Clearing up veterinary compounding confusion

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Are you wondering about the latest changes in veterinary compounding, and the impact of the US Food and Drug Administration Center for Veterinary Medicine Guidance for Industry (FDA CVM GFI) #256, Compounding Animal Drugs From Bulk Substances?¹ If so, you are not alone—and you’re in luck. At the Fetch dvm360® virtual conference last week, Michael Azzarello, MBA, BS, LVT, CVT, a territory manager at Patterson Veterinary Supply, explained the practical implications of the guidance and offered recommendations surrounding compounding veterinary medications.

Although there are many FDA-approved medications available to use when treating animal patients, sometimes medications are on backorder, no longer available, or not available in a formulation we need. In other cases, patient adherence with your recommendations drives the need for compounding, such as flavored or transdermal formulations. We have all been in situations where compounded medications are required in the course of practicing veterinary medicine.

History of compounding

Azzarello shared the interesting history of compounding, which can be traced to the origin of pharmacies.^2,3 The first documented compounding processes can be traced back to the Egyptians.²

Initially, all medications were compounded. Now, of course, we have manufactured medications. In human medicine, compounding began to decline in the 20th century when high-volume manufactured medications became widely available. But for veterinary medicine, these manufactured medications do not fit all situations, and the use of compounding has become commonplace in veterinary practice.

Compounding in veterinary medicine

It is not uncommon that we find ourselves unable to use the manufactured formulations of drugs in our veterinary patients. Patient size varies significantly, and manufactured formulations may not be the appropriate size or strength for our patients. In some cases, medications contain ingredients that are toxic to pets or to which our patients may be allergic. Some patients are not amenable to oral medication administration, requiring flavorings specific to their species or transdermal formulations for effective drug delivery. And manufactured medications today are often on backorder or unavailable, requiring a compounded substitute to be prescribed. Finally, for patients that are on multiple medications, it may be possible to combine medications into a single tablet or capsule that contains multiple active ingredients, to avoid having to administer multiple pills per dose.

How is compounding regulated?

Several agencies are involved in pharmacy regulation, Azzarello said, but not all of them regulate compounding per se versus general pharmacy ethics and guidelines. The Pharmacy Compounding Accreditation Board (PCAB) assesses and accredits compounding pharmacies. The National Association of Boards of Pharmacy ensures that pharmacists in compounding pharmacies are licensed and accredited. And state boards of pharmacy write the regulations affecting individual states.

Azzarello provided a few examples of variations in state regulations that affect compounding activities. In some states, for example, you can purchase compounded medications to use within your hospital and prescribe to patients, whereas in other states you can only order compounded medications for a specific patient on the order of a prescription for that patient. The United States Pharmacopeia chapters USP795 and USP797 provide guidelines for the compounding of nonsterile and sterile medications, respectively.^4,5 They do not provide laws, simply guidelines. The Drug Enforcement Agency’s only role is to regulate and monitor the compounding of controlled substances.

So then, what is the role of the FDA? This is where things become a bit interesting, said Azzarello. The FDA has developed draft guidance (CVM GFI #256) that permits compounding of animal drugs when the source of the active ingredient is an FDA-approved, manufactured drug. The use of bulk substances in compounding medications is not supported, under the premise that bulk substances are not regulated to confirm the active ingredient. This bill will be voted on at the government level and, if it becomes law, will likely cause a number of issues for veterinarians and our patients.

If CVM GFI #256 becomes law, the requirement to use manufactured drugs will drive costs up astronomically. Not only are manufactured drugs more expensive than bulk substances—sometimes dramatically so—but the subsequent costs of compounding the drugs will be added on top of these already high costs. For some medication this cost increase will be minor. For others, the average increase is predicted to be 300%. This will affect not only pet owners but also shelters and zoos. Further, some manufactured drugs contain inactive ingredients that are harmful to animals, such as xylitol (toxic in dogs) or benzyl alcohol (toxic in cats). In these cases, using bulk substances is necessary to avoid potentially harmful inactive ingredients such as these. The use of bulk substances also avoids variation in potency between formulations, as you are always starting with the original, pure compound. Further, when manufactured medications are unavailable, the use of bulk substances is necessary. For these reasons, veterinary organizations are opposing this proposed legislation.

Choosing a compounding pharmacy

Medications can be compounded legally either by a licensed veterinarian in cases in which a valid veterinary-client-patient relationship exists, or by a licensed pharmacist on the order of a prescribing veterinarian. Regardless of whether the compounding is performed by a veterinarian or a pharmacist, liability falls to the prescribing veterinarian. That’s why it is imperative to research pharmacies well, use a reliable compounding pharmacy, and document any discussions with pet owners regarding a medication that will be compounded.”

So, how do you choose a reputable compounding pharmacy?⁶ Ensure they are licensed with the state board of pharmacy, whose website lists any disciplinary actions that may have occurred.⁶ The FDA also keeps a list of pharmacies that have received warning letters. Referrals from other colleagues are helpful as well. Azzarello also recommends asking these questions before selecting a pharmacy⁶:

• Can you provide documentation of your certification and accreditation? They should be able to provide specific expiration dates for their accreditation by the PCAB.
• How is your staff trained? Reputable pharmacies should be able to explain what kind of training they require for their staff.
• Do you have a quality assurance program in place? They should be able to describe their protocol and what kind of sterility testing is done.
• Where do you obtain your bulk substances, and is your bulk substance distributor FDA approved? Even if the bulk substances are not FDA approved, the bulk substance distributor should be.

The importance of these things is not to be overlooked, as any liability from poor practice may ultimately be your responsibility as the prescribing veterinarian.

References

1. US Food and Drug Administration Center for Veterinary Medicine. CVM GFI #256 - Compounding Animal Drugs from Bulk Drug Substances. November 2019. Accessed November 17, 2020.https://www.fda.gov/regulatory-information/search-fda-guidance-documents/cvm-gfi-256-compounding-animal-drugs-bulk-drug-substances​
2. History and Evolution. Medisca. Accessed November 17, 2020.https://www.medisca.com/compounding/history-and-evolution​
3. February 28: Pharmacy Fun Fact. Pharmacy Times. February 28, 2020. Accessed November 17, 2020.https://www.pharmacytimes.com/news/february-28-pharmacy-fun-fact​
4. USP General Chapter Pharmaceutical Compounding – Nonsterile Preparations. (Accessed November 17, 2020.https://www.usp.org/compounding/general-chapter-795​
5. USP General Chapter Pharmaceutical Compounding – Sterile Preparations. Accessed November 17, 2020.https://www.usp.org/compounding/general-chapter-797​
6. The Doctors CBS. Should you be checking which compounding pharmacy is making your drugs? Yahoo Entertainment. September 10, 2020. Accessed November 17, 2020. https://www.yahoo.com/entertainment/checking-compounding-pharmacy-making-drugs-100128144.html​

Rebecca A. Packer, DVM, MS, DACVIM (Neurology/Neurosurgery), is an associate professor at Colorado State University College of Veterinary Medicine and Biomedical Sciences in Fort Collins. She is active in clinical and didactic training of veterinary students and residents and has developed a comparative neuro-oncology research program at Colorado State University.