a Biotechnology Research Institute, R&D Division, Celltrion Inc. , Incheon , Korea.
MAbs. 2018 Apr;10(3):380-396. doi: 10.1080/19420862.2018.1433976. Epub 2018 Mar 6.
CT-P10 (Truxima™) was recently approved as the world's first rituximab biosimilar product in the European Union (EU) and South Korea. To demonstrate biosimilarity of CT-P10 with the reference medicinal product (RMP), extensive 3-way similarity assessment has been conducted between CT-P10, EU-Rituximab and US-Rituximab, focusing on the physicochemical and biological quality attributes. A multitude of state-of-the-art analyses revealed that CT-P10 has identical primary and higher order structures compared to the original product. Purity/impurity profiles of CT-P10 measured by the levels of aggregates, fragments, non-glycosylated form and process-related impurities were also found to be comparable with those of RMPs. In terms of the post-translational modification, CT-P10 contains slightly less N-terminal pyro-glutamate variant, which has been known not to affect product efficacy or safety. Oligosaccharide profiling has revealed that, although CT-P10 contains the same conserved glycan species and relative proportion with the RMPs, the content of total afucosylated glycan in CT-P10 was slightly higher than in EU- or US-Rituximab. Nevertheless, the effect of the observed level of afucosylation in CT-P10 drug product on Fc receptor binding affinity or antibody-dependent cell-mediated cytotoxicity was found to be negligible based on the spiking study with highly afucosylated sample. Arrays of biological assays representative of known and putative mechanisms of action for rituximab have shown that biological activities of CT-P10 are within the quality range of RMPs. Recent results of clinical studies have further confirmed that the CT-P10 exhibits equivalent clinical efficacy and safety profiles compared to EU- and US-Rituximab. The current 3-way similarity assessment together with clinical study results confidently demonstrate that CT-P10 is highly similar with EU- and US-Rituximab in terms of physicochemical properties, biological activities, efficacy, and safety for its final approval as a biosimilar product.
CT-P10（Truxima™）最近在欧盟（EU）和韩国被批准为全球首个利妥昔单抗生物类似药产品。为了证明 CT-P10 与参比药品（RMP）具有生物类似性，已对 CT-P10、EU-利妥昔单抗和 US-利妥昔单抗进行了广泛的 3 路相似性评估，重点关注理化性质和生物学质量属性。大量最先进的分析表明，CT-P10 与原药具有相同的一级和高级结构。通过测定聚集物、片段、非糖基化形式和工艺相关杂质的水平，也发现 CT-P10 的纯度/杂质谱与 RMPs 相当。在翻译后修饰方面，CT-P10 含有略少的 N 末端焦谷氨酸变异体，已知该变异体不会影响产品的疗效或安全性。寡糖谱分析表明，尽管 CT-P10 含有与 RMPs 相同的保守聚糖种类和相对比例，但 CT-P10 中的总去岩藻糖基化聚糖含量略高于 EU 或 US-利妥昔单抗。然而，基于高去岩藻糖基化样品的加标研究，发现 CT-P10 药物产品中观察到的去岩藻糖基化水平对 Fc 受体结合亲和力或抗体依赖性细胞介导的细胞毒性的影响可以忽略不计。一系列代表利妥昔单抗已知和潜在作用机制的生物学测定表明，CT-P10 的生物学活性在 RMPs 的质量范围内。最近的临床研究结果进一步证实，CT-P10 与 EU 和 US-利妥昔单抗在临床疗效和安全性方面表现相当。目前的 3 路相似性评估以及临床研究结果有信心地证明，CT-P10 在理化性质、生物学活性、疗效和安全性方面与 EU 和 US-利妥昔单抗高度相似，可最终批准为生物类似药产品。
