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
|(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
|(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.