On December 7, 2023, the United States Food and Drug Administration (FDA) published a second revised draft Guidance for Industry, “Interim Policy on Compounding Using Bulk Drug Substances Under Section 503A of the Federal Food, Drug, and Cosmetic Act” (Draft Guidance). Many in the industry may recall that FDA previously published its first revised draft Guidance for Industry in 2017, similarly titled, “Interim Policy on Compounding Using Bulk Drug Substances Under Section 503A of the Federal Food, Drug, and Cosmetic Act,” which described FDA’s interim policy and ongoing categorization of nominated bulk drug substances for use in compounding. In this latest Draft Guidance, FDA aims to set a deadline for categorization of nominated bulk drug substances on the interim 503A Bulks List in an effort to focus Agency resources on making decisions on nominations for the final 503A Bulks List.
What is the “interim” 503A Bulks List?
Section 503A of the Food, Drug & Cosmetic Act (FDCA) describes the conditions that must be satisfied for human drug products compounded by a licensed pharmacist in a state-licensed pharmacy or federal facility, or by a licensed physician, to be exempt from certain provisions of the FDCA covering new drug approval. One of the conditions that must be met for a compounded drug product to qualify for these exemptions is that a licensed pharmacist or physician compounds the drug product using bulk drug substances that:
- Comply with the standards of an applicable United States Pharmacopeia (USP) or National Formulary (NF) monograph, if a monograph exists, and the USP chapter on pharmacy compounding;
- If such a monograph does not exist, are drug substances that are components of FDA-approved drugs; or
- If such a monograph does not exist and the drug substance is not a component of an FDA-approved drug, the drug substance appears on a list developed by FDA (the “final 503A Bulks List”).
Developing the final 503A Bulks List has proved to be complicated and time-consuming. As a result, since 2017, FDA has operated according to its interim policy on the use of bulk substances. Under this policy, FDA makes a preliminary decision regarding a nominated bulk substance and places it in one of three categories (Category 1, Category 2, or Category 3) that FDA then publishes in an “interim” 503A Bulks List. Bulk substances listed in Category 1 of the interim 503A Bulks List may be used in the preparation of compounded drug products. Bulk substances listed on Category 2 are those substances that, in FDA’s view, were nominated with sufficient supporting information but raise significant safety concerns and while FDA continues to evaluate those substances for inclusion on the final bulks list, it will not permit compounders to use such substances in preparing drugs. Finally, Category 3 reflects those substances that, to date, have been nominated without sufficient support.
What does the new Draft Guidance cover?
Since 2017, the compounding industry has nominated many bulk substances for inclusion on the final 503A Bulks List, and FDA has frequently updated and revised the interim 503A Bulks List as it works on processing those nominations. This has given the industry necessary clarity on which substances it can and cannot use during the interim period while FDA considers which substances to list on the final 503A Bulks List and has ensured that patients maintain access to compounded medications during that period. However, with this new Draft Guidance, FDA has signaled its intent to sunset the interim 503A Bulks List process in favor of focusing its attention and resources on processing nominations for the final 503A Bulks List.
First, the new Draft Guidance provides that FDA will no longer categorize bulk drug substances on the interim 503A Bulks List that are nominated on or after the date FDA publishes its Final Guidance on the use of bulk substances. The substances nominated on or after that date will not be considered within the scope of the 2017 interim policy. FDA believes that this deadline will provide sufficient time for compounders and other stakeholders to nominate bulk drug substances to be considered for inclusion on the interim 503A Bulks List.
FDA will continue to evaluate new substances for inclusion on the final 503A Bulks List nominated on or after the date on which the Final Guidance is published, provided they are nominated with sufficient supporting information to permit an evaluation. FDA provided no clarity on the timeline for final determination of substances for inclusion on the final 503A Bulks List, so it appears that substances nominated on or after the date on which the Final Guidance is published may not be used for compounding until FDA makes a final determination on the substance for inclusion on the final 503A Bulks List.
Second, the Draft Guidance provides that FDA will retain its interim policy published in the 2017 Draft Guidance for those substances nominated before the date on which the Final Guidance is published. In other words, compounders will still be able to refer to and rely upon the categorization of bulk substances on the interim 503A Bulks List and continue to compound with those substances listed in Category 1. In addition, FDA will continue to process nominations and update the interim 503A Bulks List for those substances nominated before the Final Guidance is published.
Whats next?
The bottom line is that industry stakeholders should nominate any new bulk substances, or submit new nominations of the bulk substances currently placed on Category 3 of the interim 503A Bulks List, as soon as possible. FDA is continuing to evaluate bulk substances nominated for inclusion on the interim 503A Bulks List on a rolling basis, but after the Final Guidance is published, FDA will no longer consider new nominations for inclusion on the interim 503A Bulks List.
FDA is currently accepting comments and suggestions regarding the Draft Guidance, which must be submitted by January 8, 2024. We encourage industry stakeholders affected by this Draft Guidance to submit comments to the Federal Register, Docket No. FDA-2015-D-3517, as well as closely monitor any future revisions made to the guidance as FDA enters the upcoming comment period.
Should you have any questions regarding the Draft Guidance, or should you wish to submit a comment to FDA regarding this guidance, please do not hesitate to reach out to any of the authors on this alert for further discussion.
Client Alert 2023-273
