Evaluation of the physicochemical and biological stability of reconstituted and diluted SB2 (infliximab).

Objectives: To evaluate the critical quality attributes that might affect the stability of an infliximab biosimilar (SB2, Flixabi) when reconstituted or diluted and stored under refrigeration and at room temperature.

Methods: We largely adhered to the UK's National Health Service guidance requirements for the design of a robust stability study and for robust testing methods. Protocol components included evaluation of visual appearance, chemical stability, physical stability, pH, particle sizes and biological activity. The stability of reconstituted SB2 was assessed for 60 days at 5°C and for 7 days at 25°C. Stability of diluted SB2 at concentrations that ranged from 240 mg/250 mL (3 mg/kg; 80 kg patient) to 400 mg/250 mL (5 mg/kg; 80 kg patient) was assessed for 7 days at both temperatures. Dilutions were made in polyethylene bags containing 0.9% NaCl. Forced degradation studies were conducted with SB2 and its reference product (USA-sourced and European Union-sourced Remicade). Stress conditions of heat or light occurred before product reconstitution.

Results: In a laboratory environment under aseptic conditions, stability acceptance criteria with regard to physicochemical and biological properties were met for all reconstituted and diluted SB2 samples for all time periods and temperatures assessed. After either heat or light stress, similar stability and biological activity were noted for SB2 and both reference products.

Conclusions: When prepared under aseptic conditions in accordance with the product's Summary of Product Characteristics, exposed for prolonged periods at 5°C and 25°C and assessed with the described methods, SB2 appears to remain a stable monoclonal antibody maintaining its expected biological function.