Comment from Eddisha C

Thank you for the opportunity to comment on FDA Docket FDA-2015-N-3534 regarding the criteria and process for evaluating bulk drug substances proposed for inclusion on the 503A bulks list. Compounded drugs serve an essential role for patients who require individualized therapies such as allergen-free formulations or pediatric doses not commercially available. The past safety failures involving contaminated or substandard compounded products underscore the need for a rigorous, evidence-driven framework. Section 503A allows exemptions from approval, labeling, and cGMP requirements only when specific conditions are met. The specific conditions include the bulk substance must have a USP or NF monograph, be an ingredient in an FDA-approved drug, or appear on the FDA-developed bulks list. Earlier nomination rounds produced hundreds of submissions lacking core information needed to determine whether substances were safe, historically used, or appropriate for compounding. I therefore strongly support the FDA’s effort to standardize required data elements, including physical and chemical characterization, safety information, historical use, and evidence of effectiveness, as well as the use of a unified Excel template to improve consistency and efficiency. However, additional refinements would further strengthen the process. Historical use, while informative, should not be weighted equally with contemporary scientific evidence, as anecdotal or low-quality historical references alone cannot establish safety or effectiveness. The docket asks nominators to identify safety concerns and provide bibliographies of efficacy data “if available.” The phrase “if available” creates the possibility that substances may be considered even when meaningful evidence is absent. To avoid this, FDA should require at least one peer-reviewed source demonstrating clinical use, pharmacologic plausibility, or safety data before a substance can be considered. In addition, FDA should more clearly distinguish the concepts of “historical use” and “evidence of effectiveness,” which vary widely across clinical contexts and are often conflated, leading to inconsistent submissions and evaluations. The FDA emphasizes that proper labeling is essential because “it communicates dosage warnings… and other health risks that could necessitate immediate discontinuation of the drug” (Cohen, 2025). Furthermore, this standard should be applied with compounded drugs to ensure safety. I also support FDA’s requirement that nominators explain why a compounded version is necessary rather than using an FDA-approved alternative but recommend that the Agency clarify what constitutes an acceptable justification. This means considering if there are temporary shortages, inability to tolerate excipients, or clinically documented patient-specific needs. Compounding should not function as a substitute for available approved therapies, and nominators should be required to provide detailed clinical scenarios and explicit rationales demonstrating that existing products cannot meet patient needs. To ensure efficient Agency review, FDA should also establish minimum completeness thresholds and automatically return nominations that lack essential components such as a certificate of analysis, UNII, or monograph search results. Transparency would further be improved if FDA issued standardized public summaries of evidence, safety considerations, and decision rationales for each nomination, like advisory committee briefing formats. These steps would promote consistent, science-based decision-making while reducing duplicative or incomplete submissions. In summary, the FDA’s reopening of this docket represents an important step toward strengthening oversight of compounded medications at a time when demand for compounded products is increasing, including due to shortages of certain GLP-1 drugs. The proposed criteria are appropriate, but should be reinforced by stronger evidentiary requirements, clear definitions of key concepts, stricter justification for compounded alternatives, and improved transparency in the review process. These enhancements will help ensure that only substances with legitimate clinical value and adequate scientific support are included on the 503A bulks list, ultimately protecting patient safety while preserving access to medically necessary compounded therapies. I appreciate the opportunity to comment and encourage the FDA to adopt the recommendations above. Cohen, M. H. (2025, August 18). What Are the OTC Drug Label Requirements? Cohen Healthcare Law Group | Healthcare Lawyers | FDA & FTC Law. https://cohenhealthcarelaw.com/otc-drug-label-requirements/