Physicochemical and biological comparison of the first Brazilian biosimilar filgrastim with its reference product

Abstract

Physicochemical and biological comparison of the first Brazilian biosimilar filgrastim with its reference product Monique Mantovani,1,2 Cecilia Sulzbacher Caruso,1 Fernanda Dell Antonio Facchini,1 Renata Pascon,1,3 Patrícia Ribeiro Vilaça Cagnacci,1 Vanda Dolabela de Magalhães1 1Department of Biotechnology, Eurofarma Laboratórios SA, São Paulo, SP, Brazil; 2Libbs Farmacêutica Ltda, Embu das Artes, SP, Brazil; 3Department of Biological Sciences, Federal University of São Paulo, Diadema, SP, Brazil Abstract: The registration of biosimilars requires comparison studies to reference products to guarantee their safety, purity, efficacy, and potency. In this study, we demonstrate the similarity of a filgrastim produced by Eurofarma (Fiprima®) and one produced by Amgen Inc. (commercialized by Hoffman-La Roche Ltd, Granulokine®) in terms of drug identity, structure, purity, and bioactivity. The methods used to compare both products were the following: peptide mapping, bidimensional electrophoresis, reduced and nonreduced polyacrylamide electrophoresis, Western blotting, reverse-phase high-performance liquid chromatography, size-exclusion high-performance liquid chromatography, far and near circular dichroism, fluorescence emission, X-ray crystallography, liquid chromatography–tandem mass spectrometry, matrix-assisted laser desorption/ionization-time of flight, receptor binding, and potency by in vitro cell proliferation. Biosimilarity to Granulokine was demonstrated in terms of identity, structure, purity, and bioactivity. Keywords: filgrastim, biosimilar, biopharmaceutical, G-CSF, comparability, neutropenia