EU Clinical Trial Regulation: What, When, Who, Why, How?

The long-anticipated European Union (EU) Clinical Trial Regulation (Regulation (EU) No 536/2014) (CTR), intended to improve and coordinate the submission and review process for clinical trials via a centralized portal, is finally knocking at our doors.

What: The way clinical trials are conducted in the EU will undergo a major change when the CTR comes into effect. The CTR will replace the European Clinical Trials Directive (2001/20/EC). The regulation harmonizes the assessment and supervision processes for all clinical trials throughout the EU, via the Clinical Trials Information System (CTIS). CTIS will contain the centralized EU portal and database for clinical trials foreseen by the regulation. The European Medicines Agency (EMA) has set up and will maintain CTIS, in collaboration with the Member States and the European Commission (EC).

When: Full functionality of CTIS through an independent audit occurred as an essential validation step. On 21 April 2021, following the audit, EMA’s Management Board confirmed that CTIS is fully functional and meets the functional specifications. In a next step, the EC will confirm that the conditions set by the regulation are met via a notice to be published in the Official Journal of the European Union. The aim is that CTIS goes live on 31 January 2022, six months after this notice. Progress updates are available here.

Who: When the regulation becomes applicable, it will repeal the existing EU Clinical Trial Directive (EC) No. 2001/20/EC and national legislation that was put in place to implement the directive. The new regulation will apply to trials authorized under the previous legislation if they are still ongoing three years after the regulation has come into operation. The authorization and oversight of clinical trials remains the responsibility of Member States, with EMA managing the CTIS and supervising content publication on the public website.

Why: The goal and benefit of the CTR is to create an environment that is favorable to conducting clinical trials in the EU, with the highest standards of safety for participants and increased transparency of trial information. The regulation requires consistent rules for conducting clinical trials throughout the EU and that information on the authorization, conduct and results of each clinical trial carried out in the EU is made publicly available.

This approach is expected to increase the efficiency of all trials in Europe, with the greatest benefit for trials conducted in multiple Member States. It aims to foster innovation and research, while helping avoid unnecessary duplication of clinical trials or repetition of unsuccessful trials. The key benefits of the regulation include:

• Harmonized electronic submission and assessment process for clinical trials conducted in multiple Member States
• Improved collaboration, information-sharing and decision-making between and within Member States
• Increased transparency of information regarding clinical trials
• Highest standards of safety for all participants in EU clinical trials

How: The CTIS will be the single entry point for submitting clinical trial information in the EU. EMA will make information stored in CTIS publicly available in line with pre-established transparency rules. The clinical trial application form and supporting dossier will cover all regulatory and ethics assessments from the Member States concerned, as well as the public registration of the clinical trial and subsequent updates. The system will:

• Support the day-to-day business processes of Member States and sponsors throughout the lifecycle of a clinical trial in a user-friendly way
• Provide regulatory oversight of clinical trials and tools for supervision and monitoring
• Contain collaboration tools as well as workflow and document management capabilities accessible via individual workspaces, the Sponsor Workspace and the Authority Workspace
• Enable members of the public to access detailed information on all clinical trials conducted in the EU, in all official EU languages, through a dedicated Public Website

The Sponsor Workspace will assist companies that run clinical trials in preparing and compiling data to submit to the system for assessment by Member States via the following functions:

• Manage users and user roles within that company
• Compile clinical trial application dossiers for new and updated trials
• Cross-reference product documents in other clinical trials
• Upload documents for clinical trial application submission
• Receive alerts and notifications for ongoing trials
• Respond to requests for information and view deadlines
• Search and access clinical trials
• Record clinical trial results

The Authority Workspace will support the activities of Member States and the EC in overseeing clinical trials, allowing Member States to:

• Manage users and user roles within their organizations
• View clinical trial application dossiers
• Manage tasks related to the assessment of clinical trials
• Collaborate within and between member states
• Receive alerts and notifications for ongoing trials
• Download documents submitted by clinical trial sponsors
• Record inspections of sites and clinical trials

The Public Website will provide the following features:

• Overview of clinical trial statistics
• Advanced search
• Download data and reports
• Site updates and announcements

To conclude, although adapting to the CTR will require a learning curve and an initial operational load, the EU CTR overall presents numerous advantages to both drug developers and regulatory assessors. Through our team of experts here at Allucent, we can help ease the CTR transition by staying on top of appropriate protocol language, updated safety-reporting requirements and efficient processes to publish trial results using CTIS.

Contact us today.