Transition of clinical trials from Directive to Regulation

11 June 2024

DKMA reminds that the deadline for the transition of clinical trials from the Directive to the EU Regulation is January 30, 2025. We therefore encourage Sponsor/Investigator to read the information below and prioritize in good time if there are ongoing trials under the Directive that need to be transitioned to the Regulation.

 

Which trials should be transitioned to the EU Regulation?

Ongoing trials that have not been completed by January 30, 2025 must be transitioned to the Regulation. If the transition has not been authorised by January 30, 2025, the trial must be stopped, otherwise the trial will be conducted illegally.

Trials that have active sites must be transitioned to the Regulation. An active site means that there has been no Last Patient/Last Visit (LPLV) and that trial-specific activities with trial participants are still taking place at the site. In the case of a multinational trial, where there are no longer active sites in Denmark (see above) and the trial is still ongoing in other member states, the trial must only be transitioned to the Regulation in these member states. For mononational trials where DKMA has received End-of-trial notification (LPLV), the trial should not be transitioned to the Regulation.

Before the trial is transitioned to the EU regulation

All applications for substantial amendments (protocol amendments) for trials under the Directive must be completed before transition. Remember to consider the assessment times for the Danish Medicines Agency and the Danish Medical Research Ethics Committees (VMK). If the submission is clearly marked "Transition", both authorities will try to prioritize expedited processing.

For multinational trials, ensure that all documents in Part I of the application are harmonized or consolidated. This means that the protocol must be the same in all member states or that any national differences must be stated in the protocol (as a single document). In addition, the Investigator's Brochure and Investigational Medicinal Product Dossier need to be harmonized or consolidated before transition. See CTCG best practice below.

If harmonization results in significant changes to the documentation, these must be approved as substantial amendments (protocol amendments) before transition. Remember to consider the assessment times for the Danish Medicines Agency and the Danish Medical Research Ethics Committees (VMK). If the submission is clearly marked "Preparing for transition", both authorities will try to prioritize fast processing.

Non-Substantial changes should be mentioned clearly in the cover letter in the transition application. The cover letter should also state which versions of the documents that have previously been approved under the Directive and the approval date and it should state which Research Ethics Committee there has approved the trial under the Directive. See also the template for the cover letter below.

Application for transition to the EU Regulation

The EU member states has agreed that the processing of transitioning applications will be shortened to one week after the application has been declared valid. Typically about 32 days from submission including time for validation. However, the processing times can be extended in case of major deficiencies in the submitted material in Part II. Please note that the application must be authorised and not just submitted by January 30, 2025.

A number of guidance have been prepared for transition to the EU regulation:

 

Requirements for updating the application according to the EU Regulation:

First Substantial Modification (SM) after transition to CTR:

Part I:

All documents must be updated to meet the requirements for CTR.

Part II in Denmark:

Only documents that has been changed as a result of the submitted SM need to be updated. Other documents can be left as submitted during the transition application, including placeholder documents. In Denmark, there is no requirement to complete the Part II dossier, including completing and submitting CTR templates at the first SM after transition. Further guidance can be found on the VMK website.  

The sponsor can wait to submit the first SM until changes are planned for the dossier, however, all Part I documents must be updated before an additional member state submission.

A number of guidance have been prepared for applying for the first SM after transition to the EU Regulation:

  • The CTCG Best Practice Guide for sponsors – first substantial modification Part I after CTR transition, and its two annexes, provide guidance for sponsors on harmonised requirements agreed by CTCG members for updating Part I documents in line with the Clinical Trials Regulation at the time of the first SM Part I after a minimum trial dossier was transitioned from the Clinical Trials Directive to the Clinical Trials Regulation. The latest version of the documents can be found under the header “Key Documents List”