Halim Liem Andhyk, Brinks Vera, Jiskoot Wim, Romeijn Stefan, Haselberg Rob, Burns Chris, Wadhwa Meenu, Schellekens Huub
Department of Pharmaceutics, Utrecht Institute for Pharmaceutical Sciences (UIPS), Utrecht University, 3584 CG Utrecht, the Netherlands.
Division of Drug Delivery Technology, Leiden Academic Centre for Drug Research, Leiden University, 2300 RA Leiden, the Netherlands.
J Pharm Sci. 2016 Feb;105(2):542-550. doi: 10.1016/j.xphs.2015.10.019. Epub 2016 Jan 9.
Comprehensive physicochemical characterization and biological assays are essential parts in assessing quality attributes of biologicals. Here, we compared the quality of different marketed recombinant human erythropoietin (epoetin) products: originators, Eprex and NeoRecormon as well as 2 biosimilars, Retacrit and Binocrit. In addition, assessment of batch-to-batch variability was included by collecting 2 or more batches of each product. Common assays which included sodium dodecyl sulfate-polyacrylamide gel electrophoresis, high-performance size-exclusion chromatography, asymmetrical flow field-flow fractionation, capillary zone electrophoresis, and potency testing were used. Of the tested products and among batches of single products, variations in epoetin content, isoform profiles, and potency were found. Ultimately, this study demonstrated the high quality of epoetin products with some degree of variation among products and batches, confirming the "similar but not identical" paradigm of biologicals.
全面的物理化学表征和生物学测定是评估生物制品质量属性的重要组成部分。在此，我们比较了不同市售重组人促红细胞生成素（促红素）产品的质量：原研产品益比奥和宁红欣，以及两种生物类似药罗可曼和倍怡。此外，通过收集每种产品的两批或更多批次产品来评估批次间的变异性。采用了包括十二烷基硫酸钠-聚丙烯酰胺凝胶电泳、高效尺寸排阻色谱、不对称流场-流分级、毛细管区带电泳和效价检测在内的常规测定方法。在所测试的产品以及单个产品的批次之间，发现促红素含量、异构体谱和效价存在差异。最终，本研究证明了促红素产品质量较高，但产品和批次之间存在一定程度的差异，证实了生物制品“相似但不相同”的范式。
