Gly­col­ic acid, TCA among FDA's pro­posed ad­di­tions to 503B bulk drugs list

Four new bulk sub­stances are up for in­clu­sion on the list of ac­tive phar­ma­ceu­ti­cal in­gre­di­ents that out­sourc­ing fa­cil­i­ties can use in drug com­pound­ing un­der sec­tion 503B of the Fed­er­al Food, Drug, and Cos­met­ic Act, ac­cord­ing to a pro­pos­al from the FDA.

The four sub­stances FDA is propos­ing to in­clude as bulk drug sub­stances are diphenyl­cy­clo­propenone, gly­col­ic acid, squar­ic acid dibutyl es­ter and trichloroacetic acid. An ad­di­tion­al 19 bulk drug sub­stances were con­sid­ered for in­clu­sion in the 503B bulk drug sub­stances list, but FDA is propos­ing not to in­clude these sub­stances, cit­ing a lack of clin­i­cal need for an out­sourc­ing fa­cil­i­ty to com­pound drugs from the 19 sub­stances. This lack of need, said the agency, meant the drugs did not meet the statu­to­ry cri­te­ria for ad­di­tion to the list.

Pa­trizia Cavaz­zoni FDA

“If the pro­pos­al is fi­nal­ized, out­sourc­ing fa­cil­i­ties would be au­tho­rized to use these sub­stances in com­pound­ing as long as they meet the oth­er con­di­tions in sec­tion 503B,” said Pa­trizia Cavaz­zoni, act­ing di­rec­tor of FDA’s Cen­ter for Drug Eval­u­a­tion and Re­search (CDER). “As part of our over­sight ef­forts to help en­sure that Amer­i­cans have ac­cess to com­pound­ed med­i­cines, we are de­vel­op­ing and eval­u­at­ing a list of bulk drug sub­stances that out­sourc­ing fa­cil­i­ties can use in com­pound­ing when it’s been de­ter­mined that there is a clin­i­cal need,” she said.

As part of the rolling re­view process of which bulk drug sub­stances to in­clude on the 503B bulks list, the agency is weigh­ing safe­ty against the need for ac­cess, said Cavaz­zoni: “While com­pound­ed drugs do not un­der­go pre­mar­ket re­view for safe­ty, ef­fec­tive­ness and qual­i­ty, we rec­og­nize they can serve an im­por­tant role for pa­tients whose med­ical needs can­not be met by an FDA-ap­proved drug prod­uct. As we de­vel­op the 503B bulks list, we are bal­anc­ing these goals of pa­tient pro­tec­tion and ac­cess to com­pound­ed drugs for pa­tients who need them, par­tic­u­lar­ly com­pound­ed drugs in­tend­ed for use in health care sys­tems, in­clud­ing use for of­fice stock.”

The agency’s Fed­er­al Reg­is­ter en­try lists the 19 sub­stances not pro­posed for in­clu­sion: di­azepam, dobu­t­a­mine hy­drochlo­ride (HCl), dopamine HCl, ede­tate cal­ci­um dis­odi­um, folic acid, gly­copy­rro­late, hy­drox­yzine HCl, ke­toro­lac tromethamine, la­betalol HCl, man­ni­tol, meto­clo­pramide HCl, mox­i­floxacin HCl, nal­buphine HCl, poli­do­canol, potas­si­um ac­etate, pro­cainamide HCl, sodi­um ni­tro­prus­side, sodi­um thio­sul­fate, and ve­r­a­pamil HCl.

“For each of these pro­pos­als, we are seek­ing com­ments from the pub­lic be­fore mak­ing a fi­nal de­ci­sion. The FDA will con­tin­ue to eval­u­ate oth­er bulk sub­stances for in­clu­sion on this list as part of our con­tin­u­ing ef­forts to help en­sure avail­abil­i­ty for pa­tients who re­quire ac­cess to med­ical­ly nec­es­sary com­pound­ed drug prod­ucts,” Cavaz­zoni said.

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