Nine More FDA Bulk Compounding Denials Proposed Post-Vasopressin
Executive Summary
Expected flurry of FDA proposals against 503B compounding from bulk drug substances follows vasopressin court ruling.
The US Food and Drug Administration proposed 3 September to restrict nine more active drug substances from being compounded in bulk by outsourcing facilities, saying these active substances already exist in dosage forms that are available in FDA-approved drug products.
This action may bolster predictions that the agency is accelerating its review and excluding more substances from compounding under Section 503B of the Food, Drug and Cosmetic Act since a recent court ruling supported the agency’s earlier decision to ban vasopressin from compounding.
The agency said that these nine substances are already available in currently approved products and there is no need for compounded versions. They are: dipyridamole, ephedrine sulfate, famotidine, hydralazine hydrochloride, methacholine chloride, sodium bicarbonate, sodium tetradecyl sulfate, trypan blue and vecuronium bromide.
On 1 March, the FDA took its first action on the bulk list since the enactment of the Drug Quality and Security Act six years ago by excluding two bulk drug substances, vasopressin and nicardipine hydrochloride, from the list of bulk drug substances that outsourcing facilities may use in compounding drugs. (Also see "FDA Begins Restricting Bulk Compounding With First DQSA Determinations" - Pink Sheet, 6 Mar, 2019.)
Athenex, the company that makes vasopressin, sued the FDA; the company argued that there is a clinical need for its ready-to-use preservative-free compounded formulation of vasopressin; the agency said however, that Vasostrict is already available in a dose without the preservative. (Also see "Athenex Sues FDA To Get Vasopressin On List Of Drugs That Can Be Compounded" - Pink Sheet, 20 Mar, 2019.)
A recent court ruling upheld the FDA’s rationale for excluding vasopressin from the list in August, and two Washington attorneys said this decision gave the agency the “green light” to move forward in reviewing and excluding more substances from compounding under Section 503B of the Food, Drug and Cosmetic Act. (Also see "Vasopressin Ruling May Greenlight More FDA Limits On Bulk Drug Compounding" - Pink Sheet, 6 Aug, 2019.)
The FDA said that the 503B bulks list should only include bulk drug substances for which there is a clinical need. The FDA is evaluating some of the bulk drug substances that were nominated for inclusion on the list, proceeding case by case under the clinical need standard provided by the statute.
The FDA has established a two-part analysis to determine whether there is a clinical need: There has to be a basis for concluding that the nominated substance has an attribute that an FDA product does not have to treat certain patients. Also, there has to be a basis to conclude that the product proposed to be compounded is produced from a bulk drug substance rather than an FDA-approved product. If the FDA answers no to either question, the agency will not place the nominated substance on the bulk drug substance list.
The FDA said that additional bulk drug substances nominated by the public for inclusion on the list are currently under consideration and will be the subject of future notices.
The deadline for public comment is 4 November. Submit comments to https://www.regulations.gov/comment?D=FDA-2018-N-3240-0033.