Understanding the EU Clinical Trials Regulations Updates

The updated European Union (EU) pharmaceutical legislation for the Clinical Trials Regulation (CTR) entered into application on January 1, 2022. The CTR aligns processes for the assessment and supervision of clinical trials throughout the EU. These updated requirements were designed to ensure a standardized approach for conducting clinical research, while emphasizing clinical trial participant safety and heightened public transparency requirements. These new regulations have significant implications for sponsors submitting trials in the EU. This blog outlines these changes and their implications.

Transitioning to EU CTR

EU Clinical Trial Regulation 536/2014 (EU CTR) replaces the EU Clinical Trial Directive (Directive 2001/20/EC). There is a three-year transition period:

Previously, sponsors had to submit clinical trial applications separately to national authorities and ethics committees (ECs) in each country to gain regulatory approval to run a clinical trial. Over the next three years, the Clinical Trial Information System (CTIS) will become the single-entry point for researchers and companies conducting clinical trials in the EU. Sponsors can apply for authorizations in up to 30 EU and European Economic Area (EEA) countries through a single application. Effectively, the single application becomes a one-stop-shop.

Submitting New Trials

Within the first year of the implementation, sponsors will have the option of submitting new trials under the current directive (2001/20/EC) or to the EU CTR before submissions under the EU CTR becomes mandatory. The EU CTR will allow sponsors to submit one combined CTA to the competent authorities (CAs) and Ethics Committees (ECs) for all EU countries intending to participate in each trial, via the CTIS. The application will entail a two-part process:

• Part I: A reporting member state (RMS) coordinates a scientific assessment
• Part II: Member state specific assessment

Understanding the Timelines of Clinical Trial Approvals

Parts I and II of the dossier can be reviewed in parallel or sequentially, depending on the sponsor’s preference. Clinical trial approvals will be released as a single member state opinion following both the CA and EC assessment per country, rather than the current process of separate CA and EC approvals, in accordance with individual country processes and timelines.

Transition of all ongoing clinical trials to the new EU CTR needs to be completed within three years of its implementation as part of a clinical trial development plan. Documents such as the protocol, investigators brochure, and investigational medicinal product dossier will need harmonization or consolidation across the EU prior to transition.

The EU CTR will have less flexibility in the way substantial modifications (SMs) are submitted. Under the new regulations, SMs will take about three months for approval. No additional SMs can be submitted during this time. This includes the addition of EU member states, making a country selection, and the associated submission strategy key factors for success.

In addition to significantly simplifying submission processes for trials taking place in multiple countries at the same time, it also facilitates participant recruitment through the easy expansion of a trial to additional member states. CTIS includes a public portal, showing which trials are open to recruiting participants, giving contact points for further information. This will make it easier for participants to find opportunities to take part in clinical research.

Additional Developments

Building on the CTR application, the launch of CTIS, and the Accelerating Clinical Trials (ACT) EU, these new requirements will strengthen the European environment for clinical trials, while maintaining high safety standards for trial participants and improved public transparency for EU citizens or diagnose diseases.

References:

• A new era for clinical trials in the EU by Emer Cooke, Executive Director of the European Medicines Agency,  Published on January 31, 2022 https://www.linkedin.com/pulse/new-era-clinical-trials-eu-emer-cooke/?trackingId=os3pZCA1QgSCjD6lh%2BpWXQ%3D%3D
• Article in regulatory rapporteur: Clinical Trial Information System: overview, opportunities and challenges, Vol. 19, No. 1, January 2022 (attached)
• The European Union (EU) Clinical Trials Regulation 536/2014/EU
• https://mhrainspectorate.blog.gov.uk/2022/02/10/new-year-new-standards-for-investigational-medicines/
• Detailed Commission guidelines on good manufacturing practice for investigational medicinal products for human use, pursuant to the second subparagraph of Article 63(1) of Regulation (EU) No 536/2014  https://ec.europa.eu/health/system/files/2017-12/guideline_adopted_1_en_act_part1_v3_0.pdf

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