Overview
On January 7, 2025, the US Food and Drug Administration (FDA) issued two parallel guidance documents for the Section 503A and Section 503B bulk drug lists, announcing the end of FDA’s 2017 interim policies.
Under the new guidance, titled Interim Policy on Compounding Using Bulk Drug Substances Under Section 503A of the Federal Food, Drug, and Cosmetic Act Guidance for Industry (503A interim policy) and Interim Policy on Compounding Using Bulk Drug Substances Under Section 503B of the Federal Food, Drug, and Cosmetic Act Guidance for Industry (503B interim policy), FDA will change certain procedures related to the collection and publication of information on bulk drug substances. Specifically, FDA will no longer categorize and publish bulk substances submitted for inclusion on the 503A and 503B bulk lists to its website. FDA states that these procedures no longer serve the agency’s objective to avoid disruption in patient care.
In Depth
BACKGROUND
Sections 503A and 503B of the Federal Food, Drug, and Cosmetic Act (FDCA) allow compounded drug products to be exempt from some otherwise fundamental statutory requirements – such as use labeling, or new drug application or abbreviated new drug application review – if certain conditions are met. Section 503A applies to compounding pharmacies, and Section 503B applies to registered outsourcing facilities that may prepare orders that are not patient specific. Both sections require that compounded products utilize bulk drug substances that:
- Comply with the standards of the US Pharmacopeia or National Formulary monograph, if applicable
- Are components of FDA-approved drugs
- Appear on the respective bulk drug list
See our previous On the Subject for a discussion of the requirements of Sections 503A and 503B in greater detail.
To assist FDA in developing the 503A and 503B bulk lists, it has historically requested nominations for bulk drug substances along with supporting detailed information regarding clinical needs. Since 2013, FDA has received thousands of nominations from industry stakeholders for certain bulk substances to be included in either or both lists. Because regulatory review would necessarily take significant time and resources, stakeholders raised concerns regarding disruptions to patient care in the interim period between nomination and publication of the final lists, during which time compounding would be prohibited.
THE 2017 INTERIM POLICIES
In 2017, to address stakeholder concerns about potential interruption to compounding services while balancing FDA’s bulk drug information requirements, the FDA issued parallel 503A and 503B interim policies. These policies allowed nominated bulk substances to be used in compounding if FDA was sufficiently reassured that the substances met safety criteria.
The policies explained that FDA would review the current nominations on a rolling basis, categorize the nominations into one of three categories discussed below, and publish the categorization to the FDA website.
- Category 1 – Substances Nominated for Bulks List Currently Under Evaluation
- Category 2 – Substances Nominated for the Bulks List That Raise Significant Safety Risk
- Category 3 – Substances Nominated for the Bulks List Without Adequate Support
Under the 2017 interim policies, Category 1 substances were substances eligible for inclusion on the bulk lists and nominated with sufficient supporting information. Category 2 and 3 substances were potentially eligible for the lists but contained safety risks or were nominated with insufficient supporting information. FDA advised that it did not intend to take action against state-licensed pharmacies, federal facilities, or licensed physicians for compounding drug products using unapproved bulk substances in Category 1 provided all of the following conditions were met:
- The original and all subsequent manufacturers of the bulk substance were registered under Section 510 of the FDCA
- The bulk substance had a valid certificate of analysis
- The compounded drug product using the bulk substance was created in compliance with all other conditions of Sections 503A and 503B.
THE 2025 INTERIM POLICIES
The new 2025 interim policies eliminate the use of Categories 2 and 3. Bulk substance nominations submitted on or after January 7, 2025, will no longer be categorized and published to the FDA website, although FDA will continue to review nominations it receives. According to FDA, the 2017 interim policies’ categorization of nominations “no longer serves the interim [policies’] stated objective of avoiding unnecessary disruption to patient treatment.” Instead, FDA notes that nominators have had ample opportunity to provide sufficient supporting information for the placement of bulk drug substances in Category 1 since the introduction of the policies in 2017.
FDA confirmed that bulk substances currently listed in Category 1 will continue to be afforded the enforcement discretion provided under the previous policies. Bulk substances listed in Categories 2 or 3 will not be afforded such discretion even where stakeholders update the nominations to provide sufficient information. FDA clarified that it will focus resources on finalizing the 503A and 503B bulk drug lists through rulemaking in batches.
ANALYSIS
The 2025 interim policies indicate FDA’s continued focus on regulating the compounding of drugs under Sections 503A and 503B. The updated policies further indicate FDA’s intention to finalize the bulk drug lists through rulemaking, a process that has spanned almost a decade. The new interim policies should not change the current practice of compounding: Category 1 drug substances will remain generally available for compounding, but FDA reserves its authority to exercise enforcement discretion. However, stakeholders should be aware that new nominations to the bulk lists will not be afforded enforcement discretion and should not be compounded until published in the finalized bulk drug lists following their complete evaluation by FDA.
THE McDERMOTT DIFFERENCE
McDermott will continue to monitor updates on these interim policies and any notices related to the bulk drug lists. For more information, please contact one of the authors or any other member of McDermott’s Food, Drug & Medical Device Regulatory Practice Group.
Tyler Barton, a law clerk in the New York office, also contributed to this article.
