Just as the U.S. Food & Drug Administration (“FDA”) promised in its 2019 compounding priorities statement, FDA published a notice and proposed rule in the Federal Register in the past week related to bulk drug substances that can be compounded subject to the conditions of Section 503A and Section 503B of the Federal Food, Drug, & Cosmetic Act (“FDCA”):
(1) On September 5, 2019, FDA published a proposed rule regarding its intent to amend its regulations to add five bulk drug substances that can be used in compounding under Section 503A (the “503A Bulks List”) and proposed excluding another 26 bulk drug substances from the 503A Bulks List. Specifically, FDA proposes to amend the 503A Bulks List to include glutaraldehyde, glycolic acid, L-citrulline, pyruvic acid, and trichloroacetic acid (TCA), and proposes not to include 7-keto dehydroepiandrosterone (DHEA), acetyl-L-carnitine (ALC), alanyl-L-glutamine, Aloe vera 200:1 freeze dried, artemisinin, astragalus extract 10:1, boswellia serrata extract (BWSE), cesium chloride, chondroitin sulfate, chrysin, curcumin, D-ribose, deoxy-D-glucose, diindolylmethane, domperidone, epigallocatechin gallate (EGCG), germanium sesquioxide, glycyrrhizin, kojic acid, nettle, nicotinamide adenine dinucleotide (NAD), nicotinamide adenine dinucleotide disodium reduced (NADH), rubidium chloride, sodium dichloroacetate, vanadyl sulfate, and vasoactive intestinal peptide (VIP).
(2) On September 3, 2019, FDA published notice of its intent to exclude nine more bulk drug substances from its 503B clinical need list (the “503B Bulks List”). These substances are: dipyridamole, ephedrine sulfate, famotidine, hydralazine hydrochloride, methacholine chloride, sodium bicarbonate, sodium tetradecyl sulfate, trypan blue, and vecuronium bromide.
If the bulk drug substances above are ultimately not included in the 503A Bulks List, compounding pharmacies will not be able to compound with the substance unless the substance appears on an applicable United States Pharmacopeia or National Formulary monograph or if the substance is part of a commercially available drug product. Additionally, if the bulk drug substance does not appear on the 503B Bulks List (which is based on FDA’s interpretation of whether there is a “clinical need” for the substance), FDA-registered outsourcing facilities will not be able to compound with that substance unless it appears on the FDA drug shortage list. The Agency’s revisions to these Bulks Lists could significantly impact the compounding practices of these facilities nationwide and their ability to get patients access to the unique and critical compounded medications they need.