Final countdown to entry into force of the Regulation (EU) No 536/2014 on clinical trials on medicinal products for human use

January 10, 2022
Final countdown to entry into force of the Regulation (EU) No 536/2014 on clinical trials on medicinal products for human use

We are only days away from the entry into force of the Regulation No 536/2014 on clinical trials on medicinal products for human use, which repeals clinical trials Directive 2001/20/EC. A lot of time has passed since it was enacted in 2014, but for its application is required EU portal and database (Clinical Trials Information System – CTIS). The full functionality of the CTIS was only announced on July 31, 2021, six months after that notice, on January 31, the Regulation will enter into force.


The change of the law will not result in immediate changes in the scope of regulatory affairs. The transitional period allowing sponsors to introduce changes related to the regulatory issues of their clinical trials will last 3 years (Fig 1.). Research that started before January 31, 2022, will be allowed to remain in the Directive until January 31, 2025. During the first year (from January 31, 2021 to January 31, 2023), the consent to conduct clinical trials may be obtained in accordance with the Directive or the Regulation, depending on the sponsor’s decision. From the second year on (from January 31, 2023), all new clinical trials will have to be evaluated / conducted in line with the Regulation. For the entire three-year period, for ongoing clinical trials under Directive longer than until January 31, 2025, it will be possible to transit clinical trials from the Directive to the Regulation, except that January 31, 2025 is the deadline for completion of the transfer. The clinical trial will fall under the regulatory framework of the Regulation as of the tacit approval date, 60 days from the submission for transition, so it is important that the transition process is started early enough. The switch procedure does not cause the need to discontinue or put on hold a clinical trial.

Figure 1. 3-year Transitional Period

If a sponsor assumes that duration of the clinical trial will cross the January 31, 2025, the clinical trial will need to be switched to the Regulation at some point before that date. Before the switch of the clinical trial to the regulatory framework of the Regulation, in multinational studies the protocol for all Member States concerned has to be harmonised or at least consolidated. Moreover, the other key documents covered by the Part I assessment report (e.g. Investigator’s Brochure, Investigational Medicinal Product Dossier), have to be harmonized. If there are substantial differences between authorized version of these documents, in order to harmonize documents, a sponsor should submit a substantial amendment under the clinical trials Directive to Competent Authorities and ethics committees in Member States concerned describing its intention to align the trial with the Regulation. If there are only non-substatnial differences (e.g. administrative) between the authorised version of documents, a sponsor may transit the clinical trial to the Regulation, however a sponsor must also declare in the cover letter that there are no substantial differences in content of these documents approved by Member States concerned. If mentioned documents are already harmonized, a sponsor during the switch procedure, in addition to the application form and trial’s documentation, in the cover letter must confirm that there are no substantial differences in these documents relative to that authorized under the Directive in all Member States concerned. In the case of  mononational clinical trials during the switch procedure, apart from the application form and the clinical trial dossier, in a cover letter sponsors must declare that the submitted documents are not different from the authorised version.


In case of any doubts regarding the transition of the clinical trial to the regulatory framework of the Regulation the (EU) No 536/2014, problems with harmonization of documents, conducting the switch, or initial submission of an application for authorization to commence a clinical trial in accordance with the Regulation, the Clinmark experts provide advice and support in all aspects related to the process itself and also in the subsequent conduct of a clinical trial in accordance with the Regulation.

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