Investigation of the Physicochemical and Biological Stability of the Adalimumab Biosimilar CT-P17.

INTRODUCTION: CT-P17 (Celltrion, Inc., Incheon, Republic of Korea) is a biosimilar of reference adalimumab (Humira®; AbbVie Inc., North Chicago, IL, USA), which has recently received regulatory approval from the European Medicines Agency. METHODS: This analysis was designed to evaluate the stability profile of CT-P17 compared with reference adalimumab and the currently licensed adalimumab biosimilars ABP 501 (Amjevita®/Amgevita®; Amgen Inc., Thousand Oaks, CA, USA) and SB5 (Imraldi®; Biogen Inc., Cambridge, MA, USA) when stored at low temperature (5 °C) or room temperature (25 °C) with 60% relative humidity for up to 28 days. RESULTS: Multiple orthogonal and complementary tests demonstrated that CT-P17 was stable for 28 days under all tested conditions, as well as for protein concentrations tested (50 vs 100 mg/mL), type of delivery device (autoinjector vs prefilled syringe), and manufacturing date (recently manufactured vs aged for 17 months). There were slight differences among products in terms of charge variants, oxidation level, purity, and number of subvisible particles; however, overall, the quality of each product was maintained over 28 days. CONCLUSION: Our data suggest that CT-P17 may be used without any significant loss of stability when stored at 5 °C or 25 °C with 60% relative humidity for up to 28 days, and was not impacted by protein concentration tested and delivery device. Comparative stability data suggest that the appropriate maximum storage period for CT-P17 may be up to 28 days at room temperature with 60% relative humidity.

In-Use Stability of the Rituximab Biosimilar CT-P10 (Truxima®) Following Preparation for Intravenous Infusion and Storage.

BACKGROUND: CT-P10 is the first biosimilar of the anti-CD20 monoclonal antibody, rituximab. CT-P10 is currently available in over 51 countries worldwide, where it is approved in the same indications as its reference product rituximab. In-use stability studies are conducted for biologics to determine how conditions (e.g., temperature, light, humidity, length of time stored) affect drug quality following dilution and storage in infusion bags. OBJECTIVE: We evaluated the in-use stability of CT-P10 for intravenous infusion stored diluted in infusion bags over longer periods than currently recommended by manufacturer guidelines. METHODS: CT-P10, within the final month of its 36-month shelf life, was diluted to 1.0 or 4.0 mg/mL and stored at 2-8 °C in polyethylene or polyvinylchloride infusion bags for 2, 4, and 6 weeks. CT-P10 infusion bags were incubated at room temperature for 24 h before analysis. Analyses included detection of sub-visible particles, formation of impurities and determination of charge variants, and heavy- and light-chain content. Cell-based CD20 binding affinity and complement-dependent cytotoxicity were also assessed. RESULTS: Diluted CT-P10 solutions remained clear, colorless, and free of visible particles irrespective of type of infusion bag, target concentration, or timepoint. Protein concentrations, sub-visible particles, pH, osmolality, and molecular weight and charge variants were stable across all timepoints and variables. The binding affinity and potency of CT-P10 remained unchanged, indicating that the efficacy of the antibody was maintained following in-use preparation. CONCLUSIONS: We demonstrated that CT-P10 was stable after refrigerated storage for up to 6 weeks followed by incubation at room temperature.

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.