The MDR (article 61 and Annex XIV) reinforces clinical data and evaluation process. Manufacturers shall provide sound clinical data and evaluation to confirm the device conformity with essential health and safety requirements.The clinical evaluation proves that the device is safe and performs according to its intended purpose, assesses the undesirable side effects, as well as the acceptability of the benefit-risk ratio. Manufacturers shall plan, conduct and document a clinical evaluation in accordance with Article 61 and Part A of Annex XIV.
How to obtain the clinical data:
- Published data on clinical experience with the device or equivalent
- Clinical investigation
- Clinical investigation with similar device
- Combination of the above
The medical devices must go through clinical evaluation which is the process of assessing clinical data and making sure that the data is in conformity with the harmonized standards and essential requirements that have been established by the European Union.
For all class IIb (Article 54(1)) and III devices, the manufacturer may, prior to its clinical evaluation and/or investigation, consult an expert panel with the aim of reviewing the manufacturer’s intended clinical proposals for clinical investigation.
The clinical evaluation must follow a certain procedure based on either:
- A critical evaluation of the relevant scientific literature currently available evaluating the design characteristics, safety, and performance of the device all based on its intended use where:
- there is demonstration of equivalence of the device to the device to which the data relates and
- the data adequately demonstrates compliance with the relevant safety and performance requirements
- A critical evaluation of results of all clinical investigations made with a consideration of alternative treatment options currently available.
- A consideration of all current alternative treatments
When a clinical data not deemed appropriate, there must be adequate justification based on risk management output and under consideration of the specifics of the device/body interaction, the performances intended and claims of the manufacturer. In that case non-clinical testing methods alone, including performance evaluation, bench testing and pre- clinical evaluation, need to be appropriate.
The clinical evaluation shall be updated throughout the life cycle of the device 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 and implantable devices, a PMCF evaluation report shall be updated yearly, and a summary of the safety and clinical performance shall be uploaded to the EUDAMED and updated yearly.
Clinical investigation for class III and implantable devices
In the case of implantable devices and class III devices, clinical investigations shall always be performed except if:
- the already marketed device has been modified by the same manufacturer, and
- the modified device has been demonstrated by the manufacturer to be equivalent to the marketed device, 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 addition, NO obligation of clinical investigation for class III and implantable devices in case a manufacturer demonstrates that its device is equivalent to an already marketed device, this demonstration has been endorsed by the notified body and the following conditions are fulfilled: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 the MDR, providing clear evidence to the Notified Body.
In addition, NO obligation of clinical investigation for class III and implantable devices :
- If the devices have been lawfully placed on the market under the former directives and for which the clinical evaluation is based on sufficient clinical data and comply with Common specification where available
NO obligation of clinical investigation for devices such as : 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.
Clinical investigation is the systematic study or investigation of safety and performance of a device being used by human beings in accordance with the device’s normal use. 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.
Manufacturer/sponsor is responsible for the:
- Design of the study
- Designation of principal investigator
- Application with ethical committee
- The non-EU manufacturer/sponsor may choose to appoint the Authorized Representative to complete the authorization of clinical investigation to EUDAMED.
- Incident Reporting-in the event of an incident during the clinical investigation, the reporting as such will need to be determined and performed by the appointed Authorized Representative through the EUDAMED database
- Documentation available-the clinical investigation data (reports) should be incorporated in the technical documentation that has to be kept available by the manufacturer of his appointed European Authorized Representative established within the Union.
- Sponsor (authorized representative) shall notify the competent authorities of the ending of the clinical investigation, and submit a report.
Clinical Investigation plan:
- Informed consent and ethical consideration
- Clear measurable objectives
- Criteria to stop the trial
- Statistical power
- Patient population equivalent to EU
The clinical evaluation and its documentation must continually be updated by its post-market surveillance information. If this post-market surveillance is not needed for some reason in following up on the medical device, an acceptable justification must be given and documented. For high risk devices, there must be a clinical follow-up report given with the final report.
Role of the Competent Authority:
Authorities are responsible to give authorization for the clinical investigation to start, after clinical investigation registration in the European Databank. The authorization procedure should take less than a month according to the MDR. Delegated acts may be taken by the commission to fine tune this procedure. The clinical investigation will receive a single registration number (SRN) for better follow-up and data exchange between member-states.
Role of the Notified Body:
Clinical investigation and evaluation are reviewed by the Notified Body who has such authority, as part of the technical documentation review before granting CE certificate:
- Assessment of clinical safety and performance
- Conclusion with justification
- Risk-benefit ratio
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