Strategic Drug Development, Design and Delivery Innovation, IQVIA, Medialaan 32/2, 1800, Vilvoorde, Belgium.
Global Analytical Characterization & Bioanalytics, Technical Development Biosimilars, Novartis BTDM, Hexal AG, 82041, Oberhaching, Germany.
AAPS J. 2018 May 10;20(4):68. doi: 10.1208/s12248-018-0230-9.
Leading regulatory agencies recommend biosimilar assessment to proceed in a stepwise fashion, starting with a detailed analytical comparison of the structural and functional properties of the proposed biosimilar and reference product. The degree of analytical similarity determines the degree of residual uncertainty that must be addressed through downstream in vivo studies. Substantive evidence of similarity from comprehensive analytical testing may justify a targeted clinical development plan, and thus enable a shorter path to licensing. The importance of a careful design of the analytical similarity study program therefore should not be underestimated. Designing a state-of-the-art analytical similarity study meeting current regulatory requirements in regions such as the USA and EU requires a methodical approach, consisting of specific steps that far precede the work on the actual analytical study protocol. This white paper discusses scientific and methodological considerations on the process of attribute and test method selection, criticality assessment, and subsequent assignment of analytical measures to US FDA's three tiers of analytical similarity assessment. Case examples of selection of critical quality attributes and analytical methods for similarity exercises are provided to illustrate the practical implementation of the principles discussed.
主要监管机构建议生物类似药的评估采用逐步进行的方式，首先详细分析比较拟议的生物类似药和参比产品的结构和功能特性。分析相似性的程度决定了必须通过下游体内研究来解决的剩余不确定性的程度。来自全面分析测试的实质性相似证据可以证明靶向临床开发计划是合理的，从而能够缩短许可途径。因此，不应低估精心设计分析相似性研究方案的重要性。在美国和欧盟等地区，按照当前监管要求设计最先进的分析相似性研究需要采用系统的方法，包括在实际分析研究方案之前进行的具体步骤。本白皮书讨论了属性和测试方法选择、关键性评估以及随后将分析方法分配给美国 FDA 的三个分析相似性评估层次过程中的科学和方法学考虑因素。提供了用于相似性研究的关键质量属性和分析方法选择的案例示例，以说明所讨论原则的实际实施情况。
