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, U.S. Food and Drug Administration (FDA) statisticians collaborated with Chemistry, Manufacturing and Control (CMC) scientists at FDA in order to develop a three-tier approach. The proposed tiered approach starts with a criticality determination of quality attributes (QAs) based on their potential impact on product quality and the clinical outcomes. Those QAs characterize the biological product in terms of structural, physico-chemical, and functional properties. Then, the QAs are assigned into three tiers based on their criticality ranking. To evaluate the analytical similarity for QAs assigned to different tiers, we recommend different statistical approaches with different statistical rigors. That is, we recommend an equivalence test for the critical quality attributes (CQAs) in Tier 1, a quality range approach for QAs in Tier 2, and a side-by-side graphic comparison approach for QAs in Tier 3. In this article, we mainly focus on the development of the FDA's recommended equivalence test for Tier 1. We also provide some discussion on the statistical challenges of the proposed equivalence test in the context of analytical similarity assessment.