by Bruno Onwukwe, PharmD Candidate, PCCA Clinical Services Intern, and Celeste Zizzamia, PharmD, BCSCP, PCCA Clinical Compounding Pharmacist

Sections of the FDA’s Drug Quality and Security Act (DQSA) distinguish compounding pharmacies (503A) from outsourcing facilities (503B). Due to several factors, many of which are related to drug shortages and the USP 797/USP 800 updates, 503A pharmacies are considering partnering with 503B entities for compounded sterile preparations and/or hazardous materials. We’ll discuss the differences between 503A pharmacies and 503B outsourcing facilities, review Section 503B and summarize how to effectively evaluate 503B compounding pharmacies for a potential partnership.

Key Differences

A 503A designated pharmacy may compound drugs only for an individual patient with a prescription from a qualified provider. In addition, 503A pharmacies are regulated by a state board of pharmacy, which may follow standards set by the United States Pharmacopeia (USP). In contrast, a 503B outsourcing facility does not require a prescription but must adhere to the FDA’s Current Good Manufacturing Practice (CGMP) regulations. Additional differences between 503A and 503B pharmacies related to compounding sterile and/or hazardous materials include:

1. For a compounded sterile product (CSP) that has been terminally sterilized, stored frozen, passed sterility and all applicable tests for Category 3.

The 503A pharmacies that compound sterile preparations and/or hazardous materials can benefit from partnering with 503B outsourcing facilities. Forming a partnership may allow the 503A pharmacy to potentially mitigate risks, reduce operational costs, provide expanded services and improve customer satisfaction.

USP chapters 797 and 800 outline the minimum standards for sterile compounding and compounding hazardous materials. Although currently not adopted by all states, 503A pharmacies should consider implementing the USP standards as best practices in patient care and safety — even if doing so may pose challenges. USP updates include increased environmental monitoring, cleaning and disinfecting, garbing requirements, media-fill testing, personnel training, safety and more.

Wholesale Prohibitions for 503B

Section 503B(a)(8) of DQSA discusses the restrictions on wholesaling for outsourcing facilities. Compounded preparations must not be sold or transferred by an entity other than the outsourcing facility that compounded the product — wholesale distributors, pharmaceutical repackagers and relabelers, marketing firms and websites cannot participate in the sale and transfer of compounded preparations. Section 503B(a)(8) does not, however, prohibit the administration of a compounded product in a healthcare setting, nor its dispensing under a prescription.

The FDA Draft Guidance, which determines standard industry practice, clarified in June 2023 that a 503B outsourcing facility may sell its compounded products to a 503A pharmacy. Therefore, 503A state-licensed pharmacies or federal facilities may dispense compounded products in partnership with outsourcing facilities, opening the possibility of increased partnership between the two entities.

Evaluation Criteria for 503B Partnership

Many factors should be taken into consideration when deciding to partner with a 503B outsourcing facility, including:

• Appropriate Licensures and Registrations — Investigate whether the 503B facility has appropriate licensure and registration within the states you intend to operate in.
• Compliance with Prohibition on Wholesaling — 503As cannot buy from brokers and must directly purchase compounded products from their 503B partner. 503As, however, may use group purchasing organizations (GPOs) to negotiate contract pricing.
• Quality Customer Service — Ensure the 503B facility provides reliable information for inventory, processing and shipping.
• Regulatory History — Review their track record of FDA Form 483s, FMD-145s, warning letters, product recalls and other events that may call into question their conditions.

In addition, 503B outsourcing facilities must comply with CGMPs to ensure that safe, quality compounds are prepared and dispensed to patients. Some facilities have not been FDA inspected; however, evaluating the facility’s systems will help to discern CGMP compliance. An evaluation should include:

• Audits
• Facility Certification
• Environmental Monitoring Data
• Cleaning and Disinfection Program
• Quality Unit
• Quality Control
• Standard Operating Procedures
• Investigations
• Personnel Training
• Validation Activities
• Supplier Qualification Program
• Master and Batch Production Records
• Equipment
• Container-Closure Systems
• Laboratory Controls (Method Suitability/Validation/Stability Studies)

Many 503A pharmacies that compound sterile preparations and whose state boards of pharmacy implemented USP 797 updates face a pivotal crossroad. Collaboration with a 503B outsourcing facility may pave the way toward a partnership which can increase efficiencies and free up time for pharmacists and technicians to focus efforts in different areas of patient care activities.

More information about FDA-registered outsourcing facilities can be found at https://www.fda.gov/drugs/human-drug-compounding/registered-outsourcing-facilities.

References

1. FDA. Prohibition on Wholesaling Under Section 503B of the Federal Food, Drug, and Cosmetic Act. Guidance Document. June 2023. Accessed January 2024 at https://www.fda.gov/regulatory-information/search-fda-guidance-documents/prohibition-wholesaling-under-section-503b-federal-food-drug-and-cosmetic-act
2. FDA. Current Good Manufacturing Practice – Guidance for Human Drug Compounding Outsourcing Facilities Under Section 503B of the FD&C Act. Guidance for Industry. Draft Guidance. January 2020. Accessed January 2024 at https://www.fda.gov/regulatory-information/search-fda-guidance-documents/current-good-manufacturing-practice-guidance-human-drug-compounding-outsourcing-facilities-under
3. FDA. 21 CFR Part 21 – Current Good Manufacturing Practice for Finished Pharmaceuticals. Accessed January 2024 at https://www.ecfr.gov/current/title-21/chapter-I/subchapter-C/part-211
4. USP <797> Pharmaceutical Compounding – Sterile Preparations. 01 May 2024. Accessed January 2024 at https://doi.usp.org/USPNF/USPNF_M99925_08_01.html

These statements are provided for educational purposes only. They have not been evaluated by the Food and Drug Administration, and are not to be interpreted as a promise, guarantee or claim of therapeutic efficacy or safety. The information contained herein is not intended to replace or substitute for conventional medical care or encourage its abandonment.