Entry into force of Regulation 2017/745 on medical devices (MDR): update on clinical investigations

The entry into force of Regulation 2017/745 on medicinal products for human use (MDR) marks the end of the applicability of the national provisions resulting from the Jardé law for the evaluation of research projects submitted from 26 May 2021 onwards and involving a device falling within the scope of the MDR.

The redesign of clinical investigations thus requires sponsors to review the entire applicable procedure, submission deadlines and declaration of vigilance.

Clinical investigations, main general requirements to be kept in mind

With the MDR, the clinical investigations (see Chapter VI, Art. 61-82 and Annex XV) must establish compliance with the performance and safety requirements, in particular

• performance
• benefits
• clinical safety, detecting possible adverse effects and assessing whether they constitute an acceptable risk in relation to the benefits of the device

Clinical investigation is designed to ensure the protection of the rights, safety, dignity and well-being of individuals, the scientific validity, reliability and robustness of clinical data.

In general, the DM undergoing clinical investigation complies with the general safety and performance requirements set out in Annex I (with the obvious exception of evidence requiring clinical investigation)and the requirements of Annex XV (general requirements, documentation of the clinical investigation application, other obligations of the sponsor in Chapter III).

All these guarantees are ensured by scientific and/or ethical review by the competent authorities.

Clinical investigations are an integral part of the broader concept of "clinical evaluation" and are mandatory for implantable medical devices (IMDs) and Class III devices (with clearly established exceptions, see Entry into force of Regulation 2017/245 on medical devices: update on clinical evaluation).

For any clinical investigation conducted at at least 1 investigator site in the EU, the sponsor or its legal representative must be established in the EU.

Towards a coordinated evaluation procedure

To date, the evaluation procedure remains purely national and is therefore the responsibility of a designated French Ethical Commitee, i.e. Comité de Protection des Personnes (CPP), and the ANSM.

In the future, for clinical investigations conducted in several Member States, the evaluation procedure will be coordinated by a coordinating Member State, but the ethical review will remain national and will therefore always be the responsibility of a CPP on French territory. This procedure will be mandatory from 26 May 2027.

Before that date, the possibility of using this procedure will depend on the establishment of the EUDAMED database, which will be the entry point for any notification or request for a clinical investigation, regardless of the procedure, and will be accompanied by the documentation referred to inAnnex XV.

Evaluation of your research project applications

The commencement of the clinical investigation is subject to coordinated validation by the ANSM and must therefore fall within the scope of the MDR (device, class, CE marking or post-marketing clinical follow-up(PMCS)) and be the subject of a complete dossier (see Annex XV).

Following validation, clinical investigations can only be implemented after a favourable opinion (even if the MDR uses the notion of no unfavourable opinion) issued by the designated CPP, and if necessary after authorisation by the ANSM.

It should be noted that several evaluation procedures and timeframes coexist depending on the type of clinical investigation envisaged: with or without CE marking, use within or outside the intended purpose, presence or absence of invasiveprocedures and class of the device.

In any case, SCAC procedures without additional procedures will not be considered clinical investigations but routine care outside the scope of clinical investigations.

Vigilance and investigations

Clinical investigations continuing beyond 26 May 2021 will continue to be governed under the national provisions of the Jardé Law (Articles L. 1121-1 and seq. and R. 1121-1 et seq. of the Public Health Code), except for the vigilance of such research, which will henceforth be governed by the provisions of the MDR.

The deadlines for vigilance reporting are as follows:

- from the investigator to the sponsor:

• without delay (immediately) and not later than 3 calendar days

- from the sponsor to the ANSM :

• without delay (immediately), and no later than 2 calendar days from the day the promoter became aware of the event, for all events resulting in death or imminent risk of death, serious injury or illness and requiring prompt corrective action or new safety information
• without delay (immediately), and not later than 7 calendar days from the day the sponsor became aware of the event for other events