Evaluation of the Physico-Chemical and Biological Stability of SB8 (Aybintio), a Proposed Biosimilar to Bevacizumab, Under Ambient and In-Use Conditions.

Abstract

No stability data of SB8 (proposed biosimilar to bevacizumab) are available for opened vials at 2-8°C or for unopened vials stored outside of this range. Furthermore, limited stability data are available for dilutions. Stability of unopened vials of SB8 at ambient temperature and in-use stability for opened vials as well as diluted SB8 in infusion bags were evaluated. SB8 stability was assessed in three scenarios in the absence of light: unopened 100-mg vials 36 months after manufacture stored at 30 ± 2°C with 65 ± 5% relative humidity for 1month, opened 100-mg and 400-mg vials stored at 5 ± 3°C for 72h and diluted (1.4mg/ml or 16.5mg/ml in 100ml 0.9% NaCl polyolefin bags) stored for 45days at 5 ± 3°C and then 3days at 30 ± 2°C; the United Kingdom's National Health Service protocol was used for the study design after dilution. Physicochemical stability (appearance, pH, protein concentration, size-exclusion high-performance liquid chromatography, non-reducing capillary electrophoresis-sodium dodecyl sulfate, imaged capillary isoelectric focusing), biological activity [vascular endothelial growth factor (VEGF) neutralization assay, VEGF binding assay] and potential safety impact properties (subvisible particulates, submicronic aggregation by dynamic light scattering) were determined. All stability-indicating criteria including those for biological activity were met for both unopened vials at ambient condition and for in-use conditions of opened vials as well as both dilutions. No noteworthy changes in terms of physicochemical stability, biological activity and properties with a potential safety impact occurred. Under the studied aspetic extreme conditions, SB8 was stable. Our data may support advanced SB8 preparation and may help prevent SB8 wastage because of exceptional temperature excursions or unused product. Sterility assurance is the responsibility of the user and is of utmost importance when opened or diluted SB8 is not immediately used.