Hong Juyong, Lee Yuhwa, Lee Changsoo, Eo Suhyeon, Kim Soyeon, Lee Nayoung, Park Jongmin, Park Seungkyu, Seo Donghyuck, Jeong Min, Lee Youngji, Yeon Soojeong, Bou-Assaf George, Sosic Zoran, Zhang Wei, Jaquez Orlando
a Quality Evaluation Team, Samsung Bioepis Co., Ltd , Incheon , South Korea.
b Department of Analytical Development , Biogen, Inc. , Cambridge , MA , USA.
MAbs. 2017 Feb/Mar;9(2):364-382. doi: 10.1080/19420862.2016.1264550. Epub 2016 Dec 22.
A biosimilar is a biological medicinal product that contains a version of the active substance of an already authorized original biological medicinal product. Biosimilarity to the reference product (RP) in terms of quality characteristics, such as physicochemical and biological properties, safety, and efficacy, based on a comprehensive comparability exercise needs to be established. SB2 (Flixabi® and Renflexis®) is a biosimilar to Remicade® (infliximab). The development of SB2 was performed in accordance with relevant guidelines of the International Conference on Harmonisation, the European Medicines Agency, and the United States Food and Drug Administration. To determine whether critical quality attributes meet quality standards, an extensive characterization test was performed with more than 80 lots of EU- and US-sourced RP. The physicochemical characterization study results revealed that SB2 was similar to the RP. Although a few differences in physicochemical attributes were observed, the evidence from the related literature, structure-activity relationship studies, and comparative biological assays showed that these differences were unlikely to be clinically meaningful. The biological characterization results showed that SB2 was similar to the RP in terms of tumor necrosis factor-α (TNF-α) binding and TNF-α neutralization activities as a main mode of action. SB2 was also similar in Fc-related biological activities including antibody-dependent cell-mediated cytotoxicity, complement-dependent cytotoxicity, neonatal Fc receptor binding, C1q binding, and Fc gamma receptor binding activities. These analytical findings support that SB2 is similar to the RP and also provide confidence of biosimilarity in terms of clinical safety and efficacy.
生物类似药是一种生物药品，其活性成分与已获批准的原研生物药品的活性成分相同。基于全面的可比性研究，需要在质量特性（如物理化学和生物学特性、安全性和有效性）方面建立与参比产品（RP）的生物相似性。SB2（Flixabi®和Renflexis®）是Remicade®（英夫利昔单抗）的生物类似药。SB2的研发是按照国际人用药品注册技术协调会、欧洲药品管理局和美国食品药品监督管理局的相关指南进行的。为确定关键质量属性是否符合质量标准，对80多个批次的欧盟和美国来源的参比产品进行了广泛的特性鉴定试验。物理化学特性研究结果表明，SB2与参比产品相似。虽然在物理化学属性上观察到一些差异，但相关文献、构效关系研究和比较生物学试验的证据表明，这些差异不太可能具有临床意义。生物学特性结果表明，作为主要作用方式，SB2在肿瘤坏死因子-α（TNF-α）结合和TNF-α中和活性方面与参比产品相似。SB2在Fc相关生物学活性方面也相似，包括抗体依赖性细胞介导的细胞毒性、补体依赖性细胞毒性、新生儿Fc受体结合、C1q结合和Fcγ受体结合活性。这些分析结果支持SB2与参比产品相似，也为其在临床安全性和有效性方面的生物相似性提供了信心。
