Liu Jennifer, Eris Tamer, Li Cynthia, Cao Shawn, Kuhns Scott
Amgen Inc., One Amgen Center Drive, Thousand Oaks, CA, 91320, USA.
BioDrugs. 2016 Aug;30(4):321-38. doi: 10.1007/s40259-016-0184-3.
ABP 501 is being developed as a biosimilar to adalimumab. Comprehensive comparative analytical characterization studies have been conducted and completed.
The objective of this study was to assess analytical similarity between ABP 501 and two adalimumab reference products (RPs), licensed by the United States Food and Drug Administration (adalimumab [US]) and authorized by the European Union (adalimumab [EU]), using state-of-the-art analytical methods.
Comprehensive analytical characterization incorporating orthogonal analytical techniques was used to compare products. Physicochemical property comparisons comprised the primary structure related to amino acid sequence and post-translational modifications including glycans; higher-order structure; primary biological properties mediated by target and receptor binding; product-related substances and impurities; host-cell impurities; general properties of the finished drug product, including strength and formulation; subvisible and submicron particles and aggregates; and forced thermal degradation.
ABP 501 had the same amino acid sequence and similar post-translational modification profiles compared with adalimumab RPs. Primary structure, higher-order structure, and biological activities were similar for the three products. Product-related size and charge variants and aggregate and particle levels were also similar. ABP 501 had very low residual host-cell protein and DNA. The finished ABP 501 drug product has the same strength with regard to protein concentration and fill volume as adalimumab RPs. ABP 501 and the RPs had a similar stability profile both in normal storage and thermal stress conditions.
Based on the comprehensive analytical similarity assessment, ABP 501 was found to be similar to adalimumab with respect to physicochemical and biological properties.
ABP 501正在作为阿达木单抗的生物类似药进行研发。已经开展并完成了全面的比较分析表征研究。
本研究的目的是使用最先进的分析方法，评估ABP 501与两种阿达木单抗参比产品（RPs）之间的分析相似性，这两种参比产品分别获得美国食品药品监督管理局许可（阿达木单抗[美国]）和欧盟批准（阿达木单抗[欧盟]）。
采用结合正交分析技术的全面分析表征来比较产品。物理化学性质比较包括与氨基酸序列相关的一级结构以及包括聚糖在内的翻译后修饰；高级结构；由靶点和受体结合介导的主要生物学特性；产品相关物质和杂质；宿主细胞杂质；成品药物的一般性质，包括强度和制剂；亚可见和亚微米颗粒及聚集体；以及强制热降解。
与阿达木单抗参比产品相比，ABP 501具有相同的氨基酸序列和相似的翻译后修饰谱。三种产品的一级结构、高级结构和生物学活性相似。产品相关的大小和电荷变体以及聚集体和颗粒水平也相似。ABP 501的残留宿主细胞蛋白和DNA含量非常低。成品ABP 501药物产品在蛋白质浓度和装量方面与阿达木单抗参比产品具有相同的强度。ABP 501和参比产品在正常储存和热应激条件下具有相似的稳定性。
基于全面的分析相似性评估，发现ABP 501在物理化学和生物学性质方面与阿达木单抗相似。
