On May 18, 2015, FDA released new draft guidance on animal drug compounding from bulk drug substances. While FDA’s current statutory framework and regulations do not permit compounding of animal drugs from bulk drug substances, FDA now recognizes that there are limited circumstances when an animal drug may be compounded from bulk substance. In particular, there are certain circumstances where there is no approved drug that can be used or modified through compounding to treat a particular animal with a particular condition. FDA’s new guidance #230: Compounding Animal Drugs from Bulk Drug Substances further describes the circumstances where the Agency does not intend to take action against state-licensed pharmacies, veterinarians, and facilities registered as outsourcing facilities, when drugs are compounded for animals from bulk drug substances. The Guidance does not apply to compounding animal drugs from approved new animal or human drugs, which may be conducted according to Section 512(a)(4) and (5) of the Federal Food, Drug and Cosmetic Act (“FD&C Act”) (21 C.F.R. Part 530). These uses are considered “extralabel use”, which has an exemption for such use under Section 502(f) of the FD&C Act e.g., use of a human chemotherapy drug to treat cancer compounded for use in dogs or cats, when the chemotherapy drug is approved for those specific animal species.

FDA’s Director of the Center for Veterinary Medicine, Bernadette, Dunham, D.V.M., Ph.D., stated: “This draft guidance, once finalized, will help to ensure that animal drugs compounded from bulk drug substances are available for patient care without compromising the animal drug approval process or jeopardizing the safety of the food supply.”

The Guidance proposes that such animal drug compounding may occur from bulk drug by or under the direct supervision of a licensed pharmacist in a state-licensed pharmacy when, among other things:

  • The drug is dispensed after receipt of valid prescription from a veterinarian for an individually-identified animal patient that comes directly from the prescribing veterinarian or the patients owner or caretaker to the compounding facility. Advance quantities may be compounded for an amount that does not exceed the amount that the state-licensed pharmacy compounded pursuant to patient-specific prescriptions based on such history for that drug product over any consecutive 14-day periods within the last 6 months.
  • The drug is not intended for food-producing animals with a prescription with the statement: “This patient is not a food-producing animal.” Whether or not the food-producing animal, e.g., cattle, swine, chicken, turkey, sheep, goats, or non-ornamental fish, is actually intended to be introduced into food chain is not relevant for this consideration.
  • If the drug contains a bulk drug substance from a human or animal drug approved for marketing by FDA, then any change in the drug must be identified by the veterinarian prescribing the compounded drug along with the documented reason why the change would produce a clinical difference for that individually-identified animal patient and cannot be compounded from the human or animal drug, e.g., the approved animal or human drug contains a dose so large that it cannot be divided or diluted to the dose required by the specific animal, i.e., extralabel use is not possible.
  • The pharmacy must receive along with the prescription documentation and a statement: “There are no FDA-approved animal or human drugs that can be used as labeled or in an extralabel manner under section 512(a)(4) or (5) and 21 CFR part 530 to appropriately treat the disease, symptom, or condition for which this drug is being prescribed.”
  • The bulk drug substances used must be manufactured by an establishment registered under Section 510 of the FD&C Act along with a valid certificate of analysis.
  • The drug is compounded according to Chapters <795> and <797> of the United States Pharmacopeia and National Formulary (“USP-NF”), including sterile drug compounding.
  • The drug is not sold or transferred by an entity other than the entity that compounded the drug.
  • Within 15 days of becoming aware of any product defect or serious adverse event associated with the drug compounded from bulk drug substances, the pharmacy reports it to FDA on Form FDA 1932a.
  • The label of the compounded drug indicates the species of the intended animal patient, the name of the animal patient, and the name of the owner or caretaker of the animal patient.

For animal drugs compounded by a licensed veterinarian, the conditions for compounding using bulk drug substances are similar with the following modifications:

  •  The drug is compounded and dispensed by a veterinarian to treat an individually-identified animal patient under his care.
  • There are no FDA-approved animal or human drugs that can be used as labeled or in an extralabel manner under section 512(a)(4) or (5) and 21 CFR Part 530 to appropriately treat the disease, symptom, or condition for which this drug is being prescribed.
  • These provisions do not appear to include similar provisions for advance compounding as with the pharmacy.

For animal drugs compounded by an outsourcing facility, the provisions are similar with the following modifications:

The drugs are compounded only from bulk substances appearing in the appendix list to be developed in conjunction with this Guidance.

  • The drug is compounded by or under the supervision of a licensed pharmacist.
  • The drug is compounded in accordance with cGMP requirements.
  • These provisions also do not appear to include similar provisions for advance compounding as with the pharmacy.
  • All drugs compounded by animals by an outsourcing facility are included in the report required by 503B of the FD&C Act to be submitted to FDA each June and December identifying the drugs made by the outsourcing facility during the previous 6-month period, along with the active ingredients and their source(s), NDC number of the source ingredient(s), strength of the active ingredient(s) per unit, the dosage form and route of administration, package description, number of individual units produced, and the NDC number of the final product, if assigned, along with which reported drugs were intended for animal use.
  • The veterinarian’s prescription or order states that the drug is intended to treat the species and condition(s) for which the substance is listed in the appendix developed in conjunction with the Guidance.
  • Certain product labeling, including language such as “Not for resale.”, “Compounded by [name of outsourcing facility]” and “Adverse events associated with this compounded drug should be reported to FDA on Form FDA 1932a.”

Along with the Guidance, FDA is developing a list of bulk drug substances that facilities registered as outsourcing facilities under section 503B of the FD&C Act can use to compound for an individual animal patient or veterinarian office use under specified conditions. FDA is soliciting in a Federal Register notice to publish tomorrow public input on which bulk drug substances should be placed on the list. The draft Guidance and nominations for the list of bulk drug substances will have 90 days for comment. Following the initial list, FDA intends to review the nominated bulk drug substances on a rolling basis to periodically update the list. Finally, FDA also withdrew Compliance Policy Guide Section 608.400 Compounding of Drugs for Use in Animals, because the Agency said it was no longer consistent with its current thinking on these issues.