FDA Publishes Order Prohibiting the Extralabel Use of Antimicrobial Cephalosporins in Food-producing Major Species

By Riëtte van Laack –

The Animal Medicinal Drug Use Clarification Act of 1994 (“AMDUCA”) amended the FDC Act § 512(a) allowing veterinarians to prescribe extralabel use of certain approved animal and human drugs for animals.  (Extralabel use includes use in species not listed in the labeling, use for other indications than listed in the labeling, use of drugs approved for humans in animals, and deviation from the labeled withdrawal time).  Such extralabel use is permitted provided the use is prescribed by a veterinarian, the drug has been approved by FDA, a veterinarian-client relationship exists, the extralabel use is for therapeutic use (i.e., not for production use), and the use does not result in a violative food residue.  Special rules apply for drugs administered in water and extralabel use in feed is not permitted.  If, however, FDA determines that the extralabel use of an approved drug “presents a risk to the public health [the Agency] may, by order, prohibit [the extralabel] use.”  FDC Act § 512(a)(4)(D).

On January 6, 2012, FDA issued an order prohibiting the extralabel use of certain Cephalosporins in food-producing major species.  As explained in the order, FDA believes that the specified extralabel uses present a risk to public health because these uses in animals have not been evaluated for safety to animals and humans.  Specifically, FDA is concerned about the possible effect of certain extralabel uses in animals on antimicrobial resistance of microorganisms that have been associated with diseases in humans, including pneumonia, skin and tissue infections, pelvic inflammatory disease, and serious gastrointestinal infections in children.  As a result, treatment of these infections in humans with human cephalosporin drugs may be ineffective or require drugs with more serious side effects.

More than three years ago, FDA issued a similar order prohibiting the extralabel use of cephalosporin antimicrobial drugs in animals.  See 73 Fed. Reg. 38110 (July 3, 2008).  However, after extending the comment period, and receiving numerous substantive comments, only few of which supported the order, FDA decided to revoke the 2008 order.  See 73 Fed. Reg. 71923 (Nov. 26, 2008).   The majority of the comments felt that the 2008 order was too broad in scope, would have negative consequences for animal health, and was not based on sound scientific evidence.  In response, the current order is more narrowly tailored to prohibit only certain extralabel uses of certain cephalosporins.

FDA’s current order prohibits the extralabel use of cephalosporin antimicrobial drugs (except cephapirin) in the food-producing major animals, i.e., cattle, swine, chicken, and turkeys, 1) for disease prevention purposes, 2) at unapproved doses, frequencies, durations, or routes of administration, and 3) for use in a species and production class for which the drug has not been approved.  Extralabel use of cephalosporins in food-producing minor species, such as rabbits, is not affected by the order.

The order has been applauded by various advocates for control of antimicrobial drugs in food-producing animals – see here, here, and here. 

Unless revoked or modified by FDA, the order becomes effective April 5, 2012.  Comments may be submitted until March 6, 2012.