Sample Size Consideration for Equivalent Test of Tier-1 Quality Attributes for Analytical Biosimilarity Assessment

Abstract

FDA recommends a stepwise approach for obtaining the totality-of-the-evidence for assessing biosimilarity between a proposed biosimilar product and its corresponding reference biologic product being considered (US Food and Drug Administration.: Guidance for industry: scientific considerations in demonstrating biosimilarity to a reference product. US Food and Drug Administration, Silver Spring, 2015 [6]). The stepwise approach starts with analytical studies for assessing similarity in critical quality attributes (CQAs), which are relevant to clinical outcomes. For critical quality attributes that are most relevant to clinical outcomes (Tier 1 CQAs), FDA requires equivalence testing to be performed for similarity assessment, based on an equivalence acceptance criteria. In practice, the number of Tier 1 CQAs might be greater than one, and should be no more than four. The number of biosimilar lots is often recommended to be no less than 10, and the ratio between the reference product sample size and biosimilar product sample size is recommended within the range from \( 2/3 \) to \( 3/2 \) (US Food and Drug Administration.: Guidance for industry: Statistical Approaches to Evaluate Analytical Similarity. US Food and Drug Administration, Silver Spring, 2017 [7]). Accordingly, we derive the formulas for the power calculation for the sample size for analytical similarity assessment based on the equivalence testing currently used in analytical biosimilar assessment (Tsong et al. J Biopharm Stat 27:197–205, (2017)[10]).