Thinning Out the Bulks List: After the D.C. District Court Upholds FDA’s Restrictive Section 503B Bulks Nomination Process, FDA Promptly Releases its Tentative “No-Go” Analysis for Nine More Substances

September 10, 2019By Karla L. Palmer

After the D.C. District Court released its decision, blogged about here, affirming FDA’s revised bulks nomination process and FDA’s removal of vasopressin from the Section 503B bulks list, FDA touted the court’s favorable decision in a press release here.  Still basking in the wake of its “victory for public health in the first such case since the Drug Quality and Security Act (DQSA) was enacted” FDA next released its preliminary determination to remove nine other substances from FDA’s Section 503B bulks list.  Is this the slow demise of the interim bulks list for Section 503B facilities …  if there is an FDA-approved product that contains that bulk substance? Will Section 503B facilities need to rely mostly on the business of compounding shortage medications?

The nine substances, which are currently on FDA’s interim bulks list for Section 503B that FDA proposes to remove from its list include the following: dipyridamole, ephedrine sulfate, famotidine, hydralazine hydrochloride, methacholine chloride, sodium bicarbonate, sodium tetradecyl sulfate, trypan blue, and vecuronium bromide. Other bulk drug substances nominated by the public for inclusion on this list are currently under consideration pursuant to FDA’s March 2019 revised nominations guidance.  Note that these nine substances are important ingredients, which are widely compounded and used ubiquitously in hospitals and clinics.  Some (i.e., sodium bicarbonate) have also been on FDA’s shortage list for a long period of time.  FDA’s removal of the substances from the Section 503B list will not affect an outsourcing facility’s ability to compound drug products to relieve FDA’s published drug shortages, however.

Most notably, however, these substances were nominated by industry pursuant to a standard promulgated and published by FDA several years back – in July of 2014 (blogged about here).  FDA published the 2014 nomination process only after FDA ran into problems with its first attempt (in December 2013) to establish a nomination process for placing bulk substances on a list for outsourcing facilities to use in compounding.  After the July 2014 nomination process, FDA reviewed hundreds of nominations and created a salient “interim” list of substances that may be used by outsourcing facilities.  FDA continued to review and accept at a good pace nominations for bulk substances to be used by outsourcing facilities until FDA was sued by Endo Pharmaceuticals in October 2017 concerning FDA’s placement of vasopressin (the bulk substance in Endo’s Vasostrict®) on FDA’s interim list.

Now, roughly five years after industry nominated these substances pursuant to the 2014 standard (in effect at the time), after FDA reviewed and approved those nominations, after facilities expended significant resources conducting stability and other studies specific to these substances to ensure their use in compounding was consistent with FDA’s current good manufacturing practice regulations, FDA intends to pull the plug (so to speak) on their use based on the new, March 2019 nominations process.  Notwithstanding a prior successful nomination and review for the nine substances, which the facilities relied on, facilities now must submit significant additional information consistent with FDA’s new evaluation standard articulated in FDA’s March 2019 final guidance,  The new submissions must address at a minimum the clinical need for the compounded formulation, and must specifically consider that need, along with the medical suitability of the FDA-approved finished drug product to meet that clinical need.  Interested parties have until November 4, 2019, to resubmit nominations for these nine substances.