In-Use Physicochemical and Biological Stability of the Trastuzumab Biosimilar CT-P6 Upon Preparation for Intravenous Infusion.

BACKGROUND: CT-P6 is a biosimilar of trastuzumab, a monoclonal antibody targeting human epidermal growth factor 2 (HER2), that is used in the treatment of breast and gastric cancers. OBJECTIVE: The aim of this study was to evaluate the in-use physicochemical and biological stability of CT-P6 following preparation for intravenous (IV) infusion. METHODS: One batch of CT-P6 within the final month of its 48-month shelf life was used to simulate sub-optimal administration conditions. CT-P6 dilutions of 0.4, 1.0, and 4.0 mg/mL, representative of actual use scenarios, were prepared in 0.9% saline solution in either polypropylene (PP) or polyvinylchloride (PVC) infusion bags. Following refrigeration at 2-8 °C for 1 month, samples were incubated at room temperature for 24 h. Physicochemical and biological stability were evaluated according to presence of sub-visible particles, pH, proportion of molecular weight variants, oxidation level of methionine residues 107, 255/256 and 432/433, and binding affinity to the Fc neonatal receptor and HER2. RESULTS: Analyses of CT-P6 preparations at all concentrations tested and in both PP and PVC infusion bags revealed no changes in sub-visible particles, pH, molecular weight variants, oxidation, or potency after 1 month at 2-8 °C followed by exposure to room temperature for 24 h. CONCLUSION: These analyses demonstrate the extended stability, after refrigerated storage for 1 month followed by 24-h exposure to room temperature, of CT-P6 under the dilution conditions required for IV infusion. This stability was sustained for all dilution factors and both infusion bag materials tested.