As the systematic investigation of the safety or performance of a medical device involving one or more human subjects, clinical investigations are an essential part of bringing safe and effective medical devices to the market. However, just like clinical trials in the context of medicinal products, clinical investigations of medical devices require careful management of ethical issues such as informed consent, impartiality and the appropriate weighing of the risks and benefits of the study to be conducted. As a reflection of a growing emphasis on the importance of safe and robust clinical research methods at EU level, there is an increased focus on clinical investigations in the EU Medical Devices Regulation 2017/745 (MDR) (Chapter VI) when compared with its predecessor, the Medical Device Directive 93/42/EEC (MDD).
Background
Article 62(3) of the MDR provides that clinical investigations shall be subject to scientific and ethical review and that this review shall be carried out by an ethics committee in accordance with national law using procedures that are compatible with the MDR. Chapter II of Annex XV of the MDR also lists a copy of the opinion(s) of the ethics committee(s)concerned (requirement 4.2) as part of the requirements for applications for clinical investigations to be submitted to the relevant Member State in accordance with Article 70 of the MDR.
The establishment and operation of a National Research Ethics Committee for Medical Devices (NREC-MD) has now been provided for under the European Union (National Research Ethics Committee for Clinical Investigations of Medical Devices) Regulations 2021 (S.I. No. 260/2021) (the 2021 Regulations), which came into operation on 26 May 2021 to coincide with the coming in to force of the MDR. Regulation 8 of the 2021 Regulations requires sponsors proposing to carry out a clinical investigation in Ireland under the MDR to apply to NREC-MD for ethical review of the proposed research. Regulation 11 of the Medical Devices Regulations 2021 (S.I. No. 261/2021) also requires sponsors of clinical investigations conducted in Ireland to submit a copy of a NREC-MD opinion to HPRA at the time of an application for an authorisation or notification of a clinical investigation, or as soon as a copy is available (see our article on the Medical Devices Regulations 2021 (S.I. No. 261/2021) here).
NREC-MD
The rules and procedures of the NREC-MD are set out in the Schedule to the 2021 Regulations and provide for the following:
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Membership: Requirements for the composition of NREC-MD, the length of members’ terms as well as resignation and removal by the Minister for Health (membership is also provided for under Regulation 5).
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Meetings: Requirements regarding quorum, notice of meetings to members of NREC-MD, and the chairing of meetings. Although not provided for in the procedures, meetings are expected to take place on a monthly basis.
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Decision Making: Rules on the majority voting system employed by NREC-MD and requirements for members with any material interest in any matter to considered by NREC-MD to disclose this to the chairman in advance of the matter being considered, and to withdraw from, and refrain from becoming involved in, any part of a decision in relation to the matter.
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Minutes: Requirements around recording of meetings which shall include the names of all members present at a meeting.
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Expenses: Allowances for reasonable expenses, as determined by the Minister for Health with the consent of the Minister for Public Expenditure and Reform.
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Procedures: Provision is made for NREC-MD to determine its own procedures subject to the existing provisions of the 2021 Regulations e.g. members attending meetings by remote means.
As can be seen, the NREC-MD is intended to operate in a manner that ensures a sufficient degree of independence and transparency. Regulation 6 also prohibits members from seeking or receiving any financial or other benefit for an application or appeal under the 2021 Regulations.
Applications for Ethical Review
The 2021 Regulations also provide the various detailed rules for the ethical review application process:
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Factors: Regulation 10(5) provides a list of 17 factors requiring consideration by NREC-MD (where applicable) in preparing its opinion. Where NREC-MD does not have a member with the requisite professional expertise, Regulations 10(6) and (7) also require NREC-MD to seek specialist input for proposed clinical investigations involving subjects who are minors, or adults incapable by reason of physical or mental incapacity of giving informed consent. Regulation 11 also provides that a clinical investigation shall not be approved unless a policy of insurance is in place providing sufficient cover (with regard to the nature and the extent of the risk) for any damage suffered by subjects as a result of their participation in the clinical investigation.
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Decisions: The decision of the NREC-MD to grant or refuse ethical approval for an application is referred to as an “opinion” and is notified to the sponsor and HPRA (Regulation 13). NREC-MD can also approve applications with conditions. Refusals shall include reasons for the refusal and a statement that the refusal may be appealed. A sponsor that has been notified of an opinion has 10 days from when the notification is sent to notify NREC-MD in writing whether he or she accepts or does not accept the opinion and, in the latter case, whether or not he or she intends to appeal (Regulation 14).
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Timelines: Regulation 10(8) provides that NREC-MD shall provide an opinion within 55 days or such extended period as required for clinical investigation applications, or 38 days for modification applications. This can be extended to 45 days where consultation is required. Appeals can be brought within 28 days of the notification of the opinion being received.
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Fees: Regulation 20 sets out fees payable by a sponsor to NREC-MD in respect of proposed research, modifications to existing research and appeals. Fees may also be reduced at the discretion of NREC-MD where it is satisfied that an application relates to a non-commercial clinical investigation.
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Transitional Arrangements: Under transitional arrangements (Regulation 21), applications for ethics opinions pending for consideration by ethics committees under the now revoked European Communities (Medical Devices) Regulations 1994 (S.I. No. 252/1994) or the European Communities (Active Implantable Medical Devices) Regulations 1994 (S.I. 253/1994) will be passed to the NREC-MD and treated as an application under the 2021 Regulations.
Offences
The 2021 Regulations also expressly provide for various offences relating to the conduct of clinical investigations. Proceedings may be prosecuted summarily by the Minister for Health, with a conviction resulting in a class B fine (between €2,500 and €4,000) or a term of not more than 6 months’ imprisonment or both. Proceedings may also be brought on indictment and may result in a fine of up to €500,000 or a term of not more than 3 years’ imprisonment or both.
Conclusion
Read alongside Chapter VI of the MDR, and in combination with Part 3 of the Medical Devices Regulations 2021 (S.I. No. 261/2021), the 2021 Regulations form part of a new national framework designed to realise the enhanced requirements pertaining to clinical investigations that must now be met by sponsors of clinical investigations under the MDR.
Further information regarding applications to NREC-MD, along with the relevant application forms, documentation checklists and an ‘applicant toolkit’ can be found on the website of the National Office for Research Ethics Committees here.
For more information and expert advice on how medical devices are regulated in Ireland and the EU, contact a member of our Life Sciences team.
The content of this article is provided for information purposes only and does not constitute legal or other advice.
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