The FDA has revised and finalized a guidance document, originally issued in draft on March 26, 2018, entitled Evaluation of Bulk Drug Substances Nominated for Use in Compounding under Section 503B of the Federal Food, Drug, and Cosmetic Act (here).  After the posting of the draft guidance, the FDA says that it received approximately sixty comments from stakeholders and, based on its review of the comments, has revised portions of the document to:

  • further explain how Congress’ limitation on bulk drug substances that can be used in compounding under Section 503B helps to preserve the integrity of the new drug approval process
  • identify the process to request that the FDA add or remove a bulk drug substance from the 503B Bulks List after the Agency has made a final determination with respect to that substance in the Federal Register.

The Guidance further reminds 503B outsourcing facilities:

  • of the Agency’s interpretation of the phrase “bulk drug substances for which there is a clinical need”
  • that to use a bulk drug substance in compounding, it must appear on a list established by the Secretary of Health and Human Services identifying bulk drug substances for which there is a clinical need
  • that the drug compounded from such bulk drug substances must appear on the drug shortage list in effect under Section 506E of the FD&C Act (21 U.S.C. 356e) at the time of compounding, distribution, and dispensing

There are other requirements that the bulk drug substance must meet in order to be used in compounding under Section 503B:

  • If an applicable monograph exists under the United States Pharmacopeia (USP), National Formulary (NF), or another compendium or pharmacopeia recognized by the Secretary under Section 503B, the bulk drug substance must comply with the monograph.
  • The bulk drug substance must be manufactured by an establishment that is registered under Section 510 of the FD&C Act.
  • The bulk drug substance must be accompanied by a valid certificate of analysis.

Closely following the tenets of the guidance will help ensure that the exemptions “from the following three sections of the FD&C Act: Section 505 (21 U.S.C. 355) (concerning the approval of drugs under new drug applications or abbreviated new drug applications); Section 502(f)(1) (21 U.S.C. 352(f)(1)) (concerning the labeling of drugs with adequate directions for use); and Section 582 (21 U.S.C. 360eee-1) (concerning drug supply chain security requirements) will apply to the product and the compounder.”