Key Laboratory of the Ministry of Health for Research on Quality and Standardization of Biotech Products , National Institutes for Food and Drug Control , No. 29, Huatuo Road, Daxing District , Beijing 102629 , China.
Anal Chem. 2020 Feb 18;92(4):3161-3170. doi: 10.1021/acs.analchem.9b04871. Epub 2020 Feb 5.
BVZ-BC (bevacizumab-biosimilar candidate) is a proposed biosimilar to bevacizumab. Bevacizumab binds to vascular endothelial growth factor (VEGF) type A and prevents the interaction of VEGF with its receptors on the surface of endothelial cells, neutralizing angiogenesis required for the growth, persistence, and metastases of solid tumors. An analytical comparison of BVZ-BC and bevacizumab was performed using state-of-the-art analytical techniques, including biochemical and biophysical characterization, biological activity, and immunological properties. Multiple attributes of the molecules were evaluated, including amino acid sequence, disulfide structure, glycan profiles, free thiol content, isoelectric point, protein content, subvisible particles, higher-order structure such as near- and far-ultraviolet circular dichroism and differential scanning calorimetry, product purity and product-related impurities, and process-related impurities. Biological activity assessment employed orthogonal assays such as the VEGF cell-based bioassay and the VEGF enzyme-linked immunosorbent assay, and Fc functional assays to interrogate all expected biological activities. An accumulation of 18 batches of bevacizumab (sourced in China, manufactured in Europe, Roche) and 10 batches of BVZ-BC representing unique drug product lots from each individual drug substance lot were utilized in this study. The analytical similarity between BVZ-BC and bevacizumab was assessed and demonstrated the similarities of all of the quality attributes between BVZ-BC and bevacizumab.
BVZ-BC（贝伐珠单抗生物类似药候选药物）是一种拟开发的贝伐珠单抗生物类似药。贝伐珠单抗与血管内皮生长因子（VEGF）A 型结合，阻止 VEGF 与其在内皮细胞表面的受体相互作用，从而中和实体瘤生长、持续存在和转移所需的血管生成。采用最先进的分析技术，包括生化和生物物理特性分析、生物学活性和免疫特性分析，对 BVZ-BC 和贝伐珠单抗进行了分析比较。评估了分子的多个属性，包括氨基酸序列、二硫键结构、聚糖谱、游离巯基含量、等电点、蛋白质含量、亚可见颗粒、近紫外和远紫外圆二色性和差示扫描量热法等高级结构、产品纯度和产品相关杂质以及工艺相关杂质。采用 VEGF 细胞生物测定和 VEGF 酶联免疫吸附测定等正交测定法以及 Fc 功能测定法评估生物学活性，以研究所有预期的生物学活性。本研究共使用了 18 批贝伐珠单抗（来自中国，在欧洲生产，罗氏）和 10 批 BVZ-BC，分别代表每个单独的药物物质批次的独特药物产品批次。评估了 BVZ-BC 与贝伐珠单抗之间的分析相似性，并证明了 BVZ-BC 和贝伐珠单抗之间所有质量属性的相似性。
