New Final Guidance on Veterinary Drug Compounding from Bulk Drug Substances

Late last week, the United States Food and Drug Administration (FDA) Center for Veterinary Medicine (CVM) published Final Guidance for Industry No. 256, “Compounding Animal Drugs from Bulk Drug Substances” (Final Guidance). FDA had issued a draft guidance on this topic in November 2019 (Draft Guidance)[1] and published the final version following a comment period. Like the Draft Guidance, the Final Guidance describes circumstances under which CVM intends to exercise enforcement discretion with regard to animal drug compounding from bulk drug substances (compounding from bulk). For background on the draft guidance and drug compounding for animals more generally, please refer to our November 27, 2019 client alert.

The Final Guidance considers the circumstances under which FDA does not generally intend to take enforcement action for animal drugs compounded:

• to fill patient-specific prescriptions for non food-producing animals;
• for office stock for nonfood-producing animals;
• for use as antidotes for food-producing animals; and
• for use as sedatives and anesthetics for free-ranging wildlife species.

FDA’s approach under the Final Guidance generally reflects the policies provided for in the Draft Guidance, with certain differences identified below:

• FDA emphasized that, to help FDA identify compounded drugs that present safety concerns and to prevent future harm, the Agency encourages veterinarians, pharmacists, and animal owners to report through FDA’s website using Form FDA 1932a adverse events associated with animal drugs compounded from bulk.
• FDA also emphasized that compounding from bulk must be performed in full compliance with State laws and regulations governing drugs, pharmacy, and veterinary medicine.
• FDA revised and further explained its enforcement discretion policy for compounded copies of marketed FDA-approved or indexed drugs if there is a difference between the compounded drug and the FDA-approved or indexed drug that will produce a “clinical difference” in the identified patient, as determined by the treating veterinarian.
  • A drug compounded from bulk is now a copy if it has the same active ingredient or active moiety and can be given by the same route of administration as a marketed FDA-approved or indexed drug, even if it does not have the same, similar, or easily substitutable strength as the marketed FDA-approved or indexed drug.
  • When compounding a copy, the pharmacist should maintain a record of the medical rationale describing the clinical difference, either by retaining a copy of a prescription on which the veterinarian has noted the medical rationale or by contacting the veterinarian to obtain his or her medical rationale and noting it on the prescription or a document kept with the prescription. This recommendation is under Office of Management and Budget review and is not for implementation currently.
  • FDA provides examples of acceptable medical rationales describing the clinical differences in the Final Guidance, including the patient is allergic to an ingredient in approved product, the ingredient is toxic to the species, using the approved product would require too many tablets, the patient needs a fraction of an approved tablet that is not scored for fractionation, and the approved capsule cannot safely be administered to the patient.
  • FDA provides examples that would not be acceptable rationales, including the compounded drug is less expensive, the prescriber or owner prefers the compounded drug, and the patient needs half the strength of the approved product.
• Two additional examples of acceptable reasons an animal drug cannot be compounded from marketed FDA-approved or indexed drugs with the same active ingredient moieties are: (1) an inactive ingredient in the FDA-approved or indexed drug is toxic to the target species and cannot be readily separated, and (2) the FDA-approved or indexed drug that contains the active moiety is not available for compounding.
• For compounding drugs for use as antidotes for food-producing animals or sedatives and anesthetics for free-ranging wildlife species, the prescribing veterinarian must ensure that the animal does not enter the food supply too soon or at all by, for example, confining the treated animal for the needed withdrawal time or identifying the animal that has been treated with a tag containing language about the withdrawal period.

In connection with the issuance of the Draft Guidance, FDA established a public docket (FDA–2018–N–4626) so that interested parties could nominate bulk drug substances to a list of bulk drug substances for compounding office stock drugs for use in nonfood-producing animals or antidotes for food-producing animals and comment on nominated and evaluated bulk drug substances. In addition to issuing the Final Guidance, FDA is now expanding the request for nominations to include drugs compounded for use as sedatives or anesthetics for free-ranging wildlife species.[2] Interested parties can now nominate bulk drug substances to either of the following lists:

1. The List of Bulk Drug Substances for Compounding Office Stock Drugs for Use in Nonfood-Producing Animals; and
2. The List of Bulk Drug Substances for Compounding Drugs for Use in Food-Producing Animals or Free-Ranging Wildlife Species.

FDA intends to keep this docket open indefinitely so that interested persons may nominate and comment on bulk drug substances at any time. FDA has provided a modified list of information that should be submitted with a nomination. Notably, FDA no longer recommends that the nominator submit a bibliography of scientific literature containing safety and effectiveness data for the drug compounded using the nominated bulk drug substances or a list of FDA-approved, conditionally approved, or indexed animal drugs in the species that the drug compounded with the nominated bulk drug substance is intended to address. FDA will also exercise enforcement discretion with respect to the use of bulk drug substances currently under review and will remove a bulk drug substance from the list if a finished drug containing that substance in the appropriate dosage form and strength is approved or indexed.

If you have any questions concerning the material discussed in this client alert, please contact the members of our Animal Food and practice.