Analytical similarity assessment

For regulatory review and approval of biosimilar products, the United States (US) Food and Drug Administration (FDA) recommended a stepwise approach for demonstrating biosimilarity between a proposed biosimilar product and an innovative (reference) biological product (e.g., an US-licensed product).1–3 The stepwise approach is to provide totality-of-the-evidence for demonstrating biosimilarity between the proposed biosimilar product and the reference product. The stepwise approach starts with analytical studies for functional and structural characterization of critical quality attributes (CQAs) at various stages of manufacturing process. For the assessment of analytical similarity of CQAs, FDA suggests, first, identifying the CQAs that are relevant to clinical outcomes, and then classifying the identified CQAs into several tiers depending upon their criticality or risk ranking. FDA also suggests different methods be used to assess similarity for CQAs from different tiers. For example, equivalence test for CQAs from Tier 1, quality range approach for CQAs from Tier 2, and descriptive raw data and graphical comparison for CQAs from Tier 3. In this article, controversial issues regarding the FDA’s recommended approaches are discussed followed by alternative methods for assessment of similarity for CQAs from Tier 1. WIREs Comput Stat 2017, 9:e1407. doi: 10.1002/wics.1407. For further resources related to this article, please visit the WIREs website.

Duke Scholars

Author Shein-Chung Chow Biostatistics & Bioinformatics, Division of Biostatistics