Marcy Bliss (top) is CEO of Wedgewood Pharmacy, a leading veterinary compounder. Dr. Andrea Johnson is co-founder of PetVet365, a veterinary practice franchiser.
New guidance from the U.S. Food and Drug Administration on the use of bulk active pharmaceutical ingredients in compounded veterinary preparations is being enforced as of this month. If you are like the majority of veterinarians who responded to a poll last summer, you likely know little about the guidance or how it will impact how you order and prescribe compounded medications.
Because so many veterinarians said their practices are not ready to comply with this guidance, known as GFI #256, the FDA delayed its enforcement by six months to allow further "education" of veterinarians. On April 1, that grace period ended. The upshot is that veterinarians no longer can stock for future use most compounded preparations made from bulk ingredients. Rather, such compounded medications can be prescribed to individual patients only, on an as-needed basis.
Virtually all veterinarians rely on compounding to customize the dosage, form, strength and flavor of medications for patients of various sizes and species, and to fill gaps caused by periodic drug backorders. Veterinarians may turn to compounded medications only when, in their clinical judgment, they believe the unique needs of their patients cannot be met by existing FDA-approved drugs. Preparing a compounded preparation may begin with FDA-approved finished drug products; or active pharmaceutical ingredients, commonly called bulk drug substances, which is the type of compounding covered in GFI #256.
In addition to curtailing office-stock use of medications compounded from bulk drug substances, the FDA guidance calls for more documentation when such drugs are ordered for individual patients. Veterinarians may need to provide a clinical rationale for why they're prescribing a compounded medication, and compounding pharmacists must document why an FDA-approved animal or human drug cannot be used as the active ingredient of a compounded medication.
The FDA's stated intent for the guidance is twofold: address health and safety concerns, and crack down on the compounding of drugs for office stock that mimic FDA-approved medications. The FDA has indicated that it does not intend to inspect veterinary practices that don't compound from bulk drug substances, but inspections at state-licensed pharmacies are anticipated. Here are a few facts to explain what's at stake.
When the FDA issues a "Guidance for Industry," it represents the agency's "current thinking." While it is neither a law nor a regulation, the FDA uses these documents as the basis for its inspection of compounding pharmacies. However, as a practical matter, it's wise for both pharmacies and veterinary practices to comply with the standards described in these documents.
Having a stable and predictable regulatory environment, which FDA guidance may help provide, is a benefit to compounding pharmacies and veterinary practices. Complying with guidance that is reasonable and workable, without harming patient care, makes sense. And, GFI #256 in its current form reflects thousands of comments that the FDA received to its earlier draft, GFI #230, which was withdrawn after significant pushback from the industry. Assuming that the FDA listens to the needs of veterinarians when rolling out enforcement, GFI #256 can be workable in its current form.
Guidance about using bulk drug substances in compounding for animal health is especially remarkable. That's because the vast majority of medications provided by compounding pharmacies are prepared using bulk drug substances. (In fact, compounding from bulk drug substances is explicitly permitted by law in human medicine, and it is typical for veterinary compounding pharmacies not to compound from finished pharmaceutical products unless specifically asked to do so by a veterinarian.) While using FDA-approved manufactured drugs as the basis for compounding is the ideal case from the FDA's perspective, we believe using bulk drug substances is the surest, safest, most scientifically sound and most cost-effective way to prepare compounded medications.
Under GFI#256, the FDA is in the process of identifying the preparations compounded from bulk drug substances that you may order for office stock, and which ones you may only prescribe for individual patients. For the typical veterinary practice treating non-food-producing animals, the crux comes down to three lists the FDA is keeping.
- Medications made from bulk drug substances may be ordered for office stock if they appear on the FDA's list of allowed medications ("listed" in FDA parlance) or on a list of medications under review. Compounded preparations on either list remain available for prescriptions.
- Medications that appear on this list (confusingly described as "not listed" in FDA parlance) may not be used as office stock. Veterinarians still may prescribe these compounded medications for individual patients, but they may need to document a medical rationale for doing so.
So, where do we stand with the above lists? Of more than 200 bulk drug substances nominated by compounding pharmacies and industry associations for inclusion on the "listed" list, the FDA so far has ruled that approximately 30 of them may be compounded for office use, and a few dozen or so others may not be compounded for office use. For example, the FDA says that apomorphine hydrochloride tablets, mirtazapine oral suspension, and enrofloxacin oral paste for horses may not be compounded for office stock.
As it works through the list of nominated bulk drug substances, the FDA has made it clear that it wants to hear from veterinarians as to why maintaining access to these compounded medications for office use is critical for patient care. If this is important to you and your patients, it is extremely important that you share your perspectives with the FDA. To expand further, the agency wants to hear your unique professional views on why specific compounded medications are needed for immediate use or dispensing from your practice, and why the compounded medication you want to order is a clinically different from and a preferred alternative to an FDA-approved drug. While the agency has stated that it has no role in regulating the practice of medicine, guidance like GFI #256 can have that practical effect.
To comment on any nominated or "not listed" bulk substance for office-use compounding, go to the FDA's GFI #256 commenting docket and provide case examples of why you need to have specific medications on hand for office use, and why you sometimes have patients with unique needs that cannot be met by the alternatives. There is likely a limited window during which veterinarians can make a difference in the future of compounded medication availability. The time to act is now.
Marcy Bliss is the CEO of Wedgewood Pharmacy, the largest compounding pet pharmacy in the U.S., based in New Jersey. Andrea Johnson, DVM, is a graduate of the University of Georgia College of Veterinary Medicine and also holds a master's degree in biological sciences from Marshall University. She began her career as an associate veterinarian at a practice in Kentucky, and later became owner of and chief medical officer of 15 Banfield Pet Hospital franchises in Kentucky, Ohio and Indiana. She has been a veterinary consultant for LegacyVet and an independent consultant. More recently, she co-founded a veterinary practice franchise company, PetVet365.