Peptide Votes Show How FDA Decides What Pharmacies May Compound

An FDA advisory panel voted narrowly on July 23 to recommend that four unapproved peptides be allowed for compounding by pharmacies, PharmExec reported, citing NBC News. The 14-member Pharmacy Compounding Advisory Committee voted 8-6, with one abstention, for BPC-157, KPV and TB-500, and 7-5, with two abstentions, for MOTS-c.

PharmExec reported that the votes came over the objections of FDA career scientists, who said they lacked the evidence to assess the compounds' safety and effectiveness. According to FDA's meeting page, the committee was to take up three more peptides on July 24: emideltide, Semax and Epitalon.

The votes do not make any of the substances approved drugs. They feed into a specific legal mechanism: the list of bulk drug substances that pharmacies may use under section 503A of the Federal Food, Drug, and Cosmetic Act.

The three routes for a bulk substance

Section 503A covers compounding by state-licensed pharmacists and physicians. FDA's 503A bulk substances page says they may compound only with bulk drug substances that comply with a United States Pharmacopeia or National Formulary monograph where one exists; that are components of FDA-approved drugs where no monograph exists; or that appear on FDA's list of bulk drug substances that can be used in compounding, known as the 503A bulks list, when neither of the first two applies.

Whatever the route, the substance must come with a valid certificate of analysis and be made by an establishment registered with FDA.

How the list is built

FDA began soliciting nominations for the list in 2015 and consults the Pharmacy Compounding Advisory Committee and the US Pharmacopeia as it evaluates them. A final rule in February 2019 placed six substances on the list, declined four others and set the criteria for evaluating nominees. A proposed rule in September 2019 would add five more and decline 26. FDA says it addresses sufficiently supported nominations on a rolling basis through notice-and-comment rulemaking.

The meeting page notes that advisory committees make non-binding recommendations, which FDA generally follows but is not legally bound to. For each substance, the committee considered the specific uses FDA had reviewed. PharmExec reported, for example, that FDA reviewed BPC-157 for ulcerative colitis and MOTS-c for obesity and osteoporosis.

The interim categories

Because rulemaking is slow, FDA issued an interim policy describing when it does not intend to act against compounders using nominated substances that are not yet on the list. It sorts them into three categories:

• Category 1: substances nominated with enough information to evaluate, which may be eligible for the list; FDA does not intend to take action against compounding with them if the guidance's conditions are met.
• Category 2: substances nominated with enough information, but for which FDA has identified significant safety risks; FDA may take action under its general enforcement policies.
• Category 3: substances nominated with too little supporting information to evaluate; they can be renominated.

FDA says a later guidance states it does not intend to place substances nominated on or after Jan. 7, 2025, into these categories. A lawyer quoted by PharmExec described three distinct legal events that are often treated as one: removal from Category 2, a committee recommendation, and placement on the list through rulemaking, a cycle he said realistically runs eight to 12 months.