Focused physicochemical stability study of reconstituted trastuzumab biosimilar SB3 (Ontruzant®) stored in the original vials over 28 days

Abstract

Abstract Objective Trastuzumab biosimilar SB3 (Ontruzant®), a HER2 binding monoclonal antibody, is available as powder for concentrate for solution for infusion. According to the summary of product characteristics, the reconstituted solution (21 mg/mL) is physicochemically stable for 7 days when stored refrigerated at 2–8 °C. The objective of this focused study was to determine the extended physicochemical stability of trastuzumab SB3 reconstituted with water for injection and stored in the original glass vials under refrigeration or at room temperature over a period of 28 days. Methods Ontruzant® vials were reconstituted with sterile water for injection and stored light protected at 2–8 °C in the refrigerator or at room temperature (15–25 °C, Ph. Eur.) over a maximum period of 28 days. At predefined time points (day 0, 7, 14, (21), 28) samples were withdrawn and analyzed by size-exclusion high-performance liquid chromatography with photodiode array detection, ultraviolet spectroscopy, and pH measurement. Test solutions were inspected for colour changes, clarity, and visible particles at each sampling time point. Results According to the size-exclusion chromatography assay, trastuzumab SB3 monomer concentrations exceeded 95 % of the initially measured concentrations over the entire study period. pH values and trastuzumab concentrations measured by UV remained unchanged. No colour changes or visible particles were detected. Results were independent from storage temperature. Conclusions According to the stability indicating methods used, physicochemical stability of reconstituted trastuzumab SB3 Ontruzant® solution in original glass vials is given over a period of 28 days either stored refrigerated or at room temperature. Results have to be substantiated by IE-HPLC or icIEF. To avoid microbiological instability storage under refrigeration is recommended.