Compounding Basics for Veterinary Practitioners

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Compounding is currently a popular topic in both human and veterinary medicine. All US Food & Drug Administration (FDA)-approved drugs are manufactured on a large scale and must pass the FDA’s vigorous drug approval process. Compounded medications, however, have few regulations but provide an avenue for medical professionals to obtain medications that are not available commercially or that require personalization to meet the needs of their patients.

A practice traditionally performed by pharmacists, compounding allows prescribers to formulate and customize medications tailored to unique patient needs. Compounding medications for animals is crucial to the practice of veterinary medicine, which requires flexible medications for a pharmacologically and physiologically variable patient base. For example, a compounding pharmacy can make a gabapentin capsule without lactose, a common inert filler, for a patient with lactose intolerance. Doing so, however, raises several questions: Is the lactose-free capsule as safe and effective as the FDA-approved, vetted, science-backed product? Is a “new” drug created every time a formulation is adjusted or tweaked, requiring testing to ensure the same safety and efficacy standards as other medications? Does compounding put patient safety at risk?

Governing US bodies provide conflicting guidance and legislation on compounding, and controversy remains in how to best regulate its scope. This article series will look at how this is addressed and what clinicians should be aware of, including compounding do’s and don’ts, regulatory requirements, quality control, clinical resources, and upcoming guidance.

What is Considered Compounding?

Compounding is different than manufacturing. Both have stringent legal requirements and regulations, but scope and practice differ. Two major authorities, the FDA and the United States Pharmacopeia (USP), define compounding slightly differently.

The USP is a nonprofit organization that sets national chemical purity standards, which are federally enforceable when compounding.¹ The USP sets a broad definition of compounding as “combining, mixing, and/or altering, packaging, and labeling medicinal products to create a custom drug formulation in accordance with a licensed practitioner’s prescription.”¹ Almost any manipulation of a finished drug product may fall under this definition.

The USP also sets best practices for nonsterile (USP <795>) and sterile compounding (USP <797>). All USP standards are set to ensure patient safety and consistency across the industry. Medications that require sterility (eg, IV infusions) have stricter preparation and quality-control requirements to achieve contamination-free products.

The FDA, the primary overseer of US drugs, defines compounding as a service performed by or under the direct supervision of a licensed pharmacist in a state-licensed pharmacy.² The FDA further narrows the definition, stating that compounding is any change to a commercially available drug, including any preparation outside its approved product labeling.²

Based on these definitions, mixing, reconstituting, and/or preparing a drug product according to the manufacturer’s labeling are not considered compounding by the FDA but are considered compounding by the USP.^1,2 Tablet-splitting can be considered compounding by both entities, as it is a change to a finished product,² but the FDA has yet to provide a clear answer.

It is important to understand whether something qualifies as compounding to know the appropriate preparation, documentation, and labeling requirements; this will be addressed in detail in the next articles in the series, but it is always a good idea to check with local state boards of pharmacy for further guidance (see Resources).

Types of Compounding Pharmacies

There are 2 legally recognized compounding entities: one small- and one large-scale, both of which will be discussed in detailed in the next article in this series. It is important for the veterinarian to know the key regulatory differences between the 2 compounding entities and how those differences may affect their practice.

Compounding Benefits for the Veterinary Practitioner

Compounding offers additional therapeutic control over commercially available drug products, including controlling what is in the product, fine-tuning a dose, changing how the drug is given, combining multiple drugs into one product, and helping to find elusive medications.

Control What is in the Drug

Pharmaceutics (ie, drug design science) is an integral part of compounding and involves the prescriber knowing and managing exactly what is in a drug formulation—from its active pharmaceutical ingredient (APIs) to excipients. Excipients are inactive vehicles included in a preparation to serve a mechanical, chemical, or pharmacologic function. There are many types of excipients, which are also used in manufactured drugs; compounders, however, can potentially change, add, and/or exclude excipients as needed to solve individual patient needs or problems without affecting the API. Often, the veterinarian does not need to specify the exact formula used, but it can be helpful to know the excipient’s indications and uses.

Common excipients include flavors, coloring agents, sweeteners, and preservatives.³ Studies have been conducted to assess species-specific preferences to improve palatability and compliance.³ Solubility, volume, stability, and flavor-masking factors are important to maintain the end product’s integrity and effectiveness.⁴

Other less commonly considered excipients include inert fillers and diluents (eg, lactose, water), which are used when the amount of drug needed is too small to make a practical dosage form. Other substances can be added to help the compounder work with loose powders. Glidants (eg, magnesium stearate) are used to improve powder flowability. Sodium lauryl sulfate is a surfactant added to neutralize static charge and keep powder from floating away. Adsorbents (ie, magnesium oxide/carbonate or kaolin) can be used to dry sticky mixtures.

Liquid formulations often need additives to achieve stable mixtures. Hydrophilic or hydrophobic solvents and buffering agents support homogenous solutions. For suspensions, levigating agents (eg, glycerin, mineral oil, polyethylene glycol) permit better incorporation of an insoluble drug into a liquid, and suspending vehicles slow precipitation rates.

Prescribers can work with compounders to enhance the drug delivery vehicle. Tablets and capsules can be formulated with binders to increase powder adhesion, disintegrants to facilitate effective dissolution and absorption, and humectants to prevent brittleness. Professional compounding organizations such as Professional Compounding Centers of America (PCCA) and Medisca have researched and developed a wide variety of bases to optimize topical formulations.^5,6

Modulating drug formulations allows veterinarians to add species-specific flavoring for improved compliance, reformulate a gabapentin suspension without xylitol, and change to a different transdermal base to achieve penetrated, soothed skin instead of messy, matted fur.⁷

Control the Dose

Vital to the practice of veterinary medicine, accurate weight-based dosing can be best achieved through compounding. Very large, very small, and exotic animals often depend on the flexibility of compounding to receive treatment. Many commercial veterinary products offer a range of dosing options but cannot cover all potential therapeutic scenarios. Compounding pharmacies can fill the gaps while maintaining potency. For example, a veterinarian can get a 50 mg/mL metronidazole suspension for a 5-lb puppy with Giardia spp infection, or a zoology specialist can get a properly dosed antifungal nasal spray developed for 10-inch walrus nostrils.⁸ Further, compounding pharmacies often have unique application devices for precision-dosing that can dispense consistent topical volumes.

Change How the Drug is Given

Compounding can be particularly beneficial in situations in which a unique administration solution is desired. Dosage forms include powders, capsules, tablets, chewables, lozenges, creams, lotions, ointments, troches, pastes, gels, and suppositories. These various forms can have several helpful uses in veterinary medicine, including:

• Making a commercially unavailable dose into tablets or capsules

• Reformulating hard-packed tablets into soft, flavored chewables

• Switching to a methimazole transdermal gel to be applied on the ear pinna⁹

• Changing a prednisolone tablet into an oral suspension

Combine Multiple Drugs Into One Product

Complicated drug regimens can sometimes be compounded into combined formulations to decrease pill burden, liquid burden, and/or the amount to be applied. Combining multiple medications into one capsule while still retaining pharmacokinetic efficacy is possible. Multiple liquids can be combined to decrease the volume given and increase ease of administration. Patients with topical or otic needs often require multiple medications, which can be achieved with one product. For example, if a patient needs a custom antifungal, antibiotic, and steroid combo to treat an otic disease, compounding can offer the creation of a amlodipine/benazepril/clopidogrel/furosemide oral suspension that is also liver flavored.

Find Elusive Medications

Compounding pharmacies can help source and dispense difficult-to-find medications or excipients. The prescriber may be able to create effective alternatives during national drug shortages. For example, if a veterinarian is looking for acetylcysteine 10% injection solution or dealing with backordered pimobendan tablets, a compounding pharmacy may be able to compound them during times of inaccessibility or help a provider find a reputable source.

What Cannot Be Compounded

Compounding offers near-endless creativity to find patient-specific options and continues to hold a crucial role in veterinary care. However, it is not meant to create a direct mimic of a commercial product with dose, formulation, or route. Precisely what can and cannot be compounded in veterinary medicine is currently controversial and unclear; this will be discussed in a future article in this series focusing on compounding rules and regulations.

How Veterinarians Can Find a Quality Veterinary Compounding Pharmacy

The versatility of compounding can be applied to many therapeutic specialties (eg, ophthalmology, pain management, neurology, behavioral health, dermatology, oncology); however, it can be difficult for veterinarians to find a good fit for their unique needs. The following offer tips for finding a quality compounding pharmacy:

Veterinary Training

Clinicians should carefully research potential compounding pharmacies to ensure their staff is trained to serve veterinary patients. The websites of compounding pharmacies should be reviewed for specialty areas; veterinary products should be emphasized if it is a major proportion of their business. The veterinary team should also consider calling the pharmacy to ask how long they have been compounding for animal patients, if they have a veterinary pharmacist, and what they use for veterinary pharmacy education and training.

All pharmacists (PharmDs, RPhs) are trained in compounding science and are qualified to prepare professional compounded products; however, not every pharmacist has veterinary pharmacy education. Veterinarians should favor compounding pharmacies that have access to good animal drug references (eg, Plumb’s Veterinary Drugs, Merck Veterinary Manual) and pharmacists with veterinary medicine training (eg, residencies, certifications, clinical experience, pharmacology courses).

Quality Assurance

There is no clear accreditation for veterinary compounding excellence, but there are some third-party associations to look for:

• The Pharmacy Compounding Accreditation Board (PCAB): Although not specific to veterinary compounding, PCAB accreditation is a gold standard that guarantees USP compliance and consistent practice of high-quality and safety standards. Not all compounding pharmacies have this endorsement, as their assessment process is expensive and not specialty specific (see Resources).

• PCCA: Being a PCCA member means the compounder is using certified drug supplies and has support services like USP implementation, compounding CE, a compounding training and education library, and veterinary pharmacy consulting. Membership requires a sizable annual fee.

Formulary Flexibility

Although compounding can theoretically create any drug/product detailed above, not every compounding pharmacy is set up for all services. Some compounders do not make tablets, and some only make nonsterile preparations. When researching new compounders, the veterinary team should ask if their formulary is set or if they are open to craft completely new formulas as needed. Working with a compounder with the latter philosophy can be additionally helpful for veterinarians, as each patient/pet owner may have different needs for the same condition—compounding’s biggest benefit is customization, after all.

Conclusion

Compounding’s utility in veterinary medicine can significantly impact patient care. Improving compliance can save an animal’s life or enhance the pet owner’s quality of life. Compounding a rare medication or unique route of administration may be the only way an animal can be treated. The potential applications are numerous and varied, but there are inherent risks to consider and a web of regulations to navigate.

Both the veterinarian and the pharmacist are responsible for adhering to a number of safety standards, so keeping up with the laws and regulations as they evolve is critical. The next article in this series will break down the major players and controversies of the veterinary compounding debate and offer resources for veterinarians to comply and stay up-to-date in their practice area.

Disclaimer: This article was written by a clinical veterinary pharmacist. The author is not a lawyer; therefore, this article should not be used as legal advice.