Background and importance

ABP 215 (MVASI) is the first approved biosimilar to Avastin (bevacizumab reference product, RP). ABP 215 presents an alternative and effective treatment option. ABP 215 is administered intravenously after dilution in an infusion bag and confers its action by binding vascular endothelial growth factor (VEGF)-A and preventing its interaction with VEGF receptors on endothelial cells, resulting in angiogenesis inhibition. Extended physicochemical stability under in use conditions is valuable to enable administration flexibility by ensuring efficacy during handling conditions not covered by standard stability studies.

Aim and objectives

The aim of the study was to evaluate the physicochemical stability of ABP 215 after dilution, storage and infusion during potentially worst case handling conditions.

Material and methods

Low and high dose ABP 215 solutions were prepared in polyvinyl chloride and polyolefin intravenous (IV) bags. Prepared bags were stored at 2–8°C for 35 days and then stored at 30°C for 2 days, followed by IV infusion simulation. Stability indicating assays were selected to assess product quality on initial dilution into the IV bags, at prespecified time points during the 2–8°C refrigerated storage, 30°C storage, and prior and following the infusion. Stability indicating assays were selected to assess drug product quality. Size variants were assessed via size exclusion chromatography. Fragmentation was assessed via reduced capillary electrophoresis. Charge heterogeneity was assessed via cation exchange chromatography. Subvisible particle formation trends were assessed via subvisible particle testing and potential visible proteinaceous particle formation trends were assessed via visual inspection. Protein concentration was monitored for changes. Product quality consistency was evaluated via potency measurements.

Results

After dilution, storage and infusion, ABP 215 solutions showed no changes outside of product acceptance criteria in molecular size or charge variants, fragmentation, particulate formation, protein concentration or potency.

Conclusion and relevance

Across the evaluated worst case handling conditions, a robust set of stability indicating assays showed that ABP 215 product quality and activity remained within the product acceptance ranges over the examined extended storage.

References and/or acknowledgements

Conflict of interest

Corporate sponsored research or other substantive relationships: All authors are employees and stockholders of Amgen Inc.

L. G. Jayewardene

Publications