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

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

Acknowledgments

Eric Sasso, Leandro Pacheco, Claudio Saes Jr, Gabriel Feliciano, João Oliveira, Thiago Oliveira Santos e Silva, Kátia Souza, Maria Noélia Silva, Lauren Camargo, José Rafael da Silveira, Diego Souza, Edinaldo Oliveira, Elenilse Moura, Vinicius Oliveira, Carlos Silverio, Fernanda Perez, and Miriam Malto are team members who contributed to the development of the biosimilar Fiprima. This work was supported by FINEP (contracts 02.06.0158.00 and 01.07.0076.00).

Disclosure

The authors report no conflicts of interest in this work.