Biosimilarity under stress: A forced degradation study of Remicade® and Remsima™
Open Access
- 8 August 2017
- journal article
- other
- Published by Taylor & Francis Ltd in mAbs
- Vol. 9 (7), 1197-1209
- https://doi.org/10.1080/19420862.2017.1347741
Abstract
Remsima™ (infliximab) is the first biosimilar monoclonal antibody (mAb) approved by the European Medical Agency and the US Food and Drug Administration. Remsima™ is highly similar to its reference product, Remicade®, with identical formulation components. The 2 products, however, are not identical; Remsima™ has higher levels of soluble aggregates, C-terminal lysine truncation, and fucosylated glycans. To understand if these attribute differences could be amplified during forced degradation, solutions and lyophilized powders of the 2 products were subjected to stress at elevated temperature (40–60°C) and humidity (dry-97% relative humidity). Stress-induced aggregation and degradation profiles were similar for the 2 products and resulted in loss of infliximab binding to tumor necrosis factor and FcγRIIIa. Appearances of protein aggregates and hydrolysis products were time- and humidity-dependent, with similar degradation rates observed for the reference and biosimilar products. Protein powder incubations at 40°C/97% relative humidity resulted in partial mAb unfolding and increased asparagine deamidation. Minor differences in heat capacity, fluorescence, levels of subvisible particulates, deamidation and protein fragments were observed in the 2 stressed products, but these differences were not statistically significant. The protein solution instability at 60°C, although quite significant, was also similar for both products. Despite the small initial analytical differences, Remicade® and Remsima™ displayed similar degradation mechanisms and kinetics. Thus, our results show that the 2 products are highly similar and infliximab's primary sequence largely defines their protein instabilities compared with the limited influence of small initial purity and glycosylation differences in the 2 products.Keywords
This publication has 33 references indexed in Scilit:
- A Multidimensional Analytical Comparison of Remicade and the Biosimilar RemsimaAnalytical Chemistry, 2017
- Forced degradation studies: current trends and future perspectives for protein-based therapeuticsExpert Review of Proteomics, 2016
- The Tortoise and the Hare: Evolving Regulatory Landscapes for BiosimilarsTrends in Biotechnology, 2016
- Intrinsic fluorescence-basedat situsoft sensor for monitoring monoclonal antibody aggregationBiotechnology Progress, 2015
- Physicochemical characterization of Remsima®mAbs, 2014
- Immunogenicity of different stressed IgG monoclonal antibody formulations in immune tolerant transgenic micemAbs, 2012
- Forced Degradation of Therapeutic ProteinsJournal of Pharmaceutical Sciences, 2012
- Chemical Modifications in Therapeutic Protein Aggregates Generated under Different Stress ConditionsJournal of Biological Chemistry, 2011
- A rapid, sensitive and economical assessment of monoclonal antibody conformational stability by intrinsic tryptophan fluorescence spectroscopyBiotechnology Journal, 2008
- Structural features of γ-immunoglobulin, antibody, and their fragments. Circular dichroism studiesBiochemistry, 1968