Accepted Article This article has been accepted for publication and undergone full peer review but has not been through the copyediting, typesetting, pagination and proofreading process, which may lead to differences between this version and the Version of Record. Please cite this article as doi: 10.1002/cpt.1270 This article is protected by copyright. All rights reserved. Article Type: State of the Art Opportunities and Challenges Related to the Implementation of Model-Based Bioequivalence Criteria Corinne Seng Yue, 1 Deniz Ozdin, 1,2 Susannah Selber-Hnatiw, 1 and Murray Ducharme. 1,2 Learn and Confirm Inc., St-Laurent, QC, Canada, 1 and Faculté de Pharmacie, University of Montreal, Montreal, QC, Canada. 2 Name and Address of Corresponding Author: Murray P. Ducharme, PharmD, FCCP, FCP Learn and Confirm Inc. 750 Marcel-Laurin, Suite 235 St-Laurent, QC, Canada, H4M 2M4 Tel/Fax: (514) 373-5346 Email: murray.ducharme@learnandconfirm.ca Funding: No funding was received for this work. Conflict of Interest: The authors declared no competing interests for this work. Abstract The science of bioequivalence and biosimilarity has greatly evolved over the past three decades. Current methods for assessing bioequivalence mostly rely on noncompartmental pharmacokinetic analyses, which have proven to be reliable and robust for most products. However, the development of more complex products is forcing scientists and regulators to consider alternative approaches, including those derived from model-based, population pharmacokinetic analyses. This manuscript will examine the strengths and weaknesses of standard noncompartmental methods and compare them to model-based approaches, including a comparison of metrics associated with each method. Specific situations for which model-based approaches could prove to be more suitable will be presented, as well as potential bioequivalence metrics that could be considered for bioequivalence comparisons. The opportunities and challenges that are associated with these novel methods will also be discussed.