AIFA stops all clinical trials that do not comply with the Clinical Trials Regulation as of January 31, 2025

Since CTR became applicable on January 31, 2022, the afore mentioned deadline expired on January 31, 2025. Therefore, as of this date, all clinical trials in Europe must be conducted according to CTR only.

In implementation of this rule, by decision published on January 31, 2025, the Italian Medicines Agency (AIFA) issued a provision revoking all authorizations for clinical trials still conducted in Italy pursuant to the Directive, whose sponsors had not yet applied for the transition to the CTR regime.

Clinical trials conducted under the Directive

We remember that – until January 31, 2025 – the following categories of trials could be conducted according to the Directive:

1. clinical trials whose request for authorization had been submitted before January 31, 2022; and
2. clinical trials whose request for authorization had been submitted between January 31, 2022, and January 31, 2023, according to the Directive and the national implementing legislation (as, during the first year from the application of the CTR, sponsors could choice between filing the request for authorization under the Directive or the CTR).

In both cases above, clinical trials were subject to the Directive for 3 years after the application of the CTR. However, sponsors could decide, at any time during this period, to apply for the trial to be transferred to the new system. Such requests should be filed through the EU Portal CTIS.

For the purpose of the transition to the CTR, according to the new ministerial decrees on the reorganization of ethics committees in Italy, it was necessary to previously submit a substantial amendment for the change from the ethics committee in charge to a new ethics committee (CET or CEN), which became competent according to the new rules. In the absence of the request for substantial amendment and related check of all the necessary harmonized documentation, the trial was likely blocked during the CTIS validation phase.

AIFA’s decision: termination of clinical trial authorizations

By decision issued on January 29, 2025, AIFA revoked all authorizations of the clinical trials currently being conducted according to the Directive, for which the sponsor had not submitted through CTIS, by January 30,  2025, the request to transfer the trial to the CTR regime. AIFA also revoked all authorizations of the clinical trials still ongoing as of January 30, 2025, authorized by other competent authorities, whose sponsors had never uploaded the documentation in the National Observatory on clinical trials of medicinal products (OsSC).

As a consequence of the above, all sponsors of clinical trials:

1. are prohibited from doing any activity related to the conduct of the clinical trial (of course this applies to all persons and entities involved);
2. must promptly communicate the stop of the clinical trial to all participants and, at the same time, assure the safety and security of all patients involved in the trial, by taking any necessary action;
3. must take care of all obligations concerning the publication of the study results on the EU Clinical Trial Register, according to the EU Guidance on posting and publication of result-related information on clinical trials.

Moreover, the AIFA’s decision specifies that data and results of discontinued clinical trials following revocation of the authorization cannot be used for registration purposes and cannot be transferred for this purpose.

Suspension of the authorizations if requests are still pending

A different scenario applies to the clinical trials if the sponsors have filed the request to move to the CTR regime before January 31, 2025, but the procedure is not yet completed. In such cases, the authorizations to conduct clinical trials are suspended, waiting for the approval of the request through the CTIS Portal.

In this scenario, all the obligations mentioned above still apply to the sponsors (i.e. prohibition to continue the activity; obligations to inform the participants and assure their safety and security).

Conversely, in this case, there is no obligation of publication of study results (as the trial is still potentially alive) and the prohibition to use for registration purposes data and results only applies to those data and results eventually collected in breach of the suspension decision.

The future of the National Observatory on clinical trials of medicinal products (OsSC)

AIFA, through its website, also provided other useful information for the management of this transitional phase, including certain information on the operation of the OsSC.

In particular, from January 31, 2025, new requests for authorization of substantial amendments via OsSC can no longer be submitted. The OsSC will remain active for consultation as an archive and for the purposes of the registration of the users of the observational studies registry.

For studies transferred to CTIS, no other updates are required to be carried out in OsSC.

Finally, for clinical trials concluded by January 30, 2025, it will be necessary to transmit the conclusion data and the summary of the results via OsSC within 1 year of the global conclusion.

[1] Regulation EU No 536/2014

[2] i.e. Directive 2002/20/EC and national implementing legislation