FDA Giveth and Taketh Away: Agency Adds Four Substances to the Section 503B Bulk Substances List and Declining to Add Eight Others

February 8, 2022By Karla L. Palmer

In what is sure to be a process that will take potentially years to complete, FDA completed its final review of twelve bulk substances to be used in compounding by Section 503B Outsourcing Facilities.   FDA announced its decision in both a Federal Register Notice, and in a separate public announcement released on January 28th (here).  This is all part of the lengthy process where Section 503B statutorily directs FDA to establish the Section 503B Bulks List by: (1) publishing a notice in the Federal Register proposing bulk drug substances to be included on the list, and including the rationale for such proposal; (2) providing a period of not less than 60 calendar days for comment on the notice; and (3) publishing a notice in the Federal Register designating bulk drug substances for inclusion on the list.  Unlike the lists for Section 503A formal notice and comment rulemaking is not required. See Section 503A(d).

FDA reviewed the substances pursuant to its final policy published in 2019 (finalized after some significant litigation blogged about here about how FDA conducts that review), and determined that the following four drug substances made the List 1 cut: diphenylcyclopropenone (DPCP) for topical use;  glycolic acid for topical use in concentrations up to 70 percent; squaric acid dibutyl ester (SADBE) for topical use; and trichloroacetic acid (TCA) for topical use. FDA importantly noted that these bulk drug substances are not components of “any currently FDA-approved drugs.”  FDA identified eight other substances for which it completed the review process, and determined that it is not including the substances on the final Section 503B Bulks List 1 at this time.  These substances include the following:  diazepam, dipyridamole, dobutamine hydrochloride (HCl), dopamine HCl, edetate calcium disodium, folic acid, glycopyrrolate, and sodium thiosulfate (except for topical administration).  FDA’s notice focused on the fact that these bulk substances are components of FDA-approved drugs and nominations did not sufficiently show that the FDA-approved product had an attribute that made it medically unsuitable to treat certain patients, and/or that the drug must be compounded from a bulk substance rather than from an FDA-approved product – all of which appears to be an extremely difficult showing for compounders to make.

The latest 503B Lists are linked here.  FDA published its notice about its review — and proposed inclusion and/or exclusion — of all but one of these substances in July 2020.  (FDA proposed to remove dipyridamole and multiple other substances from the list in 2019).  FDA has not completed its review of the other 11 other substances that were the subject of FDA’s 2020 Federal Register notice.  Substances that were also included in the July 2020 notice and for which the Section 503B compounding industry is awaiting the “thumbs up or thumbs down” include the following: hydroxyzine HCl, ketorolac tromethamine, labetalol HCl, mannitol, metoclopramide HCl, moxifloxacin HCl, nalbuphine HCl, polidocanol, potassium acetate, procainamide HCl, sodium nitroprusside, and verapamil HCl.