Pathways to first clinical use of a medical device in the United States and European Union - a narrative review.

Abstract

INTRODUCTION The number of medical devices entering global markets continues to grow, creating challenges for regulators seeking to balance patient access and protection of public health. The United States (US) and the European Union (EU) represent the two predominant regulatory systems for medical devices, yet they differ significantly in pathways to first clinical use and early patient access structure and implementation. AREAS COVERED This narrative review examines specialised regulatory pathways that enable or accelerate first clinical use of medical devices outside standard market approval processes in the US and EU. Regulatory legislation, guidance documents, and policy materials from the US Food and Drug Administration and the European Commission were analysed. Pathways reviewed include compassionate use and expanded access mechanisms, expedited programmes such as the Breakthrough Device Program, humanitarian and orphan device pathways, and exemptions for custom-made or in-house manufactured devices. Key characteristics, including eligibility criteria, clinical evidence requirements, and regulatory oversight are compared across jurisdictions. EXPERT OPINION The US framework provides more structured and centralised specialised pathways with extensive regulator-developer engagement, whereas the EU system remains decentralised and less harmonised. Greater clarity in clinical evidence requirements, improved harmonisation, and earlier regulatory engagement could strengthen EU pathways while maintaining patient safety.