EU rules for clinical studies of medical devices

Clinical studies of medical devices in the European Union are governed by Chapter VI of Regulation (EU) 2017/745, Articles 62 to 82, together with Annex XV. The full regime in Articles 62 to 80 and Annex XV applies where an investigation is carried out as part of the clinical evaluation for conformity assessment purposes, for one or more of the purposes listed in Article 62(1).¹ Those purposes are establishing and verifying that a device is suitable for its specific purpose and achieves the performance specified by the manufacturer, establishing and verifying its clinical benefits, and establishing and verifying its clinical safety together with any undesirable side-effects under normal conditions of use.¹ Studies conducted with devices for other reasons fall under Article 82, and studies of devices that already bear the CE marking fall under Article 74.¹

Which studies fall under which rules

Three routes exist in the Regulation. An investigation supporting conformity assessment for one of the Article 62(1) purposes follows Articles 62 to 80, the acts adopted under Article 81 and Annex XV.¹ An investigation that is not performed for any of those purposes complies with a reduced set of provisions.

• Article 62(2) and (3)
• points (b) to (d), (f), (h) and (l) of Article 62(4)
• Article 62(6)

Each Member State defines any additional requirements for such investigations.¹

Article 74 addresses devices that already carry the CE marking under Article 20(1). Where the investigation further assesses the device within the scope of its intended purpose, and subjects undergo procedures additional to those performed under normal conditions of use that are invasive or burdensome, the study is a post-market clinical follow-up investigation. The sponsor notifies the Member States concerned at least 30 days before commencement through the electronic system referred to in Article 73, with the Annex XV Chapter II documentation.¹ Where a CE-marked device is assessed outside the scope of its intended purpose, Articles 62 to 81 apply in full.¹

Conditions that must be satisfied

Article 62(4) sets out thirteen conditions, all of which must be met before an investigation under Article 62(1) may be conducted. The conditions are that:

• the investigation is authorised by the Member State or States in which it is to be conducted, unless otherwise stated
• an ethics committee set up under national law has not issued a negative opinion valid for that entire Member State
• the sponsor, its legal representative or a contact person is established in the Union
• vulnerable populations and subjects are protected in accordance with Articles 64 to 68
• the anticipated benefits to subjects or to public health justify the foreseeable risks and inconveniences, and compliance is constantly monitored
• informed consent has been given under Article 63 by the subject or a legally designated representative
• the subject or representative has contact details of an entity where further information can be received
• rights to physical and mental integrity, privacy and data protection are safeguarded
• the design involves as little pain, discomfort, fear and other foreseeable risk as possible, with the risk threshold and degree of distress defined in the clinical investigation plan
• medical care is the responsibility of an appropriately qualified medical doctor, dental practitioner or other person entitled under national law
• no undue influence, including financial influence, is exerted on the subject or representative
• the investigational device conforms to the applicable general safety and performance requirements in Annex I apart from the aspects covered by the investigation
• the requirements of Annex XV are fulfilled.¹

Article 62(3) requires that investigations be designed and conducted so that the rights, safety, dignity and well-being of subjects prevail over all other interests, and so that the clinical data generated are scientifically valid and reliable. Investigations are subject to both scientific and ethical review, with the ethical review performed by an ethics committee in accordance with national law. At least one lay person participates in the ethical review.¹

Sponsors established outside the Union

A sponsor not established in the Union ensures that a natural or legal person is established in the Union as its legal representative. That representative is responsible for compliance with the sponsor’s obligations under the Regulation and is the addressee for all communications with the sponsor.¹ A Member State may choose not to apply that requirement to investigations conducted solely on its territory, or on its territory and that of a third country, provided the sponsor establishes at least a contact person on its territory.¹

Investigators, staff and sites

The investigator exercises a profession recognised in the Member State concerned as qualifying for the role, on account of the necessary scientific knowledge and experience in patient care. Other personnel are suitably qualified by education, training or experience in the relevant medical field and in clinical research methodology.¹ The facilities where the investigation is conducted are suitable for it and similar to the facilities where the device is intended to be used.¹

Informed consent

Consent is written, dated and signed by the subject or a legally designated representative and by the person who conducted the prior interview. Where the subject is unable to write, consent may be given and recorded by appropriate alternative means in the presence of at least one impartial witness, who signs and dates the document. The subject or representative receives a copy, and adequate time is given for the decision.¹

The information given before consent enables the subject to understand the following.

• the nature, objectives and benefits of the investigation
• its implications, risks and inconveniences
• the right to refuse and to withdraw at any time
• the conditions and expected duration of participation
• the possible treatment alternatives

It is kept comprehensive, concise, clear, relevant and understandable, and is provided in a prior interview with an appropriately qualified member of the investigating team. It includes information on the damage compensation system referred to in Article 69, the Union-wide unique single identification number of the investigation, and information on the availability of results.¹ The interviewer verifies that the subject has understood the information.¹

A subject or representative may withdraw at any time by revoking consent, without detriment and without giving a justification. Withdrawal does not affect activities already carried out or the use of data obtained before it.¹ National law may require that a minor capable of forming an opinion also assents.¹

Application and when an investigation may start

The sponsor submits the application to each Member State concerned with the documentation in Chapter II of Annex XV, through the electronic system referred to in Article 73. That system generates the Union-wide unique single identification number used for all relevant communication.¹ Within 10 days of receiving the application, the Member State notifies the sponsor whether the investigation falls within the scope of the Regulation and whether the dossier is complete. Where it finds otherwise, it sets a time limit of up to 10 days for the sponsor to comment or complete the application, extendable by up to 20 days, and notifies the sponsor within five days of receiving the response. Each of those periods may be extended by a further five days.¹ An application on which the sponsor does not respond in time lapses. Where the sponsor considers the application in scope or complete and the Member State does not, the application is treated as rejected, and the Member State provides an appeal procedure.¹

The date of notification is the validation date, or the last day of the relevant periods where no notification is given.¹ For investigational class I devices and non-invasive class IIa and class IIb devices, the sponsor may start immediately after the validation date unless national law states otherwise, provided no valid negative ethics committee opinion has been issued. For all other investigational devices, the sponsor may start once the Member State has notified its authorisation, again subject to the absence of a negative opinion. The Member State notifies the authorisation within 45 days of the validation date, extendable by a further 20 days for consultation with experts.¹ A request for additional information during assessment suspends the running of that period until the information is received.¹

Safety reporting during the investigation

The sponsor fully records adverse events identified in the clinical investigation plan as critical to the evaluation of results. It also records all serious adverse events, device deficiencies that might have led to a serious adverse event, and new findings relating to any of these.¹ Through the Article 73 electronic system, the sponsor reports without delay to all Member States in which the investigation is being conducted. The reports cover serious adverse events with a causal relationship to the investigational device, comparator or investigation procedure or where such a relationship is reasonably possible, the device deficiencies described above, and new findings. The reporting period takes account of the severity of the event, and an incomplete initial report may be followed by a complete one.¹ Events of that kind occurring in third countries under the same clinical investigation plan are also reported.¹

For post-market clinical follow-up investigations under Article 74(1), the vigilance provisions in Articles 87 to 90 apply in place of Article 80. Article 80 still applies where a causal relationship between the serious adverse event and the preceding investigational procedure has been established.¹

Halt, early termination and reporting of results

A sponsor that temporarily halts or terminates an investigation early informs the Member State concerned within 15 days through the electronic system, with a justification. Where the halt or termination is on safety grounds, all Member States in which the investigation is being conducted are informed within 24 hours.¹ The end of an investigation coincides with the last visit of the last subject unless the clinical investigation plan sets another point. The sponsor notifies the end to each Member State within 15 days, and where the investigation ran in more than one Member State, notifies all of them of the end in all Member States within 15 days of that end.¹

Within one year of the end, the sponsor submits a clinical investigation report to the Member States concerned, irrespective of the outcome. In the case of early termination or temporary halt, the report is due within three months. The report is accompanied by a summary in terms easily understandable to the intended user. Where scientific reasons prevent submission within one year, the report is submitted as soon as it is available, and the clinical investigation plan states when results will be available with a justification.¹ The summary and report become publicly accessible through the electronic system at the latest when the device is registered under Article 29 and before it is placed on the market. After early termination or a temporary halt they become public immediately after submission. Where the device is not registered within one year of entry of the documents, they become public at that point.¹

Dates of application

The Regulation applies from 26 May 2021.¹ Article 123(3)(d) defers the obligations that relate to the electronic systems referred to in Article 33(2), including Articles 70 to 77 and Articles 79 to 82, to a date six months after publication of the notice under Article 34(3) that the relevant electronic system is functional and meets its functional specifications. Until that date, the corresponding provisions of Directives 90/385/EEC and 93/42/EEC on information relating to clinical investigations continue to apply.¹ Articles 62 to 69 are outside that deferral.

Investigations that started under Article 10 of Directive 90/385/EEC or Article 15 of Directive 93/42/EEC before 26 May 2021 may continue. Since that date, reporting of serious adverse events and device deficiencies for those investigations follows the Regulation.¹

Questions people also ask

When does a study of a CE-marked device need to be notified in the EU? Notification is required where the study further assesses the device within the scope of its intended purpose and subjects undergo additional procedures that are invasive or burdensome. The sponsor notifies the Member States concerned at least 30 days before commencement through the electronic system referred to in Article 73, enclosing the documentation in Chapter II of Annex XV. Where the device is assessed outside the scope of its intended purpose, Articles 62 to 81 apply in full.¹

How long does a Member State have to authorise a clinical investigation? For investigational devices other than class I devices and non-invasive class IIa and class IIb devices, the Member State notifies its authorisation within 45 days of the validation date, and may extend that period by a further 20 days to consult experts. A request for additional information suspends the running of the period until the information is received.¹

Can a study begin without an express authorisation decision? For investigational class I devices and non-invasive class IIa and class IIb devices, the sponsor may start immediately after the validation date of the application, unless national law states otherwise. In all cases an ethics committee in the Member State concerned must not have issued a negative opinion valid for that entire Member State under national law.¹

Must results be made public when a study is stopped early? Yes. The sponsor submits the clinical investigation report and its summary within three months of the early termination or temporary halt, irrespective of outcome. In those cases the summary and report become publicly accessible through the electronic system immediately after submission.¹

What rules apply to device studies that are not for conformity assessment? Article 82 applies. Such investigations comply with the following provisions.

• Article 62(2) and (3)
• points (b) to (d), (f), (h) and (l) of Article 62(4)
• Article 62(6)

Each Member State defines any additional requirements it considers appropriate for investigations conducted on its territory.¹

Footnotes

1. Regulation (EU) 2017/745 of the European Parliament and of the Council of 5 April 2017 on medical devices, amending Directive 2001/83/EC, Regulation (EC) No 178/2002 and Regulation (EC) No 1223/2009 and repealing Council Directives 90/385/EEC and 93/42/EEC. Consolidated version of 2026-07-19. https://eur-lex.europa.eu/legal-content/EN/TXT/?uri=CELEX:02017R0745-20260719 ↩ ↩² ↩³ ↩⁴ ↩⁵ ↩⁶ ↩⁷ ↩⁸ ↩⁹ ↩¹⁰ ↩¹¹ ↩¹² ↩¹³ ↩¹⁴ ↩¹⁵ ↩¹⁶ ↩¹⁷ ↩¹⁸ ↩¹⁹ ↩²⁰ ↩²¹ ↩²² ↩²³ ↩²⁴ ↩²⁵ ↩²⁶ ↩²⁷ ↩²⁸ ↩²⁹ ↩³⁰ ↩³¹ ↩³² ↩³³ ↩³⁴ ↩³⁵ ↩³⁶ ↩³⁷ ↩³⁸ ↩³⁹ ↩⁴⁰