Already under the MDD and AIMDD, clinical investigations with non-CE-marked devices (now Art. 62 MDR) and with CE-marked devices with new claims/intended use (now Art. 74.2 MDR) were registered in EUDAMED2 and received a EUDAMED Number, which was unique for the investigation and participating countries in EU-wide investigations. The first Member State (MS) submission was performed to generate the EUDAMED number and communicated this to the Sponsor and/or CRO. This number was subsequently added to the submission of this clinical investigation to any other participating Member State.
This approach did not change under MDR 2017/745, besides the generation of the Single Identification Number (SIN) for the clinical Investigation is to be performed by the Sponsor/CRO, shall be prior to the submission, and it shall be performed via the electronic system as of Art. 73 MDR 2017/745.
It also covers the notification of Post-Market Clinical Follow-Up Investigations as per Art 74.1 MDR 2017/745, while under MDD and AIMDD these investigations would be on the responsibility of a national basis, and mostly assessed by the Ethics Committees only, and no CA was involved.
EUDAMED was deemed to be functionally in June 2022, instead of 26 May 2021, but this is now delayed again. So, what impact does this have on Clinical Investigations?
The MDCG 2021-1 Rev.1 “Guidance on harmonised administrative practices and alternative technical solutions until EUDAMED is fully functional” lists affected articles of the MDR 2017/745 and provides practical steps until EUDAMED is functionally. For clinical investigations, solutions for the following affected MDR Articles are provided:
- Art. 70 Application for clinical investigations
- Art. 73 Electronic system on clinical investigations
- Art. 74 Clinical investigations regarding devices bearing the CE marking
- Art. 75 Substantial modifications to clinical investigations
- Art. 76 Corrective measures to be taken by Member States and information exchange between Member States
- Art. 77 Information from the sponsor at the end of a clinical investigation or in the event of a temporary halt or early termination
- Art. 78 Coordinated assessment procedure for clinical investigations
- Art. 80 Recording and reporting of adverse events that occur during clinical investigations
Regarding the SIN generated by Sponsors, MDCG 2021-20 states that “member states may encourage sponsors to obtain a CIV-ID from a Competent Authority before the first submission of application/notification. “
This means until EUDAMED is functionally, the Competent Authorities will generate the CIV-ID, as it was before, and forward it to the Sponsor/CRO.
Once EUDAMED is up and running, the Sponsor/CRO will take over this step by generating a SIN for the clinical investigation.
Generation of the CIV-ID by the Competent Authority
The main body of the MDCG 2021-20 provides explicit guidance for the CA personnel on how to generate the CIV ID, supported by pictures of the system’s forms.
These are the steps for CA personnel to create a CIV-ID:
1. Search for CIV-ID, to ensure that the CIV-ID for this investigation has not been created by another CA
2. Enter the name of the manufacturer, the title of the clinical Investigation (under MDR it should always start with MDR), the protocol code, and the primary objectives
3. Generate CIV ID, it will show as a draft version, not visible for other CAs
4. Some CIV details need to be added manually, confirmed, to have a valid CIV-ID created, that other CAs can find during “search”. These are:
a) In the Actors tab:
• The manufacturer
• Sponsor detail, as the Sponsor is the formal applicant for the CI (not the manufacturer)
b) In the Device tab:
• add new device
• check that Clinical investigation is prepopulated as device type
• indicate device name (It is mandatory to enter at least Trade name or Generic name).
• In the device listing:
• intended use
c) In the CA Information tab:
CA contact details
5. To confirm the Clinical Investigation, CIV-ID shows as “proposed”
Other helpful MDCG Guidance
In addition to the above-mentioned The MDCG 2021-1 Rev.1,
helpful guidance is provided for “actors” registration under MDR:
- MDCG 2020-15: MDCG Position Paper on the use of the EUDAMED actor registration module and of the Single Registration Number (SRN) in the Member States
- MDCG 2021-13 rev.1: Questions and answers on obligations and related rules for the registration in EUDAMED of actors other than manufacturers, authorised representatives and importers subject to the obligations of Article 31 MDR and Article 28 IVDR