Brief introduction to the CT Regulation

Several years after enactment the Regulation EU/536/2014 (CT Regulation) governing clinical trials with medicinal products in the EU eventually became applicable on 31 January 2022. After a certain transition period, the CT Regulation will fully replace the former Clinical Trials Directive (2001/20/EC) (“CT Directive”) and the implementing laws in the member states. The CT Regulation aims to create a harmonized regulatory environment favourable for conducting clinical trials in the European Union. While the CT Regulation is directly applicable in the member states, national laws are still required to fully govern clinical trials. Because the CT Regulation comes with various changes, there will be a transitional period.

Overview on the transitional period

There are four decisive time points in transitioning from the CT Directive to the CT Regulation:

1. Clinical trial applications submitted before 31 January 2022 can stay under the CT Directive for further 3 years.
2. Between 31 January 2022 until 31 January 2023, sponsors can choose to submit applications for new trials either under the CT Directive or under the CT Regulation.
3. From 31 January 2023, all applications for new trials will need to be submitted following the requirements of the CT Regulation.
4. Finally, from 31 January 2025 the CT Regulation will have fully superseded the CT Directive.

Any required transition of a clinical trial from the CT Directive to the CT Regulation needs to be well prepared, since such trial will need a new authorization under the CT Regulation. Please read in the following for more details.

Request for authorization submitted before 31 January 2022

• Ongoing trials and clinical trials, for which the authorization request was submitted before 31 January 2022, can remain under the CT Directive for a period of 3 years, i.e. until 31 January 2025 (Article 98 (1) CT Regulation). They will either have to be completed by 31 January 2025 or they will need to be transitioned to the CT Regulation until that point in time.
• Long-term clinical trials that have even started prior to the CT Directive and are not in line with the requirements of the CT Directive do not benefit from the transitional provision. Their setting needs to be assessed together with the possibilities on how to handle such trials.

Request for authorization submitted on or after 31 January 2022

• Between 31 January 2022 until 31 January 2023 clinical trial applications can be submitted under the CT Directive or under the CT Regulation giving the sponsor flexibility to either gain first experience with the CT Regulation or to stay under the familiar framework of the CT Directive for a bit longer (Article 98 (2) CT Regulation).
• For clinical trials still authorized under the CT Directive, the CT Directive remains applicable until 31 January 2025. Until then, these clinical trials will again either need to be completed or they will need to have transitioned to the CT Regulation.
• 31 January 2025 will mark the date for all transitions to the CT Regulation and the retirement of the CT Directive.
• In case the sponsor chooses to submit a clinical trial application under the CT Regulation before 31 January 2023, these clinical trials authorized under the CT Regulation will only be subject to the CT Regulation.
• From 31 January 2023 all requests for clinical trial authorizations will need to be submitted under the CT Regulation.

Careful planning for clinical trials subject to transition

All clinical trials still conducted under the CT Directive with at least one active site in the EU will have to be transitioned to the CT Regulation by 30 January 2025. Such transition to the CT Regulation will need to be carefully prepared for as – in order to transition – a new authorization under the CT Regulation is required. In case the clinical trial does not yet meet the requirements under the CT Regulation, a substantial amendment request under the CT Directive will be necessary in the respective Member States. Hence, from a planning perspective, not only do the timelines set out for the clinical trial authorization under the CT Regulation need to be considered, but also the time required to submit a substantial amendment request to the respective national authorities under national law. According to the current guidance provided by the European Commission, an authorization under the CT Regulation will not be possible while there are still pending/ongoing assessments in the relevant member states. This will also pose a challenge for clinical trials where the need for an urgent substantial modification arises during the authorization process under the CT Regulation). You may also want to refer to the “Questions & Answers” to the Clinical Trials Regulation (EU) No 536/2014, Version 5 by the European Commission.

Authored by Joerg Schickert, Arne Thiermann, Tina Welter-Birk and Marcus Kaiser.