NREC-MD reviews clinical investigations of medical devices, as determined by EU Regulations in the area of clinical investigations of medical devices – Medical Device Regulation (MDR; EU No. 2017/745) and performance studies of in vitro diagnostic medical devices – In Vitro Diagnostic Medical Devices Regulations (IVDR; EU No 2017/746).

Studies of medical devices which require ethical review by NREC-MD under MDR include:

• Clinical investigations conducted to demonstrate conformity of devices outlined in Article 62 of the Medical Devices Regulation (EU) 2017/745
• Post-market clinical follow up (PMCF) investigations regarding devices bearing the CE marking outlined in Article 74 of the Medical Devices Regulation (EU) 2017/745
• Substantial modifications to clinical investigations outlined in Article 75 of the Medical Devices Regulation (EU) 2017/745
• Other clinical investigations outlined in Article 82 of the Medical Devices Regulation (EU) 2017/745

Studies of in vitro diagnostic medical devices which require ethical review by NREC-MD under IVDR include:

• Performance studies outlined in Article 58 of In Vitro Diagnostic Medical Devices (EU) 2017/746
• Performance studies regarding devices bearing the CE marking outlined in Article 70 of In Vitro Diagnostic Medical Devices (EU) 2017/746
• Substantial modifications to performance studies outlined in Article 71 of In Vitro Diagnostic Medical Devices (EU) 2017/746

Applicants should determine if their study meets the scope of NREC review; however where an Applicant is in any doubt as to whether their study falls under the MDR or IVDR, applicants are advised to consult with the HPRA (devices@hpra.ie) and the National Office team (devices@nrec.ie).

No; the EU MDR (EU No 2017/745) has been applicable in Ireland since 26th May.

Similarly, the EU IVDR (EU No 2017/746) has been applicable in Ireland since 26th May 2022, meaning from this date all performance studies of in vitro diagnostic medical devices must be authorised under the MDR.

Applicants must therefore submit their applications for research ethics review of clinical investigations of medical devices to the NREC-MD, which can issue a single, nationally applicable ethics opinion in line with the MDR. The NREC review process will run in coordination where necessary with the HPRA to ensure Ireland meets its Member State obligations to return a ‘single national decision’ in relation to the MDR.

As of 26 May 2022 In vitro diagnostic medical devices have been subject to Regulation (EU) 2017/746 on in vitro diagnostic medical devices (IVDR). Therefore, applicants must now submit applications for ethical review to the NREC-MD who will issue single, nationally applicable ethics opinion in line with the MDR.

NREC-MD conducts review on in vitro diagnostic medical devices studies that may come under

• Performance studies outlined in Article 58 of In Vitro Diagnostic Medical Devices (EU) 2017/746
• Performance studies regarding devices bearing the CE marking outlined in Article 70 of In Vitro Diagnostic Medical Devices (EU) 2017/746
• Substantial modifications to performance studies outlined in Article 71 of In Vitro Diagnostic Medical Devices (EU) 2017/746

Other performance studies, for example certain types studies involving leftover samples only can be reviewed by local RECs. We advise that applicants consult with the HPRA (devices@hpra.ie) and the National Office team (devices@nrec.ie) in such instances.

The NREC-MD reviews:

• clinical investigations of medical devices as defined in the EU Medical Device Regulation (MDR; EU No 2017/745).
• performance studies of in vitro diagnostic medical devices as defined in the EU In Vitro Diagnostic Medical Device Regulation (IVDR; EU No 2017/746).

Pre-clinical studies do not come under the MDR and therefore should be reviewed by the relevant local RECs. Early-stage clinical investigations can be regulated studies per the MDR so they may fall within the NREC-MD remit. When in doubt, and in advance of submitting an application for ethics review, applicants are advised to seek confirmation from the national competent authority/regulatory body, the HPRA, to confirm whether a study falls under the regulations, and may need to discuss the appropriate route for ethics review of their study with the National Office.

Under the MDR (EU No 2017/745), clinical investigations of medical devices that require a ‘substantial modification’ from 26^th May 2021 must apply to the NREC-MD for an ethics opinion through the Substantial Modification process.  This includes those ongoing medical device studies approved by local RECs under the Council Directives 93/42/EEC and 90/385/EECSI 252/1994 and SI 253/1994 as amended).

Studies started under the IVDD will continue under that framework but will have to report adverse events and device deficiencies as per the requirements of the IVDR to the HPRA.   For more information on substantial modifications please visit our Guide for substantial modifications.

Submission of a Substantial Modification must be accompanied by the NREC  form, any relevant documentation as designated by the form, and evidence of fee payment.

In the case of studies previously approved by local RECs, historical documents from the study should also be submitted (if not already done) along with the submission of the Substantial Modification submission. This documentation should include the original REC submission, cover letters and approval letters for any substantial modifications, and the most recent version of the documents.

Further details on Substantial Modifications can be found here.

When applying to the NREC-MD, Applicants are asked to use the NREC-MD Application Form accompanied by the in the application checklist. Templates for the NREC-MD Application form and Site Suitability form are available here. All file names should numbered sequentially and include document version number and/or a date.

Applications that do not include the documentation listed in the application checklist or a justification for their absence will be deemed invalid and will require resubmission for further consideration by the NREC-MD.

Please note that all documents must be provided as readable non-scanned pdf documents to ensure accessibility. All applications should be sent as a zipped folder to devices@nrec.ie.

Please note that certain combination studies (where a study includes both investigative medicinal product and medical device or in vitro diagnostic medical device) are subject to review by both NREC-CT and NREC-MD, particularly if the study is subject to review by both CT and MD team of the HPRA. In such cases, a separate full application to NREC-CT and NREC-MD is necessary. Further information about applying to NREC-CT is available here.

The National Office, in consultation with the NRECs and external stakeholders, have developed a national template for Sponsors to demonstrate compliance with all applicable data protection legislation, including national legislation. The template aims to assist Sponsors with informing the respective NRECs of data protection compliance and associated ethical considerations.

Applicants now have the following options regarding demonstrating compliance with data protection legislation:

1. Submission of the national ‘Statement of Compliance’ template [Please see ‘Guidance on Statement of Compliance’] which addresses the requirement to demonstrate compliance with data protection legislation
2. Submission of a study-specific Data Protection Impact Assessment (DPIA)

NOTE: Where the NRECs believe the Statement of Compliance (or DPIA) is insufficient, such that there are ethical concerns, they reserve the right to request further information, as appropriate.

The DPIA is an integral part of the Sponsor’s accountability obligations under Article 35 of GDPR, and helps to assess and demonstrate how the Sponsor will comply with data protection obligations. The completion of a DPIA is a mandatory requirement under GDPR and the Health Research Regulations 2018 for studies that are deemed ‘high risk’ for the processing of personal data. Health data is considered a ‘special category of data’ that is ‘likely to result in high risks’ to the rights and freedoms of research participants.

A DPIA will be expected as part of an NREC-MD application submission where relevant to the study. However, if a DPIA is not required for a study, a justification outlining why this is the case must be submitted as part of the application along with a completed Statement of Compliance.

• For the purposes of NREC review, the DPIA will need to be completed by the Data Controller of the research study and accompanied by evidence of Data Protection Officer (DPO) input.
• Where the Data Controller is based in a non-EU country with an adequacy decision from the European Commission, the National Office will accept DPIAs reviewed by a person with the equivalent role and responsibilities as a DPO.
• Where the Data Controller is situated outside of Ireland, the National Office advises that the DPO of the lead Irish-based institution should be given the opportunity to provide comment on the DPIA.
• The National Office does not provide a DPIA template. Instead, institutional DPIA templates are accepted.

Please consult our guidance for more information https://www.nrecoffice.ie/committees/policies-and-procedures/guidance-on-data-protection-and-health-information/

NRECs are not expected to undertake detailed expert scrutiny of the insurance policies pertaining to the research described in the application they review. The responsibility for ensuring that cover is sufficient and adequate lies with Applicants themselves.

The NREC should receive an assurance from the Applicants that there are adequate insurance or indemnity arrangements in place for the potential legal liability arising from the research, and consider provision in proportion to the risk for compensation or treatment in the event of injury, disability or death attributable to participation.

In general, all applications should be accompanied by the following (as applicable):

• Study-specific insurance policy
• Products liability insurance
• Other organisational insurances such as employers’ liability, public liability, professional indemnity, cyber/data protection.

For more information please review the State Indemnity Guidance (SIG-10) published by the State Claims Agency.

Applicants must pay the relevant fee in advance of submission to the National Office for Research Ethics Committees. For NREC-MD, the fees are set by Statutory Instrument 670/2023 and 671/2023.  For additional information on fees please refer to  https://www.nrecoffice.ie/apply-2/fees/

The timelines for NREC-MD decisions are consistent with those required by the regulation for medical devices (EU No 2017/745). The NREC-MD endeavours to issue an ethics opinion on this application within a period of 55 days from the date of acknowledgement of a valid application.

Following the submission deadline, the National Office validates all applications.  This means that we complete a number of checks, including whether all necessary documentation is included, accessible, and marked with version numbers and dates where applicable.

Applicants should normally receive notification of whether their application is ‘Valid’ or ‘Invalid’ within seven calendar days of validation, in line with the operational requirements of the particular NREC review process. Invalid applications will require resubmission. The NREC-MD endeavours to issue an ethics opinion on this application within a period of 55 days from the date of acknowledgement of a valid application.

Applicants should align with the reporting requirements, including safety, of the national competent authority (HPRA) under the applicable EU regulations, related to studies approved by the NREC-MD.

For clinical investigations of medical devices approved under the MDD (and ongoing at implementation of the MDR (from 26^th May 2021)), the reporting relationship, including for safety, is established to the NREC-MD and not to a local REC.  To ensure compliance with the MDR, Sponsors/Principal Investigators should, as of the 26^th May 2021, notify the NREC-MD on all aspects of applicable reporting, including annual reports, safety reports, and device deficiencies, and any other matter that requires an ethical decision or notification.

All aspects of applicable reporting, including annual, safety and device deficiency reporting from studies previously approved by local RECs under the Council Directives 93/42/EEC and SI 252/1994 and SI 253/1994 as amended) , as of 26^th May 2021, should be directed to the NREC-MD. On the submission of a first such report, we ask the applicant to also submit all relevant study documentation. If submitting an annual report to the NREC-MD, applicants must do so within 30 days following the anniversary of the date on which approval was given and for every year thereafter for the duration of the study. End-of-Study reports must be submitted to the National Office within one year of the conclusion of the research. The submission of all such reports will be acknowledged by the National Office.

Reporting templates can be found on the NREC-MD website: https://www.nrecoffice.ie/committees/nrec-md/reporting-forms-templates/

The reporting relationship from an ethics perspective for all clinical investigations of medical devices ongoing on the date of effect of the EU MDR (26^th May 2021) lies with the NREC-MD. To ensure compliance with the MDR, Sponsors / Principal Investigators should notify the NREC-MD on all aspects for reporting, including annual reports, safety reports, and device deficiencies, and any other matter that requires an ethical decision or notification.

The requirement for a decision by, or report or notification to, the NREC-MD will be the ‘trigger’ for transfer of the relevant historical documentation on studies approved by the local REC system, to the National Office for the records of the NREC-MD.

Studies started under the IVDD (98/79/EC) will continue under that framework but will have to report adverse events and device deficiencies as per the requirements of the IVDR to the HPRA.

In line with good clinical practice and best practice, protocol deviations should be in the first instance notified to the competent regulatory authority and the NREC-MD. Following this, it may be necessary to submit any change to the protocol as an amendment/modification to the competent regulatory authority and ethics committee.