FDA extends educational period for new policy on compounding animal drugs from bulk drug substances

The Food and Drug Administration issued final guidance, unveiled in April, on the use of bulk drug substances for compounding animal medications. Under Guidance for Industry #256, Compounding Animal Drugs from Bulk Drug Substances, the FDA delineates the circumstances under which it will exercise enforcement discretion related to violations of the Federal Food, Drug, and Cosmetic Act for drug approval, labeling, and manufacturing when pharmacists and veterinarians compound drugs from bulk drug substances for animal patients.

The guidance does not touch on compounding under the FDA Extralabel Drug Use regulations, which apply when an FDA-approved drug or indexed drug is used as the starting material.

The FDA planned to begin enforcement of the guidance through routine pharmacy inspections starting Oct. 1, but that deadline has now been pushed to April 2023, according to a Sept. 9 letter from Dr. Amber McCoig, senior veterinary medical officer with the FDA Center for Veterinary Medicine.

“The agency recognizes that some stakeholders may need additional time to review the recommendations described in the guidance or make suggested changes to their processes, as well as to submit nominations for bulk drug substances for compounding office stock,” she wrote.

Patient-specific compounding for nonfood animals

Under the new FDA guidance, drugs compounded from bulk drug substances that are for specific non–food animal patients have the fewest restrictions. They are as follows: 

• Compounding must be by or under the direct supervision of a veterinarian or pharmacist and be performed in compliance with state law and FDA requirements for drug components.
• A pharmacist must receive a patient-specific prescription before dispensing such a drug.
• A veterinarian may dispense such a drug to a client of the practice or to another veterinarian in the same physical location.

Copies of FDA-approved products may not be compounded unless there is a change that makes a clinical difference for the animal. The FDA defines a copy as having the same active ingredient and able to be given by the same route of administration as the approved or indexed drug.

The veterinarian should document the clinical difference in the medical record, while a pharmacist must document the medical rationale. The FDA provided nonexhaustive examples of appropriate medical rationales, such as that the patient is allergic to an ingredient, the ingredient is toxic to the species, the animal would require too many tablets, or breaking up a dose of the approved product is not practical. Examples of inappropriate rationales include cost savings, preference, or obtaining a strength that is easily obtained from manipulation of an approved product.

If the drug compounded from bulk drug substances has the same active ingredient as an FDA-approved or indexed drug, the person compounding the drug must make and document the determination that the approved or indexed drugs cannot be used as the source.

Office stock and patient-specific compounding for food-producing animals

For a pharmacy or veterinarian to provide compounded drugs prepared from bulk drug substances for office stock for non–food-producing animals, among other provisions, the bulk drug substance must be on one of two lists maintained by the FDA Center for Veterinary Medicine:

• List of Bulk Drug Substances for Compounding Office Stock Drugs for Use in Nonfood-Producing Animals
• List of Nominated Bulk Drug Substances Currently Under Review

For a pharmacy or veterinarian to provide drugs compounded from bulk drug substances for either patient-specific or office stock use in food-producing animals or free-ranging wildlife, among other provisions, the bulk drug substances must be on the List of Bulk Drug Substances for Compounding Drugs for Use in Food-Producing Animals or Free-Ranging Wildlife Species or the List of Nominated Bulk Drug Substances Currently Under Review.

The FDA Center for Veterinary Medicine currently has 122 bulk drug substances on the List of Nominated Bulk Drug Substances Currently Under Review. The FDA intends to continue to provide enforcement discretion before April 2023 so veterinarians can continue to have access to these bulk drug substances, according to the Sept. 9 letter. The agency has also committed to reviewing nominations for bulk drug substances on an ongoing basis.

Advocacy efforts

The final FDA guidance reflects changes made in response to advocacy efforts by the AVMA, which included engagement and education with the FDA CVM, members of Congress, and other stakeholders on the importance of veterinarians having access to vital medications in a timely manner.

The AVMA has submitted nominations for bulk drug substances to the FDA on the basis of input from AVMA members and AVMA-allied organizations and will continue to gather information and make nominations on an ongoing basis.

“Going forward, the AVMA will continue to work to ensure veterinarians have appropriate access to the medications needed to provide for the animals under their care,” said Dr. Kent McClure, AVMA associate executive vice president and chief advocacy officer.

In the final guidance, FDA CVM officials indicate veterinarians should administer or dispense an approved drug when possible. When none is available, they should consider extralabel use of animal-use or human-use drugs that are approved, conditionally approved, or indexed, a category that allows administration to some small-population non–food-producing species.

If a patient needs a compounded drug, the compounder should try to use approved or indexed drugs as the sources of active ingredients before turning to bulk drug substances.

Dr. Steven M. Solomon, director of the FDA Center for Veterinary Medicine, explained in a press release earlier this year about the final guidance , “We are taking this step because we recognize the need for veterinarians to have access to compounded animal drugs that aren’t available as approved products and that would make a clinical difference in patient care.

“We believe this policy strikes the right balance between maintaining access to drugs veterinarians need to treat diverse animal populations, while ensuring human and animal health is protected from poorly-compounded products, or ones that attempt to copy existing FDA-approved drugs.”