Biotechnology Research Institute, R&D Division, CELLTRION, Inc., 20, Academy-ro 51 Beon-gil, Yeonsu-gu, Incheon, 22014, Republic of Korea.
BioDrugs. 2019 Apr;33(2):221-228. doi: 10.1007/s40259-019-00336-7.
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.
CT-P10 是抗 CD20 单克隆抗体利妥昔单抗的首个生物类似药。CT-P10 目前在全球 51 个国家/地区上市，其适应证与原研药利妥昔单抗相同。生物制剂需要进行在使用稳定性研究，以确定在稀释并储存在输液袋中后，条件（例如温度、光照、湿度、储存时间）如何影响药物质量。
我们评估了 CT-P10 在静脉输注中的在使用稳定性，与制造商指南目前推荐的相比，将稀释液在输液袋中储存的时间延长。
在其 36 个月有效期的最后一个月内，将 CT-P10 稀释至 1.0 或 4.0mg/mL，并在 2-8°C 下储存在聚乙烯或聚氯乙烯输液袋中 2、4 和 6 周。在分析前，将 CT-P10 输液袋在室温下孵育 24 小时。分析包括检测亚可见颗粒、杂质的形成以及测定电荷变体和重链和轻链含量。还评估了基于细胞的 CD20 结合亲和力和补体依赖性细胞毒性。
无论输液袋类型、目标浓度或时间点如何，稀释后的 CT-P10 溶液均保持清澈、无色且无可见颗粒。无论时间点和变量如何，蛋白浓度、亚可见颗粒、pH 值、渗透压、分子量和电荷变体均保持稳定。CT-P10 的结合亲和力和效价保持不变，表明抗体的疗效在使用准备后得以维持。
我们证明 CT-P10 在冷藏储存长达 6 周后，随后在室温下孵育，其稳定性良好。
