Following the entry into force of Italian Legislative Decree 137/2022 in September 2022, 2 long-awaited Decrees of the Italian Ministry of Health concerning clinical investigations of medical devices were published in the Italian Official Gazette on 13 June 2023. These Decrees, in order to implement the provisions of Article 16 paragraphs 2 and 3 of the aforementioned Legislative Decree 137/2022, are aimed at adapting the Italian legal system to the provisions of EU Regulation 2017/745 (MDR), also taking into account that - at present - the Eudamed database is not yet fully operational.
Specifically, the Ministerial Decree of 12 April 2023 concerns the "administrative modalities of national relevance for the submission of applications for clinical investigations for devices that are not CE marked or CE marked but used outside their intended purpose" [...], while the Ministerial Decree of 12 April 2023 is inherent to the "administrative modalities of national relevance for communications relating to clinical investigations on CE marked devices used within their intended purpose [...]".
The aforementioned Ministerial Decrees, which came into force on 13 July 2023, are similar in content, having the aim of
- identify the persons entitled to submit applications and send notices concerning clinical investigations;
- clarify the procedures for submitting clinical investigation requests and communications
- define the modalities and timeframe for obtaining a nationally valid opinion expressed by an Ethics Committee;
- define the modalities for notifying the commencement of investigations.
The Ministerial Decree concerning the submission of applications for the investigation of devices that are not marked or marked but used outside their intended purpose, which consists of 7 articles in total, defines:
- Who is authorised to submit clinical investigation applications: applications and all communications relating to clinical investigations are submitted by the person who assumes responsibility for initiating, managing and taking care of the financing of the clinical investigation (and, if the sponsor is different from the manufacturer, the details of the manufacturer must also be indicated); in the event that the sponsor proposer is established outside the EU, there is a specific duty for the latter to appoint a representative resident within the EU territory in writing (in compliance with the provisions of Art. 62 MDR). The declaration concerning compliance with the safety and performance requirements made by the person responsible for manufacturing the device must be signed by a person identified within his organisation and appointed to perform this function. All communications relating to clinical investigations, sent electronically and signed, are only accepted if they comply with the provisions of Article 65 of Italian Legislative Decree 82/2005 (Digital Administration Code);
- Modalities for submitting applications and initiating investigations: until the Eudamed database is fully operational, the operating procedures set out in the decree and the technical specifications published on the Ministry of Health website will apply. The clinical investigation application must be accompanied by a favourable opinion issued by the competent Territorial Ethics Committee (TEC) or, depending on the type of investigation, by the National Ethics Committee (CEN). Measures of the Ministry of Health to initiate clinical investigations can only be taken in the presence of the unconditional favourable opinion of the Ethics Committee. The sponsor, or the person duly authorised by the sponsor, notifies the Ministry of Health in advance of the start of the investigation.
On the other hand, as regards the Ministerial Decree concerning communications relating to clinical investigations on CE marked devices used in the context of their intended use, it largely reflects the provisions of the decree just referred to. From an analysis of the 7 articles of which it is composed, we can highlight:
- Who is entitled to submit communications: communications related to clinical investigations are submitted by the sponsor, who is the holder of the obligations relating to the clinical investigation and the addressee of communications from the competent authority. Communications with the competent authority may be provided by contact persons duly authorised by the sponsor. These individuals, at the request of the Ministry of Health, may be called upon to present the documents relating to the conferment of representation; the attestations of sponsors/referents established in the EU territory, may be made by means of declarations in lieu of affidavit (pursuant to Italian Presidential Decree 445/00). For sponsors/referring parties not established in the European Union, their qualities must be attested - where necessary - by certificates issued by the competent authority of the foreign country, accompanied by an Italian translation authenticated by the Italian consular authority certifying its conformity to the original.
- Modalities for sending notifications, acquiring the favourable opinion of the Ethics Committee and initiating investigations: with regard to the sending of notifications, the operating procedures set out in the decree and the technical specifications published on the website of the Ministry of Health shall apply. Again, the decree will only apply until the Eudamed database is fully operational. Notifications concerning clinical investigations are made after a favourable opinion has been issued by a Territorial Ethics Committee (TEC) or a National Ethics Committee (CEN). Finally, the sponsor, or the sponsor's duly authorised representative, notifies the Ministry of Health within thirty days of the start of the investigation.
In the Official Gazette of 14 June 2023, two further Ministerial Decrees were published relating to (i) the guarantees to be submitted by the entities in charge of processing clinical investigation applications and (ii) the requirements for facilities eligible to conduct clinical investigations conducted to demonstrate compliance of medical devices.
An analysis of these Ministerial Decrees will follow in a subsequent article.