Tolerance Intervals for Assessing Biosimilarity

• Activity Number: 658
• Type: Contributed
• Date/Time: Thursday, August 13, 2015 : 8:30 AM to 10:20 AM
• Sponsor: Biopharmaceutical Section
• Author(s): Ginto Pottackal* and Thomas Mathew
• Companies: University of Maryland, Baltimore County and University of Maryland, Baltimore County
• Keywords: Biosimilar ; Non-Parametric Tolerance Limits ; Follow-on biologics ; Bootstrap Calibration ; Biosimilarity ; Upper Tolerance Limits

Abstract

Biosimilars or follow-on biologics are defined as biological medicinal products that are expected to be similar to a licensed biological product. The standard procedures for assessing bioequivalence may not be applicable in establishing biosimilarity due to the complexity of the protein structure. Also, any criterion based on only the means will ignore the possible difference in variability between the test and reference products. In the talk we propose using tolerance limits to assess biosimilarity, and this naturally takes into account possible differences between the means, as well as the possibility of a larger variance for the test drug. Tolerance limits are developed for random variables that measure the response difference between the drugs. A non-parametric approach, along with a bootstrap calibration, is used to develop accurate tolerance limits. Numerical results on the performance of the proposed solution will be reported.