The U.S. Food and Drug Administration (FDA) has released new proposed guidelines that, if approved, would for the first time permit animal drugs to be compounded from bulk drug substances in certain circumstances. FDA officials have recognized that there are times when such actions may be appropriate treatment options.
Guidance for Industry No. 230 (GFI 230), “Compounding Animal Drugs from Bulk Drug Substances,” released in May, outlines specific conditions under which the FDA generally would deem compounding acceptable. FDA officials note that in cases where there are no drugs available to treat an animal with a particular condition—because either no drug is approved for a specific animal species or no drug is available under the extralabel drug use provisions—an animal drug compounded from bulk drug substances may be appropriate.
We asked Ashley Morgan, DVM, assistant director of the American Veterinary Medical Association (AVMA) Governmental Relations Division, to help sort out the proposed guidelines and what they mean for the veterinary field.
dvm360: What are the highlights of the changes FDA officials are recommending?
Morgan: GFI 230 represents a major shift from the FDA’s Compliance Policy Guide 608.400, which, last updated in 2003, reflected the agency’s thinking on the compounding of drugs for use in animals. Although the FDA still considers all compounding from bulk drug substances to be illegal, the new draft GFI 230 outlines provisions in which the agency does not intend to take action against state-licensed pharmacists, veterinarians and outsourcing facilities for compounding medications using these substances.
To be clear, the draft guidance specifically addresses compounding from bulk drug substances, not compounding when using the FDA-approved drug product. Highlights of the changes are as follows:
- Pharmacists and veterinarians may compound only for an individually identified animal patient.
- Outsourcing facilities will be veterinarians’ go-to source for preparations to be used in the office and may only compound using a bulk drug substance on the FDA’s approved list. The FDA, until Nov. 16, is currently accepting nominations for substances that should be on this list.
- Veterinarians would be able to dispense only preparations that they personally compound for a specific patient. They would not be able to dispense preparations obtained from an outsourcing facility. Pharmacies must dispense the preparations directly to the patient’s owner or caretaker.
- All pharmacists and veterinarians engaged in compounding must follow U.S. Pharmacopeial Convention (USP) standards for nonsterile preparations and for sterile preparations. Outsourcing facilities would be required to comply with current good manufacturing practice requirements.
- Pharmacists, veterinarians and outsourcing facilities would be required to submit adverse event reports to the FDA within 15 days of learning about an event associated with a medication they prepared.
- The FDA would now ask for a number of documentation requirements from prescribing veterinarians.
dvm360: Can you offer an example of when a compounded drug would be appropriate and allowable under the new guidelines—that is, something that’s not currently permissible but would be under the new guidance?
Morgan: The FDA’s interpretation of current law does not allow for any compounding from bulk drug substances for animals. However, the agency recognizes that there are limited circumstances when an animal drug compounded from a bulk drug substance may be an appropriate treatment option, and this draft guidance describes the conditions under which the FDA would generally not take action against violators.
An example of compounding that will still technically be illegal—but would be allowed under the draft guidance pending that certain provisions are met—is compounding preparations of cisapride for an individually identified animal patient. Using the bulk drug substance of cisapride to compound a medication is necessary, because there is no FDA-approved product to use.
dvm360: You mentioned earlier that, if approved, the new guidelines would be specific about what a veterinarian who is prescribing a compounded drug must document. Can you give us some of the salient points in that regard?
Morgan: Veterinarians prescribing medications that need to be compounded using a bulk drug substance would have to include the following:
- A statement that says the compounded preparation produces a clinical difference for the individually identified animal patient with an explanation of what that difference is when bulk ingredients are used to prepare a compound that contains the same active ingredient as an FDA-approved animal or human drug.
- The following 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 CFT part 530 to appropriately treat the disease, symptom or condition for which this drug is being prescribed.”
- A statement confirming that the product is to be used in a manner and on a species that complies with the list of permitted bulk ingredient uses under Appendix A in the proposed guidelines when the preparation is obtained from an outsourcing facility.
- The following statement: “This patient is not a food-producing animal.”
- Veterinarians also must note the species of the animal being treated.
dvm360: Why do you think the FDA has made these new recommendations? That is, what is its underlying imperative?
Morgan: FDA’s former guidance document, “Compounding of Drugs for Use in Animals” (CPG 608.400), has not been updated since 2003. Over the past several years, many organizations and individuals, including the AVMA, have come forward asking that appropriate provisions related to animal drug compounding be included in federal legislation. Unfortunately, the Drug Quality and Security Act of 2013 passed and substantially changed only human drug compounding. The FDA issued GFI 230, withdrawing the CPG, in response to the changes in compounding regulations caused by the law, in order to bring the regulatory enforcement for animal compounding more in line with that for humans.
dvm360: If the new rules are approved, who in the veterinary profession would be affected?
Morgan: The provisions of the guidance would apply to any veterinarian who prescribes or maintains office stock of compounded preparations that are prepared using bulk drug substances. The provisions would also apply to veterinarians who personally compound using bulk drug substances.
dvm360: Do you have any concerns about the proposed guidelines?
Morgan: In general, the AVMA supports veterinarians having the ability to adequately treat their animal patients, while doing so in compliance with the agency’s interpretation of the law. At the same time, the AVMA asserts that there are three general sets of medically necessary circumstances in which compounding from bulk substances might be needed for non-food animals:
- the approved product is not commercially available
- the needed compounded preparation cannot be made from the approved product
- there is no approved product from which to compound the needed preparation.
The draft guidance does not address all of these circumstances.
The AVMA also advocates for compounding from bulk drug substances for food animals for poison antidotes, euthanasia and depopulation medications. The FDA’s draft guidance specifically prohibits compounding from bulk drug substances for food animals.
GFI 230 also requires veterinarians to write prescriptions to pharmacies and for them to personally compound for individually identified animal patients. This requirement does not allow veterinarians the ability to address the needs of herds, flocks, groups of shelter animals, laboratory animal colonies or groups, and zoo-animal and aquaria collections. This is also inconsistent with AVMA’s Model Practice Act definition of “patient,” which refers to an animal or group of animals examined or treated by a veterinarian.
dvm360: If approved, when would these changes from the FDA take effect?
Morgan: GFI 230 will not become enforceable or official until a public comment period has closed and a final version is issued. Even then, it represents only the FDA’s current thinking on this topic, which the agency will use as a baseline for determining whether to pursue enforcement action against certain compounding activities. The comment period for feedback on the overall guidance document was originally scheduled to close Aug. 17; however, the agency extended the comment period 90 days to close Nov. 16, 2015. The FDA is accepting through Nov. 16 nominations of bulk drug substances that can be used by outsourcing facilities.
dvm360: What actions are you urging veterinarians to take right now?
Morgan: We are urging veterinarians to provide—to us, their state veterinary medical association and directly to the FDA—information on what they need with respect to compounding. It is crucial that the agency hear from veterinarians so they understand exactly how they need to care for animal patients and any implications the draft guidance may have on how they practice veterinary medicine.