The CTR will apply from 31 January 2022 as published in the Official Journal of the European Union on July 31, 2021 (EU commission decision 2021/1240). The Directive 2001/20/EC will be repealed on the day of application of the CTR. Paragraph 5a of the Dutch Act on Research Involving Human Subjects (WMO) will also be repealed. There is, however, a transition period of three years starting from that day for clinical trials authorised under Directive 2001/20/EC legislation.
This transition period is as follows (see also questions 1.2 and 11.2 of the Q&A CTR):
- 1st year: initial application according to old (Directive 2001/20/EC) and new legislation (CTR EU no 536/2014) is allowed
- 2nd and 3rd year: all initial applications according to Clinical Trial Regulation
- 4th year and later: all ongoing clinical trials should comply with the requirements of the Clinical Trial Regulation
During the three years transition period, substantial modifications of clinical trials approved under Directive 2001/20/EC can be submitted according to this old legislation.
Clinical trials not authorised under the regime of the CTR and still ongoing in EEA (Last Visit Last Patient has not taken place yet) at the end of the transitional period have to be ended or should switch before the end of this period into the regime of the CTR. If the duration of the clinical trial is expected to be more than two years at the date of the primary application in the first year of the transitional period it is strongly recommended to apply for an authorisation under the regime of the CTR.
Clinical trials authorised under Directive 2001/20/EC
Clinical trials authorised on the basis of the Directive 2001/20/EC should be re-authorised under the regime of CTR without requiring a “temporary hold” of the clinical trial. This switch to the new regime should have started at least six months before the end of the transitional period. The procedures for this transition are described in question 11 of the Q&A document on the CTR. The CTFG has released a best practice guide on the transition of multinational clinical trials.
Clinical trials authorised before Directive 2001/20/EC
There is no transition period for clinical trials authorised before the the Directive 2001/20/EC was applicable. In the Netherlands, the Directive 2001/20/EC came into effect on March 1, 2016. This means that all clinical trials authorised or submitted before March 1, 2006 and still ongoing at 31 January 2022 (date CTR is applicable) has to be ended or re-authorised under the CTR . These clinical trials do not have a Dutch national dossier number beginning with NL (NL12345.xxx.yy) and have no declaration of no objection from the competent authority (CCMO or Ministry of Health). The sponsor should determine whether the clinical trial still fulfills the definition of a clinical trial or is a non-interventional study. For instance, a study can be considered a non-interventional study if there is only a long-term safety follow-up ongoing via quarterly telephone calls or filling in simple questionnaires. These studies may continue without transition to CTR legislation.
If the trial is still to be considered as interventional and it is not possible to terminate a trial for reasons related to patient safety or scientific soundness, there are two possible procedures to continue these trials at the time CTR is applicable:
- Submit a substantial amendment to the MREC and competent authority at least 3 months before the CTR is applicable (31 January 2022) in which the clinical trial is brought in line with CTR legislation. The clinical trial must/has to be registered in the EudraCT portal. After approval of the substantial amendment the transition rules for clinical trials authorised under Directive 2001/20/EC will apply; or
- Submit a full application dossier through CTIS as from 31 January 2022 and all CTR rules apply.