Navigating Compounding Regulations: What the Veterinary Community Needs to Know

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Compounding has traditionally been a service provided by pharmacists since the origin of pharmacy practice. For many veterinarians, compounding is an indispensable part of practicing veterinary medicine. The need for customizable medicines is clear and apparent in veterinary medicine, as there are a variety of species, sizes, weights, and situations that arise—from zoo animals and exotic species to avian species and, of course, pets. The needs for unique formulations, ingredients, strengths, and dose forms arise on a regular basis. However, understanding how the industry works has become increasingly complex.

This article, which is the second in a series of 4, intends to give the practicing veterinarian a deeper understanding of veterinary compounding regulations, including the legal framework, relevant authorities, and controversies.

Understanding the regulations governing veterinary compounding can be complicated, as a multitude of regulations both at the federal and state level touch veterinary compounding. It is overseen, mostly indirectly, through state boards of pharmacy rules and some veterinary medicine laws (eg, the Animal Medicinal Drug Use Clarification Act). Within these laws, most veterinary compounding regulations default to general (ie, human) compounding laws, making it critical for veterinarians to understand human compounding laws and regulations. These laws affect all veterinarians and clinics that use compounded products, whether through their own compounding in-house or a third-party pharmacy. These laws, standards, and procedures are what compounders and veterinarians must follow to avoid citations, fees, and revoked licenses when producing or dispensing these types of products.

Who Makes the Decisions When It Comes to Veterinary Compounding?

There are 3 main bodies that have some oversight of compounded veterinary medications: the Food and Drug Administration (FDA), state boards of pharmacy (SBOP), and the US Pharmacopeia (USP).

The FDA

Historically, control over the practice of compounding has mainly been exerted at the state level, with the FDA focused more on regulation of manufacturing or compounding for veterinarian use in office. However, the FDA has recently issued draft guidance specific to compounding for veterinary purposes (GFI #256), which seeks to clarify the federal policy in this space.¹ At the time of this publication, comments on the draft are being reviewed by the FDA.¹

Compounds are not required to pass through FDA approval processes for use (eg, new drug applications [NDAs], new animal drug applications [NADAs]).² Compounding is considered a different legal entity from drug manufacturing, so the same requirements do not apply. Manufacturers must adhere to current good manufacturing practices (GMPs) and are regulated by FDA rules and powers as compared with compounders.^2,3

State Boards of Pharmacy

Individual SBOP are the main compounding regulators, with each state having their own rules and standards (see Resources for your particular SBOP). Per state pharmacy practice acts, each state has authority to govern all pharmacy practices, including veterinary compounding, when performed by a pharmacy.⁴ SBOP set compounding standards and policies according to USP compounding guidelines, but these standards and policies vary among states, with some being more strict than others.

Although not veterinary-specific, SBOP do many things that help keep veterinary drugs safe. SBOP regulate pharmacists, in- and out-of-state prescription drug wholesalers, pharmacies, and those who compound. Acting to protect patient safety and public health, SBOP grant licensure of qualified personnel and have authority to inspect facilities, enforce regulations, and investigate complaints. Subpar compounding procedures and drug products can lead to disciplinary action, including fines and/or revoked licenses of pharmacies, pharmacists, and pharmacy technicians. State boards of veterinary medicine can get involved if a veterinarian is found to be using compounded drug products inappropriately.

Compounding pharmacies must follow the regulations of the SBOP that granted their licensure. Pharmacies can also hold licensure for many states. In most states, if a pharmacy is shipping a dispensed product out of state, the pharmacy must be licensed in the state it is shipped out of and the state to which it is shipped. Veterinarians ordering compounded drugs from out-of-state pharmacies should ideally be familiar with pharmacy rules regarding compounded drug products and confirm that the pharmacies and, if required, pharmacist are licensed in their destination state. If any facility—compounding pharmacy or not—procures, dispenses, and/or sells controlled substances, the Drug Enforcement Agency (DEA) has regulation jurisdiction.

State boards of veterinary medicine oversee veterinary practice, including prescribing. However, they do not set compounding standards, as compounding falls under pharmacy rules. Authority for veterinary compounding is often deferred to the SBOP. There is often interplay between the board of pharmacy and board of veterinary medicine; the latter can have input in their state’s pharmacy regulations, and the degree of this involvement varies by state. For veterinarians, the state veterinary board may be the first port of call in making their voices heard by regulators to create change or bring up concerns.

The US Pharmacopeia

The USP is a nonprofit, nongovernmental public health organization that sets national chemical purity standards for all medicines and healthcare products sold in the United States. The USP sets compounding quality standards but does not have enforcement authority. It also lacks guidance specific to veterinary compounding. Regardless, veterinarians should be familiar with the USP, as it sets the quality standards that all veterinary compounders must follow.

Each section of the USP is called a chapter; most SBOP require compounding pharmacies to be compliant with USP chapters <795> and <797> for nonsterile and sterile compounding, respectively.⁵ USP standards are in the process of being updated, as they are reviewed periodically as science and technology evolve. Most clinicians are familiar with chapter <800>, which provides guidance on the handling, storage, and use of hazardous materials. See Resources to review appeals and proposed changes, one of which is to include a veterinary pharmacy chapter.

The interplay among these bodies can sometimes overlap and, at other times, dovetail, working in coordination. Although the SBOP are the main compounding regulators, the FDA can get involved if it finds reason to believe a compounding pharmacy or veterinary clinic is not compounding legally. The FDA also writes Guidance for Industry documents that can affect how veterinary compounding can be performed (eg, Guidance for Industry document #256).¹

Who Is Actually Doing the Compounding?

When a veterinarian in a busy general practice needs a compounded drug, they often refer to a list of pharmacies, in- or out-of-state, that are used frequently in the practice and generally seen by the team as trusted sources of the medications they need. But who are these compounding pharmacies? Why are different pharmacies used for different drugs or formulations?

503A Facilities

503A facilities are traditional compounding pharmacies that make custom, patient-specific formulations pursuant to a prescription and in response to an immediate medical need.⁶ Most 503A facilities specialize in either nonsterile (ie, general) or sterile compounding, but some facilities perform both. Compounding at a 503A pharmacy is not subject to manufacturing standards such as GMPs.

Sterile compounding requires specific and expensive licensing, space, equipment, and trained personnel.⁶ In addition to having its pharmacy license, the facility must also be licensed to perform sterile compounding, as well as adhere to compounding standards if applicable. Some states may choose not to accept or impose greater restrictions beyond those found in USP <795> and/or USP <797>.⁶

503A facilities can sometimes sell a limited amount of product for office use (ie, not patient-specific) to practitioners.⁶ The rules regarding office use are defined by each SBOP, as well as by laws regarding the sale of compounded products across state lines, which vary a great deal between states. These rules often intersect with requirements for wholesale distribution or manufacturing.

503B Facilities

The 2013 Drug Quality and Security Act led to the creation of 503B facilities, also known as outsourcing facilities, which allow for compounding drugs for office use and resale.^7,8 These facilities are allowed to make non-patient–specific batches; the larger scale and scope of practice of these facilities require additional oversight, similar to manufacturers.

The FDA has much more jurisdiction over 503B facilities than it does over 503A facilities. 503Bs must register with the FDA and are required to comply with select drug manufacturing regulations. Current GMPs must be followed, and the facility must maintain their own quality-assurance department.^6,9,10

From a federal perspective, 503B facilities do not technically have to be additionally licensed as a pharmacy, as they are treated more like drug manufacturers.⁶ Nevertheless, nonsterile and/or sterile drug compounding must still be conducted under a supervising pharmacist, which is required at all licensed pharmacies. If licensed as a pharmacy, 503B facilities must follow all SBOP laws.

For 503B facilities, office-use sale is allowed and is not subject to the same limits that a 503A pharmacy would have imposed on these types of sales. Many states have restrictions on the total volume of compounded products that a 503A can sell to practitioners for office use.⁶ Because laws vary among states, it is the responsibility of the compounding entity—whether a 503A pharmacy or a 503B outsourcing facility—to gain appropriate licensure and lawfully sell products for office stock use. It is the responsibility of the prescribing veterinarian to also follow these laws as it relates to their use (ie, administration in clinic or dispensing for pets). Because office-use laws can be confusing, it is highly recommended that veterinarians meticulously document patient-specific use of any compounded products they may purchase. This is a fundamental way to achieve compounding compliance.

The compounding pharmacies used by practicing veterinarians, ranging from small local businesses to large facilities shipping drugs nationwide, fall into 1 of the 2 above categories, and their classification and location will partially dictate what products they are able to produce, sell, and ship. Veterinarians should confirm that any pharmacies offering compounded drugs are licensed to do so. Veterinarians should also be familiar with the regulations in their state regarding keeping compounded products for office use and/or resale.

A combination of SBOP and FDA efforts ensure drugs are safe and effective. The individual compounder also bears the responsibility of maintaining the quality of their products, and there are many voluntary quality and accreditation groups that pharmacies can belong to. These groups help indicate to potential customers that the facility they have partnered with is working to industry standards.

The safety of a pharmacy’s final compounded product is the culmination of relevant rules and regulations, the pharmacy’s procedures and expertise, and teamwork with veterinarians. Reporting adverse events caused by products compounded by 503A facilities is voluntary at the federal level. Adverse event reporting may be required at the 503A level by the state, which can lead to reporting to the FDA. 503B compounders, however, are required to report adverse events related to their compounded products to the FDA.⁶

Where Should Veterinarians Order Compounded Medication & Go for More Information?

In general, veterinarians should seek compounding pharmacies that specialize in veterinary medicine, as these pharmacies typically have more specialized experience pertinent to veterinary customers.

One of the prime sources for reviewing the compounding industry is the Pharmacy Compounding Accreditation Board (PCAB).¹¹ A PCAB-accredited compounding pharmacy assures gold standard compounding practices are consistently met. PCAB only provides assessment and guidance services and does not impose disciplinary action or impart mastery in veterinary compounding.¹¹

PCAB-accredited pharmacies are listed on the PCAB website.

The National Association of Boards of Pharmacy is a great place to research local regulations. In addition, several professional organizations for both pharmacy and veterinary medicine have developed evidence-based guidelines for practitioners, often with local guides:

• The American Society of Health System Pharmacists is a large, national pharmacist organization with compounding guidance for pharmacists. They support all compounding, as it remains a tenet of pharmacy practice.

• The Society of Veterinary Hospital Pharmacists and the American College of Veterinary Pharmacists are recognized leaders in veterinary pharmacy and veterinary compounding. Both organizations support compounding as a vital component of veterinary care.

• The American Veterinary Medical Association offers compounding guidance for veterinarians, as well as a more cautious view on compounding, and it prioritizes animal safety.

Conclusion

Compounding law is actively evolving; the more practicing veterinarians know about this landscape, the more they can get involved in shaping it. Backed by reasonable patient safety and public health concerns, the FDA is becoming increasingly involved in veterinary compounding practice. State veterinary medical associations and SBOP can often help solicit veterinary opinion and help make this heard. Proposed federal guidelines also solicit feedback and input, which is particularly important for the veterinary community to get involved in, as there are so many unique situations in the veterinary field that may not be considered without input from veterinarians in practice.

For veterinary professionals, the oversight and regulation of compounding is important not only for legal reasons but for ethical ones as well. Compounded drugs continue to be a valuable part of veterinary practice. In part 3 of this series, the current quality standards of veterinary compounding and how compliance is facilitated will be discussed.

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.