FDA Statement about Product Quality of Parenteral Vancomycin Products

[3-9-2012] In response to a publication suggesting possible quality issues associated with parenteral vancomycin products,¹ the U.S. Food and Drug Administration (FDA) performed testing on five parenteral generic vancomycin products and one brand name vancomycin product, and results of these studies have been recently published.  All six products are FDA-approved and marketed in the United States (see Table 1).  As described in the summary below, the testing revealed no evidence of quality issues for the vancomycin products tested.

In the first study, FDA evaluated the quality of the six FDA-approved parenteral vancomycin products. Results show that these products surpassed the United States Pharmacopeia (USP) acceptance criteria for purity by having higher vancomycin B levels (the active component of vancomycin) and far lower levels of individual impurities than those specified in the USP monograph. Two different analytical methods (Ultra High-Pressure Liquid Chromatography and High Performance Liquid Chromatography) were used, one at each of two laboratories operated by FDA’s Office of Testing and Research.  The results were consistent between analytical methods.  A recently published article by Nambiar et al. contained the results of this FDA study.² 

FDA’s second study used a novel method, incorporating liquid chromatography, high resolution mass spectrometry, and diode array detection to identify vancomycin impurities, and to quantify a specific impurity:  crystalline degradation product (CDP-1). CDP-1 is hypothesized to affect the potency of vancomycin products.  The study also included an assessment of the in vitro potency of vancomycin using a microbiological assay.  All six vancomycin products tested met the potency standards provided in the USP monograph, even when spiked with CDP-1 at the individual impurity limit (the maximum allowable impurity peak per the USP monograph for the vancomycin product).  The results of this FDA study may be found in a recently published article by Hadwiger et al.³

All tested vancomycin products have met the quality specifications for potency and impurities contained in the USP monograph (Vancomycin hydrochloride for injection). In the next phase of the evaluation, FDA will assess the in vivo activity of these products in an appropriate animal model. This work will be done in collaboration with the National Institute of Allergy and Infectious Diseases.  FDA will provide information about this evaluation when results become available. 
 

Table 1: Vancomycin products tested

REFERENCES:

1. Vesga O, Agudelo M, Salazar BE, et al. Generic vancomycin products fail in vivo despite being pharmaceutical equivalents of the innovator.  Antimicrob Agents Chemother. 2010; 54(8): 3271-9.
2. Nambiar S, Madurawe RD, Zuk S, et al. Product quality of parenteral vancomycin products in the United States.  [published online ahead of print February 6 2012] Antimicrob Agent Chemother. 2012. http://aac.asm.org/content/early/2012/02/01/AAC.05344-11.full.pdf+html. Accessed February 13, 2012.
3. Hadwiger ME, Sommers CD, Mans, DJ, et al. Quality assessment of US marketplace vancomycin for injection products using high resolution LC-MS and potency assays. [published online ahead of print February 27 2012] Antimicrob Agent Chemother. 2012. http://aac.asm.org/content/early/2012/02/22/AAC.00164-12.full.pdf+html. Accessed February 28, 2012