Biostatistics and Bioinformatics, Duke University School of Medicine, Durham, NC, U.S.A.
Stat Med. 2013 Feb 10;32(3):442-8. doi: 10.1002/sim.5566. Epub 2012 Aug 17.
Unlike traditional small molecule (chemical) drug products, the development of biologic products is very different and variable with respect to the manufacturing process and environmental factors such as light and temperature. The complexity and heterogeneity of the molecular structure, complicated manufacturing process, different analytical methods, and possibility of severe immunogenicity reactions make quantitative evaluation of follow-on biologics a great challenge to both scientific community and regulatory agencies. In this article, we propose a general approach for development of a biosimilarity index based on the concept of reproducibility probability for quantitative evaluation of biosimilarity and interchangeability. The proposed method is robust regardless the biosimilarity criteria used and/or study design employed.
与传统的小分子（化学）药物产品不同，生物制品的开发在制造工艺和环境因素（如光和温度）方面存在很大的差异和可变性。分子结构的复杂性和异质性、复杂的制造工艺、不同的分析方法以及严重免疫原性反应的可能性，使得对后续生物类似物进行定量评估成为科学界和监管机构的一大挑战。在本文中，我们提出了一种基于重复性概率概念的生物类似性指数的开发方法，用于定量评估生物类似物的相似性和可互换性。所提出的方法具有很强的稳健性，无论使用的生物类似性标准和/或研究设计如何。
