Regulatory Basics (Annex X)?

Annex X Requirements
What are the overall basic requirements for any clinical investigation of a medical device in Europe?


1.   General provisions
1.1.      As a general rule, confirmation of conformity with the requirements concerning the characteristics and performances referred to in Sections 1 and 3 of Annex I, under the normal conditions of use of the device, and the evaluation of the side-effects and of the acceptability of the benefit/risk ratio referred to in Section 6 of Annex I, must be based on clinical data. The evaluation of this data, hereinafter referred to as ‘clinical evaluation’, where appropriate taking account of any relevant harmonised standards, must follow a defined and methodologically sound procedure based on:

1.1.1.   Either a critical evaluation of the relevant scientific literature currently available relating to the safety, performance, design characteristics and intended purpose of the device, where:

  • there is demonstration of equivalence of the device to the device to which the data relates, and
  • the data adequately demonstrate compliance with the relevant essential requirements.

1.1.2.   Or a critical evaluation of the results of all clinical investigations made.

1.1.3.   Or a critical evaluation of the combined clinical data provided in 1.1.1 and 1.1.2.

1.1a  In the case of implantable devices and devices in Class III clinical investigations shall be performed unless it is duly justified to rely on existing clinical data.

1.1b The clinical evaluation and its outcome shall be documented. This documentation shall be included and/or fully referenced in the technical documentation of the device.

1.1c The clinical evaluation and its documentation must be actively updated with data obtained from the post-market surveillance. Where post-market clinical follow-up as part of the post-market surveillance plan for the device is not deemed necessary, this must be duly justified and documented.

1.1d Where demonstration of conformity with essential requirements based on clinical data is not deemed appropriate, adequate justification for any such exclusion has to be given based on risk management output and under consideration of the specifics of the device/body interaction, the clinical performances intended and the claims of the manufacturer. Adequacy of demonstration of conformity with the essential requirements by performance evaluation, bench testing and pre-clinical evaluation alone has to be duly substantiated.

1.2.  All the data must remain confidential, in accordance with the provisions of Article 20.

2.   Clinical investigations
2.1.   Objectives
The objectives of clinical investigation are:

  • to verify that, under normal conditions of use, the performance of the devices conform to those referred to in Section 3 of Annex I, and
  • to determine any undesirable side-effects, under normal conditions of use, and assess whether they constitute risks when weighed against the intended performance of the device.

2.2.   Ethical considerations
Clinical investigations must be carried out in accordance with the Helsinki Declaration adopted by the 18th World Medical Assembly in Helsinki, Finland, in 1964, as last amended by the World Medical Assembly. It is mandatory that all measures relating to the protection of human subjects are carried out in the spirit of the Helsinki Declaration. This includes every step in the clinical investigation from first consideration of the need and justification of the study to publication of the results.

2.3.   Methods
2.3.1.   Clinical investigations must be performed on the basis of an appropriate plan of investigation reflecting the latest scientific and technical knowledge and defined in such a way as to confirm or refute the manufacturer’s claims for the device; these investigations must include an adequate number of observations to guarantee the scientific validity of the conclusions.

2.3.2.   The procedures used to perform the investigations must be appropriate to the device under examination.

2.3.3.   Clinical investigations must be performed in circumstances similar to the normal conditions of use of the device.

2.3.4.   All the appropriate features, including those involving the safety and performances of the device, and its effect on patients must be examined.

2.3.5. All serious adverse events must be fully recorded and immediately notified to all competent authorities of the Member States in which the clinical investigation is being performed.

2.3.6.   The investigations must be performed under the responsibility of a medical practitioner or another authorized qualified person in an appropriate environment.

The medical practitioner or other authorized person must have access to the technical and clinical data regarding the device.

2.3.7.   The written report, signed by the medical practitioner or other authorized person responsible, must contain a critical evaluation of all the data collected during the clinical investigation.