Subunit Comparability Analysis of Etanercept and Biosimilar
Researchers at the Free University of Berlin have performed a comparability study of the Fc-fusion protein etanercept and a biosimilar using FabRICATOR® and subunit analysis. The etanercept molecule consists of an IgG1 Fc domain fused to a tumor necrosis factor alpha receptor (TNFaR) and is used for autoimmune diseases such as rheumatoid arthritis. The originator etanercept (Enbrel®) was compared to its biosimilar Altebrel™ (AryoGen Pharmed), that has been launched in Iran.
The scientists used FabRICATOR to digest the Fc-fusion protein and studied the subunits, TNFaR and Fc/2 separately using middle-up mass spectrometry. Interestingly, differences in the glycosylation pattern, the level of C-terminal lysine clipping and oxidation status of the two biopharmaceuticals were observed. The c-terminal lysine clipping was only observed in the originator molecule whereas the biosimilar showed no lysine clipping. Looking at the Fc/2 glycosylation profile using middle-up is a rapid way of determining the glycan content and the relative abundance of the species. In this case, the pattern was similar although the peak intensities differed, indicating a variation between the originator and the biosimilar.
Taken together, this paper highlights the use of FabRICATOR for comparability assessment of Fc-fusion proteins and shows that the middle-level approach can be used for fingerprinting of originator and biosimilar biopharmaceuticals.
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