Transitioning From CTD to CTR

EU Clinical Trial Regulation

The regulation allows for a transition period of three years after the date of applicability for trials already in progress.

For ongoing studies which close before January 31, 2025, there are no additional requirements under the CTR. All studies ongoing after this date must comply with the CTR, with the deadline for transition application to fall at the end of November 2024. The figure on the right provides an overview of this timeline.

Date of application and transition period

Steps Required for Transitioning Ongoing Studies

1. Sponsor Evaluation

Evaluate your clinical trial’s current compliance with the Clinical Trial Regulation and identify the need for transition
Determine whether the dossier needs to be harmonized between Member State Committees
Confirm if the clinical trial is eligible for transition (no pending/ongoing assessment in any EU or EEA countries)

2. Harmonization

Harmonize dossiers via SA application according to CTD

3. Transition

Make formal application for transition (simplified dossier, no re-assessment!) in the new Clinical Trial Information System
A new cover letter and new application form module are required to be completed in CTIS (see following page)
For multinational clinical trials: Sponsor’s declaration that part I/part II documents do not contain significant differences/are identical to the versions approved by each Member State (as applicable)

The standard timeline for the review of the transition application is 60 days.

During this period, the trial cannot be amended. If and when the trial undergoes the next substantial modification following the date of applicability, the full requirements of the new CTR will apply.

Documents required to be uploaded in the CTIS for transition (Part 1)

New cover letter

New application form

Sponsor’s declaration that part I/part II documents are similar/identical

Consolidated/Harmonized protocol

GMP relevant documents

New labels for primary packaging (if the expiry date is not listed on the primary packaging)

IMPD

Documents related to auxiliary medicinal products, submitted for the assessment in the context of the initial application (if applicable)

Documents required to be uploaded in the CTIS for transition (Part 2)

ICFs

ECs opinion

Blank pages, as applicable

Special Case: Transitioning Clinical Trials Included in VHP

The EU CTR isn’t the first attempt to simplify the regulatory submission process in the EU. In 2004, the Heads of Medicines Agencies launched the Clinical Trial Facilitating Group (CTFG) to coordinate the implementation of Directive 2001/20 EC across Member States. The CTFG introduced the Voluntary Harmonization Procedure (VHP) pilot project in 2009, making it possible for sponsors to obtain a coordinated assessment when applying for a clinical trial in several European countries [4].

The VHP project will close when the EU CT Regulation comes into force. As of October 15, 2021, no initial clinical trial applications or substantial modifications applications via VHP will be accepted by the VHP administrator. Clinical trials approved via VHP will qualify to transition as multinational CTs to the CT Regulation

through the process outlined above in “Steps Required for Transitioning Ongoing Studies.” Some additional points worthy of note include:

Assessment from Sponsor still required
If a harmonized protocol does not exist, the sponsor must prepare one consolidated protocol reflecting acceptable differences in authorized national trials
For CTs approved via VHP, the MS of the VHP Ref-NCA becomes the Reporting MS

To benefit from harmonization, a sponsor should transition trials as soon as possible after the regulation comes into force – and at the latest before any new submission concerning a trial (such as a substantial amendment).