MDR – Article 62 – General requirements regarding clinical investigations conducted to demonstrate conformity of devices

Article 62

General requirements regarding clinical investigations conducted to demonstrate conformity of devices

1. Clinical investigations shall be designed, authorised, conducted, recorded and reported in accordance with the provisions of this Article and of Articles 63 to 80, the acts adopted pursuant to Article 81, and Annex XV, where carried out as part of the clinical evaluation for conformity assessment purposes, for one or more of the following purposes:

(a)to establish and verify that, under normal conditions of use, a device is designed, manufactured and packaged in such a way that it is
suitable for one or more of the specific purposes listed in point (1) of Article 2, and achieves the performance intended as specified by itsmanufacturer;
(b)to establish and verify the clinical benefits of a device as specified by its manufacturer;
(c)to establish and verify the clinical safety of the device and to determine any undesirable side-effects, under normal conditions of use of the device, and assess whether they constitute acceptable risks when weighed against the benefits to be achieved by the device.

2. Where the sponsor of a clinical investigation is not established in the Union, that sponsor shall ensure that a natural or legal person is established in the Union as its legal representative. Such legal representative shall be responsible for ensuring compliance with the sponsor’s obligations pursuant to this Regulation, and shall be the addressee for all communications with the sponsor provided for in this Regulation. Any communication with that legal representative shall be deemed to be a communication with the sponsor.

Member States may choose not to apply the first subparagraph to clinical investigations to be conducted solely on their territory, or on their territory and the territory of a third country, provided that they ensure that the sponsor establishes at least a contact person on their territory in respect of that clinical investigation who shall be the addressee for all communications with the sponsor provided for in this Regulation.

3. Clinical investigations shall be designed and conducted in such a way that the rights, safety, dignity and well-being of the subjects participating in a clinical investigation are protected and prevail over all other interests and the clinical data generated are scientifically valid, reliable and robust.

Clinical investigations shall be subject to scientific and ethical review. The ethical review shall be performed by an ethics committee in accordance with national law. Member States shall ensure that the procedures for review by ethics committees are compatible with the procedures set out in this Regulation for the assessment of the application for authorisation of a clinical investigation. At least one lay person shall participate in the ethical review.

4. A clinical investigation as referred to in paragraph 1 may be conducted only where all of the following conditions are met:

(a)the clinical investigation is the subject of an authorisation by the
Member State(s) in which the clinical investigation is to be
conducted, in accordance with this Regulation, unless otherwise
stated;
(b)an ethics committee, set up in accordance with national law, has notissued a negative opinion in relation to the clinical investigation,
which is valid for that entire Member State under its national law;
(c)the sponsor, or its legal representative or a contact person pursuant to paragraph 2, is established in the Union;
(d)vulnerable populations and subjects are appropriately protected in accordance with Articles 64 to 68;
(e)the anticipated benefits to the subjects or to public health justify the foreseeable risks and inconveniences and compliance with this
condition is constantly monitored;
(f)the subject or, where the subject is not able to give informed
consent, his or her legally designated representative has given
informed consent in accordance with Article 63;
(g)the subject or, where the subject is not able to give informed
consent, his or her legally designated representative, has been
provided with the contact details of an entity where further
information can be received in case of need;
(h)the rights of the subject to physical and mental integrity, to privacy
and to the protection of the data concerning him or her in
accordance with Directive 95/46/EC are safeguarded;
(i)the clinical investigation has been designed to involve as little pain,
discomfort, fear and any other foreseeable risk as possible for the
subjects, and both the risk threshold and the degree of distress are
specifically defined in the clinical investigation plan and constantlymonitored;
(j)the medical care provided to the subjects is the responsibility of an
appropriately qualified medical doctor or, where appropriate, a
qualified dental practitioner or any other person entitled by national law to provide the relevant patient care under clinical investigation conditions;
(k)no undue influence, including that of a financial nature, is exerted on the subject, or, where applicable, on his or her legally designated representatives, to participate in the clinical investigation;
(l)the investigational device(s) in question conform(s) to the applicablegeneral safety and performance requirements set out in Annex I
apart from the aspects covered by the clinical investigation and that, with regard to those aspects, every precaution has been taken to
protect the health and safety of the subjects. This includes, where
appropriate, technical and biological safety testing and pre-clinical
evaluation, as well as provisions in the field of occupational safety
and accident prevention, taking into consideration the state of the
art;
(m)the requirements of Annex XV are fulfilled.

5. Any subject, or, where the subject is not able to give informed consent, his or her legally designated representative, may, without any resulting detriment and without having to provide any justification, withdraw from the clinical investigation at any time by revoking his or her informed consent. Without prejudice to Directive 95/46/EC, the withdrawal of the informed consent shall not affect the activities already carried out and the use of data obtained based on informed consent before its withdrawal.

6. The investigator shall be a person exercising a profession which is recognised in the Member State concerned as qualifying for the role of investigator on account of having the necessary scientific knowledge and experience in patient care. Other personnel involved in conducting a clinical investigation shall be suitably qualified, by education, training or experience in the relevant medical field and in clinical research methodology, to perform their tasks.

7. The facilities where the clinical investigation is to be conducted shall be suitable for the clinical investigation and shall be similar to the facilities where the device is intended to be used.

MDR – Article 61 – Clinical evaluation

Article 61

1. Confirmation of conformity with relevant general safety and performance requirements set out in Annex I under the normal conditions of the intended use of the device, and the evaluation of the undesirable side-effects and of the acceptability of the benefit-risk- ratio referred to in Sections 1 and 8 of Annex I, shall be based on clinical data providing sufficient clinical evidence, including where applicable relevant data as referred to in Annex III.

The manufacturer shall specify and justify the level of clinical evidence necessary to demonstrate conformity with the relevant general safety and performance requirements. That level of clinical evidence shall be appropriate in view of the characteristics of the device and its intended purpose.

To that end, manufacturers shall plan, conduct and document a clinical evaluation in accordance with this Article and Part A of Annex XIV.

2. For all class III devices and for the class IIb devices referred to in point (b) of Article 54(1), the manufacturer may, prior to its clinical evaluation and/or investigation, consult an expert panel as referred to in Article 106, with the aim of reviewing the manufacturer’s intended clinical development strategy and proposals for clinical investigation. The manufacturer shall give due consideration to the views expressed by the expert panel. Such consideration shall be documented in the clinical evaluation report referred to in paragraph 12 of this Article.

The manufacturer may not invoke any rights to the views expressed by the expert panel with regard to any future conformity assessment procedure.

3. A clinical evaluation shall follow a defined and methodologically sound procedure based on the following:

(a)a critical evaluation of the relevant scientific literature currently
available relating to the safety, performance, design characteristics
and intended purpose of the device, where the following conditions are satisfied:
— it is demonstrated that the device subject to clinical evaluation for the intended purpose is equivalent to the device to which the data
relate, in accordance with Section 3 of Annex XIV, and
— the data adequately demonstrate compliance with the relevant
general safety and performance requirements;
(b)a critical evaluation of the results of all available clinical
investigations, taking duly into consideration whether the
investigations were performed under Articles 62 to 80, any acts
adopted pursuant to Article 81, and Annex XV; and
(c)a consideration of currently available alternative treatment options
for that purpose, if any.

4. In the case of implantable devices and class III devices, clinical investigations shall be performed, except if:

—the device has been designed by modifications of a device already
marketed by the same manufacturer,
— the modified device has been demonstrated by the manufacturer to
be equivalent to the marketed device, in accordance with Section 3 of Annex XIV and this demonstration has been endorsed by the notified body, and
— the clinical evaluation of the marketed device is sufficient to
demonstrate conformity of the modified device with the relevant
safety and performance requirements.

In this case, the notified body shall check that the PMCF plan is appropriate and includes post market studies to demonstrate the safety and performance of the device.

In addition, clinical investigations need not be performed in the cases referred to in paragraph 6.

5. A manufacturer of a device demonstrated to be equivalent to an already marketed device not manufactured by him, may also rely on paragraph 4 in order not to perform a clinical investigation provided that the following conditions are fulfilled in addition to what is required in that paragraph:

—the two manufacturers have a contract in place that explicitly allows the manufacturer of the second device full access to the technical
documentation on an ongoing basis, and
—the original clinical evaluation has been performed in compliance
with the requirements of this Regulation,

and the manufacturer of the second device provides clear evidence thereof to the notified body.

6. The requirement to perform clinical investigations pursuant to paragraph 4 shall not apply to implantable devices and class III devices:

(a)which have been lawfully placed on the market or put into service
in accordance with Directive 90/385/EEC or Directive 93/42/EEC and
for which the clinical evaluation:
— is based on sufficient clinical data, and
— is in compliance with the relevant product-specific CS for the
clinical evaluation of that kind of device, where such a CS is
available; or
(b)that are sutures, staples, dental fillings, dental braces, tooth crowns, screws, wedges, plates, wires, pins, clips or connectors for which
the clinical evaluation is based on sufficient clinical data and is in
compliance with the relevant product-specific CS, where such a CS is available.

7. Cases in which paragraph 4 is not applied by virtue of paragraph 6 shall be justified in the clinical evaluation report by the manufacturer and in the clinical evaluation assessment report by the notified body.

8. Where justified in view of well-established technologies, similar to those used in the exempted devices listed in point (b) of paragraph 6 of this Article, being used in other devices, or where justified in order to protect the health and safety of patients, users or other persons or other aspects of public health, the Commission is empowered to adopt delegated acts in accordance with Article 115 to amend the list of exempted devices referred to in the second subparagraph of Article 52(4) and in point (b) of paragraph 6 of this Article, by adding other types of implantable or class III devices to that list or removing devices therefrom.

9. In the case of the products without an intended medical purpose listed in Annex XVI, the requirement to demonstrate a clinical benefit in accordance with this Chapter and Annexes XIV and XV shall be understood as a requirement to demonstrate the performance of the device. Clinical evaluations of those products shall be based on relevant data concerning safety, including data from post-market surveillance, PMCF, and, where applicable, specific clinical investigation. Clinical investigations shall be performed for those products unless reliance on existing clinical data from an analogous medical device is duly justified.

10. Without prejudice to paragraph 4, where the demonstration of conformity with general safety and performance requirements based on clinical data is not deemed appropriate, adequate justification for any such exception shall be given based on the results of the manufacturer’s risk management and on consideration of the specifics of the interaction between the device and the human body, the clinical performance intended and the claims of the manufacturer. In such a case, the manufacturer shall duly substantiate in the technical documentation referred to in Annex II why it considers a demonstration of conformity with general safety and performance requirements that is based on the results of non-clinical testing methods alone, including performance evaluation, bench testing and pre- clinical evaluation, to be adequate.

11. The clinical evaluation and its documentation shall be updated throughout the life cycle of the device concerned with clinical data obtained from the implementation of the manufacturer’s PMCF plan in accordance with Part B of Annex XIV and the post-market surveillance plan referred to in Article 84.

For class III devices and implantable devices, the PMCF evaluation report and, if indicated, the summary of safety and clinical performance referred to in Article 32 shall be updated at least annually with such data.

12. The clinical evaluation, its results and the clinical evidence derived from it shall be documented in a clinical evaluation report as referred to in Section 4 of Annex XIV, which, except for custom-made devices, shall be part of the technical documentation referred to in Annex II relating to the device concerned.

13. Where necessary to ensure the uniform application of Annex XIV, the Commission may, having due regard to technical and scientific progress, 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).