The U.S. Food and Drug Administration has proposed adding a list of bulk drug substances that can be used in compounding to Section 503A of the Federal Food, Drug and Cosmetic Act. The rule proposed on Dec. 15, 2016, includes six bulk drug substances: Coomassie Brilliant Blue G-250, cantharidin, diphenylcyclopropenone, N-acetyl-D-glucosamine, squaric acid dibutyl ester and thymol iodide. The FDA also identified four bulk drug substances that it decided not to include on the list: oxitriptan, piracetam, silver protein mild and tranilast.

Section 503A outlines the requirements for exempting a compounded drug product from the more stringent provisions of the FD&C Act. To comply with the section, a licensed pharmacist in a state-licensed pharmacy or federal facility or a licensed physician must compound drug products using bulk drug substances that:

  • Comply with the standards of an applicable U.S. Pharmacopeial Convention or National Formulary monograph, if a monograph exists, and also with the USP chapter on pharmacy compounding.
  • If such a monograph does not exist, the drug substance must be a component of drugs approved by the FDA secretary.
  • If such a monograph does not exist and the drug substance is not a component of a drug approved by the FDA secretary, then it must appear on the 503A bulks list.

Currently, there is no official 503A bulks list, and the FDA intends to fill the legislative gap with this proposed rule.

The FDA’s Pharmacy Compounding Advisory Committee has met three times in 2016, most recently in November, to discuss the inclusion and exclusion of other drug substances on the 503A bulks list.

If the rule is finalized, it would establish criteria to evaluate future bulk drug substances for inclusion on the list. The evaluation criteria include the physical and chemical characterization of the substance, safety issues raised by use of the substance in compounded drug products, available evidence of effectiveness or lack of effectiveness of a drug product compounded with the substance, and historical use of the substance in compounded drug products. The FDA would use a balancing test on a substance-by-substance basis in assessing drug substances for the 503A bulks list.

The FDA has not identified specific costs and benefits of the proposed rule. However, the proposal suggests that enacting the rule would lead to better outcomes for pharmaceutical consumers and minimal negative effects for small entities in the industry.

The FDA has asked stakeholders in the compounding pharmacy community to provide feedback through comments submitted online. The comment period will last until March 16, 2017. If the FDA decides to publish the final version of the rule after the comment period, it will become effective 30 days after the final rule is published.