The evaluation of biosimilarity index based on reproducibility probability for assessing follow‐on biologics

Abstract

Unlike small molecule drug products, biological products are therapeutic agents producted using of a living system or organism. Thus, the development of biologic products is a very different and complicated process that is sensitive to environmental factors such as light and temperature. Therefore, the therapeutic effect of follow-on biologic products may not be equivalent to the innovative products even though the average biosimilarity has been established. Thus, Chow et al. suggested that the assessment of biosimilarity between biologic products should be conducted on the basis of variability in 2010. In this article, we propose a biosimilar index that is derived on the basis of estimated reproducibility probability approach and Bayesian approach, respectively. We conducted simulation studies to empirically investigate the relationship of reproducibility probability under various parameter combinations. The simulation results demonstrate that the proposed method based on biosimilar index can reflect the characteristics and impact of variability on the therapeutic effect of biologic products.

Avoiding ambiguity with the Type I error rate in noninferiority trials

“…As more biological products are going off patent protection, the assessment of the biosimilarity between a biosimilar product and an innovative product has recently been receiving considerable attention (Chow et al 2010, 2013a, 2013b, Hsieh et al 2013, Kang and Chow 2013, Kang and Kim 2014, US FDA 2012, WHO 2009. The most widely used design for a phase III comparative study for demonstrating the biosimilarity between a biosimilar product and a renovator biological product is the equivalence trial, whose aim is to show that the difference between the two population means of a primary endpoint is less than a pre-specified equivalence margin.…”

Evaluation of Biosimilarity Based on an Empirical Bayes Method

“…Some literatures published in recent years to deal with the development of statistical methodology for evaluation of "biosimilarity" between biosimilar products and innovator's biologics [5][6][7][8][9][10][11][12][13][14]. As indicated by Chow et al [7], current regulation for assessment of bioequivalence may be too loose to be applied for assessment of biosimilarity.…”

Sample Size Calculations for the Development of Biosimilar Products Based on Binary Endpoints

“…Many best-selling biological products are set to lose their patents over the next few years; constantly, the assessment of biological product biosimilarity for regulatory approval has received significant attention (Chow, 2014;Chow and Liu, 2010;Chow et al, 2009;Chow et al, 2013;Hsieh et al, 2013;Kang and Chow, 2013;Li et al, 2013;US FDA, 2012;World Health Organization, 2009). It is therefore necessary to demonstrate similar qualities, efficacy, and safety for biosimilar products and renovator biological products in order to obtain regulatory approval.…”