With reference to the Ministerial Decree of 30 January 2023 on "Determination of the single fee for clinical trials, of the attendance fee and reimbursement of expenses for participation in meetings of the National Coordination Centre of local ethics committees for clinical trials on medicinal products for human use and medical devices, of local ethics committees and of ethics committees of national relevance"(hereinafter the "Single Fee Decree"), published on 7 February 2023 on the Official Journal, General Series no. 31, and entered into force on 22 February 2023, the following operational instructions are provided:

• As of 22 February 2023, the new fees established by the Single Fee Decree shall apply to applications for authorisation of substantial amendments to clinical trials submitted through OsSC and applications for authorisation of clinical trials and related substantial modifications submitted through CTIS.
• The fees identified in Annex 1 of the Single Fee Decree must be paid through AIFA's On-line Payment System (POL) by means of a single payment according to the instructions contained in the POL invoice that the system will generate, with the same methods applied until now (see also communication of 13 January 2023 accessible from the "related links box").
  The POL system has been updated with the specific fees indicated in the aforementioned Annex 1, which the sponsor/applicant must select based on the applicable situation. The POL system handles all fees relating to applications for authorisation of clinical trials (and substantial modifications thereto) of all trial phases.
• Any amounts already paid for authorisation applications not yet submitted by 22 February 2023 (either through the OsSC or the CTIS) will have to be claimed back by the sponsor/applicant. It is not possible to use any of these amounts to cover the Single Fee applicable to authorisation applications submitted on or after 22 February 2023. For these applications, a new POL must be generated bearing the amounts established by the Single Fee Decree.
  For trials applications submitted through the National Observatory on Clinical Trials (OsSC), please refer to each Ethics Committee (EC) concerned for any fees already paid for authorisation applications that have not been submitted by 22 February 2023.
• Applications for authorisation of substantial amendments submitted through the OsSC in accordance with Directive 2001/20/EC, which are assessed by the EC only, shall be subject to the fee due to the EC as indicated in Annex 1 of the Single Fee Decree (currently set at € 2,500 -, amount subject to subsequent updates), to be paid to the EC based on the payment methods established by the EC itself. With the exception of the fee for substantial amendments to be evaluated by the EC only, no further fees may be required by the ECs as from 22 February 2023.
• For applications for authorisation of substantial modifications (SM) submitted through CTIS pursuant to EU Regulation 536/2014, the full fee established for SMs in the aforementioned Annex 1 to the Single Fee Decree shall apply, to be paid through the POL system, described above.

Final Note

As of 22 February 2023, the operational instructions on the payment of the Single Fee described in the "Guidance for the temporary management of clinical trials pursuant to EU Regulation 536/2014 pending the full implementation of the Ministerial Decrees reforming the Ethics Committees and the single fee" published on the AIFA Portal on 31 January 2022, still available in the "related links box", are no longer applicable.