Evaluation of Compounded Bevacizumab Prepared for Intravitreal Injection

Abstract

n an era of increasing health care costs and qualitycontrol mandates, compounding pharmacies have been under intense scrutiny. The health care system, including ophthalmologists, relies on compounded drug formulations particularly intravitreal bevacizumab (Avastin; Genentech/Roche) for the treatment of a variety of choroidal and retinal vascular diseases. Clinical trials, such as the Comparison of AMD Treatments Trials 1 and the Inhibition of Vascular Endothelial Growth Factor (VEGF) in Age-related choroidal Neovascularization trial, 2 support the effectiveness of intravitreal bevacizumab for the treatment of age-related macular degeneration. While both bevacizumab and ranibizumab (Lucentis; Genentech/Roche) have been found to have similar safety and efficacy, 1,2 substantial cost savings may be derived from using bevacizumab, which is reimbursed approximately $50 from Medicare in comparison with nearly $2000 for ranibizumab. 3 Indeed, the researchers of the Inhibition of Vascular Endothelial Growth Factor (VEGF) in Age-related choroidal Neovascularization trial estimated that the National Health Service in the United Kingdom could potentially save an estimated £84.5 million (US $140.9 million) per year by switching from ranibizumab to bevacizumab and administering medication on an as-needed basis.Compounding pharmacies prepare intravitreal bevacizumab for clinical use but the quality, consistency, and safety IMPORTANCE Bevacizumab acquired from compounding pharmacies for intravitreal injection may cause infectious and noninfectious inflammation. In addition to safety issues, the drug itself may have variable efficacy associated with product aliquoting, handling, and distribution.OBJECTIVE To conduct surveillance cultures, evaluate endotoxin levels, and assess protein concentrations of bevacizumab obtained from compounding pharmacies in the United States.DESIGN AND SETTING Prospective in vitro study of syringes containing intravitreal preparations of bevacizumab from compounding pharmacies. This study was conducted at a university-based, good manufacturing practice facility and academic ophthalmology practice.MAIN OUTCOMES AND MEASURES Microbial culture growth, endotoxin levels, and quantity and binding affinity of protein in each sample.RESULTS There were no microbial contaminants or endotoxin detected in any of the samples. Of the 21 compounded samples of bevacizumab obtained from 11 pharmacies, 17 (81%) had lower protein concentrations (mean [SD], 22.2 [4.9] mg/mL; range, 19.2-24.5 mg/mL) compared with bevacizumab acquired directly from Genentech (25 mg/mL; P < .05). In 3 of 10 compounding pharmacies where more than 1 sample was available, there were statistically significant differences in the protein concentration between samples from the same compounding pharmacy. CONCLUSIONS AND RELEVANCETest results from intravitreal preparations of bevacizumab acquired from compounding pharmacies were negative for microbial contaminants and endotoxin. However, there were significant variations in protein concentration th...

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