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Critical evaluations of generic piperacillin/tazobactam compared to the branded product: a worldwide sampling of 26 intravenous formulations

Abstract number: P1041

Moet G., Sader H., Fritsche T., Jones R.

Objective: To evaluate generic piperacillin/tazobactam (P/T) intravenous product activity by diffusion and MIC assays compared to branded product (Zosyn® or Tazocin®; Wyeth). P/T is a widely used penicillin/b-lactamase inhibitor combination (8:1 ratio). Recently, generic formulations have been introduced into various global markets said to possess bioequivalence and the original brand was reformulated using proprietary methods to enhance quality.

Methods: We studied ``non-branded'' generic lots for antimicrobial potency against 4 assay organisms (triplicate testing; P/T MICs, 1–4 mg/L), and directly compared to current branded agent. Generic P/T products (26 samples from 23 lots) were from Greece (3 lots), India (5), Philippines (10), Portugal (1), Taiwan (2), China (2), Jordan (1) and Spain (2). CLSI susceptibility testing applied reconstituted product sample vial contents to prepare panels having 20 dilution steps between 0.5–8 mg/L. Each strain was tested and the lowest reproducible MIC value was used for calculating lot potency compared to control (Zosyn® lot B75011).

Results: All tests were performed on the same day from fresh stock solutions. 4 manufacturers (Astral, Meditrina, YSS and Zurentus) had 2 or more lots. The branded formulation consistently produced the lowest MIC results (range, 1.0–3.5 mg/L) and generic products had MIC results that were consistently elevated, indicating reduced activity varying from -3 to -35% (ave. -16%; only Orchid Piptamate was equal). Largest differences were observed with Zopercin (151018; -21%), Tazidron (07077; -27%) and Vigocid (8001C; -35%), and the tazobactam effect also appeared diminished. A second sampling of 3 lots (PIPTAZ AUPM-601 and AUPI-601; Vigocid 8002C) exhibited consistently decreased activity that varied from -3 to -20%, demonstrating reproducibility of the MIC-based assay.

Conclusions: In vitro activities of various formulations of intravenous P/T products can vary significantly as assessed by this incremental MIC assay system when applying product vial content to reference dilution testing. Per-label activity was noted for the branded formulation and all but one generic lot (among 26 sampled from 15 manufacturers) had decreased potencies. Hospital formularies should be cautious when applying generic products without well-documented equivalence by chemical parameters, biologic tests related to in vivo bioavailability or clinical outcomes and direct in vitro potency assays.

Session Details

Date: 19/04/2008
Time: 00:00-00:00
Session name: 18th European Congress of Clinical Microbiology and Infectious Diseases
Subject:
Location: Barcelona, Spain
Presentation type:
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