FDA’s newly configured, 14-member Pharmacy Compounding Advisory Committee (PCAC) convened on February 23–24 at FDA headquarters in suburban Washington, DC, to vote on compounding certain drugs under sections 503A and 503B of the Federal Food, Drug, and Cosmetic Act (FFDCA).
The matters at hand were deciding whether to include a list of 27 drugs on FDA’s withdrawn or removed list, which comprises drugs that can’t be compounded because of safety and efficacy reasons, and if certain bulk substances for compounding should be on the 503A bulk list.
PCAC voted to add 25 drugs to the list of drugs that may not be compounded because their components are unsafe or ineffective.
These include the following: all drug products containing alatrofloxacin mesylate, aminopyrine, astemizole, bromfenac sodium (except ophthalmic solutions), cerivastatin sodium, and cisapride; all parenteral drug products containing esmolol HCl that supply 250 mg/mL of concentrated esmolol per 10-mL ampule; etretinate; gatifloxacin (except ophthalmic solutions); grepafloxacin; methoxyflurane; novobiocin sodium; pemoline; pergolide mesylate; phenylpropanolamine; propoxyphene; rapacuronium bromide; rofecoxib, sibutramine hydrochloride; tegaserod maleate; troglitazone; trovafloxacin mesylate; valdecoxib.
In addition, they include all extended-release drug products containing oxycodone hydrochloride that have not been determined by FDA to have abuse-deterrent properties; all drug products containing polyethylene glycol 3350, sodium chloride, sodium bicarbonate, and potassium chloride for oral solution; and 10 mg or more of bisacodyl delayed-release tablet. The committee also voted to add only the oral drug products containing chloramphenicol to the list and to update the current entry for adenosine phosphate, which currently reads, “All drug products containing adenosine phosphate,” to state, “All drug products containing adenosine 5’–monophosphate (AMP), adenosine 5’–diphosphate (ADP), and adenosine 5’–atriphosphate (ATP).”
Only two of the six bulk drug substances were deemed unfit for FDA’s bulk list. They are silver protein mild and piracetam. Those voted to be included on the list are thymol iodide, squaric acid dibutyl ester, diphenylcyclopropenone, and cantharidin.
FDA’s 2015 proposed 503A list evaluation criteria for this category included the physical and chemical characterization of the substance; any safety issues raised by the use of the substance in compounded drug products; and the historical use of the substance in compounded products, including information about the medical conditions the substance has been used to treat. In addition, the evaluation criteria included references in peer-reviewed medical literature or available evidence of effectiveness or lack of effectiveness.
PCAC is made up of pharmacists and physicians with expertise in compounding, as well as representatives from patient and public health advocacy organizations. Two members also represent the National Association of Boards of Pharmacy and the United States Pharmacopeia.
The Food and Drug Administration Modernization Act created the first PCAC in the late 1990s. But as a result of litigation over the validity of section 503A in FFDCA, FDA suspended its efforts to implement that section of the statute, and the committee was dissolved.
In 2012, FDA filed the charter to reestablish the committee. The new 503B section related to compounding outsourcing facilities established under the Drug Quality and Security Act in 2013 requires FDA to consult with an advisory committee on compounding.
“It’s been a long process, but at last we’ve arrived at this point and are ready to begin our work to address several important issues concerning compounding,” said Jane A. Axelrad, JD, Associate Director for Policy, CDER, and the Agency Lead on Compounding at FDA, during introductory remarks. Many FDA experts spoke before the committee.
Members of the audience—which was modest in size—were also given a chance to voice their opinions during the open public hearing portion of the agenda and before committee members voted. Several representatives of pharmacy groups—including APhA, the International Academy of Compounding Pharmacists, and the National Community Pharmacists Association—were in attendance.