Simplified Model-Dependent and Model-Independent Approaches for Dissolution Profile Comparison for Oral Products: Regulatory Perspective for Generic Product Development.

Dissolution profile comparison among different formulations plays a critical role during new drug as well as generic product development. In the generic product development, dissolution profile comparison is a mandate for biowaivers (BCS-based, for lower strengths and IVIVC-based biowaivers) and also from quality control perspective. Even though traditionally similarity factor or f2 is used as a metric for dissolution profile comparison, it comes with multiple limitations and requirements (e.g., number of time points and variability). To overcome this, regulatory agencies suggested model-independent (e.g., MSD) and model-dependent (e.g., zero order, Weibull) dissolution profile comparison methods. Although most of regulatory guidance documents mention about such approaches, their usage in reality is limited probably due to lack of clear, detailed, and step-wise procedure. In this context, the present article describes simplistic yet detailed procedures of dissolution profile comparison with case studies covering generic product development scenario's from a regulatory perspective. Detailed review of regulatory guidances from various agencies was made along with examples of such approaches in regulatory submissions. Data from three formulations-Formulations A, B, and C-were utilized to perform dissolution profile comparison using MSD, zero-order, and Weibull release profile-based comparisons. Dissolution profile comparisons were made using all of these three approaches complying with regulatory requirements. These examples demonstrated value and utility of these approaches and the simplified and detailed procedure explained in this manuscript can be adapted for generic product applications.