Doctoral Dissertation Defense: Ginto Pottackal

Title: Some Tests, Confidence Limits and Tolerance Limits for Assessing Biosimilarity

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 of generic drugs may not be applicable in establishing biosimilarity due to the complexity of the protein structure. In particular, any criterion based on only the means will ignore the possible difference in variability between the test and reference products. Nevertheless, average biosimilarity is clearly a minimum requirement in the process of biosimilarity assessment, and some procedures are already available in the literature for testing average biosimilarity. However, these test procedures are not accurate in terms of maintaining the type I error probability. This will clearly impact the power, and hence the sample size. Thus two aspects of biosimilarity testing are investigated in the thesis:  (i) the development of accurate tests for assessing average biosimilarity, and (ii) the development of alternative criteria that incorporate the variances, along with accurate test procedures for the alternative criteria. In addition, biosimilarity assessment based on binary responses is also investigated. Illustrative examples  will be provided based on biosimilarity data available from the European Medicines Agency. Open problems and future work will also be indicated.