FDA seeks to clear up confusion about compounding

The Food and Drug Administration announced the availability of a revised Compliance Policy Guide section 608.400 titled "Compounding of Drugs for Use in Animals" in the July 14, 2003, Federal Register.

The purpose of the revised CPG is to ensure that the agency's enforcement policy regarding the compounding of drugs intended for use in animals is consistent, to the extent practicable, with its enforcement policy regarding the compounding of drugs intended for use in humans.

The use of compounded drugs in food animals has received scrutiny in the past because of the potential for drug residues to end up in food products, questions about animal safety, and the efficacy of compounded drugs.

"In the past, many of these guidances have been focused on protecting the public from exposure to food animal drugs," said Dr. Dawn Boothe, a professor of clinical pharmacology at Auburn University and a member of the AVMA Council on Biologics and Therapeutic Agents. "Small animal practitioners haven't had to worry about it as much."

The revised guidance, however, clarifies what kinds of compounding the agency opposes for both large and small animal practitioners.

"Compounding is supposed to be patient-driven," Dr. Boothe explained. Veterinarians and pharmacists are allowed to alter or mix drugs, as needed, for treatment of an animal or ease of administration. They are not allowed to create large batches of compounded drugs in anticipation of a future need.

Compounding is not allowed when it is done to circumvent the drug approval process or when a drug company's product is being pirated.

"Compounded products do not meet the same standards for quality control and good manufacturing practices," said Dr. Gatz Riddell, an at-large member of the AVMA COBTA and a professor of large animal medicine at Auburn University. "You can't necessarily ensure the purity, potency, or stability of the product."

Efficacy and safety also are not guaranteed, according to Dr. Boothe.

Compounding is acceptable under some circumstances, according to Dr. Riddell. "To me, acceptable compounding is either the safe production of a drug from FDA-approved animal or human drugs, or it's the formation of a new product from a bulk substance for which there is a medically necessary indication and for which approved products or combinations of (approved products) will not suffice. This latter circumstance (compounding from bulk drugs) is not likely to ever be defensible for food animals, excluding specific, rarely indicated antidotes."

While many veterinarians, including some members of the COBTA, say that in some cases, the use of bulk drugs is medically necessary, the FDA regulations forbid the use of bulk drugs. The revised guide, however, provides a list of bulk substances for compounding and subsequent use in animals that the FDA will not normally object to:

• ammonium molybdate
• ammonium tetrathiomolybdate
• ferric ferrocyanide
• methylene blue
• picrotoxin
• pilocarpine
• sodium nitrite
• sodium thiosulfate
• tannic acid

If veterinarians feel that other drugs should be added to the list, they should contact the FDA or constituent groups, such as the COBTA, Dr. Boothe said.

"The veterinary profession is going to have to come forward and talk to the FDA," she said.

The CPG represents the agency's current thinking on the enforcement of the Federal Food, Drug, and Cosmetic Act with regard to drug products compounded for use in animals.

This CPG is intended to provide guidance and instructions to FDA staff, industry, and the public for obtaining information to help fulfill the agency's plans regarding the compounding of drugs for use in animals. The CPG does not create or confer any rights for or on any person and does not operate to bind the FDA or the public.

A copy of the CPG is available at www.fda.gov/ora/compliance_ref/cpg/. Individuals who prefer a paper copy may submit written requests for single copies of the CPG to the Director, Division of Compliance Policy (HFC-230), Office of Enforcement, Food and Drug Administration, 5600 Fishers Lane, Rockville, MD 20857. Send one self-addressed, adhesive label.

Comments on the CPG may be submitted at any time to Dockets Management Branch (HFA-305), Food and Drug Administration, 5630 Fishers Lane, Room 1061, Rockville, MD 20852. Comments should be identified with the full title of the CPG and Docket Number 2003D-0290.

Additional information about the CPG may be found in the July 14 Federal Register notice. Technical questions concerning this CPG should be directed to Dr. Neal Bataller, Center for Veterinary Medicine, HFV-230, Food and Drug Administration, 7500 Standish Place, Room E441, Rockville, MD 20855; (301) 827-0163, nbatallecvm [dot] fda [dot] gov.