Navigating Safety Reporting Compliance During the EU Transition from CTD to CTR

Navigating safety reporting compliance during the EU transition from CTD to CTR

As the European Union progresses from the Clinical Trials Directive (CTD) to the Clinical Trial Regulation (EU No 536/2014, CTR), it is imperative for stakeholders to grasp the evolving safety reporting requirements. From January 31, 2025, the CTR will exclusively govern all clinical trials, superseding the CTD as per Article 98. Clinical trials continuing under the CTD beyond this date must transition to the CTR framework to remain compliant. Failure to transition will result in non-compliance, potentially leading to corrective measures, penalties, and civil or criminal liability under Articles 77, 94, and 95 of the CTR.

The transition process: From CTD to CTR

Transitioning clinical trials from the CTD to the CTR involves an administrative process requiring a "transitioning application submission." Member States will conduct a minimal assessment to ensure compliance with key CTR principles, such as transparency and trial categorization. Sponsors are strongly encouraged to register their clinical trials under the Clinical Trials Information System (CTIS) as early as possible, considering the time required for the approval of transitioning applications.

Key Principles for Transition

1. Document Submission: Only documents already assessed under the CTD should be submitted to CTIS to avoid reassessment.
2. Template Updates: No need to update templates.
3. Site Suitability Forms: No requirement to retrospectively create site suitability forms.

Safety reporting requirements: During and after the Transition

The safety reporting obligations to national competent authorities (NCAs) and ethics committees (ECs) differ depending on whether the trial is governed by the CTD or the CTR during this transitional phase.

Reporting Suspected Unexpected Serious Adverse Reactions (SUSARs)

• Unified Process: SUSARs must be reported through Eudravigilance, ensuring a standardized and centralized submission process, regardless of the governing framework (CTD or CTR).

Development Safety Update Report (DSUR) submission

 For CTD Trials: DSURs must be submitted directly to the Member State that authorized the trial.

1. For CTR Trials: DSURs should be submitted centrally through the CTIS.
2. For Mixed CTD and CTR Trials: If any trial within a group falls under the CTR, submitting the DSUR to CTIS suffices. Include a cover letter listing all Member States where the trials are authorized, including those under the CTD.

Reporting to Ethics Committees (ECs)

1. For CTD Trials: Follow the established rules per CT-3 guidelines and any national legislation.
2. For CTR Trials: EC reporting is generally not required, except in certain cases like Luxembourg. Member States will decide if ECs need to be involved and how they will access relevant information.
3. For Mixed CTD and CTR Trials: EC reporting is required only for Member States where the trials fall under the CTD.

Key features and timelines of CTR

Centralization

The CTR ensures uniform application across the EU by not requiring national implementation, unlike directives. This centralization simplifies the regulatory environment and fosters a more cohesive approach to clinical trials across member states.

Clinical Trials Information System (CTIS)

CTIS serves as a central hub for all clinical trial submissions, significantly reducing administrative burdens by eliminating the need for parallel processes and enhancing communication between sponsors, Member States, and the European Medicines Agency (EMA).

Key Milestones

1. Completed Milestones:
   • January 31, 2022: The CTR took effect alongside the CTIS.
   • January 31, 2022: The CTR repealed the CTD, allowing it to remain applicable only until January 30, 2025.
   • From January 31, 2023: All new initial Clinical Trial Applications (CTAs) had to be submitted via CTIS. Ongoing CTAs under the CTD could optionally transition to the CTR.

1. Upcoming Milestone:
   • January 31, 2025: Mandatory transition for all ongoing clinical trials under the CTD with active sites in the EU/EEA to comply with the CTR.

Detailed considerations for sponsors

Ensuring Timely Transition

Sponsors must prioritize transitioning their clinical trials to the CTR framework before the January 31, 2025 deadline. This involves:

1. Early Registration: Registering trials under CTIS promptly to account for approval time.
2. Compliance Check: Ensuring all submitted documents align with the CTR requirements and principles.

Adapting to new safety reporting protocols

Understanding the nuances of safety reporting under both the CTD and CTR is essential for compliance:

1. SUSAR Reporting: Maintain consistent SUSAR reporting through Eudravigilance.
2. DSUR Submission: Differentiate between CTD and CTR trials for DSUR submissions, ensuring correct submission pathways.
3. EC Reporting: Adapt EC reporting processes based on the governing framework of the trial.

Leveraging technology and expertise

Utilizing the CTIS for centralized submissions not only simplifies the process but also enhances communication and transparency. Sponsors should invest in training and technology to navigate this system efficiently.

Seeking assistance with safety reporting?

Navigating the complexities of safety reporting during this transition can be challenging. AWINSA offers expert guidance and support to ensure compliance with both CTD and CTR requirements. Our services include:

1. Consultation and Training: Providing in-depth training on new regulatory requirements and CTIS usage.
2. Documentation Review: Assisting with the preparation and review of transition applications and safety reports.
3. Ongoing Support: Offering continuous support to ensure smooth transitions and compliance.

Contact AWINSA today to learn how we can help you manage your safety reporting obligations efficiently, ensuring your clinical trials remain compliant with evolving regulations.