a Pfizer, Biotechnology & Aseptic Sciences Group , Dublin , Ireland.
b Department of Rheumatology , Hospital Albert Einstein and Hospital AACD , São Paulo , Brazil.
MAbs. 2018 Jan;10(1):166-176. doi: 10.1080/19420862.2017.1387346. Epub 2017 Nov 7.
Fusion protein and monoclonal antibody-based tumor necrosis factor (TNF) inhibitors represent established treatment options for a range of inflammatory diseases. Regulatory authorities have outlined the structural characterization and clinical assessments necessary to establish biosimilarity of a new biotherapeutic product with the innovator biologic drug. Biologic products that would not meet the minimum World Health Organization's standard for evaluation of similar biotherapeutic products are available in some countries; in some cases relevant data to assess biosimilarity and appropriate regulatory approval pathways are lacking. Batches of seven intended copy (IC) products for etanercept (Enbrel®) were subjected to a subset of test methods used in the routine release and heightened characterization of Enbrel®, to determine key attributes of identity, quality, purity, strength, and activity. While a number of quality attributes of the IC lots tested met the release specifications for Enbrel®, none fell within these limits across all methods performed, and there were no IC lots that satisfied the criteria typically applied by the innovator to support comparability with Enbrel®. Although the consequences of these differences are largely unknown, the potential for unanticipated clinical outcomes should not be overlooked.
融合蛋白和单克隆抗体类肿瘤坏死因子（TNF）抑制剂是一系列炎症性疾病的既定治疗选择。监管机构已经概述了建立新型治疗性生物产品与创新生物药物生物相似性所需的结构特征和临床评估。在一些国家，不符合世界卫生组织评估类似治疗性生物产品最低标准的生物产品仍然可用；在某些情况下，缺乏评估生物相似性和适当监管批准途径的相关数据。依那西普（Enbrel®）的七个仿制（IC）产品批次接受了 Enbrel®常规放行和强化特征评估中使用的部分测试方法，以确定身份、质量、纯度、效力和活性的关键属性。虽然测试的 IC 批次的许多质量属性符合 Enbrel®的放行规格，但没有一个批次在所有进行的方法中都符合这些限制，也没有任何 IC 批次符合创新者通常应用的标准，以支持与 Enbrel®的可比性。尽管这些差异的后果在很大程度上尚不清楚，但不应忽视潜在的意外临床结果。
