FDA Publishes New Guidance on Compounding Animal Drugs from Bulk Drug Substances

The wait is finally over. On April 14, 2022, the Food and Drug Administration (FDA) published its guidance for industry #256 (GFI 256), describing FDA’s position on the legality of compounding animal drugs from bulk ingredients and the limited circumstances under which FDA will exercise enforcement discretion. While FDA reiterates its long-standing position that all compounding of animal drugs from bulk drug ingredients is subject to the animal drug provisions of the Food, Drug, and Cosmetic Act (FD&C Act), and therefore unlawful, FDA will not take enforcement action against certain compounding activities in the following three areas:

• Patient-specific prescriptions for nonfood-producing animals;
• Limited nonpatient-specific (office stock) use for nonfood-producing animals; and
• Limited antidote and anesthetic use in food-producing animals.

This article provides a brief overview of the circumstances in which FDA generally does not intend to take enforcement action against compounding in the areas listed above. We will also take a look at some of the differences when compared to compounding human drugs from bulk under Section 503A of the FD&C Act.

Patient-Specific Use:

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

• Compounding is by or under the direct supervision of a veterinarian or a pharmacist. If by a pharmacist, the compounding is in a state licensed pharmacy or a “federal [outsourcing] facility”;
• The drug is compounded in compliance with all state laws and regulations;
• All bulk ingredients (including inactive ingredients) meet applicable compendial standards and FD&C Act requirements for drug components;
• The drug is only dispensed after receipt of a valid prescription directly to the prescribing veterinarian or the patient's owner/caregiver;
• The drug is not essentially a copy of a legally marketed drug, except when use of the copy will produce a clinically meaningful difference for the patient.
  • A copy is a drug that has the same active moiety and same route of administration.
  • Any clinically meaningful difference must be documented on the prescription or other record kept with the prescription.
  • Drugs on FDA's drug shortage list are not considered "marketed" for purposes of the guidance.
• If a compounded drug has the same active ingredient as a legally marketed drug the compounder must document why bulk ingredients must be used and why that approved drug cannot serve as the source for the active ingredient.
• Known adverse events or product defect must be reported to FDA within 15 business days; and
• Labels must include all information designated in the guidance, in addition to any other information required by state law.

Several of these requirements go beyond current practice for many compounders and may represent some compliance difficulties. Specifically, the requirement that the pharmacist document why the product is not a copy and why a legally marketed drug cannot serve as a source of active ingredient. Note, these two requirements are under review by the Office of Management and Budget, under the Paperwork Reduction Act of 1995, and are not for current implementation.

Office Stock:

Similarly, FDA will permit compounding of drug products without a patient-specific prescription in limited conditions:

• Compounding is by or under the direct supervision of a veterinarian or a pharmacist. If by a pharmacist, the compounding is in a state licensed pharmacy or a “federal [outsourcing] facility”;
• The drug is compounded in compliance with all state laws and regulations;
• All bulk ingredients (including inactive ingredients) meet applicable compendial standards and FD&C Act requirements for drug components;
• Known adverse events or product defect must be reported to FDA within 15 business days;
• Labels must include all information designated in the guidance;
• The active drug substance must be listed on FDA's “List of Bulk Drug Substances for Compounding Office Stock Drugs for Use in Nonfood-Producing Animals”; and
• The drug can only be transferred from the stocking veterinarian to another veterinarian in the same practice, or to the patient's owner/caregiver.

Limited Food-Producing Animal Use:

GFI 256 permits limited compounding from bulk for food-producing animals, including antidotes for toxicoses in food-producing animals, and for sedatives and anesthetics for free-range animals. Other uses of compounded drugs in food-producing animals are prohibited.

• Compounding is by or under the direct supervision of a veterinarian or a pharmacist. If by a pharmacist, the compounding is in a state licensed pharmacy or a “federal [outsourcing] facility;
• Known adverse events or product defect must be reported to FDA within 15 business days;
• Labels must include all information designated in the guidance;
• The active drug substance must be listed on FDA's “List of Bulk Drug Substances for Compounding Drugs for Use in Food-Producing Animals or Free-Ranging Wildlife Species”; and
• The prescribing veterinarian take steps to ensure that drug residues do not enter the food supply.

Differences Between Compounding Drugs for Human and Animal Use:

GFI #256 confirms that animal drug compounding is not subject to the same requirements of Section 503A compounding human drugs from bulk substances.

Here are some of the similarities and differences between compounding from bulk for humans and animals.

Quarles & Brady will be closely watching the implementation of the policies outlined in GFI #256. If you have any questions, please contact your Quarles & Brady attorney or:

• Theodore M. Sullivan: (202) 372-9533 / theodore.sullivan@quarles.com
• Brenda Maloney Shafer: (602) 229-5774 / brenda.shafer@quarles.com
• Michael Elkins: (239) 434-4908 / michael.elkins@quarles.com