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ASSESSMENT OF THERMAL AGGREGATION BEHAVIOR OF BEVACIZUMAB BIOSIMILARS COMPARED WITH THE INNOVATOR: CORRELATION WITH N-GLYCAN PROFILE BY LC-MS AND SEC-HPLC


Author: S. R. Vuyyuru and B. Palakeeti
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Abstract

This study primarily examined the thermal aggregation behaviour of bevacizumab biosimilars in comparison totheinnovator. It focused on the variations in their N-glycan compositions. The percentages of aggregate variations werequantified using size exclusion chromatography. The study successfully measured and quantified the N-glycans of four bevacizumab biosimilars (AVZ, BRX, BVZ, and IVZ) and the innovator (AST) using LC-MS/Q-TOF. It wasidentified that all bevacizumab biosimilars contained different quantities of N-glycan compositions compared totheinnovator. Compared to all biosimilars, innovators have a higher percentage of fucosylated N-glycans (86.50%), while Bryxta (BRX) has a lower percentage (65.40%). This study revealed variations in glycan composition, emphasising that fucose-related glycans play a substantial role in the stability and formation of aggregates inmonoclonal antibodies. Research showed that higher levels of fucose-related glycans are linked to a lower percentage of aggregates observed during thermal aggregation studies. Conversely, lower levels of these glycansresult in a higher percentage of aggregates.

Keywords: Bevacizumab, N-glycans, Avastin, SEC-HPLC, LC-MS






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