As the January 31, 2025, deadline approaches for active clinical trials to transition to the European Union Clinical Trial Regulation (CTR), sponsors who wish to continue trials in EU member states beyond this date faced an October 16, 2024 submission deadline for regulatory review. This transition, governed by the EU Clinical Trial Directive 2001/20/EC for over two decades, aims to streamline trial applications and enhance patient engagement.
In January 2022, the EU CTR was established to provide trial sponsors with a single application submission process for trials in EU member states while advocating for stronger patient engagement. The regulation also included a three-year period for ongoing trials to transition to the new requirements.
EMA's Efforts to Simplify Transition
From January 31, 2022, to January 30, 2023, sponsors could submit clinical trials under either the EU CT Directive or the EU CTR. Data indicated a preference for the established CTD processes, with 80% of trials uploaded to the EudraCT database during that period. However, the European Medicines Agency (EMA) estimated that up to 4,000 ongoing trials would need to transition to EU CTR to continue beyond January 30, 2025.
In July 2023, the EMA issued new guidance to simplify the transition, which included:
- Not requiring document templates to be updated for CTR submission.
- Providing guidance on defining 'active sites' for transition.
Late in 2023, the EMA revised rules on publicly available trial documentation, reducing requirements for publishing information on the EU Public Portal. Effective June 2024, this revision encouraged sponsors to transition trials, particularly with the removal of the deferral mechanism that previously allowed sponsors to delay publication of specific data and documents for up to seven years after trial completion to protect commercially confidential information.
Open Communication and Sponsor Guidance
Given the novelty of CTR requirements, nuances arose during trial transitions, including ongoing revisions, potential transparency liabilities, and CTIS technical insights. Experts in ongoing discussions with the EMA and country-specific regulators played a crucial role in ensuring sponsors and CRO teams remained informed and adaptable.
Throughout the transition, dialogue with the EMA and member state regulatory agencies was essential. CROs familiarized themselves with the EMA Service Desk, which offered assistance in resolving technical issues within CTIS, providing live support, and maintaining a list of known issues with resolution steps.
CRO's Role in Prioritizing Transition Strategies
With many sponsors focused on new trial submissions, CRO partners provided guidance to prioritize transition strategies for active trials before the deadline. Experienced study start-up managers, regulatory experts, and operational leads collaborated to consolidate and disseminate EMA guidance to sponsors and team members.
This involved:
- Conducting regular training sessions and providing materials on transition needs and EMA updates.
- Hosting open forums for CRO team members to discuss transition strategy pain points, lessons learned, and best practices.
- Ensuring clear understanding among CRO team members and sponsors regarding roles, responsibilities, and timeframes.
- Creating template documents for trial submission packages.
- Communicating regularly with sponsors regarding transition needs, accommodating plans for other submissions, and addressing potentially unrealistic expectations.
Consequences of Non-Compliance
The EU Commission's May 2024 guidance emphasized that trials not successfully transitioned before the deadline would breach the regulation, potentially subjecting sponsors to corrective measures, penalties, and civil or criminal liability.
Future Implications
As the trial transition deadline approaches, CROs assisting sponsors must continue to monitor the regulation's evolution and its impact on clinical programs. Sponsors and CROs should remain informed, adaptable, and apply best practices to meet future regulatory requirements and changes effectively.
