Navigating Regulatory Scrutiny in Combined Clinical Trials

This article is a technical report that examines the regulatory challenges associated with combined clinical trials involving in vitro diagnostic (IVD) medical devices and investigational medicinal products (IMPs) under the EU's Clinical Trial Regulation (CTR) and In Vitro Diagnostic Regulation (IVDR). It outlines the complexities faced by sponsors in navigating dual submission processes and highlights the increasing regulatory scrutiny that has emerged since the implementation of the IVDR. The authors analyze common requests for information (RFIs) issued by national competent authorities (NCAs) and ethics committees (ECs) during the review of performance studies. They provide practical guidance and actionable recommendations for managing RFIs effectively, focusing on key documentation types and recurring themes such as risk analysis, document consistency, and scientific validity. The report aims to support regulatory professionals in enhancing submission quality and compliance while addressing the fragmented regulatory landscape across EU Member States.