Photo courtesy of Wedgewood Pharmacy
Drug compounding is a process by which medications are customized for patients by making changes in form, dosage or flavoring.
The U.S. Food and Drug Administration has delayed plans to inspect compounding pharmacies for at least six months to allow the veterinary community more time to adapt to industry changes. The inspections technically could have begun this week.
The agency said it needs more time to educate the veterinary community about its "Guidance for Industry #256 — Compounding Animal Drugs from Bulk Drug Substances," published on April 13. In the guidance, the FDA Center for Veterinary Medicine describes how it will enforce the Federal Food, Drug, and Cosmetic Act regarding the compounding of animal drugs from bulk ingredients. Veterinary compounding is the practice of creating medications tailored to the needs of an individual animal patient or a small group of animals by altering the dosage, form and/or flavor of drugs.
The law prohibits compounding animal drugs from bulk substances — that is, raw materials. Instead, compounded medications are supposed to be made by manipulating finished drugs. According to the FDA, compounding drugs from bulk ingredients can be dangerous because they aren't vetted for safety and efficacy via the agency's drug approval process. In addition, the agency aims to crack down on compounded preparations that mimic medications manufactured by pharmaceutical companies.
But the agency also wants to provide some leeway for special circumstances.
For example, veterinarians usually prescribe compounded medications when there isn't a manufactured version of a drug that meets a patient's needs — whether a medication needs to be flavored or come in a lower dosage than available — and they sometimes keep stock on hand of compounded drugs that they commonly use. The FDA frowns on compounded office stock, maintaining that it "potentially exposes large numbers of animals to drugs of unproven safety, effectiveness, and quality." However, it says in the guidance that it "recognizes that in some limited cases an animal drug is urgently needed, and the time needed to compound a drug in response to an individual patient prescription may result in animal suffering or death." Therefore, the agency's policy is to refrain from enforcement action for compounding office stock under certain limited circumstances.
The FDA has put together a list of nearly 20 bulk drug substances that veterinarians may stock for anticipatory use in non-food animals, and the agency is considering at least 122 more potential drug exemptions that have been requested, mostly by the compounding industry. The FDA expects to receive still more nominations for exemptions.
"[W]e are extending ongoing outreach and education that we previously announced," the agency said in a statement to the public last week. "At this time, we do not intend to shift our resources toward routine inspectional activities until April 2023. ... We will continue to engage stakeholders to address questions and clarify certain aspects of the guidance."
The agency's policy and consideration of compounding drug exemptions "strikes the right balance between maintaining access to drugs veterinarians need to treat diverse animal populations, while ensuring human and animal health is protected from poorly compounded products, or ones that attempt to copy existing FDA-approved drugs," Dr. Stephen Solomon, director of the FDA CVM, said in a press release earlier this year.
For now, veterinarians may keep office stock of compounded drugs made from bulk substances that appear on the list under review, as well as on the list of allowed products.
Wedgewood Pharmacy, one of the largest veterinary compounding pharmacies in the country, has submitted more than 100 of the nominations.
As an example, one is for metronidazole benzoate, an antibiotic made for human use but prescribed off-label (or extra-label) by veterinarians to treat bacterial and parasitic infections, such as Giardia, in dogs, cats and horses. The drug, commercially manufactured as Flagyl and any number of generics, is a "prime example of the necessity of flavorings and/or alternate dosage forms," reads the nomination, submitted in June.
Office stock of compounded metronidazole benzoate is needed "to begin treatment as soon as possible as to not allow any of the conditions being treated to escalate to further injury, suffering, or death," the nomination says. Speaking to the need for office stock of metronidazole benzoate, Wedgewood CEO Marcy Bliss told the VIN News Service that it's not ideal for veterinarians to have to "write individual prescriptions to have this drug compounded, so that patients have to then wait seven to 10 days for it to arrive in the mail."
Covetrus, which provides a variety of veterinary services including drug compounding, nominated another antibiotic made for people, azithromycin. "Having access to azithromycin in the various compounded dosage forms allows the veterinarian to choose the correct antibiotic as determined from clinical review of the disease state that is being managed, and it allows for compliance in accessible dosage options in capsules, tablets, liquids, and otic preparations that can be flavored or tailored to the species being treated in the hospital setting," the nomination reads.
While the FDA works out which drugs may be exempted from the prohibition on bulk compounding, wider rules about when and how compounded drugs may be used in veterinary medicine are in effect:
- Compounding must be created by or under the direct supervision of a veterinarian or pharmacist and performed in compliance with state law and FDA requirements for drug components.
- A pharmacist must receive a patient-specific prescription before dispensing such a drug.
- A veterinarian may dispense such a drug to a client of the practice or to another veterinarian in the same physical location.
- FDA-approved drugs cannot be copied via compounding unless doing so makes a clinical difference for the patient, such as when administering the drug is impractical because it requires too many tablets. (The FDA defines copies as compounded drugs that contain all active ingredients and can be administered the same way as the approved drug.)
- Veterinarians and pharmacists should document the clinical difference and need for a compounded version of an FDA-approved drug. The FDA offers examples of appropriate rationales to do this, such as if administering the approved version requires too many tablets, or breaking up a dose is impractical. Cost and preference are inappropriate rationales.
- If a drug compounded from bulk drug substances has the same active ingredient as an FDA-approved drug, the compounding pharmacist must document why the FDA-approved cannot be used as the source.
Veterinarians may compound or use compounded drugs and keep them as office stock for food-producing animals and free-range wildlife species, so long as the substances are permitted for use by the FDA or nominated for review.
"When using these drugs, we expect the prescribing veterinarian, acting within a valid veterinarian-client-patient relationship (VCPR), to establish scientifically-based withdrawal, withholding, and discard times to ensure that animals treated with these drugs do not contain residues of the antidote, sedative, or anesthetic, or alternatively, to ensure that the treated animals do not enter the food supply," the agency says.
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