The U.S. Food and Drug Administration today made good on a decade-old promise to provide updated guidance on the regulatory complexities of compounding animal drugs from bulk substances.
A draft of the policy will be published in Tuesday’s Federal Register. It replaces "Compounding of Drugs for Use in Animals," a compliance policy guide initiated in 1996 and last updated in 2003.
"This draft guidance, once finalized, will help to ensure that animal drugs compounded from bulk drug substances are available for patient care without compromising the animal drug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 ...," Dr. Bernadette Dunham, director of the FDA’s Center for Veterinary Medicine, said in a news release.
Stakeholders have 90 days to offer comments. The FDA also is inviting the public to submit a list of bulk drug substances important to animal health and veterinary medicine.
Advocates for federal oversight say greater supervision is needed to enforce quality-control standards and ensure that pharmacies aren't compounding cheaper mimics of commercially available FDA-approved drugs — an illegal practice that many observers say is rampant.
Even so, FDA guidance has no legal teeth. The policy says it "should be viewed only as recommendations" that are "reflective of the agency's thinking."
That "thinking" has reverberated across veterinary medicine — a profession that, for decades, has been impacted by the regulatory agency's ongoing fight for jurisdiction over the centuries-old practice of mixing bulk chemicals to create tailored medications for individual patients.
Compounding is needed, supporters say, because the animal health market often is too small to support a compounded drug's application for the FDA’s approval. At the same time, the system is unsafe and weakens the drug-approval process, detractors add.
Whether the FDA has authority to regulate compounding for animals is hotly contested by many compounding pharmacies serving the animal health arena. Some legal experts maintain that regulations and recent amendments to the Federal Food, Drug and Cosmetic Act (FDCA) are specific to compounding for human health; animal health and veterinary medicine is not mentioned.
State pharmacy boards traditionally govern compounding, as reflected in the FDA's previous compliance policy guide: "Generally, FDA will defer to state authorities regarding the day-to-day regulation of compounding by veterinarians and pharmacists of animal and human drugs that are intended for use in animals. FDA anticipates that, in such cases, cooperative efforts between the states and the Agency will result in coordinated investigations, referrals, and follow-up actions by the states."
The FDA's new policy doesn't mention the authority of state pharmacy regulators. According to the 11-page document, FDA officials consider animal drugs to be generally subject to the FDCA's adulteration, misbranding and approval provisions. The agency accepts that veterinarians must sometimes use compounded drugs to treat animals but insists that it must be performed under certain conditions and restrictions.
For that reason, veterinarians should only be using compounded medications on a select, case-by-case basis, the draft guidance states. It continues: “FDA is concerned about the use of animal drugs compounded from bulk drug substances, especially when approved alternatives exist that can be used as labeled or in an extra-label manner consistent with the requirements of FDA’s extra-label provisions. Compounded drugs have not undergone premarket FDA review of safety, effectiveness, or manufacturing quality."
The FDA won't take enforcement action against a compounding entity if these conditions, among others, are met:
- The drug is compounded by or under the direct supervision of a licensed pharmacist and in accordance with chapters 795 and 797 of the United States Pharmacopeia and National Formulary, which pertain to the sterility of preparations.
- The drug is dispensed after the receipt of a valid prescription from a veterinarian for an individually identified animal patient that comes directly from the prescribing veterinarian or from the patient’s owner or caretaker to the compounding pharmacy. A drug may be compounded in advance of receipt of a prescription in a quantity that does not exceed the amount of drug product that the state-licensed pharmacy compounded pursuant to patient-specific prescriptions based on a history of receipt of such patient-specific prescriptions for that drug product over any consecutive 14-day period within the previous six months.
- If a pharmacist determines that the compounded drug cannot be made from an available FDA-approved animal or human drug with the same active ingredients, they must document that determination.
- The drug is not sold or transferred by an entity other than the entity that compounded such drug. For purposes of this condition, a sale or transfer does not include administration of a compounded drug by a veterinarian to a patient under his or her care.
FDA spelled out several conditions for veterinarians who compound medications, including:
- The drug is compounded and dispensed by the veterinarian to treat an individually identified animal patient under his or her care.
- There are no FDA-approved animal or human drugs that can be used as labeled or in an extra-label manner to appropriately treat the disease, symptom or condition for which the drug is being prescribed.
- The drug is not sold or transferred by the veterinarian compounding the drug. For purposes of this condition, a sale or transfer does not include administration of a compounded drug by the veterinarian to a patient under his or her care, or the dispensing of an animal drug compounded by the veterinarian to the owner or caretaker of an animal under his or her care.
- The label of any 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.
Prescriptions must feature the following language:
- "There are no FDA-approved animal or human drugs that can be used as labeled or in an extra-label manner under section 512(a)(4) or (5) and 21CFR part 530 to appropriately treat the disease, symptom, or condition for which this drug is being prescribed."
- "This patient is not a food-producing animal."
- If the drug contains a bulk drug substance that is a component of any marketed FDA-approved animal or human drug, there must be a change in the compound that produces a clinical difference in the drug, which must be intended for an individual patient. The prescription also must include a statement such as, "Compounded drug X would produce a clinical difference for the individually identified animal patient because the approved drug is too large a dose for the animal and cannot be divided or diluted into the small dose required."
To submit a comment electronically, visit the government's online forum for federal regulatory content. Written submissions can be mailed to the Division of Dockets Management (HFA-305), Food and Drug Administration, 5630 Fishers Lane, rm. 1061, Rockville, MD 20852.
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