Transitioning from the Directive to CTR

The Sponsor/Investigator is reminded that the deadline for transferring clinical trials from the Directive to the EU Regulation is approaching. The deadline is 30 January 2025. We therefore encourage the Sponsor/Investigator to familiarize themselves with the information below and to plan and prioritize well in advance if there are ongoing trials authorized under the Directive that need to be transferred to the EU Regulation.

Which trials should be transferred to the EU Regulation?

Ongoing trials that have not been completed by 30 January 2025 must be transferred to the EU Regulation. If the transfer has not been approved by 30 January 2025, the trial must be stopped, otherwise, it will be conducted illegally.

Trials that have active sites must be transferred to the EU Regulation. An active site means that there has not been a Last Patient/Last Visit (LPLV) and that trial-specific activities with trial participants are still taking place at the site. If it is a multinational trial where there are no longer active sites in Denmark, according to the above, but which is still ongoing in other member states, the trial must only be transferred to the EU Regulation in these countries. If it is a mononational trial where the Danish Medicines Agency has received notification of trial termination (LPLV), the trial does not need to be transferred to the EU Regulation.

Before the trial is transferred to the EU Regulation

All applications for substantial amendments (protocol amendments) for trials under the Directive must be completed before transfer. Remember to account for the processing time at the Danish Medicines Agency and the Scientific Ethical Medical Committees (MREC). If the submission is clearly marked "Preparing for transition", both authorities will try to prioritize expedited processing.

For multinational trials, it must be ensured that all documents in Part I of the application are harmonized or consolidated. This means that the protocol must be identical in all member states, or any national differences must be included in the protocol (as a single document). Additionally, the Investigator's Brochure and the Investigational Medicinal Product Dossier may need to be harmonized or consolidated before transfer. See CTCG's best practice below.

If harmonization results in significant changes to the documentation, these must be approved as substantial amendments (protocol amendments) prior to transfer. Remember to take into account the processing time at the Danish Medicines Agency and MREC. If the submission is clearly marked "Preparing for transition", both authorities will try to prioritize expedited processing.

If the changes are not significant, it must be clarified in the cover letter when submitting the application for transfer. The cover letter must also state which versions of the documents have previously been approved under the Directive, as well as the approval date for these and which Scientific Ethics Committee has approved the trial under the Directive. See also the template for the cover letter below.

Application for transfer to the EU Regulation

It has been agreed between the EU member states that the actual processing of "transitioning applications" will be shortened to one week after the application has been declared valid - typically about 32 days from submission, as the application must first be validated. However, longer processing times may apply in the event of significant deficiencies in the submitted material in Part II. Note that the application must be approved and not just submitted by 30 January 2025.

A number of guidelines have been prepared for use in applications for transfer to the EU Regulation:

Updating the application in accordance with the regulation's requirements

When submitting the first Substantial Modification (SM) after the transition to CTR:

Part I: All documents of the application must be updated to comply with the requirements for CTR.

Part II in Denmark: Only documents that are changed as a result of the submitted SM need to be updated. Other documents can remain as submitted under the transition application, including "placeholder documents". In Denmark, there is no requirement to complete the Part II dossier, including filling out and submitting CTR templates at the first SM after transition. See here for further guidance.

The sponsor may delay submitting the first SM until there are planned changes for the dossier, however, all Part I documents must be updated before applying for the addition of a new member state to the trial.

A number of guidelines have been prepared for use in application for the first SM after the transition to CTR:

Stay updated

From now on, you can specifically subscribe to the Danish Medicines Agency's news about clinical trials. The newsletter subscription is available here: Subscribe to newsletters (laegemiddelstyrelsen.dk)

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Last updated 10-04-2024

Please note that the text on this page has been translated with the help of AI. If you find any errors in the text or something is unclear, please contact us for clarification.

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