Post-Approval Change Management for Modified Release Solid Oral Dosage Forms: A Comparative Regulatory Review of the United States, the Republic of Korea and the GCC Variation Guidelines

Abstract

Post-approval change (PAC) management is a key aspect of pharmaceutical lifecycle regulation, ensuring that any modifications made after product approval do not compromise the efficacy, safety and quality of the medicine. It is particularly important for modified-release (MR) solid oral dosage forms (SODFs), where changes in formulation, manufacturing processes, or equipment can significantly influence drug release and therapeutic performance. This review compares the PAC regulatory frameworks of the United States, the Republic of Korea, and the Gulf Cooperation Council (GCC) region. The United States follows a comprehensive risk-based approach supported by the SUPAC-MR guidance, which provides detailed recommendations and clearly defined reporting pathways, including Prior Approval Supplements (PAS), Changes Being Effected (CBE) Supplement, and Annual Reports (AR). In contrast, Korea and the GCC employ variation-based systems that classify changes according to their potential impact but offer less product-specific guidance for MR formulations. Despite these differences, all three regions rely heavily on dissolution testing and, where necessary, bioequivalence studies to demonstrate that post-approval changes do not alter product performance. The comparison highlights notable differences in change classification, reporting requirements, and supporting data expectations across the regions. These findings emphasize the importance of greater regulatory harmonization and suggest that the adoption of more detailed risk-based approaches, comparability protocols, and MR-specific guidance in Korea and the GCC could improve regulatory consistency, facilitate efficient change management, and support the continued availability of high-quality pharmaceutical products.