Yujie Liu, Jianhua Xie, Zhuxiang Li, Xiong Mei, Di Cao, Shengfeng Li, Linda Engle, Suli Liu, Hans C Ebbers, Cuihua Liu
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Primary structure, higher-order structure, and physicochemical properties were assessed using liquid chromatography, mass spectrometry, various spectroscopy techniques/methods, capillary electrophoresis, and thermoanalytical techniques. Fragment antigen-binding (Fab)- and fragment crystallizable (Fc)-mediated biological properties were assessed using cell-based assays, immunoassays, flow cytometry, and kinetic binding assays.</p><p><strong>Results: </strong>BAT1806/BIIB800 and TCZ (irrespective of source) were shown to be similar in terms of structural and functional properties. No differences were observed in terms of the most critical quality attributes, that is, soluble-IL-6R binding and inhibition of IL-6-mediated cell proliferation. BAT1806/BIIB800 and TCZ demonstrated similarity in terms of Fab- and Fc-mediated binding and biological activity. 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引用次数: 0
摘要
背景和目的托西珠单抗是一种靶向白细胞介素-6受体（IL-6R）的免疫球蛋白G1单克隆抗体。BAT1806/BIIB800（tocilizumab-bavi）已被开发为参考产品托西珠单抗（TCZ）的生物类似药。本研究的目的是通过全面的可比性实验证明 BAT1806/BIIB800 与 TCZ 在理化和功能上的相似性：方法：采用20多种方法生成数据集，比较10批次BAT1806/BIIB800和44批次TCZ（16批次来自中国，16批次来自欧盟，12批次来自美国）的关键和非关键产品质量属性。采用液相色谱法、质谱法、各种光谱技术/方法、毛细管电泳法和热分析技术对一级结构、高阶结构和理化性质进行了评估。使用细胞检测法、免疫测定法、流式细胞仪和动力学结合检测法评估了片段抗原结合（Fab）和片段可结晶（Fc）介导的生物特性：结果表明，BAT1806/BIIB800 和 TCZ（无论来源如何）在结构和功能特性方面相似。在最关键的质量属性方面，即可溶性 IL-6R 结合和抑制 IL-6 介导的细胞增殖方面，没有观察到差异。BAT1806/BIIB800 和 TCZ 在 Fab 和 Fc 介导的结合和生物活性方面表现出相似性。BAT1806/BIIB800和TCZ在糖基化（afucosylation和sialylation）、糖化、聚集和电荷变异方面存在微小差异，但这些差异已被证明与临床无关：BAT1806/BIIB800和TCZ在所有关键质量属性方面都非常相似。结论：BAT1806/BIIB800和TCZ在所有关键质量属性上高度相似，在不太关键的质量属性上出现差异时，额外的分析评估和临床研究结果表明这些差异没有临床意义。
Demonstration of Physicochemical and Functional Similarity of the Biosimilar BAT1806/BIIB800 to Reference Tocilizumab.
Background and objective: Tocilizumab is an immunoglobulin G1 monoclonal antibody targeting the interleukin-6 receptor (IL-6R). BAT1806/BIIB800 (tocilizumab-bavi) has been developed as a biosimilar to the reference product tocilizumab (TCZ). The objective of this study was to demonstrate physicochemical and functional similarity between BAT1806/BIIB800 and TCZ in a comprehensive comparability exercise.
Methods: A comprehensive panel of over 20 methods was used to generate datasets comparing critical and non-critical product quality attributes for 10 BAT1806/BIIB800 lots and 44 TCZ lots (16 sourced from China, 16 from the EU, and 12 from the US). Primary structure, higher-order structure, and physicochemical properties were assessed using liquid chromatography, mass spectrometry, various spectroscopy techniques/methods, capillary electrophoresis, and thermoanalytical techniques. Fragment antigen-binding (Fab)- and fragment crystallizable (Fc)-mediated biological properties were assessed using cell-based assays, immunoassays, flow cytometry, and kinetic binding assays.
Results: BAT1806/BIIB800 and TCZ (irrespective of source) were shown to be similar in terms of structural and functional properties. No differences were observed in terms of the most critical quality attributes, that is, soluble-IL-6R binding and inhibition of IL-6-mediated cell proliferation. BAT1806/BIIB800 and TCZ demonstrated similarity in terms of Fab- and Fc-mediated binding and biological activity. Minor differences were observed in glycosylation (afucosylation and sialylation), glycation, aggregation, and charge variants, which were demonstrated to be not clinically relevant.
Conclusion: BAT1806/BIIB800 and TCZ were highly similar for all critical quality attributes. Where differences were observed in less critical quality attributes, additional analytical assessments and clinical study results determined these to be not clinically meaningful.
期刊介绍：
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