Bridging Innovation and Regulation: A Lifecycle Approach to Complex Drug-Device Combination Products

Abstract

This review provides an integrated lifecycle framework for complex drug-device combination products, focusing on regulatory innovation, formulation science, and post-approval flexibility. Products such as transdermal drug delivery systems (TDDS), inhalers, prefilled syringes, autoinjectors, implantable systems, and other advanced delivery platforms are becoming increasingly important because they combine drug action with device-based delivery. Their clinical performance depends on both the active ingredient and how formulation, device materials, manufacturing, delivery, and patient use interact. As a result, traditional regulatory methods that assess drugs and devices separately may not fully address the complexity of these integrated products. This review examines three interconnected areas that shape how combination products are developed and managed throughout their lifecycle, namely global regulatory reliance and convergence, critical quality attributes driven by formulation and materials, and the management of post-approval changes using comparability protocols. Regulatory reliance and convergence help reduce redundant work, streamline scientific reviews, and improve access to medicines and devices across regions. The choice of monomers and polymers in TDDS, for example, affects adhesion, cohesion, drug release, stability, residual monomers, and patient safety. Comparability protocols provide a clear way to address anticipated post-approval changes in chemistry, manufacturing, and controls while maintaining product quality and performance. This article brings together regulatory strategy, product design, the identification of critical quality attributes, analytical testing, and lifecycle change management to propose a framework that connects innovation with regulation. This approach can make development more predictable, provide stronger scientific support, help with efficient global reviews, and promote ongoing improvement after approval.