503A Compounding – regulatory basis and good industry practices for pharmacies

These resources are intended to benefit the existing pharmaceutical compounding industry, those considering entering this space, or third parties working with pharmaceutical compounding companies, such as hospitals. The guide aims to help the compounding community better understand existing requirements and good industry practice, thereby enabling them to deliver safer medicines.¹

Although most U.S. patients receive their prescriptions from traditional manufacturers, the role of compounding pharmacies is growing. It is estimated that the value of the US compounding pharmacy market in 2023 will be over USD 5 billion, of which almost three-quarters of it will be the 503A segment. The total market is expected to grow to over $10 billion over the next decade.²

“Several factors are driving this trend, including increased interest in personalized medicine among both patients and physicians.^“ Compounding pharmacies can provide customized medications, formulated based on individualized prescriptions, dosage strengths, and delivery methods. This is especially useful for people with allergies or sensitivities, people suffering from certain rare diseases or people requiring specialized preparations that are not available on the market.

By law, compounding pharmacies cannot make generic drugs from products approved and marketed by the U.S. Food and Drug Administration (US FDA), except in cases of published information about drug shortages. Compounding pharmacies may also produce versions of products discontinued by manufacturers, and both drug shortages and discontinuations have led to increased demand for combination products.² Pain management, hormone replacement, dermatological applications, and dietary supplements make up a significant portion of the combination drug market, but many other drugs would also be classified as combination products.³

Parties seeking to enter the drug compounding market have sometimes found it difficult to synthesize, interpret, and implement existing pharmacy compounding guidelines, which are regulated differently than traditional mass-produced products.

Under the original U.S. Federal Food, Drug, and Cosmetic Act (FDCA), manufacturers of traditional prescription drugs are required to provide evidence supporting the safety and effectiveness of drugs, such as through clinical trials and other requirements. However, individual compounding pharmacies were initially exempt from these federal mandates.⁴

To this day, states are the primary regulators of most prescription drug compounding practices, but the U.S. federal government plays a role in requirements and oversight. In 1997, Congress created an additional section to the FDCA, Section 503A, which directly applies to compounding pharmacies.

In 2013, Congress passed the Drug Quality and Safety Act (DQSA) to further clarify the U.S. FDA’s authority to oversee the compounded drug market, in part in response to an outbreak of fungal meningitis originating at a drug compounding facility. large scale. The bill amended 503A and added another section to the FDCA, section 503B, which would apply to larger mixing facilities.⁴

503A pharmacies are smaller establishments that prepare medications for individual patients based on a doctor’s prescription. In contrast, 503B companies are registered as outsourcing facilities that must comply with additional regulations. They can produce large batches of combination drugs to be sold to health care facilities, without having to compound prescription drugs for a specific patient.⁴

The recently released ISPE Guide provides advice and insights specifically related to FDCA Section 503A pooling. Reviews key details and provides additional context regarding the criteria set forth in the United States Pharmacopoeia (USP), Chapters 795, 797, 800, and 1163, and sections of other chapters that all 503A pharmacies are expected to follow. Additionally, while it does not provide individual state-specific guidance, it explains the authority of State Boards of Pharmacy and their coordination with the U.S. FDA.¹

ISPE Guide: 503A Compounding – Regulatory Basis and Industry Good Practices for Pharmacies provides general information on drug compounding, sterile and non-sterile drugs, general drug compounding requirements such as those relating to prescriptions and staffing, quality management systems, training, material acquisition, and facilities and equipment. It also includes information on environmental, quality and maintenance inspections, as well as product testing and the handling, storage and transportation of complex products.¹

Another key benefit of the guide is its inclusion of suggested lists of standard operating procedures (SOPs). They outline the requirements that must be met to meet the applicable USP sections for pharmaceutical compounding.¹

This ISPE 503A Linking Guide provides supplemental information to the ISPE 503B Linking Guide released in 2023: ISPE Guide: 503B Compounding – regulatory basis and good industry practices for outsourcing facilities. This latest guide provides targeted information for outsourcing facilities that must meet additional requirements.⁵

“The information contained in the ISPE compounding guides represents a significant first step in ISPE’s efforts to provide resources to the compounding industry,” said Rebecca (Becky) Welton, senior consultant in the Regulatory Practice at Lachman Consultant Services, Inc., an ISPE active partnership member, co-secretary of the Community of Practice (CoP) on Blending, and lead author of the ISPE Blending Guides 503A and 503B. “The Community of Practice (CoP) that ISPE has developed for compounding further highlights their recognition of this segment of the pharmaceutical industry as critical to patient care and creates a collaborative space where individuals and organizations in the compounding industry can be brought together to share best practices and address the ever-evolving practice of compounding.”

Author: Dr. Ruth Jessen Hickman