Challenging issues in assessing analytical similarity in biosimilar studies

Abstract

For assessing biosimilarity of biosimilar products, the US Food and Drug Administration (FDA) proposed a stepwise approach for providing totality-of-the-evidence of similarity between a proposed biosimilar product and a US-licensed (reference) product. The stepwise approach starts with an assessment of critical quality attributes (CQAs) that are relevant to clinical outcomes in structural and functional characterization in manufacturing process of the proposed biosimilar product. The FDA suggests that these critical quality-relevant attributes be identified and classified into three tiers depending their criticality or risk ranking. To assist the sponsors, the FDA also suggests some statistical approaches for the assessment of analytical similarity for CQAs from different tiers, namely equivalence test for Tier 1, quality range approach for Tier 2, and descriptive raw data and graphical comparison for Tier 3. In this paper, challenging issues to the FDA's recommended approaches are discussed followed by alternative methods for the assessment of analytical similarity (mainly for CQAs from Tier 1).