Legislative context for COMBINE
In the EU, there are legal requirements for the individual authorisation processes of:
- clinical trials of medicinal products
- clinical investigations of medical devices
- performance studies of in vitro diagnostics (IVDs).
The requirements are laid out in Regulation (EU) 536/2014 on clinical trials on medicinal products for human use (CTR), Regulation (EU) 2017/745 on medical devices (MDR) and Regulation (EU) 2017/746 on in vitro diagnostic medical devices (IVDR) respectively.
These Regulations are applied together to develop innovative treatments that combine medicinal products with medical devices or in vitro diagnostics (IVDs). The COMBINE programme addresses the interface between the three Regulations.
Combined studies
In this context, combined studies can be understood as studies that involve:
- a clinical trial of a medicinal product in parallel with a performance study of an in vitro diagnostic
- a clinical trial of a medicinal product in parallel with a clinical investigation of a medical device.
The ‘COMBINE’ initiative
The Member States’ competent authorities for clinical trials and medical devices and the European Commission launched the COMBINE initiative in June 2023, with the aim of:
- analysing the root causes of the challenges encountered by sponsors in conducting combined studies
- identifying possible solutions.
The initiative involves representatives of Member States’ competent authorities, the European Commission, medical research ethics committees, the European Medicines Agency and relevant stakeholders from both the medicinal product and the medical device sectors.
The groups affiliated with this project are the Medical Device Coordination Group and relevant clinical trial groups (Clinical Trials Coordination Group, Clinical Trials Coordination and Advisory Group).
The initiative includes two phases:
- analysis of the challenges at the interface of MDR/IVDR/CTR (including collecting and analysing the challenges reported by various actors involved, mapping relevant national processes and already ongoing work)
- possible development of solutions that aim to address some of the challenges.
Deliverables
COMBINE completed its first phase with the publication of the analysis report in May 2024, which includes proposals for possible solutions to address the most important issues.
In December 2024, the Member States endorsed the strategy for the second phase, which is organised as a programme consisting of several projects. This programme will develop some of the solutions presented in the analysis report.
In June 2025, a pilot coordinated assessment process for multinational combined studies was launched as part of Project 1 of the COMBINE programme. The pilot is expected to streamline the authorisation process, reduce administrative burden for sponsors and accelerate patient access to innovative treatments.
Next steps
The projects within the COMBINE programme are progressing according to the timelines set out in the strategy. Progress will be reviewed regularly, and updates will be published on this page.
Background
The presentations below include further information on the initiative’s background, parties involved, the highlights of the analysis phase and the COMBINE programme strategy.
Before this project, the Member State competent authorities on clinical trials and IVDs jointly endorsed a guidance document about the status of assays used in clinical trials of medicinal products.
MDCG 2022-10 Q&A on the interface between Regulation (EU) 536/2014 on clinical trials for medicinal products for human use (CTR) and Regulation (EU) 2017/746 on in vitro diagnostic medical devices (IVDR)
