Comments needed on new Draft FDA guidance for Industry #256, Compounding Animal Drugs from Bulk Substances

  |   Federal Regulatory

The U.S. Food and Drug Administration (FDA) has released new draft Guidance for Industry (GFI), titled #256 “Compounding Animal Drugs from Bulk Substances.” In May 2015, the FDA CVM introduced draft guidance for animal drug compounding that did not meet the needs of veterinarians. Following significant feedback from the AVMA, other veterinary organizations, and individual veterinarians, the agency formally withdrew that guidance in November 2017. The FDA intends for its new guidance to balance its concerns regarding safety, effectiveness, and quality of animal drugs compounded from bulk substances with the desire to provide treatment options for the diversity of veterinary species with their myriad of disease conditions. The FDA states that because of the safety benefits and protections derived from pre-market review and post-market monitoring of FDA-approved, conditionally approved, and indexed drugs, a veterinarian should only use drugs compounded from bulk drug substances if FDA- approved, conditionally approved, or indexed drugs are not available to treat their patient.

While the Agency maintains that compounding of a new animal drug from bulk drug substances results in a new animal drug that must comply with the federal Food Drug and Cosmetic Act’s approval, conditional approval, or indexing requirements, the FDA does not intend to take enforcement action for violations when the following conditions are met:

  • compounding is performed by or under the direct supervision of a veterinarian or pharmacist;
  • the product is dispensed by a pharmacist after receiving a prescription from a veterinarian who has an established veterinarian-client-patient relationship or dispensed directly by the veterinarian;
  • compounding occurs according to USP <795> “Pharmaceutical Compounding ― Nonsterile Preparations” and USP <797> “Pharmaceutical Compounding ― Sterile Preparations” and complies with the standards of all applicable USP-NF monographs;
  • the pharmacist or veterinarian reports an adverse event or drug defect to the FDA within 15 days;
  • labeling requirements as outlined in the GFI are met.

However, the FDA has indicated that additional requirements apply depending on whether the product is intended as a patient-specific product in a non-food-producing animal, as office stock for non-food- producing animals, or as an antidote for food-producing animals.

For patient-specific prescriptions for non-food-producing animals:

  • the compounded drug cannot be a copy of a marketed FDA-approved, conditionally approved, or indexed animal drug or FDA-approved human drug. A copy contains the same active pharmaceutical ingredient, can be given by the same route of administration and is of the same, similar, or a substitutable strength. The FDA will not consider a compounded product a copy if the prescribing veterinarian determines there is a difference between the compounded drug and the approved/indexed drug that will produce a clinical difference in the identified patient and the medical rationale is documented.
  • if the compounded drug has the same active pharmaceutical ingredient as an FDA-approved, conditionally approved, or indexed drug or an FDA-approved human drug, but is a different salt, ester, or other noncovalent derivative (e.g., erythromycin stearate as compared with erythromycin ethyl succinate), then the compounded product must produce a clinical difference, and the medical rationale for such use must be documented on the prescription if dispensed by the pharmacist, or on the medical record if dispensed by the veterinarian.
  • if the compounded drug has the same active pharmaceutical ingredient as one or more marketed FDA-approved, conditionally approved, or indexed drugs or an FDA-approved human drug, then the compounder must determine and document why the approved product cannot be used to prepare the compound before using a bulk drug substance as the source of the active ingredient.

For office stock (compounding without patient-specific prescriptions) for non-food-producing animals:

For antidotes for food-producing animals:

The FDA is seeking comments on draft GFI #256 and has requested submission of those comments by February 18, 2020. We encourage members to submit their feedback to AVMA at [email protected] by February 3, 2020.

In addition, the FDA is requesting nominations to the list of bulk drug substances for compounding: “List of Bulk Drug Substances for Compounding Office Stock Drugs for Use in Non-Food-Producing Animals or Antidotes for Food-Producing Animals”. Those interested in submitting nominations need to refer to and include the information requested by the FDA for each drug nomination.

The FDA has posted two related lists:

The AVMA will submit a collated response to the FDA as they continue our efforts to advocate for access to needed medications on behalf of the profession.


Posted January 24, 2020