Animal drug compounding is the process of combining, mixing, or altering ingredients to create a medication tailored to the needs of an individual animal or a small group of animals, and these drugs can play a critical role in veterinary medicine. Compounded animal drugs are typically made by pharmacists or veterinarians. The Federal Food, Drug, and Cosmetic Act (FD&C Act) permits compounding of animal drugs when the source of the active ingredient is a finished FDA-approved drug, and not a bulk drug substance. A “bulk drug substance” is a substance used to make a drug that becomes an active ingredient in the finished dosage form of the drug.
Animal drugs compounded from bulk drug substances are not FDA-approved and have not been reviewed by FDA for evidence that they are safe, effective, properly manufactured, accurately labeled, and adequately packaged. Further, when the compounded drug is for a food-producing animal, FDA has not reviewed evidence supporting conditions of use to protect against harmful drug residues in edible tissues (meat, milk, eggs, etc.) Compounded animal drugs also lack post-market controls. Unlike sponsors of approved animal drugs, compounders are not required to report adverse events and product defects to FDA regarding animal drugs compounded from bulk drug substances.
However, when there is no medically appropriate drug that is FDA-approved, conditionally approved, or on the Index of Legally Marketed Unapproved New Animal Drugs for Minor Species (indexed) to treat the animal, an animal drug compounded from bulk drug substances may be a medically necessary treatment.
On April 14, 2022, FDA issued Guidance for Industry #256, entitled “Compounding Animal Drugs from Bulk Drug Substances.” The GFI describes the agency’s approach to situations where veterinarians need access to these unapproved drugs to provide appropriate care for the medical needs of the diverse species they treat. FDA’s final guidance balances the agency’s objectives of (1) ensuring veterinarians have access to drugs to treat the broad diversity of animal patients; (2) protecting animals and humans from unsafe animal drugs; and (3) preserving the integrity of the FDA animal drug approval process, which requires agency scientific review before approval and monitoring for continued safety and effectiveness once the drug is marketed. FDA recognizes that this final guidance will impact a wide range of stakeholders. The agency intends to focus on education and stakeholder engagement for the new animal drug compounding policies until April 2023 and will work flexibly and cooperatively with stakeholders during this period.
FDA is especially concerned about the potential risk of harm when animal drugs are compounded from bulk drug substances for office stock – meaning product meant to be kept in a veterinarian’s inventory. Because these products are made in larger quantities and may be widely distributed to veterinary hospitals, they could endanger a large number of animals if compounded improperly or under unsanitary conditions. The guidance describes FDA’s policies to monitor the safety of office stock products compounded from bulk drug substances. These policies recognize veterinarians’ need for access to certain office stock drugs for urgent or immediate use to avoid animal suffering or death. These policies include our dynamic lists, the “List of Bulk Drug Substances for Compounding Office Stock Drugs for Use in Nonfood-Producing Animals” and the “List of Bulk Drug Substances for Compounding Drugs for Use in Food-Producing Animals or Free-Ranging Wildlife Species.” Under the circumstances described in GFI #256, FDA intends to exercise enforcement discretion for office stock for nonfood-producing animals and antidotes for food-producing animals or sedatives and anesthetics for free-ranging wildlife compounded from bulk drug substances on these lists. FDA will accept nominations of additional bulk drug substances at any time and will continue to review nominations and update lists on a rolling basis. The agency will prioritize other office stock for enforcement action, as well as those products made under poor compounding practices. FDA continues to work to identify and address problems before animals are endangered.
Resources on Animal Drug Compounding from Bulk Drug Substances
- CVM GFI #256 - Compounding Animal Drugs from Bulk Drug Substances
- Checklist for Pharmacists: Compounding Animal Drugs
- Checklist for Veterinarians: Compounding Animal Drugs
- Compounding Animal Drugs for Nonfood-producing animals from Bulk Drug Substances: Determining Eligibility under GFI #256
- Compounding Animal Drugs for Nonfood-Producing Animals From Bulk Drug Substances: Determining Eligibility Under GFI 256 Graphic
- FDA Regulation of Animal Drugs
- Nominations for Bulk Drug Substances for Compounding: (1) Office Stock Drugs for Use in Nonfood-Producing Animals or (2) Antidotes or Sedatives for Food-Producing Animals
- List of Bulk Drug Substances for Compounding Office Stock Drugs for Use in Nonfood-Producing Animals
- List of Bulk Drug Substances for Compounding Drugs for Use in Food-Producing Animals or Free-Ranging Wildlife Species
- FDA-TRACK: Center for Veterinary Medicine - Compounded Animal Drugs