Desenvolvimento e emprego de metodologias analíticas complementares para avaliação da estabilidade do medicamento constituído pelo anticorpo monoclonal bevacizumabe (avastin®) fracionado por farmácias de manipulação

Abstract

Avastin®(bevacizumabe) is a humanized anti-VEGF monoclonal antibody approved as a first-line therapy for different types of cancer and used by intravitreal administration as off-label drug for the treatment of ocular diseases. This new clinical application of bevacizumab associated to the cost-benefit of the drug has generated a demand for its division into unit doses to meet the low doses used in intraocular administration. Thus, several studies have been conducted in order to verify the quality of repackaged bevacizumab. To study the quality of repackaged bevacizumab obtained from Brazilian suppliers we purchased the repackaged product from three external pharmacies specialized in ophthalmology, sterile or special compounding. Based on the complexity of the antibody structure, we investigated the quality of repackaged bevacizumab associating size-exclusion chromatography, polyacrylamide gel electrophoresis, turbidimetry, diffraction laser spectroscopy, nanoparticle tracking analysis and an enzyme-linked immunosorbent assay. In general, there were no detectable differences in the physicalchemical properties between repackaged and reference bevacizumab. The only difference observed is the variation in the volume of the samples among the suppliers. This study suggests that if precautions are taken the formulation remains stable after compounding.