In the European Union, there are different regulatory requirements for clinical trials of medicinal products, clinical investigations of medical devices, and performance studies of IVDs. The applicable regulations are Regulation (EU) 536/2014 on clinical trials of 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), depending on the case.
When a medical device or IVD involves the use of a medicinal product, or vice versa, these requirements may apply together. In such cases, the study is called “combined study”. Specifically, combined studies are studies that include:
- A clinical trial of a medicinal product in parallel with a performance study of an in vitro diagnostic medical device
- A clinical trial of a medicinal product in parallel with a clinical investigation of a medical device
Competent authorities have been receiving an increasing number of questions on the design and submission of clinical trials with candidate investigational medicinal products used together medical devices or IVDs. Similarly, the requirements for clinical investigation or performance studies conducted with a medicinal product have been object of many questions for competent authorities of medical devices and IVDs. Additionally, there has been concern over the delays in conducting such studies caused by the regulatory complexity of the combination of requirements from three regulations.
In this context, a recent report published by the European Commission analyses the challenges presented when conducting combined studies.
Core obstacles: regulatory complexity and lack of alignment
The report published by the Commission includes the results of the COMBINE project launched in June 2023 conducted among different stakeholders and authority groups. The project aimed to address the mentioned challenges and clarify and align intersections between clinical trials of investigational medicinal products, performance studies of in vitro diagnostics, and clinical investigations of medical devices.
Essentially, the report highlights that the main challenges derive from a lack of alignment between the three regulations involved, such as different rules and criteria for clinical research and when this is required. Documentation, timelines, processes, and applications also differ, and conducting a study implies assessing all these requirements first and reconciling the differences. Notably, these three regulations – CTR, IVDR, and MDR – are relatively new and still under implementation.
As mentioned, understanding the dense regulatory landscape and related uncertainty in applying the correct provisions cause delays in conducting such studies. In this respect, additional complexity is posed by further national requirements or interpretations, which lead Member State to ask for specific territorial requirements, protocol amendments, positions, and application processes. Inevitably, this results to be particularly burdensome for multinational combined studies.
Survey among Member States: highlighted results
Conducted among all EU countries and Norway, the results includes replies from 24 Member States. Some of the highlighted findings include:
- About 15 Member States have the same regulator authority that deals with clinical trials of medicines, clinical investigations of medical devices, and performance studies of IVDs.
- Approximately 15 Member States have at least one ethics committee entity that can give an opinion on all three types of study.
- Competent authorities of 14 Member States offer advice to sponsors of combined studies prior to application.
- Competent authorities of 14 Member States offer pre submission meetings prior to the application of combined studies (10 of these free of charge).
- Three Member States indicated that only one ethics application is sufficient for combined studies involving clinical trials in their country.
- Currently no Member State responding to the survey accepts a single competent authority application for combined studies which involve a clinical trial.
In conclusion, the report outlines that improving coordinated assessment could have a positive impact on the conduction of combined studies, solving a great part of the issues highlighted by the COMBINE project.
Do you have any questions on how to conduct clinical studies in the EU? Contact us.
References:
European Commission (2024) Combined studies. Retrieved on 17.05.2024.
European Commission (2024). ‘COMBINE’ project – analysing the regulatory landscape for combined studies on the IVDR/MDR/CTR interface. Retrieved on 17.05.2024.
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