In-Use Stability of the Rituximab Biosimilar CT-P10 (Truxima®) Following Preparation for Intravenous Infusion and Storage
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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.
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.
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.
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.
We demonstrated that CT-P10 was stable after refrigerated storage for up to 6 weeks followed by incubation at room temperature.
Medical writing support (including development of a draft outline and subsequent drafts in consultation with the authors, assembling tables, collating author comments, copyediting, fact checking, and referencing) was provided by Emma Evans, PhD at Aspire Scientific Limited (Bollington, UK), and funded by Celltrion Healthcare Co., Ltd. (Incheon, Republic of Korea). Drafts were reviewed by Sang-Wook Yoon, PhD and Dasom Choi at Celltrion Healthcare Co., Ltd.
SJK and WYH were involved in the conception and design of the study. SJK, KWK, YKS, JWK, HYK, YAP, and JYS were involved in the acquisition of data and/or analysis and interpretation of the data. SJK, KWK, YKS, JWK, HYK, YAP, JYS, and SYK reviewed drafts of the manuscript and approved the final version for submission. Won Yong Han will serve as the guarantor for the overall content.
Compliance with Ethical Standards
This study was sponsored by CELLTRION, Inc. (Incheon, Republic of Korea). Funding for medical writing assistance was provided by Celltrion Healthcare Co., Ltd. (Incheon, Republic of Korea).
Conflict of interest
Su Jung Kim, Kwang Woo Kim, Yeon Kyeong Shin, Ji Woong Kwon, Hye Young Kang, Yoon A. Park, Ji Young Shin, So Young Kim, and Won Yong Han are employees of CELLTRION, Inc. The authors have no other conflicts of interest related to this work.
All data generated or analyzed during this study are included in this published article (and its supplementary information files).
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