Analysis of Impact of European Medical Device Regulation and

Brexit on the Regulatory Approaches in a Clinical Investigation

Study on a New Class III Medical Devices Conducted in Europe and

United Kingdom

Candice Houg

1,2

, Thomas Lihoreau

1,2

, Martina Hennessy

, Helene Esperou

Rachel Benamore

, Jean Palussiere

and Lionel Pazart

1,2

Centre Hospitalier Universitaire de Besançon, Centre d'Investigation Clinique,

INSERM CIC 1431, 25030, Besançon, France

Tech4Health network - FCRIN, France

Wellcome-HRB Clinical Research Facility, St James’s Hospital and School of Medicine Trinity College Dublin,

Dublin, Ireland

Clinical Research Unit, National Institute of Health and Medical Research, Paris, France

Department of Radiology, Oxford University Hospital Trust, Oxford, U.K.

Department of Interventional Radiology, Bergonie Institute, Bordeaux, France

Keywords: Clinical Investigation, Regulatory Approach, Medical Device, CE Marking, European Medical Device

Regulation 2017/745, Brexit, Ethics Committee, Competent Authority, High-risk Device.

Abstract: The evolution of technological innovations and medical devices requires particular reflections in terms of

regulation. In order to harmonise practices between European countries and to reinforce clinical investigations,

the European Regulation on medical devices 2017/745 has come to give a regulatory framework to the world

of devices. A summary of the regulatory approaches for a clinical investigation of a new class III device

conducted in France, Ireland and England is proposed in this article to illustrate the complexity of the

processes, ending with an example. This illustrates the impact of the EU regulation and Brexit on the conduct

of clinical investigations.

1 INTRODUCTION

Clinical investigations conducted in Europe were

regulated until the end of May 2021 by the Directive

90/385/EEC on active implantable medical devices

(EUR-lex, 1990) and the Directive 93/42/EEC on

medical devices (EUR-lex, 1993). Each European

country could thus transpose the directives into its

national law, as for example France with the Jardé

law (Legifrance, 2016), which separated research into

three categories according to the risks incurred for the

persons participating in this research.

https://orcid.org/0000-0002-8028-276X

https://orcid.org/0000-0001-8417-6609

https://orcid.org/0000-0002-2153-5288

https://orcid.org/0000-0002-1654-4868

https://orcid.org/0000-0001-7186-2677

https://orcid.org/0000-0001-6118-8543

https://orcid.org/0000-0002-9104-0862

The year 2021 is a year of major regulatory

change, including the European medical device

regulation and Brexit. The implementation of the

European regulation on medical devices 2017/745

(EUR-lex, 2017) has thus aimed to harmonise

practices between European countries. During 2021,

the United Kingdom (UK) separates from the

European Union (EU), known as Brexit, so that all

European laws and regulations no longer apply in the

UK, including the new European Medical Device

Regulation.

250

Houg, C., Lihoreau, T., Hennessy, M., Esperou, H., Benamore, R., Palussiere, J. and Pazart, L.

Analysis of Impact of European Medical Device Regulation and Brexit on the Regulatory Approaches in a Clinical Investigation Study on a New Class III Medical Devices Conducted in Europe

and United Kingdom.

DOI: 10.5220/0010968600003123

In Proceedings of the 15th International Joint Conference on Biomedical Engineering Systems and Technologies (BIOSTEC 2022) - Volume 1: BIODEVICES, pages 250-258

ISBN: 978-989-758-552-4; ISSN: 2184-4305

Here, we present the impact of these changes on

the preparation and regulatory submission of a

clinical investigation of a new class III medical

device.

2 MEDICAL DEVICE

REGULATION 2017/745

The European Medical Device Regulation 2017/745

(EU MDR) entered into force on 26 May 2021 after a

year of delay due to the Covid crisis (EUR-lex, 2017).

The EU MDR replaces Directives 90/385/EEC and

93/42/EEC on active implantable medical devices

and medical devices respectively. A regulation,

unlike a directive, is not transposed into the national

regulations of each country; the Member States must

apply it in full and directly. The regulation therefore

aims to harmonise practices within Europe.

This EU MDR aims to strengthen market

surveillance and the clinical evaluation process,

to improve transparency through the European

Database on Medical Devices (Eudamed)

(https://ec.europa.eu/tools/eudamed/) and the unique

device identifier (UDI), and to strengthen the quality

and missions of notified bodies.

Manufacturers in order to market their device

must obtain the CE marking. CE marking (figure1) is

a guarantee that the product meets the essential safety

and performance European requirements.

Figure 1: CE marking.

The manufacturer must therefore provide

evidence of conformity with the requirements in

accordance with Article 5 of the EU MDR: "The

demonstration of conformity with the general safety

and performance requirements shall include a clinical

evaluation as provided for in Article 61".

The purpose of this clinical evaluation is to collect

clinical data on the medical device in order to verify,

under normal conditions of use, that its performance

corresponds to that claimed, to identify any

undesirable side effects and to assess the risks for the

patient.

Manufacturers, in order to demonstrate

compliance with the essential requirements, must

plan, perform and document a clinical evaluation of

the medical device. The clinical evaluation may be

based on:

- a critical evaluation of scientific publications

on equivalent devices

- a critical evaluation of the results of clinical

investigations

- and the consideration of currently available

alternatives

EU MDR specifies that, in the case of implantable

devices and Class III devices, clinical investigations

(CI) must be conducted. However, manufacturers are

not required to conduct a clinical investigation if the

following three criteria are met:

- the device has been designed by modifying a

device already marketed by the same

manufacturer

- equivalence with that device is demonstrated

and approved by a Notified Body

- the clinical evaluation of the device currently

marketed is sufficient to demonstrate

compliance of the modified device with the

relevant safety and performance requirements.

In the case of a brand new class III product

without equivalent on the EU market, clinical

investigation is required for its marketing in all

European countries.

3 BREXIT AND CLINICAL

INVESTIGATION

The United Kingdom (England, Scotland, Wales and

Northern Ireland) withdrew from the EU on 1

February 2020. The withdrawal agreement (EUR-lex,

2019) between the EU and the UK provided for a

transition period until 31 December 2020. The UK is

thus considered a "third country" by the EU as of 1

January 2021.

3.1 Regulation of Medical Device and

Clinical Investigation

Although the Medical Devices Regulation 2017/745

was written and came into force in 2017 when the UK

was still part of the European Union, medical devices

and clinical investigations in UK are not covered by

this EU regulation anymore. Medical devices remain

regulated by the UK Medical Device Regulation 2002

(Legislation.gov.uk, 2002). This regulation is the

adaptation of the European Directive 90/385/EEC

and the European Directive 93/42/EEC into UK law.

Analysis of Impact of European Medical Device Regulation and Brexit on the Regulatory Approaches in a Clinical Investigation Study on a

New Class III Medical Devices Conducted in Europe and United Kingdom

251

3.2 The CE Mark and UKCA Mark in

Following the UK's separation from the European

Union, the CE mark, which guarantees the conformity

of devices to the essential performance and safety

requirements of the EU, is no longer applicable to

medical devices in the UK. Medical devices must

now be UKCA (UK Conformity Assessed) certified

in order to move freely in the UK. There is a transition

period for CE marked devices to be recognised in the

UK until 1

January 2023, allowing manufacturers to

build up the required dossiers for UKCA marking

(figure 2). The UKCA marking is, in some ways,

similar to the CE marking as the majority of UK

standards follow the European standards. One of the

main differences lies in the bodies responsible for

issuing the UK or CE mark.

Figure 2: UKCA marking.

The UKCA certificate must be issued by

approved Notified Bodies responsible for assessing

the conformity of the device with UK requirements.

The guide "UK approved bodies for medical

devices" listing the notified bodies is available on

the UK government website (https://www.gov.uk/

government/publications/medical-devices-uk-

approved-bodies/).

UK-based notified bodies, which were competent

to assess the conformity of European products and

issue the CE certificate, are no longer recognised in

the EU and therefore can no longer issue these CE

mark certificates.

3.3 Data Protection

In the course of a clinical investigation, the personal

and health data of participants are processed,

collected and analysed for scientific research

purposes. The sponsor, person or institution

responsible for the implementation, management or

financing of a clinical study is thus responsible for the

protection and confidentiality of collection, transfer

and treatment of personal data during the study.

The General Data Protection Regulation (GDPR)

(EUR-lex, 2016) governs the processing of personal

data and the rules on the free movement of personal

data in Europe. The UK has special provisions

regarding the GDPR. Thanks to the Trade and

Cooperation Agreement (EUR-lex, 2021b) concluded

on 24

December 2020, the GDPR remained in force

throughout the UK until 1

July 2021. This meant that

data transfer with the UK could take place under the

terms of the GDPR until 1

July 2021 without it being

considered a third country. After 1

July, if there was

no European Commission decision authorising the

transfer of personal data to the UK ("adequacy

decision"), the country would have been listed as a

third country for the transfer of data and the UK

would have had to demonstrate that it had a sufficient

and adequate level of data protection for transfers to

continue. Instead, the European Commission adopted

an adequacy decision on the UK and the General Data

Protection Regulation on 28

June 2021 (EUR-lex,

2021a). The European Commission found, through its

decisions, that the UK enjoys a level of protection

substantially equivalent to that guaranteed by EU law

and thus transfers of personal data from the EU to the

UK could proceed without further specific directives.

4 REGULATORY APPROACHES

FOR CLINICAL

INVESTIGATION

In the EU MDR, clinical investigation is defined as

“any systematic investigation involving one or more

human participants to assess the safety or

performance of a device”. Clinical investigations are

time-consuming and expensive studies with complex

regulatory procedures.

4.1 Multinational Clinical Investigation

Multinational clinical investigations are

investigations conducted with a common

methodology in more than one country and a common

recruitment pool across all participating countries. In

this way, the multinational dimension allows access

to a larger number of subjects and thus reduces the

duration of the study and its cost while also improving

generalisability of participant characteristics. It

allows the device to be evaluated in different

environments and so ensures that it is compatible with

different organisations.

Finally, the results can be extrapolated more

easily as the study is conducted in more

ClinMed 2022 - Special Session on Dealing with the Change in European Regulations for Medical Devices

252

representative country and manufacturers benefit

from better exposure of their product, which can

facilitate its market penetration once it has been CE

marked.

The main challenge of multinational studies is to

apply for a clinical investigation authorisation from

the regulatory authorities - ethics committee and

competent authority. Although European projects are

subject to the same regulations, these regulations

leave some room for manoeuvre to national law.

Moreover, evaluation of the study by the ethics

committee is specific to each country and the

procedures for submission to the competent

authorities of each Member State are not harmonised

between European countries as yet and until

establishment of this function under the Eudamed

platform.

4.2 Common Rules for Clinical

Investigations

Clinical investigation, regardless of their size

(monocentric, multicentre, international) and their

purpose (compliance with essential requirements,

post-marketing clinical follow-up, etc.), must be

conducted in accordance with rules on ethics and

good clinical practice.

4.2.1 Ethics Rules

A clinical investigation must be designed and

conducted in an ethical manner. The first ethics

principles were proclaimed in 1947 by the Nuremberg

Code, which followed the crimes against humanity

committed during the Second World War. This text

was then completed by the Helsinki Declaration

(Wold Medical Association, 2013) in 1964. These

international texts now constitute the key principles

of ethical research.

4.2.2 Conduct Rules

The clinical investigation should also be designed and

conducted in accordance with good clinical practice.

ICH Good Clinical Practice (GCP: ICH E6(R2)) is an

international ethical and scientific quality standard

for clinical trials involving human subjects

(International Council for Harmonisation of

Technical Requirements for Pharmaceuticals for

Human Use, 2016). This standard has its origin in the

Declaration of Helsinki. GCP: ICH E6 describes a

standard for the design, conduct, recording and

reporting of clinical studies.

Recently, an expert group has established the ISO

14155 (International Organization for

Standardization, 2020) standard which cites Good

Clinical Practice specific to clinical investigations.

This standard is based on ICH GCP E6: R2 and uses

terminology more appropriate to medical devices.

ISO 14155 has its origins in the Declaration of

Helsinki, whose objective is to protect the rights,

safety and well-being of subjects and to ensure that

these principles prevail over the interests of science

and society.

The ISO 14155 standard states in part that a

clinical investigation:

- must be conducted under the responsibility of

a sponsor and should be conducted at the

research site by qualified investigators

- must be conducted in accordance with a

clinical investigation plan (protocol)

- must have received the approval/favourable

opinion of the local ethics committee

- must have received no objection from the local

regulatory authorities (if applicable)

- the subject must have been adequately

informed about their participation and the

risks involved. The subject must have freely

given consent before participating in the

clinical investigation

- medical devices used in clinical investigations

should be used in accordance with the

investigator's brochure, the protocol and the

instructions for use

4.2.3 Data Protection Rules

Clinical investigations conducted in the EU and

United Kingdom must also comply with the GDPR.

To ensure the protection of the rights and freedoms of

individuals, technical and organisational measures

must be taken.

The study sponsor must therefore ensure that the

study complies with the GDPR, since health data,

which is both personal data and sensitive data, is

processed. The person must be informed about the

processing of his data and give his consent to the

processing of his data.

4.3 Regulation of Clinical Investigation

in Europe

Clinical investigations are governed in Europe by the

European Medical Devices Regulation 2017/745. The

establishment of a common regulation as EU MDR is

a real opportunity to harmonize the evaluation time

but also to develop a system of vigilance of medical

Analysis of Impact of European Medical Device Regulation and Brexit on the Regulatory Approaches in a Clinical Investigation Study on a

New Class III Medical Devices Conducted in Europe and United Kingdom

253

devices, absent until now. Chapter VI of the EU MDR

is entirely devoted to the regulation of clinical

evaluations and clinical investigations.

For medical devices of class III, invasive and

implantable device, the study must get the following

requirements:

- validated by the Member State: it must ensure

that the study falls within the scope of the EU

MDR and that the application dossier is

complete

- authorised by the Member State after a full

assessment of the application file

- authorised by the Ethics Committee after

evaluation of the dossier

- covered by insurance/indemnity in case of

injury to participants due to their participation

in the research

- any adverse events must be recorded and

reported to the Member State

- carried out under the responsibility of a

sponsor established in the UE

For clinical investigations of class I medical

devices and class IIa and IIb non-invasive devices, the

requirements are the same, except that the study does

not require Member State authorisation. Article 70

paragraph 7a stipulates that clinical studies require

only a validation from the Member state and the

favourable opinion of the ethics committee unless

otherwise stated by national law. French and Irish law

make use of the opening clause in Article 70(7a) for

clinical investigations with low risk medical devices.

Annex XV of MDR details documents to submit

to member states for validation and/or authorisation

by the member state. Each Member State may request

the submission of specific documents to make its

assessment. Files to submit to the ethics committee

are dependent on the local committee.

The EU MDR specifies that the application for a

clinical investigation must be submitted via the

Eudamed and that the summary and results of the

application must be filed on the portal. The clinical

investigation module of the Eudamed electronic

system is currently not available and will only be

deployed from 2022 onwards, the application must be

made according to national procedures during the

transitional period according to the MDCG 2021-16

(Medical Devices Coordination Group, 2020).

4.3.1 Specific Country Regulation

We will present the specific regulation in three

countries by detailing the regulatory authority with

responsibility for the clinical investigation, the

documents required for submission and the

evaluation timeframes: France, Ireland and England

France. The competent authority in France is the

National Agency for Medicines and Health Products

– ANSM (https://ansm.sante.fr/). It is in charge of

authorising and monitoring clinical studies on

medicines, medical devices, non-health products and

cosmetics in France.

Ethics committee responsible for issuing an

opinion on research projects in France is the “Comité

de Protection des Personnes (CPP)”. There are 40

CPPs in France and the opinion of a single CPP is

required at national level, regardless of the number of

centres. The study files will be submitted on a

national platform and the appointment of a CPP is

done by drawing lots.

The requirements specific to the class of the

device are summarised in the Table 1 and the

difference from the EU MDR are indicated by (*),

using of the opening clause in Article 70(7a).

Table 1: Regulatory procedures required in France to

conduct a clinical investigation to establish the conformity

of a medical device according to its class.

ANSM

validation

ANSM

authorisation

CPP

inion

Class I

Class IIa non-invasive

x x

Class IIb non-invasive*

Class IIa and IIb invasive

Class III

x x x

Researchers and manufacturers can refer to the

guide "Avis aux promoteurs - Investigations cliniques

de dispositifs médicaux relevant du Réglement

Européen N° 2017/745 Partie I" (ANSM, 2021)

available on the ANSM website for the conduct of

their clinical investigations.

To obtain authorisations from the regulatory

authorities, the applicant must first obtain an IDRCB

registration number for its research and obtain the

designation of a CPP. The complete application file

must then be submitted to the designated CPP and to

the ANSM on the same day but separately: by email

or on the Eudralink platform for the ANSM

(https://eudralink.ema.europa.eu/) and on the

CNRIPH platform for the CPP

(https://cnriph.sante.gouv.fr/).

The ANSM has 10 days to validate the application

in accordance with the EU MDR. Then the ANSM

and the CPP must give their opinion within 45 days.

This period may be extended by 20 days by the

ANSM if experts’ consultation is needed.

ClinMed 2022 - Special Session on Dealing with the Change in European Regulations for Medical Devices

254

Ireland. The Health Products Regulatory Authority –

HPRA - (http://www.hpra.ie/homepage/medical-

devices) is the regulatory authority for health

products as medicines, medical devices, cosmetics for

humans and animals in Ireland. The HPRA is the

authority responsible for assessing and authorising

clinical trials of medicines and medical devices.

The ethics committee in Ireland is the National

Research Ethics Committee - NREC, a national ethics

committee (https://www.nrecoffice.ie/).

The requirements specific to the class of the

device are summarised in the Table 2 and the

difference from the EU MDR are indicated by (*),

using of the opening clause in Article 70(7a).

Table 2: Regulatory procedures required in Ireland to

conduct a clinical investigation to establish the conformity

of a medical device according to its class.

HPRA

validation

HPRA

authorisation

NREC

inion

All class of devices* * x x

The "Guide to Clinical Investigations Carried Out

in Ireland"(HPRA, 2021a) is a reference for

researchers and manufacturers.

The authorisation application to be submitted to

the HPRA must be filed on the Common European

Submission Portal (https://cespportal.hma.eu/). For

the ethics committee, the file must be sent by email to

the NREC.

The HPRA has a period of 45 calendar days to

evaluate the application after validation of the file.

The HPRA may consult experts and an additional 20

calendar days is added. The NREC meets once a

month to assess applications. The investigator must

submit the application 12 days before the date of the

plenary meeting and receives a response within 55

days of meeting.

The sponsor must pay fees to the HPRA (HPRA,

2021b) and NREC (https://www.nrecoffice.ie/apply-

2/fees/) for their initial evaluation of the application.

NREC fees are function of industrial or academic lead

and raised at 500€ and 75€ respectively. Fees for

HPRA are dependant of the class of the device:

- class III and IIb medical devices or active

implantable device: 4300€

- class IIa and class I medical devices: 1900€

In case of substantial amendment or resubmission,

supplementary fees are required.

4.3.2 Regulation of Clinical Investigation in

The United Kingdom is a "third country" by the EU.

The EU Medical Devices Regulation 2017/745

therefore does not apply to the UK and clinical

investigations in the UK are governed by the UK

Medical Devices Regulations 2002

(Legislation.gov.uk, 2002).

For a clinical investigation of all class of devices,

the following requirements are needed:

- sponsor is established in UK or in a country

listed in the EU and/or the European

Economic Area.

- a favourable opinion from the ethics

committee

- the authorisation of the competent authority

- the consent of each included subjects

- an insurance/indemnity in case of injury

- to report the adverse event

The competent authority in United Kingdom is

the Medicines and Healthcare Products Regulatory

Agency – MHRA (https://www.gov.uk/government/

organisations/medicines-and-healthcare-products-

regulatory-agency). The MHRA is the body

responsible for assessing and authorising applications

for clinical investigations.

There are over 80 different Research Ethics

Committees (RECs) in the UK within the Research

Ethics Department of the UK Departments of Health

(https://www.hra.nhs.uk/about-us/committees-and-

services/res-and-recs/search-research-ethics-

committees/). RECs are classified as "flagged RECs"

according to the professional, academic and ethical

expertise of the committee members. For clinical

investigations, 10 flagged RECs are listed in England.

Approval of only one REC is required, regardless of

the number of centres involved in the clinical

investigation.

The requirements specific to the class of the

device are summarised in the Table 3.

Table 3: Regulatory procedures required in England to

conduct a clinical investigation to establish the conformity

of a medical device according to its class.

MHRA

authorisation

REC

opinion

All class of devices x x

The application to the MHRA and the REC must

be submitted on the Integrated Research Application

System by the principal investigator of the research in

England (https://www.myresearchproject.org.uk/).

Where the clinical investigation involves the NHS,

patients or NHS staff, approval from the HRA is

required. This application is made in conjunction with

the REC application. The MHRA and the REC each

have 5 days to confirm receipt and completeness of

the application after receipt and 60 days to assess the

application.

Analysis of Impact of European Medical Device Regulation and Brexit on the Regulatory Approaches in a Clinical Investigation Study on a

New Class III Medical Devices Conducted in Europe and United Kingdom

255

The sponsor must pay a fee for the initial

evaluation of the application by the MHRA

(https://www.gov.uk/government/publications/mhra-

fees/current-mhra-fees), which depends on the class

of the device:

- Group A includes Class I, IIa and IIb devices

other than long-term implantable/invasive

devices: £3820

- Group B includes Class IIb implantable/long

term invasive, Class III, active implantable

devices: £5040

In case of amendment or resubmission,

supplementary fees are required by MHRA.

5 PRACTICAL EXAMPLE

The Selio project is a multi-partner European funded,

project on the development of a new medical device

which will be class III in Europe. This project is

supported by EIT Health. It was born during the

period of transition from the European Medical

Device Directive to the European Medical Device

Regulation and the separation of the UK from the

European Union. The EU Medical Device Regulation

2017/745 and Brexit has directly affected the project

and the regulatory steps required to obtain

authorisations to start a clinical investigation

involving French, Irish and English partners. We

present here the expected flow chart of regulatory

steps for the preparation and submission of a clinical

investigation on a new class III medical device.

Class III medical device products without

equivalent on the EU market, require a clinical

investigation in the framework of the clinical

evaluation. A Notified Body will then have to assess

the conformity of the device with the European

requirements in terms of safety and performance in

order to issue the CE mark.

In order to reduce recruitment time and increase

recognition of scientific value, one option for this

project is to conduct a multinational clinical study

with French, Irish and English centres. Science is

stronger when it is collaborative. The UK has been

one of the most important scientific partners in

Europe for decades. Their lack of participation in

such large-scale projects, due to policies different

from those of Europe or regulatory procedures too

complex to include them in such projects, would have

an impact on the value of science.

For the conduct of this clinical investigation, the

sponsor will have to prepare and submit an

application for authorisation in each of the countries

participating in the study. He will thus have to prepare

the documents required for the competent authorities

and ethics committees for their evaluation of the

study and their authorisation.

Although some of the documents are common -

the clinical investigation plan, the information note

and consent form, the investigator's brochure and the

proof of insurance - the latter part of the documents is

specific to each authority and thus requires additional

time and regulatory expertise to draft.

The work required for a multinational study is

much more time and resource intensive than a

national study. It is necessary to have a regulatory

contact in each of the countries participating in the

study for the preparation of the regulatory procedures.

The project team is composed of scientific experts,

project managers, clinical research associates and

clinical study technicians. In addition, an operational

and scientific committee participates in the

construction, validation and follow-up of the study.

The study can start in a given country once the

competent authority has given its authorisation and

the ethics committee has given a favourable opinion.

In an ideal situation, which means without the need

for the regulatory authorities to consult experts or

issue comments and/or modifications to the research,

the research could start approximately two months

after the submission of the application in each country

(table 4).

Table 4: Delay of assessment in days for competent

authorities and ethics committee of France, Ireland and

England. The delay indicated are minimal delay, i.e.

without expert consultation or question to the sponsor.

Competent authority Ethics

committee

France 55 55

Ireland 45 + x days for

validation

England 65 65

In most cases, studies receives from regulatory

authorities opinions subject to minor or major

changes, which can extend the assessment period by

up to 6 months. Furthermore, in the case of

multinational studies, requests for changes to the

study protocol must be carried over all countries in

the form of amendments. This not only lengthens the

evaluation periods but also leads to additional costs

when the activities of the regulatory authorities are

invoiced.

ClinMed 2022 - Special Session on Dealing with the Change in European Regulations for Medical Devices

256

In accordance with the previously announced

costs, the budget for the initial submission of a

clinical study to the regulatory authorities can amount

to more than 10,000€. The budget is consequent and

should not be neglected during the financial set-up.

The variation in evaluation time and cost is

significant when considering best and worst case

scenarios. Investigators and project leaders need to be

able to explain this to funders and investors.

6 WHAT ABOUT THE

COORDINATED EVALUATION

PROCEDURE WITH THE EU

MDR AND THE EUDAMED

PLATFORM?

A coordinated evaluation procedure for clinical

investigations taking place in more than one Member

State will be introduced with the establishment of the

Eudamed, and this procedure will be made mandatory

for European clinical investigations from 26 May

2027.

The coordinated evaluation procedure will thus

simplify the sponsor's procedures, who will only have

to submit one application for authorisation of a clinical

investigation in Europe, regardless of the number of

European countries participating in the study.

A coordinating Member State will be identified

among the Member States participating in the clinical

investigation. The coordinating Member State will be

responsible for assessing whether the clinical

investigation falls within the scope of the EU MDR,

for verifying that the application is complete in

accordance with Annex XV with the exception of

certain documents which are subject to assessment by

each Member State, and for issuing an assessment

report. This report will have to be communicated to

the Member States in order to obtain their comments

on the project. The coordinating Member State will

then have to issue a final evaluation report to the

sponsor taking into account the comments of the

Member States within 45 days of the validation of the

application. This period may be extended to 95 days

if the study concerns a class IIb or III DM and expert

consultation is required.

7 CONCLUSION

Clinical investigations are long and costly studies.

The regulatory approaches could be cumbersome,

even more in the context of a multinational study. The

submission system to be used differ from one country

to another, the documents expected by the regulatory

authorities must be adapted to each regulatory

authority in respect of their national regulations and

the time period for the evaluation is also different and

dependant of certain factors. One potential risk could

be that investigators would seek to limit their study to

one jurisdiction or leave the UK out, resulting in poor

science and less confidence in the quality and

applicability of the devices after authorisation.

Although the European regulation tends to

harmonise practices for European countries, in the

absence of the Eudamed platform, these remain

complex and can therefore be a hindrance to

conducting a study of this scale.

The main advice to be drawn from this example is

that the sponsor should surround himself with people

with appropriate regulatory expertise at the design

stage of the project. For example identifying a

regulatory contact in each of the countries involved in

the study, which will enable him to be informed of the

regulatory steps to be taken for his clinical

investigation: the documents to be prepared, the

authorities in charge of the evaluation and the

deadlines to be respected.

The time needed for the assessment of the study

by the regulatory authorities should not be neglected

when planning the study (best or worst case scenario).

This time, together with the preparation of regulatory

documents, can sometimes exceed one year,

especially in projects of this size. It should therefore

be anticipated for smart project management.

In Europe, project sponsors of multinational

clinical trials can also be supported by the European

Clinical Research Infrastructure Network (ECRIN),

which can conduct by delegation some sponsor tasks

(https://ecrin.org/).

ACKNOWLEDGMENTS

The Selio project has received funding from the EIT

Health (https://eithealth.eu/): ID 20186.

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