Biosimilarity Under Stress: A Forced Degradation Study of Remicade® and Remsima™

Pisupati K, et al., 9(7):1197-1209, MAbs, 2017

RemsimaTM (infliximab) is a biosimilar monoclonal antibody and Remicade® is its reference product. Described herein is the use of humidity and temperature induced forced-degradation studies to evaluate biosimilarity of RemsimaTM and Remicade® under stress. Structural and chemical changes that occurred due to stress were analyzed in order to understand infliximab’s degradation pathways, and to identify possible modifications in the sequence. Furthermore, the effect of these modifications on biologic activity was assessed by gauging how stress affects infliximab’s potential to bind tumor necrosis factor (TNF) and FcγRIIIa. The binding affinity of infliximab to FcγRIIIa was studied by using Bio-Layer Interferometry (BLI). A Pall ForteBio BLItz system equipped with Protein G (ProG) Biosensor tips was used to perform all BLI assays. ProG sensor tips were immobilized with infliximab. The association and dissociation kinetics of FcgRIIIa was measured by immersing the infliximab loaded biosensor probes into various concentrations of FcγRIIIa solutions. The biosensor tips were regenerated after each cycle. Binding data obtained were globally fitted to a 1:1 binding model. The dissociation constant (KD) was also determined. Overall results suggest that the Remicade® and RemsimaTM behaved similarly in the forced degradation studies and provide a comprehensive biosimilarity comparison of the two mAbs.

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