed order and will continue to communicate the concerns of our members to FDA. If you are interested in submitting comments you may do so electronically at http://www.regulations.gov. Refer to Docket No. FDA-2008-N-0326. The deadline for submitting comments has been extended until November 1st. The original order banning the extralabel use of cephalosporins is available online for review.