After Several Attempts to Get it Right: FDA Releases Final Guidance on Evaluation of Bulk Substances for Use in Section 503B Outsourcing Facilities

By Karla L. Palmer

On Monday, March 4, 2019,  FDA released its Final Guidance , titled “Evaluation of Bulk Drug Substances Nominated for Use in Compounding Under Section 503B of the Federal Food, Drug, and Cosmetic Act.”  We blogged about FDA’s draft guidance here, which FDA published about a year ago in March 2018.  As noted in that prior blog post, FDA’s impetus for re-doing – for a third time – the process for its evaluation of bulk substances was largely driven by a lawsuit filed against the Agency after it determined in the summer of 2017 to include the bulk substance vasopressin on the list – vasopressin bulk products likely would compete with Endo/Par’s FDA-approved Vasostrict.  (See the Complaint filed by Endo International and Par Sterile Products against FDA and blogged about here).  More to follow soon on the exciting saga of vasopressin, Athenex, Endo/Par, and FDA ….

FDA’s Federal Register Notice on the final bulks evaluation guidance states that it received about 60 comments on the revamped evaluation process.  Although FDA did not address specifically in its Notice any of those comments, it did (in response to comments received and “on its own”), for example, further explain how “Congress’ limitation on bulk drug substances that can be used in compounding … helps to preserve the integrity of the new drug approval process and identified the process to request that FDA add or remove a bulk drug substance from the 503B Bulks List after the Agency has made a final determination” concerning the substance.  The evaluation process itself that FDA sets forth in the Final Guidance remains unchanged from FDA’s March 2018 draft evaluation process, as shown in this comparison of the draft and the final guidances.   The first consideration FDA makes in its evaluation process is whether the bulk substances is a component of an FDA-approved drug product.

What is somewhat disconcerting is that FDA undertook this third and final review of its bulks nomination process based on the Endo/Par challenge under the Administrative Procedure Act.  FDA states its changes to the Final Guidance underscore the importance of protecting the integrity of the drug approval process, securing a safe drug supply and enhancing innovation.  Notwithstanding, vasopressin, which has been used in hospitals and on crash carts for decades, was approved as part of FDA’s unapproved drugs initiative, and to our knowledge has likely resulted in a dramatically increased price for the FDA-approved drug product, which leaves a complicated issue for consumers of drug products – and FDA.