MDR – Article 78 – Coordinated assessment procedure for clinical investigations

Article 78

Coordinated assessment procedure for clinical investigations

1. By means of the electronic system referred to in Article 73, the sponsor of a clinical investigation to be conducted in more than one Member State may submit, for the purpose of Article 70, a single application that, upon receipt, is transmitted electronically to all Member States in which the clinical investigation is to be conducted.

2. The sponsor shall propose in the single application referred to in paragraph 1 that one of the Member States in which the clinical investigation is to be conducted acts as coordinating Member State. The Member States in which the clinical investigation is to be conducted shall, within six days of submission of the application, agree on one of them taking the role of the coordinating Member State. If they do not agree on a coordinating Member State, the coordinating Member State proposed by the sponsor shall assume that role.

3. Under the direction of the coordinating Member State referred to in paragraph 2, the Member States concerned shall coordinate their assessment of the application, in particular of the documentation referred to in Chapter II of Annex XV.

However, the completeness of the documentation referred to in Sections 1.13, 3.1.3, 4.2, 4.3 and 4.4 of Chapter II of Annex XV shall be assessed separately by each Member State concerned in accordance with Article 70(1) to (5).

4. With regard to documentation other than that referred to in the second subparagraph of paragraph 3, the coordinating Member State shall:

(a)within six days of receipt of the single application, notify the
sponsor that it is the coordinating Member State (‘notification date’);
(b)for the purpose of the validation of the application, take into
account any considerations submitted within seven days of the
notification date by any Member State concerned;
(c)within 10 days of the notification date, assess whether the clinical
investigation falls within the scope of this Regulation and whether
the application is complete, and shall notify the sponsor accordingly.Article 70(1) and (3) to (5) shall apply to the coordinating Member State in relation to that assessment;
(d)establish the results of its assessment in a draft assessment report to be transmitted within 26 days of the validation date to the Member States concerned. By day 38 after the validation date, the other
Member States concerned shall transmit their comments and
proposals on the draft assessment report and the underlying
application to the coordinating Member State which shall take due
account of those comments and proposals in its finalisation of the
final assessment report, to be transmitted within 45 days of the
validation date to the sponsor and the other Member States
concerned.

The final assessment report shall be taken into account by all Member States concerned when deciding on the sponsor’s application in accordance with Article 70(7).

5. As regards the assessment of the documentation referred to in the second subparagraph of paragraph 3, each Member State concerned may request, on a single occasion, additional information from the sponsor. The sponsor shall submit the requested additional information within the period set by the Member State concerned, which shall not exceed 12 days from the receipt of the request. The expiry of the last deadline pursuant to point (d) of paragraph 4 shall be suspended from the date of the request until such time as the additional information has been received.

6. For class IIb and class III devices, the coordinating Member State may also extend the periods referred to in paragraph 4 by a further 50 days, for the purpose of consulting with experts.

7. The Commission may, by means of implementing acts, further specify the procedures and timescales for coordinated assessments to be taken into account by Member States concerned when deciding on the sponsor’s application. Such implementing acts may also set out the procedures and timescales for coordinated assessment in the case of substantial modifications pursuant to paragraph 12 of this Article, in the case of reporting of adverse events pursuant to Article 80(4) and in the case of clinical investigations of combination products between medical devices and medicinal products, where the latter are under a concurrent coordinated assessment of a clinical trial under Regulation (EU) No 536/2014. Those implementing acts shall be adopted in accordance with the examination procedure referred to in Article 114(3).

8. Where the conclusion of the coordinating Member State concerning the area of coordinated assessment is that the conduct of the clinical investigation is acceptable or acceptable subject to compliance with specific conditions, that conclusion shall be deemed to be the conclusion of all Member States concerned.

Notwithstanding the first subparagraph, a Member State concerned may only disagree with the conclusion of the coordinating Member State concerning the area of coordinated assessment on the following grounds:

(a)when it considers that participation in the clinical investigation
would lead to a subject receiving treatment inferior to that received in normal clinical practice in that Member State concerned;
(b)infringement of national law; or
(c)considerations as regards subject safety and data reliability and
robustness submitted under point (b) of paragraph 4.

Where one of the Member States concerned disagrees with the conclusion on the basis of the second subparagraph of this paragraph, it shall communicate its disagreement, together with a detailed justification, through the electronic system referred to in Article 73, to the Commission, to all other Member States concerned and to the sponsor.

9. Where the conclusion of the coordinating Member State concerning the area of coordinated assessment is that the clinical investigation is not acceptable, that conclusion shall be deemed to be the conclusion of all Member States concerned.

10. A Member State concerned shall refuse to authorise a clinical investigation if it disagrees with the conclusion of the coordinating Member State as regards any of the grounds referred to in the second subparagraph of paragraph 8, or if it finds, on duly justified grounds, that the aspects addressed in Sections 1.13, 3.1.3, 4.2, 4.3 and 4.4 of Chapter II of Annex XV are not complied with, or where an ethics committee has issued a negative opinion in relation to that clinical investigation, which is valid, in accordance with national law, for that entire Member State. That Member State shall provide for an appeal procedure in respect of such refusal.

11. Each Member State concerned shall notify the sponsor through the electronic system referred to in Article 73 as to whether the clinical investigation is authorised, whether it is authorised subject to conditions, or whether authorisation has been refused. Notification shall be done by way of one single decision within five days of the transmission, pursuant to point (d) of paragraph 4, by the coordinating Member State of the final assessment report. Where an authorisation of a clinical investigation is subject to conditions, those conditions may only be such that, by their nature, they cannot be fulfilled at the time of that authorisation.

12. Any substantial modifications as referred to in Article 75 shall be notified to the Member States concerned by means of the electronic system referred to in Article 73. Any assessment as to whether there are grounds for disagreement as referred to in the second subparagraph of paragraph 8 of this Article shall be carried out under the direction of the coordinating Member State, except for substantial modifications concerning Sections 1.13, 3.1.3, 4.2, 4.3 and 4.4 of Chapter II of Annex XV, which shall be assessed separately by each Member State concerned.

13. The Commission shall provide administrative support to the coordinating Member State in the accomplishment of its tasks under this Chapter.

14. The procedure set out in this Article shall, until 27 May 2027, be applied only by those of the Member States in which the clinical investigation is to be conducted which have agreed to apply it. After 27 May 2027, all Member States shall be required to apply that procedure.

MDR – Article 77 – Information from the sponsor at the end of a clinical investigation or in the event of a temporary halt or early termination

Article 77

Information from the sponsor at the end of a clinical investigation or in the event of a temporary halt or early termination

1. If the sponsor has temporarily halted a clinical investigation or has terminated a clinical investigation early, it shall inform within 15 days the Member State in which that clinical investigation has been temporarily halted or terminated early, through the electronic system referred to in Article 73, of the temporary halt or early termination, providing a justification. In the event that the sponsor has temporarily halted or terminated early the clinical investigation on safety grounds, it shall inform all Member States in which that clinical investigation is being conducted thereof within 24 hours.

2. The end of a clinical investigation shall be deemed to coincide with the last visit of the last subject unless another point in time for such end is set out in the clinical investigation plan.

3. The sponsor shall notify each Member State in which a clinical investigation was being conducted of the end of that clinical investigation in that Member State. That notification shall be made within 15 days of the end of the clinical investigation in relation to that Member State.

4. If an investigation is conducted in more than one Member State, the sponsor shall notify all Member States in which that clinical investigation was conducted of the end of the clinical investigation in all Member States. That notification shall be made within 15 days of that end of the clinical investigation.

5. Irrespective of the outcome of the clinical investigation, within one year of the end of the clinical investigation or within three months of the early termination or temporary halt, the sponsor shall submit to the Member States in which a clinical investigation was conducted a clinical investigation report as referred to in Section 2.8 of Chapter I and Section 7 of Chapter III of Annex XV.

The clinical investigation report shall be accompanied by a summary presented in terms that are easily understandable to the intended user. Both the report and summary shall be submitted by the sponsor by means of the electronic system referred to in Article 73.

Where, for scientific reasons, it is not possible to submit the clinical investigation report within one year of the end of the investigation, it shall be submitted as soon as it is available. In such case, the clinical investigation plan referred to in Section 3 of Chapter II of Annex XV shall specify when the results of the clinical investigation are going to be available, together with a justification.

6. The Commission shall issue guidelines regarding the content and structure of the summary of the clinical investigation report.

In addition, the Commission may issue guidelines for the formatting and sharing of raw data, for cases where the sponsor decides to share raw data on a voluntary basis. Those guidelines may take as a basis and adapt, where possible, existing guidelines for sharing of raw data in the field of clinical investigations.

7. The summary and the clinical investigation report referred to in paragraph 5 of this Article shall become publicly accessible through the electronic system referred to in Article 73, at the latest when the device is registered in accordance with Article 29 and before it is placed on the market. In cases of early termination or temporary halt, the summary and the report shall become publicly accessible immediately after submission.

If the device is not registered in accordance with Article 29 within one year of the summary and the report having been entered into the electronic system pursuant to paragraph 5 of this Article, they shall become publicly accessible at that point in time.

MDR – Article 76 – Corrective measures to be taken by Member States and information exchange between Member States

Article 76

Corrective measures to be taken by Member States and information exchange between Member States

1. Where a Member State in which a clinical investigation is being or is to be conducted has grounds for considering that the requirements set out in this Regulation are not met, it may take at least any of the following measures on its territory:

(a)revoke the authorisation for the clinical investigation;
(b)suspend or terminate the clinical investigation;
(c)require the sponsor to modify any aspect of the clinical
investigation.

2. Before the Member State concerned takes any of the measures referred to in paragraph 1 it shall, except where immediate action is required, ask the sponsor or the investigator or both for their opinion. That opinion shall be delivered within seven days.

3. Where a Member State has taken a measure referred to in paragraph 1 of this Article or has refused a clinical investigation, or has been notified by the sponsor of the early termination of a clinical investigation on safety grounds, that Member State shall communicate the corresponding decision and the grounds therefor to all Member States and the Commission by means of the electronic system referred to in Article 73.

4. Where an application is withdrawn by the sponsor prior to a decision by a Member State, that information shall be made available through the electronic system referred to in Article 73 to all Member States and the Commission.

MDR – Article 75 – Substantial modifications to clinical investigations

Article 75

Substantial modifications to clinical investigations

1. If a sponsor intends to introduce modifications to a clinical investigation that are likely to have a substantial impact on the safety, health or rights of the subjects or on the robustness or reliability of the clinical data generated by the investigation, it shall notify, within one week, by means of the electronic system referred to in Article 73 the Member State(s) in which the clinical investigation is being or is to be conducted of the reasons for and the nature of those modifications. The sponsor shall include an updated version of the relevant documentation referred to in Chapter II of Annex XV as part of the notification. Changes to the relevant documentation shall be clearly identifiable.

2. The Member State shall assess any substantial modification to the clinical investigation in accordance with the procedure laid down in Article 71.

3. The sponsor may implement the modifications referred to in paragraph 1 at the earliest 38 days after the notification referred to in that paragraph, unless:

(a)the Member State in which the clinical investigation is being or is tobe conducted has notified the sponsor of its refusal based on the
grounds referred to in Article 71(4) or on considerations of public
health, subject and user safety or health, of public policy, or
(b)an ethics committee in that Member State has issued a negative
opinion in relation to the substantial modification to the clinical
investigation, which, in accordance with national law, is valid for
that entire Member State.

4. The Member State(s) concerned may extend the period referred to in paragraph 3 by a further seven days, for the purpose of consulting with experts.

MDR – Article 74 – Clinical investigations regarding devices bearing the CE marking

Article 74

Clinical investigations regarding devices bearing the CE marking

1. Where a clinical investigation is to be conducted to further assess, within the scope of its intended purpose, a device which already bears the CE marking in accordance with Article 20(1), (‘PMCF investigation’), and where the investigation would involve submitting subjects to procedures additional to those performed under the normal conditions of use of the device and those additional procedures are invasive or burdensome, the sponsor shall notify the Member States concerned at least 30 days prior to its commencement by means of the electronic system referred to in Article 73. The sponsor shall include the documentation referred to in Chapter II of Annex XV as part of the notification. Points (b) to (k) and (m) of Article 62(4), Article 75, Article 76, Article 77, Article 80(5) and the relevant provisions of Annex XV shall apply to PMCF investigations.

2. Where a clinical investigation is to be conducted to assess, outside the scope of its intended purpose, a device which already bears the CE marking in accordance with Article 20(1), Articles 62 to 81 shall apply.

MDR – Article 73 – Electronic system on clinical investigations

Article 73

Electronic system on clinical investigations

1. The Commission shall, in collaboration with the Member States, set up, manage and maintain an electronic system:

(a)to create the single identification numbers for clinical investigations referred to in Article 70(1);
(b)to be used as an entry point for the submission of all applications ornotifications for clinical investigations referred to in Articles 70, 74, 75 and 78 and for all other submission of data, or processing of data in this context;
(c)for the exchange of information relating to clinical investigations inaccordance with this Regulation between the Member States and
between them and the Commission including the exchange of
information referred to in Articles 70 and 76;
(d)for information to be provided by the sponsor in accordance with
Article 77, including the clinical investigation report and its
summary as required in paragraph 5 of that Article;
(e)for reporting on serious adverse events and device deficiencies and related updates referred to in Article 80.

2. When setting up the electronic system referred in paragraph 1 of this Article, the Commission shall ensure that it is interoperable with the EU database for clinical trials on medicinal products for human use set up in accordance with Article 81 of Regulation (EU) No 536/2014 of the European Parliament and of the Council (1) as concerns combined clinical investigations of devices with a clinical trial under that Regulation.

3. The information referred to in point (c) of paragraph 1 shall only be accessible to the Member States and the Commission. The information referred to in the other points of that paragraph shall be accessible to the public, unless, for all or parts of that information, confidentiality of the information is justified on any of the following grounds:

(a)protection of personal data in accordance with Regulation (EC) No
45/2001;
(b)protection of commercially confidential information, especially in
the investigators brochure, in particular through taking into account the status of the conformity assessment for the device, unless there
is an overriding public interest in disclosure;
(c)effective supervision of the conduct of the clinical investigation by
the Member State(s) concerned.

4. No personal data of subjects shall be publicly available.

5. The user interface of the electronic system referred to in paragraph 1 shall be available in all official languages of the Union.

(1) Regulation (EU) No 536/2014 of the European Parliament and of the Council of 16 April 2014 on clinical trials on medicinal products for human use, and repealing Directive 2001/20/EC (OJ L 158, 27.5.2014, p. 1).

MDR – Article 72 – Conduct of a clinical investigation

Article 72

Conduct of a clinical investigation

1. The sponsor and the investigator shall ensure that the clinical investigation is conducted in accordance with the approved clinical investigation plan.

2. In order to verify that the rights, safety and well-being of subjects are protected, that the reported data are reliable and robust, and that the conduct of the clinical investigation is in compliance with the requirements of this Regulation, the sponsor shall ensure adequate monitoring of the conduct of a clinical investigation. The extent and nature of the monitoring shall be determined by the sponsor on the basis of an assessment that takes into consideration all characteristics of the clinical investigation including the following:

(a)the objective and methodology of the clinical investigation; and
(b)the degree of deviation of the intervention from normal clinical
practice.

3. All clinical investigation information shall be recorded, processed, handled, and stored by the sponsor or investigator, as applicable, in such a way that it can be accurately reported, interpreted and verified while the confidentiality of records and the personal data of the subjects remain protected in accordance with the applicable law on personal data protection.

4. Appropriate technical and organisational measures shall be implemented to protect information and personal data processed against unauthorised or unlawful access, disclosure, dissemination, alteration, or destruction or accidental loss, in particular where the processing involves transmission over a network.

5. Member States shall inspect, at an appropriate level, investigation site(s) to check that clinical investigations are conducted in accordance with the requirements of this Regulation and with the approved investigation plan.

6. The sponsor shall establish a procedure for emergency situations which enables the immediate identification and, where necessary, an immediate recall of the devices used in the investigation.

MDR – Article 71 – Assessment by Member States

Article 71

Assessment by Member States

1. Member States shall ensure that the persons validating and assessing the application, or deciding on it, do not have conflicts of interest, are independent of the sponsor, the investigators involved and of natural or legal persons financing the clinical investigation, as well as free of any other undue influence.

2. Member States shall ensure that the assessment is done jointly by an appropriate number of persons who collectively have the necessary qualifications and experience.

3. Member States shall assess whether the clinical investigation is designed in such a way that potential remaining risks to subjects or third persons, after risk minimization, are justified, when weighed against the clinical benefits to be expected. They shall, while taking into account applicable CS or harmonised standards, examine in particular:

(a)the demonstration of compliance of the investigational device(s)
with the applicable general safety and performance requirements,
apart from the aspects covered by the clinical investigation, and
whether, with regard to those aspects, every precaution has been
taken to protect the health and safety of the subjects. This includes, where appropriate, assurance of technical and biological safety
testing and pre-clinical evaluation;
(b)whether the risk-minimisation solutions employed by the sponsor
are described in harmonised standards and, in those cases where
the sponsor does not use harmonised standards, whether the
risk-minimisation solutions provide a level of protection that is
equivalent to that provided by harmonised standards;
(c)whether the measures planned for the safe installation, putting into service and maintenance of the investigational device are adequate;
(d)the reliability and robustness of the data generated in the clinical
investigation, taking account of statistical approaches, design of the
investigation and methodological aspects, including sample size,
comparator and endpoints;
(e)whether the requirements of Annex XV are met;
(f)in the case of devices for sterile use, evidence of the validation of the manufacturer’s sterilisation procedures or information on the
reconditioning and sterilisation procedures which have to be
conducted by the investigation site;
(g)the demonstration of the safety, quality and usefulness of any
components of animal or human origin or of substances, which maybe considered medicinal products in accordance with Directive 2001/83/EC.

4. Member States shall refuse the authorisation of the clinical investigation if:

(a)the application dossier submitted pursuant to Article 70(1) remains
incomplete;
(b)the device or the submitted documents, especially the investigation
plan and the investigator’s brochure, do not correspond to the state of scientific knowledge, and the clinical investigation, in particular, is not suitable for providing evidence for the safety, performance
characteristics or benefit of the device on subjects or patients,
(c)the requirements of Article 62 are not met, or
(d)any assessment under paragraph 3 is negative.

Member States shall provide for an appeal procedure in respect of a refusal pursuant to the first subparagraph.

MDR – Article 70 – Application for clinical investigations

Article 70

Application for clinical investigations

1. The sponsor of a clinical investigation shall submit an application to the Member State(s) in which the clinical investigation is to be conducted (referred to for the purposes of this Article as ‘Member State concerned’) accompanied by the documentation referred to in Chapter II of Annex XV.

The application shall be submitted by means of the electronic system referred to in Article 73, which shall generate a Union-wide unique single identification number for the clinical investigation, which shall be used for all relevant communication in relation to that clinical investigation. Within 10 days of it receiving the application, the Member State concerned shall notify the sponsor as to whether the clinical investigation falls within the scope of this Regulation and as to whether the application dossier is complete in accordance with Chapter II of Annex XV.

2. Within one week of any change occurring in relation to the documentation referred to in Chapter II of Annex XV, the sponsor shall update the relevant data in the electronic system referred to in Article 73 and make that change to the documentation clearly identifiable. The Member State concerned shall be notified of the update by means of that electronic system.

3. Where the Member State concerned finds that the clinical investigation applied for does not fall within the scope of this Regulation or that the application dossier is not complete, it shall inform the sponsor thereof and shall set a time limit of maximum 10 days for the sponsor to comment or to complete the application by means of the electronic system referred to in Article 73. The Member State concerned may extend this period by a maximum of 20 days where appropriate.

Where the sponsor has not provided comments nor completed the application within the time limit referred to in the first subparagraph, the application shall be deemed to have lapsed. Where the sponsor considers the application does fall under the scope of this Regulation and/or is complete but the Member State concerned does not, the application shall be considered to have been rejected. The Member State concerned shall provide for an appeal procedure in respect of such refusal.

The Member State concerned shall notify the sponsor within five days of receipt of the comments or of the requested additional information, whether the clinical investigation is considered as falling within the scope of this Regulation and the application is complete.

4. The Member State concerned may also extend the period referred to in paragraph 1 and 3 each by a further five days.

5. For the purposes of this Chapter, the date on which the sponsor is notified in accordance with paragraph 1 or 3 shall be the validation date of the application. Where the sponsor is not notified, the validation date shall be the last day of the periods referred to in paragraphs 1, 3 and 4 respectively.

6. During the period when the application is being assessed, the Member State may request additional information from the sponsor. The expiry of the period laid down in point (b) of paragraph 7 shall be suspended from the date of the first request until such time as the additional information has been received.

7. The sponsor may start the clinical investigation in the following circumstances:

(a)in the case of investigational class I devices or in the case of
non-invasive class IIa and class IIb devices, unless otherwise stated by national law, immediately after the validation date of the
application pursuant to paragraph 5, and provided that a negative
opinion which is valid for the entire Member State, under national
law, has not been issued by an ethics committee in the Member State concerned in respect of the clinical investigation;
(b)in the case of investigational devices, other than those referred to
in point (a), as soon as the Member State concerned has notified the sponsor of its authorisation, and provided that a negative opinion
which is valid for the entire Member State, under national law, has
not been issued by an ethics committee in the Member State
concerned in respect of the clinical investigation. The Member State shall notify the sponsor of the authorisation within 45 days of the
validation date referred to in paragraph 5. The Member State may
extend this period by a further 20 days for the purpose of consulting with experts.

8. The Commission is empowered to adopt delegated acts in accordance with Article 115 amending, in the light of technical progress and global regulatory developments, the requirements laid down in Chapter II of Annex XV.

9. In order to ensure the uniform application of the requirements laid down in Chapter II of Annex XV, the Commission may adopt implementing acts to the extent necessary to resolve issues of divergent interpretation and of practical application. Those implementing acts shall be adopted in accordance with the examination procedure referred to in Article 114(3).

MDR – Article 69 – Damage compensation

Article 69

Damage compensation

1. Member States shall ensure that systems for compensation for any damage suffered by a subject resulting from participation in a clinical investigation conducted on their territory are in place in the form of insurance, a guarantee, or a similar arrangement that is equivalent as regards its purpose and which is appropriate to the nature and the extent of the risk.

2. The sponsor and the investigator shall make use of the system referred to in paragraph 1 in the form appropriate for the Member State in which the clinical investigation is conducted.