Part 2: Physicochemical characterization of bevacizumab in 2 mg/mL antibody solutions as used in human i.v. administration: Comparison of originator with a biosimilar candidate

Abstract

The physicochemical properties of Avastin® manufactured in the USA (Originator USA) and in Europe (Originator EU) and ABX-BEV, a bevacizumab biosimilar drug product candidate produced by Apobiologix Inc., were characterized at a clinically relevant concentration of 2 mg/mL following dilution of the 25 mg/mL drug products with 0.9% NaCl. Measurements using 14 orthogonal analytical methods performed within 5 h after dilution showed good similarity of the three antibodies as regards secondary structure, conformation, aggregation properties, subvisible and visible particles. No significant protein aggregation was observed within 5 h at 24 °C in the 2 mg/mL bevacizumab solutions. The same solutions that were measured within 5 h after dilution were analyzed again after 24 h overnight refrigeration at 2–8 °C: all 2 mg/mL bevacizumab solutions showed an increase in the number and sizes of aggregates, especially the particles larger than 10 μm and 25 μm. The data show the very good similarity in the physicochemical properties of ABX-BEV with Originators USA and EU at a clinically relevant concentration.