Establishing Level A IVIVC for Extended-Release Formulations: A Regulatory Perspective

Abstract

Establishing a Level A In Vitro–In Vivo Correlation (IVIVC) is a critical step in the development and regulatory evaluation of extended-release (ER) drug formulations. Level A IVIVC provides a direct, point-to-point relationship between in vitro dissolution profiles and in vivo drug absorption, enabling reliable prediction of a drug’s pharmacokinetic behavior from laboratory tests. This correlation is particularly valuable for ER products, where controlled release mechanisms significantly influence therapeutic outcomes. From a regulatory perspective, Level A IVIVC supports streamlined product development, facilitates biowaivers for post-approval changes, and enhances risk management by reducing the need for extensive in vivo studies. This article explores the scientific principles, methodological approaches, and regulatory expectations underpinning the establishment of Level A IVIVC for ER formulations. Additionally, it highlights practical challenges, presents successful case studies, and discusses future trends shaping regulatory strategies and formulation innovation.