MDR – Article 106 – Provision of scientific, technical and clinical opinions and advice

Article 106

Provision of scientific, technical and clinical opinions and advice

1. The Commission shall, by means of implementing acts and in consultation with the MDCG, make provision for expert panels to be designated for the assessment of the clinical evaluation in relevant medical fields as referred to in paragraph 9 of this Article and to provide views in accordance with Article 48(6) of Regulation (EU) 2017/746 on the performance evaluation of certain in vitro diagnostic medical devices and, where necessary, for categories or groups of devices, or for specific hazards relating to categories or groups of devices, observing the principles of highest scientific competence, impartiality, independence and transparency. The same principles shall apply where the Commission decides to appoint expert laboratories in accordance with paragraph 7 of this Article.

2. Expert panels and expert laboratories may be designated in areas where the Commission, in consultation with the MDCG, has identified a need for the provision of consistent scientific, technical and/or clinical advice or laboratory expertise in relation to the implementation of this Regulation. Expert panels and expert laboratories may be appointed on a standing or temporary basis.

3. Expert panels shall consist of advisors appointed by the Commission on the basis of up-to-date clinical, scientific or technical expertise in the field and with a geographical distribution that reflects the diversity of scientific and clinical approaches in the Union. The Commission shall determine the number of members of each panel in accordance with the requisite needs.

The members of expert panels shall perform their tasks with impartiality and objectivity. They shall neither seek nor take instructions from notified bodies or manufacturers. Each member shall draw up a declaration of interests, which shall be made publicly available.

The Commission shall establish systems and procedures to actively manage and prevent potential conflicts of interest.

4. Expert panels shall take into account relevant information provided by stakeholders including patients’ organisations and healthcare professionals when preparing their scientific opinions.

5. The Commission, following consultation with the MDCG, may appoint advisors to expert panels following publication in the Official Journal of the European Union and on the Commission website following a call for expressions of interest. Depending on the type of task and the need for specific expertise, advisors may be appointed to the expert panels for a maximum period of three years and their appointment may be renewed.

6. The Commission, following consultation with the MDCG, may include advisors on a central list of available experts who, whilst not being formally appointed to a panel, are available to provide advice and to support the work of the expert panel as needed. That list shall be published on the Commission website.

7. The Commission may, by means of implementing acts and following consultation with the MDCG, designate expert laboratories, on the basis of their expertise in:

—physico-chemical characterisation, or
—microbiological, biocompatibility, mechanical, electrical, electronic
or non-clinical biological and toxicological testing

of specific devices, categories or groups of devices.

The Commission shall only designate expert laboratories for which a Member State or the Joint Research Centre has submitted an application for designation.

8. Expert laboratories shall satisfy the following criteria:

(a)have adequate and appropriately qualified staff with adequate
knowledge and experience in the field of the devices for which theyare designated;
(b)possess the necessary equipment to carry out the tasks assigned to
them;
(c)have the necessary knowledge of international standards and best
practices;
(d)have an appropriate administrative organisation and structure;
(e)ensure that their staff observe the confidentiality of information and data obtained in carrying out their tasks.

9. Expert panels appointed for clinical evaluation in relevant medical fields shall fulfil the tasks provided for in Article 54(1) and Article 61(2) and Section 5.1 of Annex IX or Section 6 of Annex X, as applicable.

10. Expert panels and expert laboratories may have the following tasks, depending on the requisite needs:

(a)to provide scientific, technical and clinical assistance to the
Commission and the MDCG in relation to the implementation of thisRegulation;
(b)to contribute to the development and maintenance of appropriate
guidance and CS for:
— clinical investigations,
— clinical evaluation and PMCF,
— performance studies,
— performance evaluation and post-market performance follow-up,— physico-chemical characterisation, and
— microbiological, biocompatibility, mechanical, electrical,
electronic or non-clinical toxicological testing

for specific devices, or a category or group of devices, or for specific hazards related to a category or group of devices;

(c)to develop and review clinical evaluation guidance and performance evaluation guidance for performance of conformity assessment in
line with the state of the art with regard to clinical evaluation,
performance evaluation, physico-chemical characterisation, and
microbiological, biocompatibility, mechanical, electrical, electronic
or non- clinical toxicological testing;
(d)to contribute to the development of standards at international level,ensuring that such standards reflect the state of the art;
(e)to provide opinions in response to consultations by manufacturers
in accordance with Article 61(2), notified bodies and Member States
in accordance with paragraphs 11 to 13 of this Article.
(f)to contribute to identification of concerns and emerging issues on
the safety and performance of medical devices;
(g)to provide views in accordance with Article 48(4) of Regulation (EU) 2017/746 on the performance evaluation of certain in vitro
diagnostic medical devices.

11. The Commission, shall facilitate the access of Member States and notified bodies and manufacturers to advice provided by expert panels and expert laboratories concerning, inter alia, the criteria for an appropriate data set for assessment of the conformity of a device, in particular with regard to the clinical data required for clinical evaluation, with regard to physico-chemical characterisation, and with regard to microbiological, biocompatibility, mechanical, electrical, electronic and non-clinical toxicological testing.

12. When adopting its scientific opinion in accordance with paragraph 9, the members of the expert panels shall use their best endeavours to reach consensus. If consensus cannot be reached, the expert panels shall decide by a majority of their members, and the scientific opinion shall mention the divergent positions and the grounds on which they are based.

The Commission shall publish the scientific opinion and advice delivered in accordance with paragraphs 9 and 11 of this Article, ensuring consideration of aspects of confidentiality as set out in Article 109. The clinical evaluation guidance referred to in point (c) of paragraph 10 shall be published following consultation with the MDCG.

13. The Commission may require manufacturers and notified bodies to pay fees for the advice provided by expert panels and expert laboratories. The structure and the level of fees as well as the scale and structure of recoverable costs shall be adopted by the Commission by means of implementing acts, taking into account the objectives of the adequate implementation of this Regulation, protection of health and safety, support of innovation and cost-effectiveness and the necessity to achieve active participation in the expert panels. Those implementing acts shall be adopted in accordance with the examination procedure referred to in Article 114(3).

14. The fees payable to the Commission in accordance with the procedure under paragraph 13 of this Article shall be set in a transparent manner and on the basis of the costs for the services provided. The fees payable shall be reduced in the case of a clinical evaluation consultation procedure initiated in accordance with point (c) of Section 5.1 of Annex IX involving a manufacturer who is a micro, small or medium-sized enterprise within the meaning of Recommendation 2003/361/EC.

15. The Commission is empowered to adopt delegated acts in accordance with Article 115 to amend the tasks of expert panels and expert laboratories referred to in paragraph 10 of this Article.

MDR – Article 82 – Requirements regarding other clinical investigations

Article 82

Requirements regarding other clinical investigations

1. Clinical investigations, not performed pursuant to any of the purposes listed in Article 62(1), shall comply with the provisions of Article 62 (2) and (3), points (b), (c), (d), (f), (h), and (l) of Article 62(4) and Article 62(6).

2. In order to protect the rights, safety, dignity and well-being of subjects and the scientific and ethical integrity of clinical investigations not performed for any of the purposes listed in Article 62(1), each Member State shall define any additional requirements for such investigations, as appropriate for each Member State concerned.

MDR – Article 80 – Recording and reporting of adverse events that occur during clinical investigations

Article 80

Recording and reporting of adverse events that occur during clinical investigations

1. The sponsor shall fully record all of the following:

(a)any adverse event of a type identified in the clinical investigation
plan as being critical to the evaluation of the results of that clinical
investigation;
(b)any serious adverse event;
(c)any device deficiency that might have led to a serious adverse event if appropriate action had not been taken, intervention had not
occurred, or circumstances had been less fortunate;
(d)any new findings in relation to any event referred to in points (a) to(c).

2. The sponsor shall report, without delay to all Member States in which the clinical investigation is being conducted, all of the following by means of the electronic system referred to in Article 73:

(a)any serious adverse event that has a causal relationship with the
investigational device, the comparator or the investigation
procedure or where such causal relationship is reasonably possible;
(b)any device deficiency that might have led to a serious adverse event if appropriate action had not been taken, intervention had not
occurred, or circumstances had been less fortunate;
(c)any new findings in relation to any event referred to in points (a)
and (b).

The period for reporting shall take account of the severity of the event. Where necessary to ensure timely reporting, the sponsor may submit an initial report that is incomplete followed up by a complete report.

Upon request by any Member State in which the clinical investigation is being conducted, the sponsor shall provide all information referred to in paragraph 1.

3. The sponsor shall also report to the Member States in which the clinical investigation is being conducted any event referred to in paragraph 2 of this Article that occurred in third countries in which a clinical investigation is performed under the same clinical investigation plan as the one applying to a clinical investigation covered by this Regulation by means of the electronic system referred to in Article 73.

4. In the case of a clinical investigation for which the sponsor has used the single application referred to in Article 78, the sponsor shall report any event as referred to in paragraph 2 of this Article by means of the electronic system referred to in Article 73. Upon receipt, this report shall be transmitted electronically to all Member States in which the clinical investigation is being conducted.

Under the direction of the coordinating Member State referred to in Article 78(2), the Member States shall coordinate their assessment of serious adverse events and device deficiencies to determine whether to modify, suspend or terminate the clinical investigation or whether to revoke the authorisation for that clinical investigation.

This paragraph shall not affect the rights of the other Member States to perform their own evaluation and to adopt measures in accordance with this Regulation in order to ensure the protection of public health and patient safety. The coordinating Member State and the Commission shall be kept informed of the outcome of any such evaluation and the adoption of any such measures.

5. In the case of PMCF investigations referred to in Article 74(1), the provisions on vigilance laid down in Articles 87 to 90 and in the acts adopted pursuant to Article 91 shall apply instead of this Article.

6. Notwithstanding paragraph 5, this Article shall apply where a causal relationship between the serious adverse event and the preceding investigational procedure has been established.

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 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 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).