A Multidimensional Analytical Comparison of Remicade and the Biosimilar Remsima

作者:Pisupati Karthik; Tian Yuwei; Okbazghi Solomon; Benet Alexander; Ackermann Rose; Ford Michael; Saveliev Sergei; Hosfield Christopher M; Urh Marjeta; Carlson Eric; Becker Christopher; Tolbert Thomas J; Schwendeman Steven P; Ruotolo Brandon T*; Schwendeman Anna*
来源:Analytical Chemistry, 2017, 89(9): 4838-4846.
DOI:10.1021/acs.analchem.6b04436

摘要

In April 2016, the Food and Drug Administration approved the first biosimilar monoclonal antibody (mAb), Inflectra/Remsima (Celltrion), based off the original product Remicade (infliximab, Janssen). Biosimilars promise significant cost savings for patients, but the unavoidable differences between innovator and copycat biologics raise questions regarding product interchangeability. In this study, Remicade and Remsima were examined by native mass spectrometry, ion mobility, and quantitative peptide mapping. The levels of oxidation, deamidation, and mutation of individual amino acids were remarkably similar. We found different levels of C-terminal truncation, soluble protein aggregates, and glycation that all likely have a limited clinical impact. Importantly, we identified more than 25 glycoforms for each product and observed glycoform population differences, with afucosylated glycans accounting for 19.7% of Remicade and 13.2% of Remsima glycoforms, which translated into a 2-fold reduction in the level of Fc gamma IIIa receptor binding for Remsima. While this difference was acknowledged in Remsima regulatory filings, our glycoform analysis and receptor binding results appear to be somewhat different from the published values, likely because of methodological differences between laboratories and improved glycoform identification by our laboratory using a peptide map-based method. Our mass spectrometry-based analysis provides rapid and robust analytical information vital for biosimilar development. We have demonstrated the utility of our multiple-attribute monitoring workflow using the model mAbs Remicade and Remsima and have provided a template for analysis of future mAb biosimilars.

  • 出版日期2017-5-2