Physicochemical characterization of Remsima®

Abstract

Remsima® (infliximab) was recently approved as the world's first biosimilar monoclonal antibody (mAb) in both the European Union and Korea. To achieve this, extensive physicochemical characterization of Remsima® in relation to Remicade® was conducted in order to demonstrate the highly similar properties between the two molecules. A multitude of state-of-the-art analyses revealed that Remsima® has identical primary as well as indistinguishable higher order structures compared with the original product. Monomer and aggregate contents of Remsima® were also found to be comparable with those of Remicade®. In terms of charge isoforms, although Remsima® was observed to contain slightly less basic variants than the original antibody, the difference was shown to be largely due to the presence of C-terminal lysine. On the other hand, this lysine was found to be rapidly clipped inside serum in vitro and in vivo, suggesting it has no effect on the biological potency or safety of the drug. Analysis of the glycan contents of the antibodies showed comparable glycan types and distributions. Recent results of clinical studies have further confirmed that the two antibody products are highly similar to each other. Based on this research as well as previous clinical and non-clinical comparability studies, Remsima® can be considered as a highly similar molecule to Remicade® in terms of physicochemical properties, efficacy, and safety for its final approval as a biosimilar product to Remicade®.

Comparison of originator and biosimilar therapeutic monoclonal antibodies using comprehensive two-dimensional liquid chromatography coupled with time-of-flight mass spectrometry

“…8. Consistent with the work of Jung et al, 9 the 2 most abundant glycan compositions identified were H3N4F1 and H4N4F1 ( Fig. 8c and 8d).…”

“…Jung et al reported the physicochemical characterization of Remsima Ò , and observed H3N4F1 and H4N4F1 as the top 2 most abundant glycan compositions. 9 The 2D separations of infliximab and infliximab-B following IdeS digestion or IdeS digestion followed by DTT reduction are shown in Fig. 7.…”

“…9 Many different analytical tools and techniques were applied for the thorough characterization at different levels, including: amino acid analysis, peptide mapping, reduced intact mass analysis, free thiol analysis, Fourier transform infrared spectroscopy, differential scanning calorimetry, antibody conformational array, X-ray crystallography, various modes of chromatography, light scattering, analytical ultracentrifugation, electrophoresis, isoelectric focusing, monosaccharide analysis, sialic acid analysis, glycopeptide analysis, N-glycan analysis, enzyme-linked immunosorbent assay, and surface plasmon resonance. 9 Biosimilar antibodies must have the same amino acid sequence as the reference marketed product. 10 However, because mAbs are large molecules with highly complex structures, the products are sensitive to changes in host cells, media, and manufacturing process.…”

“…1 Remsima (infliximab) is the world's first approved biosimilar mAb. 9 Extensive physicochemical characterization of Remsima in relation to Remicade, the reference product, was conducted to demonstrate the highly similar properties between the 2 molecules. Remsima has identical primary and higher order structures compared to Remicade.…”

The infliximab biosimilar in the treatment of moderate to severe plaque psoriasis

“…1,2 Cheaper biosimilars (drugs designed to have the same pharmacodynamic and pharmacokinetic properties as their previously licensed reference drugs) are available, but were not tested in patients with psoriasis. 3,4 Most regulatory agencies have approved the use of infliximab biosimilars for the treatment of psoriasis by extrapolating efficacy from studies in other diseases. [5][6][7][8] Here, we describe our experience in the use of the infliximab biosimilar Remsima (CT-P13, Celltrion, Korea) in the treatment of patients affected by moderate to severe plaque psoriasis.…”