Abstract
PF-06439535 (bevacizumab-bvzr; Zirabev®) is a biosimilar of bevacizumab reference product (RP; Avastin®). This study describes the formulation development for PF-06439535. PF-06439535 was formulated in several buffers and stored for 12 weeks at 40°C to determine the optimal buffer and pH under stressed conditions. Subsequently, PF-06439535 at 100 and 25mg/mL was formulated in a succinate buffer with sucrose, edetate disodium dihydrate (EDTA), and polysorbate 80, and in the RP formulation. Samples were stored at -40°C to 40°C for ≤22 weeks. The physicochemical and biological properties relevant to the safety, efficacy, quality, or manufacturability were investigated. When stored at 40°C for 13 days, PF-06439535 demonstrated optimal stability in histidine or succinate buffers and was more stable in the succinate formulation than the RP formulation, under both real-time and accelerated stability conditions. There were no significant changes in the quality attributes of 100 mg/mL PF-06439535 after storage at -20°C and -40°C for 22 weeks, and there were no changes in the quality attributes of 25 mg/mL PF-06439535 after storage at 5°C (recommended storage temperature). Changes were observed at 25°C for 22 weeks or at 40°C for 8weeks as expected. No new degraded species were observed in the biosimilar succinate formulation compared with the RP formulation. Results demonstrated that 20 mM succinate buffer (pH5.5) is the PF-06439535 preferred formulation, and that sucrose is an effective cryoprotectant for processing and frozen storage, and an effective stabilizing excipient for 5°C liquid storage of PF-06439535.
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