On Friday, FDA issued a Final Rule prohibiting certain extra-label uses of cephalosporin drugs in animals. The order narrows the scope of the Agency’s 2008 Final Rule, which prohibited all such uses, but which never took effect. (Only months after the order’s publication, FDA issued a notice revoking the ban to allow for full consideration of the “many substantive comments” the Agency received in response to its Final Rule.)
By way of background, cephalosporins are antimicrobials used to treat a variety of bacterial infections in humans and animals. Unlike with human drugs, FDA’s regulatory jurisdiction reaches the provider-patient relationship in the case of animal drugs. In particular, FDA may by regulation prohibit a particular extra-label use of an animal drug if that use “presents a risk to the public health.” See 21 U.S.C. § 360b(a)(4)(D). FDA views this authority as extending to uses of approved human drugs in animals. See 21 C.F.R. § 530.1. The Agency has invoked this authority in the case of cephalosporins.
The ban stems from a concern that certain extra-label uses of cephalosporins result in the proliferation of drug-resistant strains of bacteria in food-producing animals. If these strains enter the food supply, their resistance complicates the treatment of infections in humans. In response to comments, FDA narrowed the scope of the 2008 ban to improve the “fit,” i.e., to tailor the prohibition to address the public health concern.
In particular, FDA limited the ban’s application to unapproved uses of cephalosporins other than cephapirin products, which are approved for use in animals only and which “are formulated and dispensed in a manner that limits their suitability for other uses or routes of administration” in animals. The Agency also banned extra-label use of non-cephapirin cephalosporins in just four species—cattle, swine, chickens, and turkeys—thereby excluding so-called minor food-producing species (e.g., goats, ostriches). Further, the narrowed ban applies to only certain deviations from the labeling of qualifying cephalosporins when used in the major food-producing species, specifically:
- disease prevention uses (as opposed to uses for treating or controlling diseases);
- uses of unapproved doses, frequencies, durations, or routes of administration (e.g., so-called biobullets); and
- uses in species and production classes other than those for which the drug is approved.
While FDA narrowed the ban’s application in response to some comments, others failed to persuade the Agency to alter its course. For example, one commenter argued that FDA could not use this authority to address concerns about health outcomes in humans because FDA’s implementing regulations authorize the issuance of prohibition orders only when “FDA has evidence that demonstrates that the use of the drug has caused or is likely to cause an adverse event.” See 21 C.F.R. § 530.3(e) (defining the phrase “use of a drug presents a risk to the public health”). FDA rejected this “technical” argument, explaining that interpreting the term “adverse event” as limited to an outcome in animals treated with the drug “would be squarely inconsistent with the statutory provisions authorizing FDA to ban extralabel uses that present a risk to the public health.” The Agency also rejected assertions that it lacks the types of data required to institute such a ban, in effect reasoning that the implementing regulations afford FDA flexibility as to the information on which it may rely.
FDA’s Federal Register notice requests that comments on the narrowed order be submitted by April 6, 2012. Leaving open the possibility that the Agency may extend the comment period or either revoke or modify the order, the notice provides that the ban will take effect on April 5, 2012. It remains to be seen whether the narrowed order will draw significant opposition in comments or otherwise.
Tags: animal drugs, antimicrobials, cephalosporins, extra-label use, FDA, food-producing species, resistant strains.
