A compounded drug is one produced when the required flavor, dosage, or formulation is otherwise not available as an FDA-approved drug.
Photo: Anne M. Eberhardt/The Horse
Compounding, the practice of changing the preparation, strength, or even flavor of a drug to meet a particular therapeutic requirement for a specific patient, is a long-established practice in veterinary medicine. Especially before major pharmaceutical companies dove into the veterinary arena, practitioners commonly mixed preparations from human drugs into dosages or forms that suited their equine patients. Over time, as veterinary medicine has become a busier and more specialized field, the drug compounding role has shifted to specific pharmacies.
As a veterinarian, I’ve used compounding pharmacies to formulate a variety of medications for my patients and consider myself fairly well-informed on the basics of veterinary drugs. Yet, prior to my recent visit to the University of California, Davis, California Animal Health and Food Safety Laboratories, if someone had asked me to explain the rules around drug compounding, or any of the issues or questions at hand, I’d have been lost.
Talking with Scott Stanley, PhD, an associate professor of veterinary medicine at the university, proved enlightening in many ways. Stanley, who has investigated a number of compounded drug formulations and published analyses of some of these drugs, succinctly sums up why drug compounding seems to hit the news every few years: Because there’s some sort of catastrophe, he says, citing for example the 2009 incident in which 21 polo ponies died due to a misformulation of a compounded supplement. Or, more recently, drug compounding hit the human health news after a contaminated batch of methyl prendisolone resulted in lethal cases of fungal meningitis.
After reading such headlines, you might be inclined to steer clear of compounding pharmacies and the drugs they produce. Yet, these establishments meet important needs. “There are very legitimate reasons for compounding,” says Stanley, the main one being the lack of pharmaceutical options available for many conditions veterinarians must treat.
As David Miller, RPh, CEO of the International Academy of Compounding Pharmacists (ICAP), describes it, “Compounding pharmacists assist veterinarians with difficult cases involving felines, canines, and other animals that require specific dosing depending on their breed and size, as well as exotic and large animal patients that present their own unique medication requirements, many of which are not met by commercially available medications.”
History of Drug Compounding
In the United States both animal and human drug manufacturing and use falls under the Food and Drug Administration’s (FDA) supervision. The FDA oversees drug manufacturing facilities and grants licenses for producing the specific pharmaceuticals. However, Stanley says, federal regulations involving animal drugs are outdated (the last revision was in 2003), explaining that prior to the Animal Medicinal Drug Use Clarification Act of 1994 (AMDUCA), veterinarians were in the sticky position of having to use off-label drugs illegally to treat their patients.
The FDA defines extra-label (off-label) drug use as:
“Actual use or intended use of a drug in an animal in a manner that is not in accordance with the approved labeling. This includes, but is not limited to, use in species not listed in the labeling, use for indications (disease and other conditions) not listed in the labeling, use at dosage levels, frequencies, or routes of administration other than those stated in the labeling, and deviation from labeled withdrawal time based on these different uses.”
Because many drugs veterinarians use to treat animals are not labeled for the species or use in question, they frequently treat their patients by going off-label with available drugs. The AMDUCA gives veterinarians leeway to prescribe medications in ways inconsistent with the drug label under very specific circumstances:
Under the provisions of the Animal Medicinal Drug Use Clarification Act of 1994, the FDA recognizes the professional judgment of veterinarians, and allows the extra-label use of drugs by veterinarians under certain conditions (21 CFR 530). Any drug used in an extra-label manner is by definition a prescription drug since the involvement of a veterinarian is required. Extra-label use of drugs may only take place within the scope of a valid veterinarian-client-patient relationship (VCPR). In the absence of a valid VCPR, if an approved new animal drug is used for a use for which it is not labeled, such use has caused the drug to be deemed unsafe and therefore adulterated under the Act (21 U.S.C. 351(a)(5)).
An approved new animal drug or human drug intended to be used for an extra-label purpose in an animal is not unsafe under the Act (21 U.S.C. 360b) and is exempt from the labeling requirements the Act (21 U.S.C. 502(f)), if such use is by or on the lawful written or oral order of a licensed veterinarian within the context of a valid veterinarian-client-patient relationship and such use complies with the extra-label use regulation (21 CFR Part 530). Extra-label use is limited to circumstances when the health of an animal is threatened, or suffering or death may result from failure to treat.
The emphasized phrases get to the meat of extra-label drug use and how it relates to drug compounding. Simply put, compounded drugs are extra-label drugs. That means a compounded drug is also a prescription drug. A veterinarian cannot prescribe it unless he or she has communicated with the owner and seen the horse in its current condition. These rules also mean a pharmacy can only compound a drug if no other suitable labeled drug exists. For example, now that an FDA-approved pergolide product (Prascend) exists for treating horses with equine Cushing’s disease, it would be unacceptable to use compounded pergolide unless the horse had special formulation requirements not met in the FDA-labeled drug.
What is a Compounded Drug?
Miller says drug compounding provides “flexibility in strengths and concentrations, dosage forms such as topical, chewable treats, and liquids, and flavoring options.” A licensed veterinarian or a licensed pharmacist must perform drug compounding under a veterinarian’s prescription for a specific patient.
Compounded drugs may not be made in bulk, says Stanley, and if there is already an FDA-approved product on the market, pharmacies compounding any form of that drug must make it from the FDA-labeled product rather than from raw materials. For example, let’s say your horse with Cushing’s disease doesn’t care for his Prascend. Your veterinarian might write a prescription to a compounding pharmacy to have the medication made into a different flavor or form for your horse; however, the pharmacist must make the drug using Prascend rather than bulk pergolide.
So, to review, a legally compounded drug is:
- Made from an FDA-approved product (unless one is not currently available and the FDA has permitted compounding the drug from raw material).
- One where the required flavor, dosage, or formulation (powder, liquid, etc.) is not otherwise available as an FDA-approved product for that animal.
- Prepared by a licensed veterinarian or a licensed pharmacist with a valid veterinary prescription.
- Made for a specific patient.
- One that addresses a legitimate medical need. Cost-savings and performance enhancement are not considered legitimate reasons for drug compounding.
A compounded drug is not:
- A “generic” drug. Generic drugs, medications for which the original patent has expired, are made in FDA-inspected facilities and undergo the same labeling requirements and testing as name-brand drugs. While state pharmacy boards monitor compounding pharmacies and the pharmacists should use drugs from FDA-inspected sources, the FDA does not oversee the process the same way it does FDA-approved name-brand or generic drug manufacturing.
- A cost-saving measure. Because pharmacists must make compounded drugs from the FDA-approved product if one exists, a compounded drug should almost by definition cost more than the original product. If the compound is far cheaper than the label product, says Stanley, pharmacists likely made it using inexpensive raw materials and it is not a legitimately compounded drug.
Compounding Pharmacy Regulation
Miller explains that state boards of pharmacies license and regulate all pharmacies and pharmacists, including compounding. Additionally, compounding pharmacies incorporate United States Pharmacopeia standards into their practice, and “the Pharmacy Compounding Accreditation Board has developed national standards to accredit pharmacies that perform a significant amount of compounding.” However, says Stanley, “Some (FDA) guideline changes allowed loopholes for compounding pharmacies. There’s really not a tight guideline that oversees and enforces penalties.” Because the FDA doesn’t consider compounding pharmacies pharmaceutical manufacturers, it cannot regulate these facilities as closely as it is does companies that manufacture new or even generic drugs.
In its Compliance Policy Guideline (CPG Sec 608.400 “Compounding of Drugs for Use in Animals), the FDA states that it “is greatly concerned about veterinarians and pharmacies that are engaged in manufacturing and distributing unapproved new animal drugs in a manner that is clearly outside the bounds of traditional pharmacy practice and that violates the Act (e.g., compounding that is intended to circumvent the drug approval process and provide for the mass marketing of products that have been produced with little or no quality control or manufacturing standards to ensure the purity, potency, and stability of the product.)”
However, the same guideline states, “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.”
Know Your Pharmacist
You don’t need to bond over cocktails with the pharmacist compounding your horse’s medication, but it is important, says Stanley, to know the source of your horse’s medications. “There are tens of thousands of pharmacies advertising (compounding) services,” he says. “Some of the products appear very legitimate.” However, some of the legitimate-looking products found on the Internet are deliberately marketed and designed as FDA-approved knockoffs.
In his university offices, Stanley showed me an array of pastes and liquids obtained from so-called compounding pharmacies. Some had labels saying nothing whatsoever about the drug or concentration in the bottle. Others, including a knockoff ulcer medication, had packaging so slick even a veterinarian in a hurry might not realize the box was missing the proper FDA language on the label.
These are the drugs that cause Stanley concern—drugs that are clearly manufactured and marketed in bulk, in defiance of the FDA guidelines. Stanley’s laboratory has tested a number of these drugs and found significant variation in shelf-stability and even concentration in the same-labeled product. Although many of these drugs are marketed as legitimate pharmaceuticals, Stanley worries that their quality and safety are inconsistent and in some cases that they contain dangerous levels of drug.
Stanley says he encourages veterinarians to develop a relationship with the compounding pharmacy. “Ask questions. Ask who is doing the compounding. Ask about products that you know have been compounded where there is a legitimate pharmaceutical source. They should say ‘no’ if there is a legitimate product. It’s a red flag if they say, ‘We’ll make anything.’ ”
Knowing the pharmacist, the pharmacy practices and protocols, and that the right drug is being manufactured specifically for your horse, according to your veterinarian’s prescription, can help ensure your horse’s medication is safe and effective. h
About the Author
Christy Corp-Minamiji, DVM, practices large animal medicine in Northern California, with particular interests in equine wound management and geriatric equine care. She and her husband have three children, and she writes fiction and creative nonfiction in her spare time.
POLL: Checking for Gastric Ulcers