The clock is ticking on EU-CTR transitions: To meet the deadline, act now

Regulatory-blog-image_100x100.jpgThis blog is part of The Regulatory Navigator series, where we explore the evolving regulatory landscape with actionable insight from Parexel's experts, sharing their experience to maximize success for clinical development and patient access.

 

EU Clinical Trial Regulation 536/2014 (EU-CTR) provides a grace period for transitioning existing studies to the Clinical Trial Information System (CTIS) platform. But with fewer than nine months until all sponsors must be in full compliance with the new regulations, thousands of clinical trials have yet to start the transition process. Studies that aren’t fully compliant by Jan. 30, 2025, risk termination in all 30 countries of the European Economic Area (EEA).

In our experience, sponsors need up to six months to transition a study using a full dossier, particularly if harmonization or a substantial amendment is needed. Slim transitions are currently allowed — and recommended by Member States concerned (MSCs) — but only until October 16, 2024.

We strongly recommend that sponsors take advantage of the slim transition opportunity, which requires fewer documents than the full transition and offers shorter timelines — though often not as short as predicted. While the official estimated timeline for slim transitions is 22 days, we’ve found that the approval process for multinational trials can take 60 days or more. And with nearly two-thirds of studies not yet in the transition process, those timelines could stretch even longer as demand on regulatory resources increases in the final months of the grace period. In the current landscape, we suggest completing all slim transition submissions by September at the latest.

Parexel recently presented a webinar to help sponsors navigate this complex and consequential process. Our regulatory experts shared insights into EU-CTR requirements and actionable recommendations for best complying with them. For the most successful trial transitions, we’re urging sponsors to:

Ensure document alignment. As part of any transition application, a sponsor must either harmonize or consolidate the study protocol, investigator's brochure (IB), and the investigational medicinal product dossier (IMPD). Harmonized documents are identical to those already approved by MSCs under EU-CTD, the precursor to EU-CTR. In a harmonization, all trial procedures are identical for studies in all Member States. Consolidated documents, on the other hand, may include MSC-specific procedures in an appendix. Submitting harmonized documents will make it simpler to modify the trial in the future but if harmonization — a lengthy process — has not already taken place, we recommend opting for document consolidation instead.

Prepare all elements of a slim transition dossier. A dossier for slim transition should be based on the latest version of the dossier authorized under EU-CTD. Part I of the dossier must include the harmonized or consolidated protocol, IB and IMPD; good manufacturing practice (GMP) documentation; and documents related to non-authorized auxiliary medicinal products (AxMPs) and modified AxMPs. Part II must include approved versions of the participants’ information sheet and the informed consent form.

The slim transition dossier must also include a cover letter, proof of payment, a list of sites participating in the ongoing trial, and a General Data Protection Regulation (GDPR) statement. When drafting the cover letter, we recommend referring to the cover letter template adopted by the Clinical Trials Coordination Group (CTCG), as it includes a required statement regarding compliance with regulatory guidance.

To help expedite review, we strongly recommend that sponsors include in the dossier only the required information and documents. If Member States need additional information, sponsors can provide it upon request.

Be strategic in proposing a Reporting Member State: When submitting an application dossier for a multinational trial, a sponsor should propose one MSC to be the Reporting Member State (RMS) — a request that will be evaluated and decided on by all involved MSCs. Because the RMS is responsible for leading the assessment of Part I of the transition dossier, sponsors should propose an RMS with a history of expedient reviews. In about half of all EU-CTR transitions that Parexel has helped lead, we’ve worked with Spain, Germany, or France as RMS. These countries, in our experience, have among the lowest average times from submission to conclusion.

Create a plan for substantial modifications: If a study will be changed in a way that substantially impacts the safety or rights of patients or the reliability and robustness of the data generated, the sponsor must submit a substantial modification (SM) for approval. Sponsors can apply for such approval prior to EU-CTR transition, but we have seen some unexpected delays in pre-transition reviews. Sponsors should be prepared to withdraw any SM applications that cannot be completed in time for transition.

If sponsors plan to apply for post-transition SMs, they should prepare SM documentation in tandem with the transition application to expedite the process and ensure consistency within documentation. SMs are not permitted during transition but sponsors may implement non-substantial changes in accordance with Annex IV of EudraLex Volume 10.

Be aware of unpublicized MSC-specific requirements: We have found that some Member States use the request-for-information (RFI) process to require sponsors to submit documentation specific to that country.

  • Belgium requires the scientific protocol synopsis in French and Dutch.
  • Czechia (the Czech Republic) requires that its fee be paid through RFI.
  • Greece requires that sponsors register all study vendors that will provide clinical trial-related services within Greece.
  • Hungary requires that some documents be provided in both Hungarian and English.
  • Italy requires a stamp duty payment.
  • Poland requires the completion of documents associated with the Polish Protection Act and a new insurance measure.
  • Spain sometimes requires the data safety monitoring board (DSMB) charter and scientific protocol synopsis in Spanish.

Perhaps most importantly, we’re advising sponsors to include sites and vendors in the process from the start as every stakeholder will have a role in the success of a transition.

A partner like Parexel can also contribute to a transition’s success. We have more than 200 regulatory leads in all time zones supported by more than 4,000 regulatory professionals, including CTIS submission specialists. As we approach the deadline for submissions, we can help sponsors take advantage of these final months for action. To date, we have been instrumental in more than 350 EU-CTR applications, including 110 transitions, with 65 approved as of April 2024.

For more on the transition process, our webinar is available on demand. And if you need more personalized advice, our experts can help. Contact us to discuss your options for managing the transition and keeping your studies on track.

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