Quality Assurance in Veterinary Compounding

Sponsored by Covetrus

There are many types of compounding pharmacies, so how does a veterinarian identify quality when choosing a compounding pharmacy to work with? The laws and regulations that vary by state make it difficult to establish a universal benchmark of quality for veterinary compounding; however, there are things clinicians and veterinary practices can look for to find a trustworthy pharmacy or compounding partner.

In this article, which is the third in a series of four, a basic overview of the United States Pharmacopeia (USP) guidelines compounding pharmacies must meet to produce safe, effective, and consistent compounds will be discussed.

USP Quality Compounding Components

Most quality components are based on human compounding laws, USP standards, and best practices. This is how the current compounding system operates, regardless of patient species. Accreditation through the Pharmacy Compounding Accreditation Board (PCAB) is the only compounding-specific credential available for pharmacies.¹ If a compounding pharmacy is PCAB-accredited, which is usually noted on the pharmacy’s website, the pharmacy voluntarily adheres to a comprehensive set of nationally recognized standards for the compounding pharmacy industry. For more on accreditation, please refer to the previous article on compounding regulations at cliniciansbrief.com/article/navigating-compounding-regulations-what-veterinary-community-needs-know.

USP Monographs

The USP is the repository for many monographs involving chemicals used in contemporary compounding. Led by the USP compounding expert committee, the USP publishes compounded preparation monographs, scientifically backed formulations with ingredients, compounding directions, stability data, and packaging/storage recommendations for a specific compound.^2,3

USP monographs can be of particular use in veterinary compounding, in which dozens of compounds are available but are dose-, route-, and ingredient-specific. Further, the USP publishes studies of failed compounded formulations to help avoid the creation of poor preparations.⁴

A Qualified Compounding Team

In general, the compounding team is made up of pharmacists, a pharmacist manager, and pharmacy technicians. The pharmacist manager, often titled the pharmacist in charge, is analogous to the medical director at a veterinary practice. Staff pharmacists are individually liable for regulatory compliance and therapeutic outcomes, and the pharmacist in charge is additionally responsible for the entire pharmacy’s compounding practice.

Staff compounding pharmacists can have two different credentials: PharmD (Doctor of Pharmacy) or RPh (Registered Pharmacist). Both are state licensed and have equal authority in compounding science.

There are valuable credentials pharmacists can earn as evidence of their expertise and experience in the field of veterinary medicine. These options include postgraduate residencies in veterinary pharmacy, specialized internships at veterinary teaching hospitals, CE programs, and/or clinical work experience.

Veterinarians should be aware of the growing efforts pharmacists are making to better support animal drug therapy. Working with a veterinary compounding pharmacy, where pharmacists have veterinary-specific training and experience, carries significant advantages for veterinary professionals. These pharmacists are familiar with the unique challenges veterinarians face in prescribing medications for multiple species (eg, exotics that require tiny doses or special flavorings) and ingredients that may be toxic to certain species. The veterinarian’s ability to discuss the needs of specific patients with knowledgeable pharmacists can improve patient care and client compliance.

Compounding Training

All licensed pharmacists are legally qualified to conduct and supervise compounding and may receive additional training in specific areas (eg, veterinary compounding). Sterile compounding requires additional training in contamination avoidance, including aseptic technique, garbing and gloving technique, hand hygiene, and cleaning and disinfecting procedures.

A Clean Workspace

Although most veterinarians may never see the inside of a compounding pharmacy, it can be helpful to get a feel for the general guidelines a pharmacy must follow to ensure the production of safe and effective drug products.

Typical compounding pharmacies will have a retail space, workspace, and a dedicated laboratory area with equipment appropriate for safe and accurate preparation of drug products. If only nonsterile (general) compounding is performed, there should be a general laboratory area that meets USP <795> requirements.

Sterile compounding demands strict preparation criteria in USP <797> standards. The preparation of high-risk drug products (eg, ophthalmic or IV medicines) requires precise environmental and technical control to omit any risk for contamination.

Environmental Control & Monitoring

To ensure a safe compounding environment, standards have been set for environmental sampling and cleaning of nearly all equipment and surfaces. For example, parameters including air quality (temperature, pressure, particle load) and cleaning of equipment must be regularly monitored and maintained.

Equipment Monitoring

All equipment must be routinely recalibrated or assessed, with documentation to support accuracy and consistency. Each machine must have standard operating procedures in place for proper use, cleaning, maintenance, and calibration according to the manufacturer or USP standards.

How Do I Know Compounds Are High-Quality & Safe?

From receipt to disposal, all ingredients must be tracked and handled according to state and federal regulations. USP/National Formulary grade bulk chemicals with Certificates of Analysis and Material Safety Data Sheets that document identification, source, strength, and purity of the substance are preferred for active pharmaceutical ingredients.

How Are Sterile Products Monitored?

Sterile products must have accompanying documentation to support true sterility. Veterinarians should use compounders who additionally perform pyrogen and bacterial endotoxin testing of sterile products. Isotonicity, osmolarity, and pH should also be confirmed with new sterile formulations. On-site or outsourced testing is acceptable, as long as critical safety parameters are confirmed before patient use.

Compounding Records

Each compounded product must have records citing the original master formulation, each ingredient used, accurate calculations, date of preparation and expiration, and who performed the compounding. There must also be evidence that a pharmacist quality-checked all crucial steps and evaluated the finished product.

Beyond-Use Dates

Pharmacists must assign beyond-use dates (BUDs), which are analogous to expiration dates, to each completed compound in accordance with USP recommendations. Generally, compounds that include aqueous ingredients have shorter shelf lives (≈14 days), and oil-based products have longer shelf-lives (≈180 days). In-house or third-party stability data may be cited to show potency with prolonged BUDs.

Labeling

Finished compounds must be adequately labeled to meet federal state regulations, including a declaration that clearly states that the drug product was compounded specific to the pet. Details such as drug name, strength, instructions, quantity, BUD, patient name, veterinarian, and pharmacy information must be displayed. Auxiliary labels are often applied to highlight pertinent storage information (eg, refrigerate), common adverse effects (eg, may cause sedation), and helpful guidance (eg, do not give with cheese). High-alert medications, which have extreme risks if administered improperly, receive additional warning labels.

Counseling

All pharmacists working in a licensed pharmacy are required to counsel or make a reasonable attempt to counsel. A quality-assurance component itself, counseling patients/pet owners is a basic tenet of pharmacy practice; pharmacists use this important opportunity to provide basic medication (eg, drug name, when to contact the veterinarian) and prescription information (eg, how to use a syringe, frequency of use) to the pet owner. Counseling is a great way to support the TRIAD: the pharmacist–patient–prescriber relationship.

Veterinary-trained pharmacists can be a valuable resource for veterinarians who need to find effective yet practical ways to treat exotic species or difficult cases. Veterinarians and pharmacists can and should work as a team and pool their knowledge and experience to problem-solve.

Adverse Effects Reporting

Drug product feedback is among the most important quality-assurance components. Problems with small-scale compounded drug products are not required to be reported to state or federal authorities, but doing so is considered standard of practice. Large-scale compounders (ie, 503B facilities) are required to report adverse effects to the FDA as part of their registration requirements. When counseling pet owners, pharmacists highly encourage them to report adverse effects and/or unexpected problems to both the compounding pharmacist and veterinarian.

Good compounding requires team-based care and communication; the pharmacist and veterinarian should work together if the drug product did not produce satisfactory outcomes. Therapeutic failure can arise due to many potential causes that both the drug maker and prescriber can investigate and possibly fix.

Recall Plans

The compounding pharmacy should have clear procedures in place for when a single product or batch has been identified as adulterated or misbranded. If the product was dispensed, the pet owner and veterinarian should be immediately notified and properly guided.

How Is Quality Assurance Enforced?

State boards of pharmacy (SBOP) are the primary compounding quality enforcers. SBOP set quality standards according to their state’s pharmacy practice act, which may or may not adopt USP standards. SBOP can inspect and audit any licensed pharmacy without notice. Inspectors will provide a list of any infractions and a time period to make improvements; failure to do so can result in a revoked pharmacy license and/or fines.

In 2012, a fatal human fungal meningitis outbreak originating at the New England Compounding Center called attention to unregulated compounding practices.^5,6 Subsequently, Congress passed a new law for human compounding, the Drug Quality and Security Act, which introduced 503B pharmacies (ie, outsourcing facilities) that conduct large-scale compounding more akin to drug manufacturing (like the New England Compounding Center).^7,8 Federal-level quality standards were set and stipulated that 503Bs must additionally follow good manufacturing practices in addition to USP compounding standards.<sup9sup> These are procedures required by drug manufactures to document safe, efficacious large-scale drug preparation.

Conclusion

Quality assurance is critical in compounding. Staff, space, equipment, ingredients, and procedures should be of the highest caliber and routinely assessed. Teamwork and communication between the veterinarian, the compounding pharmacist, and the pet owner should be prioritized to uphold patient safety.

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.