Bio-Thera Solutions, Ltd, Floor 5, Building A6, 11 Kai-Yuan Blvd, Huangpu District, Guangzhou, 510530, Guangdong, China.
Biogen Inc, Cambridge, MA, USA.
BioDrugs. 2024 Jul;38(4):571-588. doi: 10.1007/s40259-024-00662-5. Epub 2024 Jun 18.
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.
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.
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.
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.
托珠单抗是一种针对白细胞介素 6 受体（IL-6R）的免疫球蛋白 G1 单克隆抗体。BAT1806/BIIB800（托珠单抗-bavi）已被开发为与参照产品托珠单抗（TCZ）的生物类似药。本研究的目的是在一项全面的可比性研究中证明 BAT1806/BIIB800 与 TCZ 在理化性质和功能方面的相似性。
使用超过 20 种方法的综合方法，生成了用于比较 10 个 BAT1806/BIIB800 批次和 44 个 TCZ 批次（16 个来自中国，16 个来自欧盟，12 个来自美国）的关键和非关键产品质量属性的数据集。使用液相色谱、质谱、各种光谱技术/方法、毛细管电泳和热分析技术评估一级结构、高级结构和理化性质。使用基于细胞的测定、免疫测定、流式细胞术和动力学结合测定评估 Fab-和 Fc-介导的生物学特性。
BAT1806/BIIB800 和 TCZ（无论来源如何）在结构和功能特性方面表现出相似性。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-介导的结合和生物学活性方面表现出相似性。在糖基化（去岩藻糖基化和唾液酸化）、糖化、聚集和电荷变体方面观察到一些微小差异，但这些差异被证明没有临床意义。
BAT1806/BIIB800 和 TCZ 在所有关键质量属性方面高度相似。在不太关键的质量属性方面观察到差异时，通过额外的分析评估和临床研究结果确定这些差异没有临床意义。
