Expanded studies of piperacillin/tazobactam formulations: variations among branded product lots and assessment of 46 generic lots

Abstract

The experience with analyzing the potency of piperacillin/tazobactam generic formulations by a precise multiorganism in vitro assay was expanded to 46 lots (29 manufacturers, 17 countries). Across all generic lots, the range of activity compared with a reference branded lot (RLOT; Zosyn; Wyeth Pharmaceuticals, Philadelphia, PA) was +10% to -42% (average, -16%). Eight lots of Zosyn were also tested with a range of +7 to -19 (average, only -6%), and the reproducibility (13 replicates) of the RLOT assay was confirmed (+/-3%). This ongoing quality assurance project demonstrated wide activity variations in piperacillin/tazobactam generic lots with a consistent trend toward subpotent performance (-16%) compared with the branded product. Generic substitutions within hospital formularies should consider parameters of in vitro activity, in addition to applied chemical analyses and measures of bioavailability to avoid potential adverse clinical consequences.