Determination of Equivalence Margin of Analytical Biosimilar Assessment

• Activity Number: 160
• Type: Topic Contributed
• Date/Time: Monday, August 1, 2016 : 10:30 AM to 12:20 PM
• Sponsor: Biopharmaceutical Section
• Author(s): Yi Tsong* and Cassie Dong and Meiyu Shen
• Companies: FDA/CDER and FDA and FDA/CDER
• Keywords: Equivalence test ; analytical biosimilar ; equivalence margin ; power ; confidence level

Abstract

Analytical biosimilarity is assessed by showing equivalence of mean attributes of biosimilar and reference products. In the lack of any existing scientific justified margin of each attribute, we propose to determine the margin with accommodation of the variability of variances of various attributes. We propose an equivalence margin to be determined in order reach more than 85% power for products their means are within a pre-specified difference from reference products given the proper number of lots. Once the sample size dependent margin is determined, we convert it to a margin that can be unified regardless of variability of sample sizes and variances. It is done through simulations and discussion among the statisticians, biologists and FDA regulatory authorities. In this presentation, we will illustrate the approach and address a few related issues.