T-18: Analysis of US Food and Drug Administration (FDA)’s Process for Evaluating Bulk Drug Substances for Use in Compounding
FDA United States
To describe the process for evaluating substances nominated for inclusion on the list of bulk drug substances that can be used in compounding under section 503A of the Federal Food, Drug, and Cosmetic (FD&C) Act (503A bulks list)
Information included in the FDA websites, regulations, guidance documents, and other public documents was searched to analyze the process that FDA currently employs to evaluate bulk drug substances nominated for use in compounding under section 503A.
Drug products compounded by licensed pharmacists in State-licensed pharmacies or Federal facilities, or licensed physicians in accordance with the conditions in section 503A of the FD&C Act are exempt from current good manufacturing practice, labeling with adequate directions for use, and new drug approval requirements. Among these conditions is that bulk drug substances used to compound the drug product must (1) comply with a United States Pharmacopeia (USP) or National Formulary monograph, if one exists, and the USP chapter on pharmacy compounding; (2) be components of FDA-approved human drug products, if an applicable monograph does not exist; or (3) if such monograph does not exist and the drug substance is not a component of an FDA-approved human drug product, be on a list of bulk drug substances that may be used for compounding developed by FDA through regulation.
To develop the 503A bulks list, FDA requested and received nominations from the public (81 FR 91071). FDA evaluates those substances nominated with adequate supporting information using four criteria described in 81 FR 91071.
FDA reviewers from various scientific disciplines evaluate the nominated substances based on information provided by the nominators and from publicly accessible sources such as PubMed, Web of Science, SciFinder, foreign Pharmacopoeia, clinical practice guidelines and recommendations by subspecialty groups or government agencies. The FDA’s Adverse Event Reporting System (FAERS) and the Center for Food Safety and Nutrition’s Adverse Event Reporting System (CAERS) are also searched for adverse events. FDA presents the results of its review to the Pharmacy Compounding Advisory Committee (PCAC) to obtain its advice on whether to include a substance on the 503A bulks list. The 503A bulks list itself is developed through notice and comment rulemaking.
The FDA review of substances nominated to the 503A bulks list highlights the importance of publicly available scientific literature, guidelines and FAERS and CAERS databases for FDA to conduct its evaluation of substances nominated for inclusion on the bulk drug substances list. Since July 2014, six PCAC meetings have been held where approximately 40 substances have been discussed. A proposed rule, identifying ten substances discussed at PCAC meetings, six of which have been proposed for inclusion on the 503A bulks list, was published in December 2016. Additional substances will be addressed in future rulemakings.
This abstract reflects the views of the authors and should not be construed to represent FDA's views or policies.