Inhaltsübersicht

Inhaltsübersicht

1. Introduction
2. Scope
3. References
4. Definitions
5. Abbreviations
6. General principles of clinical evaluation
6.1 What is clinical evaluation?
6.2. When is clinical evaluation undertaken and why is it important?
6.3 How is a clinical evaluation performed?
6.4 Who should perform the clinical evaluation?
7. Definition of the scope of the clinical evaluation (Stage 0)
8. Identification of pertinent data (Stage 1)
8.1 Data generated and held by the manufacturer
8.2 Data retrieved from literature
9. Appraisal of pertinent data (Stage 2)
9.1 General considerations
9.2 The appraisal plan
9.3 Conduct of the appraisal
10. Analysis of the clinical data (Stage 3)
10.1 General considerations
10.2 Specific considerations
10.3 Where demonstration of conformity based on clinical data is not deemed appropriate
11. The clinical evaluation report (CER, Stage 4)
12. The role of the notified body in the assessment of clinical evaluation reports

Anhänge

A1 Demonstration of equivalence
A2 When should additional clinical investigations be carried out?
A3 Device description – typical contents
A4 Sources of literature
A5 Literature search and literature review protocol, key elements
A5.1 Background to the literature search and the literature review
A5.2 Objective
A5.3 Methods
A6 Appraisal of clinical data – examples of studies that lack scientific validity for demonstration of adequate clinical performance and/or clinical safety
A7 Analysis of the clinical data – compliance to specific Essential Requirements
A7.1 Conformity assessment with requirement on safety (MDD ER1 / AIMDD ER1)
A7.2 Conformity Conformity assessment with requirement on acceptable benefit/risk profile (MDD ER1 / AIMDD ER1)
A7.3 Conformity assessment with requirement on performance (MDD ER3 / AIMDD ER2)
A7.4 Conformity assessment with requirement on acceptability of undesirable side-effects (MDD ER6 / AIMDD ER5)
A8 Devices for unmet medical needs – aspects to consider
A9 Clinical evaluation report – proposed table of contents, examples of contents
A10 Proposed checklist for the release of the clinical evaluation report
A11 Information on declarations of interests
A12 Activities of notified bodies
A12.1 Notified body assessment of clinical evaluation by conformity assessment route
A12.2 Examination of a design dossier (Annex II.4; Annex 2.4) or of a type examination dossier (Annex III; Annex 3)
A12.3 Evaluation as part of quality system related procedures
A12.4 Notified body specific procedures and expertise

Appendices

A1. Demonstration of equivalence

Pursuant to Annex X of Directive MDD and Annex 7 AIMDD, the evaluation of clinical data (i.e. the clinical evaluation), where appropriate taking account of any relevant harmonised standards, must follow a defined and methodologically sound procedure based on:

  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. or a critical evaluation of the results of all clinical investigations made.
  2. or a critical evaluation of the combined clinical data provided from 1 and 2.

Clinical, technical and biological characteristics shall be taken into consideration for the demonstration of equivalence:

  • Clinical:
    • used for the same clinical condition (including when applicable similar severity and stage of disease, same medical indication), and
    • used for the same intended purpose, and
    • used at the same site in the body, and
    • used in a similar population (this may relate to age, gender, anatomy, physiology, possibly other aspects), and
    • not foreseen to deliver significantly different performances (in the relevant critical performances such as the expected clinical effect, the specific intended purpose, the duration of use, etc.).
  • Technical:
    • be of similar design, and
    • used under the same conditions of use, and
    • have similar specifications and properties (e.g. physicochemical properties such as type and intensity of energy, tensile strength, viscosity, surface characteristics, wavelength, surface texture, porosity, particle size, nanotechnology, specific mass, atomic inclusions such as nitrocarburising, oxidability), and
    • use similar deployment methods (if relevant), and
    • have similar principles of operation and critical performance requirements.
  • Biological: Use the same materials or substances in contact with the same human tissues or body fluids.
    Exceptions can be foreseen for devices in contact with intact skin and minor components of devices; in these cases risk analysis results may allow the use of similar materials taking into account the role and nature of the similar material. Different aspects of equivalence and compliance to different Essential Requirements can be affected by materials. Evaluators should consider biological safety (e.g. in compliance to ISO 10993) as well as other aspects necessary for a comprehensive demonstration of equivalence. A justification explaining the situation should be provided for any difference.

For assuming equivalence,

  • equivalence can only be based on a single device14;
  • all three characteristics (clinical, technical, biological) need to be fulfilled;
  • similar means that no clinically significant difference in the performance and safety of the device would be triggered by the differences between the device under evaluation and the device presumed to be equivalent;
  • the differences between the device under evaluation and the device presumed to be equivalent need to be identified, fully disclosed, and evaluated; explanations should be given why the differences are not expected to significantly affect the clinical performance and clinical safety of the device under evaluation;
  • the manufacturer should investigate if the medical device presumed to be equivalent has been manufactured via a special treatment (e.g. a surface modification, a process that modifies material characteristics); if this is the case, the treatment could cause differences in respect to technical and biological characteristics; this should be taken into account for the demonstration of equivalence and documented in the CER;
  • if measurements are possible, clinically relevant specifications and properties should be measured both in the device under evaluation and the device presumed to be equivalent, and presented in comparative tabulations;
  • comparative drawings or pictures should be included in order to compare shapes and sizes of elements that are in contact with the body;
  • the manufacturer is expected to:
    • include the supporting non-clinical information (e.g. pre-clinical study reports) in the technical documentation of the device, and
    • in the clinical evaluation report, summarise the information and cite its location in the technical documentation;
  • for the evaluation of the technical characteristics, devices that achieve the same therapeutic result by different means cannot be considered equivalent;
  • for the evaluation of the biological characteristics:
    • when a detailed chemical characterisation of materials in contact with the body is needed, ISO 10993-18 Annex C can be used to show toxicological equivalence but this is just a part of the evaluation of the biological criteria;
    • sourcing and manufacturing procedures may adversely affect impurity profiles; analytical methods chosen to characterise medical devices should appropriately take into consideration knowledge concerning expected impurity profiles (tests may have to be repeated when production methods or sourcing are changed);
    • it may be necessary to show from histopathological studies that the same host response is achieved in vivo in the intended application and the intended duration of contact;
    • for animal tests, differences between species may limit the predictive value of the test; the choice of the test and its predictive value should be justified;
    • abrasion, if relevant, and host response to particles may also need to be considered.
  • the only clinical data that are considered as relevant are the data obtained when the equivalent device is a CE-marked medical device used in accordance with its intended purpose as documented in the IFU.

Note: Exceptions can be considered. When the equivalent device is not a CE-marked device, information concerning the regulatory status of the equivalent device and a justification for the use of its data should be included in the clinical evaluation report. The justification should explain if the clinical data is transferrable to the European population, and an analysis of any gaps to good clinical practices (such as ISO 14155) and relevant harmonised standards.

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