Especially for animal drugs, compounding plays a crucial role in providing medically appropriate treatments for a wide variety of species of all different shapes and sizes―specifically, those for whom a single dosage form or level will not be medically appropriate.

On April 13, 2022, the FDA issued Guidance for Industry #256 about the enforcement policy regarding the compounding of animal drugs from bulk drug substances by or under the direct supervision of veterinarians or pharmacists in either state-licensed pharmacies or federal facilities. FDA has spent several years and gone through multiple iterations trying to develop new industry guidance on compounding animal medications. While changes have been made from previous iterations, FDA has implemented significant administrative burdens for documentation of clinical need and limitations on drug substances that can be compounded for office use.

FDA has taken the current position that drugs compounded from bulk substances violate the Federal Food, Drug and Cosmetic Act (FD&C Act) because they are not approved or indexed, are not made according to current good manufacturing practice and cannot satisfy the FD&C Act’s adequate directions for use provision. However, FDA has generally refrained from taking enforcement action against animal drugs compounded from bulk drug substances under certain circumstances when no other medically appropriate treatment options exist. Especially for animal drugs, compounding plays a crucial role in providing medically appropriate treatments for a wide variety of species of all different shapes and sizes―specifically, those for whom a single dosage form or level will not be medically appropriate.

Currently, FDA generally does not intend to take enforcement action against the compounding of animal drugs from bulk substances for any nonfood-producing animal when the following circumstances are present:

1. The drug is compounded by or under the direct supervision of a veterinarian or a pharmacist in a state-licensed pharmacy or federal facility;
2. The drug is compounded in full compliance with state laws and regulations governing drugs, pharmacy and veterinary medicine;
3. All bulk drug substances, inactive ingredients and finished drug products used in compounding meet the standard set in any applicable USP-NF monograph and comply with other FD&C Act requirements for drug components;
4. The drug is dispensed by a pharmacy or the veterinarian to the owner or caretaker of a patient in his or her practice; and
5. The compounded drug is not a copy of a marketed FDA-approved or indexed drug.

Under this exception, when compounding a potential copy of a marketed FDA-approved or indexed drug, the pharmacist should maintain a record of the medical rationale describing the clinical difference between the copy and the marketed FDA-approved or indexed drug. FDA is broadly considering a compounded drug a copy of a marketed FDA-approved drug if (1) it has the same active ingredient or active moiety and (2) can be given by the same route of administration as the marketed FDA-approved drug. For anything that falls within that broad definition of a copy, the drug can only be compounded if the pharmacy maintains a record of the medical rationale for a clinical difference in the compounded formula as determined by the treating veterinarian.

This creates significant administrative burdens on both veterinarians and pharmacists. Although FDA does not intend to question documented prescriber determinations, it does intend to consider whether a prescription or notation relied upon by a compounder both documents that the determination was made and contains a medical rationale describing the clinical difference. The FDA guidelines illustrate compliant and noncompliant examples of maintaining proper records.

The second circumstance under which the FDA does not intend to take enforcement action includes the compounding of animal drugs from bulk drug substances as office stock for nonfood-producing animals when the following circumstances are present:

1. The drug is compounded by or under the direct supervision of a veterinarian or a pharmacist in a state-licensed pharmacy or federal facility;
2. The drug is intended for use in a nonfood-producing species and is compounded from a bulk drug substance listed on FDA’s List of Bulk Drug Substances for Compounding Office Stock Drugs for Use in Nonfood-Producing Animals;
3. The drug is compounded in full compliance with state laws and regulations governing drugs, pharmacy and veterinary medicine;
4. The veterinarian who stocks the drug dispenses or transfers it only to the owner or caretaker of the animal patient or to another veterinarian in the same practice;
5. Upon becoming aware of any adverse event or product defense associated with the drug, the pharmacist or veterinarian must report the event to the FDA within 15 business days; and
6. The compounded drug must be labeled to include all of the following (but not limited to): (a) name of drug; (b) strength of drug; and (c) the species of the patient(s) and indication(s) for which the drug will be used.

Lastly, FDA generally does not intend to take enforcement action against the compounding of drugs from bulk drug substances intended for use as antidotes for treating toxicoses in food-producing animals or for use as sedatives or anesthetics in free-ranging wildlife species when the following circumstances are present:

1. The drug is compounded by or under the direct supervision of a veterinarian or a pharmacist in a state-licensed pharmacy or federal facility;
2. The drug is compounded from a bulk drug substance on the List of Bulk Drug Substances for Compounding Drugs for Use in Food-Producing Animals or Free-Ranging Wildlife Species;
3. The prescribing veterinarian has a valid veterinarian-client-patient relationship and ensures the antidote, sedative or anesthetic are not present in the animal at the time of slaughter or harvest;
4. The prescribing veterinarian ensures that the animal does not enter the food supply too soon or at all;
5. Upon becoming aware of any adverse event or product defense associated with the drug, the pharmacist or veterinarian must report the event to the FDA within 15 business days; and
6. The compounded drug must be labeled to include all of the following (but not limited to): (a) name of drug; (b) strength of drug; and (c) the species of the patient(s) and indication(s) for which the drug will be used.

The guidance also illustrates the process by which an applicant can submit a bulk drug substance to the FDA bulk drug substance list.

Overall, the policies issued by FDA are perhaps less onerous than earlier iterations of the guidance, but still will place significant burdens on veterinarians and pharmacists that may impede their efforts to provide animals with the most medically appropriate treatments.

For More Information

If you have any questions about this Alert, please contact Patrick C. Gallagher, Ph.D., Frederick R. Ball, Irfan Malani, any of the attorneys in our Life Sciences and Medical Technologies Industry Group or the attorney in the firm with whom you are regularly in contact.

Disclaimer: This Alert has been prepared and published for informational purposes only and is not offered, nor should be construed, as legal advice. For more information, please see the firm's full disclaimer.