New ISPE Guide Provides Support for 503A Compounding Community
Ruth Jessen Hickman, MD
A recently released guidance document, the ISPE Guide: 503A Compounding – Regulatory Basis and Industry Good Practices for Pharmacies, summarizes and contextualizes key information from US governmental bodies relevant to 503A pharmacies. The resource is intended to benefit the existing pharmacy compounding industry, those considering entering that space, or third parties working with pharmacy compounders, such as hospitals. The guide is designed to help the compounding community better understand existing requirements and good industry practices, thus enabling them to deliver safer drug products.1
1ISPE. ISPE Guide: 503A Compounding – Regulatory Basis and Industry Good Practices for Pharmacies. ISPE; 2024. https://ispe.org/publications/guidance-documents/guide-503a-compounding.
Although most US patients receive their medical prescriptions via traditional manufacturers, the role of compounding pharmacies is increasing. The US compounding pharmacies market was estimated to be over $5 billion in 2023, with the 503A segment accounting for almost three-fourths of this. The total market is expected to increase to over $10 billion in the next decade.2
“This trend is fueled by several factors, including an increased interest in personalized medicine by both patients and clinicians,” according to the guidance document.2 Compounding pharmacies can provide customized medicines formulated based on individualized prescriptions, dosage strengths, and delivery form. This is particularly helpful for people with allergies or sensitivities, people with certain rare diseases, or people who require specialized formulations which aren’t commercially available.
By law, compounding pharmacies cannot make generics of US Food and Drug Administration (US FDA)-approved and marketed products, except in the case of published drug shortages. Compounding pharmacies can also produce versions of products that have been discontinued by manufacturers, and both drug shortages and discontinuations have led to increased demand for compounded products.2 Pain management, hormone replacement, dermatology applications, and nutritional supplements have made up a significant portion of the compounding market, but a variety of other drugs would be categorized as compounded products as well.3
Parties looking to enter the compounding space have sometimes found it challenging to synthesize, interpret, and implement existing guidance on compounding pharmacies, which are regulated differently than mass-produced traditional products.
Under the original US Federal Food, Drug, and Cosmetic Act (FDCA), traditional prescription drug manufacturers are required to submit evidence of the safety and efficacy of drugs, e.g., through clinical trials and other requirements. However, individual compounding pharmacies were initially excluded from these federal mandates.4
To this day, states are the main regulators for most prescription-based drug compounding practices, but the US federal government does play some role in requirements and oversight. In 1997, Congress created an additional section to the FDCA, Section 503A, which applies directly to compounding pharmacies.
In 2013, Congress passed the Drug Quality and Security ACT (DQSA) to further clarify the US FDA’s authority in oversight of the compounded drug market, partly in response to an outbreak of fungal meningitis traced to a large-scale drug compounding facility. The act both amended 503A and added another section to the FDCA, Section 503B, which would apply to larger compounding facilities.4
503A pharmacies are smaller facilities which compound medications for individual patients based on a doctor’s prescription. In contrast, 503B compounders are registered as outsourcing facilities which must follow additional regulations. They can manufacture large batches of compounded drugs to be sold to healthcare facilities, without necessarily compounding for patient specific prescriptions.4
The recently released ISPE Guide provides advice and insights pertaining specifically to compounding under FDCA Section 503A. It reviews key details and provides additional context surrounding the criteria set out by the United States Pharmacopoeia (USP), chapters 795, 797, 800, and 1163, and sections of other chapters to which all 503A pharmacies are expected to adhere. Additionally, although it does not provide individual state-based guidance, it clarifies the authority of State Boards of Pharmacy and their coordination with the US FDA.1
The ISPE Guide: 503A Compounding – Regulatory Basis and Industry Good Practices for Pharmacies provides general background on compounding, sterile and nonsterile drugs, general compounding requirements such as those pertaining to prescriptions and personnel, quality management systems, training, material sourcing, and facilities and equipment. It also includes information on environmental controls, quality, and maintenance, as well as product testing and the handling, storage, and transport of compounded products.1
Another key benefit of the guide is its inclusion of suggested Standard Operating Procedures (SOPs) lists. These outline the requirements that need to be performed to satisfy the relevant USP chapters for pharmaceutical compounding.1
The information provided in the ISPE guides on compounding are a significant first step in ISPE’s efforts to provide resources for the compounding industry. The Community of Practice (CoP) that ISPE has developed for compounding further emphasizes their recognition of this segment of the pharmaceutical industry as critical to patient care and creates a collaborative space for bringing together individuals and organizations in the compounding industry to share best practices and address the ever-evolving practice of compounding.
3Global Market Insights. Compounding pharmacies market size. August 2022. https://www.gminsights.com/industry-analysis/compounding-pharmacies-market
4National Academies of Sciences, Engineering, and Medicine; Health and Medicine Division; Board on Health Sciences Policy; Committee on the Clinical Utility of Treating Patients with Compounded Bioidentical Hormone Replacement Therapy; Jackson LM, Parker RM, Mattison DR, editors. 3, Regulatory framework for compounded preparations. The Clinical Utility of Compounded Bioidentical Hormone Therapy: A Review of Safety, Effectiveness, and Use. Washington (DC): National Academies Press (US); 2020 Jul 1. https://www.ncbi.nlm.nih.gov/books/NBK562888/
5ISPE. ISPE Guide: 503B Compounding – Regulatory Basis and Industry Good Practices for Outsourcing Facilities. ISPE; 2023. https://ispe.org/publications/guidance-documents/guide-503b-compounding
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“This trend is fueled by several factors, including an increased interest in personalized medicine by both patients and clinicians,” according to the guidance document.2 Compounding pharmacies can provide customized medicines formulated based on individualized prescriptions, dosage strengths, and delivery form. This is particularly helpful for people with allergies or sensitivities, people with certain rare diseases, or people who require specialized formulations which aren’t commercially available.
