title: Development of statistical methods for analytical similarity assessment.
abstract: To evaluate the analytical similarity between the proposed biosimilar product and the US-licensed reference product, a working group at Food and Drug Administration (FDA) developed a tiered approach. This proposed tiered approach starts with a criticality determination of quality attributes (QAs) based on risk ranking of their potential impact on product quality and the clinical outcomes. Those QAs characterize biological products in terms of structural, physicochemical, and functional properties. Correspondingly, we propose three tiers of statistical approaches based on the levels of stringency in requirements. The three tiers of statistical approaches will be applied to QAs based on the criticality ranking and other factors. In this article, we discuss the statistical methods applicable to the three tiers of QA. We further provide more details for the proposed equivalence test as the Tier 1 approach. We also provide some discussion on the statistical challenges of the proposed equivalence test in the context of analytical similarity assessment.
authors.affiliation: a Office of Biostatistics, Office of Translational Science, CDER, FDA , Silver Spring , Maryland , USA.
authors.forename: Yi
authors.initials: Y
authors.lastname: Tsong
authors.affiliation: b Global Biostatistical Science, Amgen Inc. , Washington , DC , USA.
authors.forename: Xiaoyu
authors.initials: X
authors.lastname: Dong
authors.affiliation: a Office of Biostatistics, Office of Translational Science, CDER, FDA , Silver Spring , Maryland , USA.
authors.forename: Meiyu
authors.initials: M
authors.lastname: Shen
mesh_terms: D059451:Biosimilar Pharmaceuticals / Q000592:standards*; D006801:Humans; D011786:Quality Control; D012107:Research Design; D014481:United States; D014486:United States Food and Drug Administration
chemical_list: D059451:Biosimilar Pharmaceuticals
keywords: Analytical similarity; equivalence test; quality attribute; tiered approach