title: Analytical Similarity Assessment in Biosimilar Studies.
abstract: For assessment of biosimilarity, the US Food and Drug Administration (FDA) recommends a stepwise approach for obtaining the totality-of-the-evidence for demonstrating biosimilarity between a proposed biosimilar product and an innovative (reference) biological product. The stepwise approach starts with analytical studies for functional and structural characterization at various stages of manufacturing process of the proposed biosimilar product. Analytical similarity assessment involves identification of critical quality attributes (CQAs) that are relevant to clinical outcomes. FDA proposes first classifying the identified CQAs into three tiers according to their criticality or risking ranking relevant to clinical outcomes and then performing equivalence test (for CQAs in Tier 1), quality range approach (for CQAs in Tier 2), and raw data or graphical presentation (for CQAs in Tier 3) for obtaining totality-of-the-evidence for demonstrating biosimilarity between the proposed biosimilar product with the reference product. In practice, some debatable issues are evitably raised due to this complicated process of analytical similarity assessment. In this article, these debatable are described and discussed.
authors.affiliation: School of Medicine, Duke University, 2424 Erwin Road, Hock Suite 1102, Room 11068, Durham, North Carolina, 27705, USA. sheinchung.chow@duke.edu.
authors.forename: Shein-Chung
authors.initials: SC
authors.lastname: Chow
authors.affiliation: Peking University Clinical Research Institute, Peking University Health Science Center, Beijing, China.
authors.forename: Fuyu
authors.initials: F
authors.lastname: Song
authors.affiliation: Department of Drug and Cosmetics Registration, China Food and Drug Administration, Beijing, China.
authors.forename: He
authors.initials: H
authors.lastname: Bai
mesh_terms: D059451:Biosimilar Pharmaceuticals / Q000592:standards*; D006801:Humans; D011786:Quality Control; D014481:United States; D014486:United States Food and Drug Administration
chemical_list: D059451:Biosimilar Pharmaceuticals
keywords: equivalence test; fixed SD approach; quality range approach; stepwise approach; tiered approach; totality-of-the-evidence