FDA Updates List of Drugs that May Not Be Compounded Under 503A and 503B: Preamble Reminds Industry when Listed Drugs Can Still Be CompoundedOctober 9, 2016
On October 6, 2016, the Food and Drug Administration (FDA or the Agency) amended its regulations to update the list of drugs that may not used in compounding under the exceptions set forth in sections 503A and 503B of the Federal Food, Drug, and Cosmetic Act (FDCA). This list reflects those drugs that have been withdrawn or removed from the market because the drugs or components of such drugs have been found to be unsafe or not effective. See 21 C.F.R. § 216.24. FDA originally published its withdrawn or removed list back in 1999. FDA states its primary focus since the 1999 final rule (and the 2014 proposed rule) has been on whether the drug products are unsafe. FDA notes that it may add to the list to include products that are not effective, or update the list to include additional products that are unsafe. These updates will continue to occur through notice and comment rulemaking; FDA will also (typically) only add to or modify the list after consultation with the Pharmacy Compounding Advisory Committee (PCAC). FDA also states it will create and maintain a web page about proposed drugs that it is considering adding to the list. A single list will apply to both sections 503A and 503B.
Revisions to the Withdrawn or Removed List
Consistent with the July 2, 2014 proposed rule (which we covered here), public comment thereon, and after soliciting input from FDA’s PCAC, the final rule adds the following 24 drugs to the withdrawn or removed list, which is codified at 21 C.F.R. § 216.24:
Esmolol hydrochloride (all parenteral dosage form drug products containing esmolol hydrochloride that supply 250 milligrams/milliliter of concentrated esmolol per 10-milliliter ampule)
Gatifloxacin (except ophthalmic solutions)
Polyethylene glycol 3350, sodium chloride, sodium bicarbonate, potassium chloride, and bisacodyl (all drug products containing polyethylene glycol 3350, sodium chloride, sodium bicarbonate, and potassium chloride for oral solution, and 10 milligrams or more of bisacodyl delayed-release tablets)
In addition, the rule creates an exception for ophthalmic solutions of bromfenac. No drugs previously listed were removed from the list.
Exceptions to the List
While most drugs on the list may not be compounded in any form, in FDA’s preamble to the rule, the Agency clarifies two exceptions. First, when FDA provides an exclusion for a particular formulation, indication, dosage form, or route of administration for a drug on the list (e.g., ophthalmic solutions of bromfenac), this indicates that there is an approved drug containing the same active ingredients that has not been withdrawn or removed from the market because it has been found to be unsafe or not effective. As such, that particular formulation, indication, dosage form, or route of administration that is expressly excluded from the list may still be compounded under sections 503A and 503B.
Second, some drugs are listed only with regard to certain formulations, concentrations, indications, routes of administration, or dosage forms because they have been found to be unsafe or not effective (e.g., oral and parenteral diethylstilbestrol containing 25 mg or more per unit dose). As such, other formulations, concentrations, indications, routes of administration, and dosage forms not on the list may still be compounded.
In addition, the preamble notes that just because a drug is on the withdrawn or removed list “does not mean it is banned completely and absolutely from compounding.” If warranted, FDA states that drugs on this list could be made available under an expanded access program under 21 C.F.R. part 312, subpart I.