In June 2016, the new version (Rev.4) of MEDDEV 2.7.1 European guidance on the clinical evaluation of medical devices (MD) was published. It does not revolutionize the clinical evaluation approach but significantly increases the demands on the content of the file.
The new guidance is longer and more detailed, in order to provide numerous supporting examples and to clarify some terms. It does not introduce new requirements per say.
This newsletter presents the changes introduced by the guidance revision, applicable since June as there is no transitional period planned in the text.
The issuance of this guidance happened shortly after the publication of the text of the future Regulation on the Medical Device of 15 June 2016, which anticipates many new requirements for clinical evaluation. So, the new revised MEDDEV guidance is beginning to align with the upcoming new Regulation. It is certainly a very helpful tool in helping to transition to the new regulatory requirements.
Let’s have a look on the Key Changes introduced by the Revision 4
NEW- When does the Clinical Evaluation Report (CER) have to be prepared and how often does it need to be updated?
In Clause 6.2, the new MEDDEV clarifies this point. Clinical evaluation is a process that must be carried out throughout the life of the Medical Device. In all cases the CER has to be completed during the pre-market phase, to support the demonstration of safety and performance of the device before placing it on the market. Then, the CER must be actively updated in order to demonstrate the continuous safety and performance of the device.
The CER need to be updated at least annually for high risk (i.e. Class III devices) or new devices (if their usage is not established), and every 2 to 5 years for lower risk or well-established devices.
NEW- Need for demonstration of qualifications of report authors and evaluators.
The person or team conducting the clinical evaluation (CER authors and evaluators) must be properly qualified (this must be documented). Revision 4 requires that each evaluator fulfills a "Statement of Interest" and must also have a higher education degree and 5 years’ related professional experience, or 10 years of professional experience if the degree is not required. Deviations from these requirements have to be duly justified and documented.
NEW – Several clarifications in the methodology undertaken for the clinical evaluation
- Clarification on what constitutes the objectives and scope of the CER and how they are correlated with the endpoints (safety, performance and risk-benefit);
- Clarification on how to identify the pertinent data and establish the state of art: Literature data should cover the concerned MD or MD which equivalency has been demonstrated (this is not new), but also the state of the art and current knowledge. The current knowledge/ state of the art therefore need to be identified and defined. The research of data on the state of the art (applicable standards, guidance, MD gold standard, other MD, medical alternatives available to the target population) should now be done using a search method at least as rigorous as the method used for literature review (in terms of pertinence, reliability, and objectivity);
- Clarification of the scientific validity of data: Revision 4 highlights the need for the evaluator of the CER to verify the scientific validity of the data presented to guarantee, as a result, the scientific validity of the conclusions relating to undesirable side-effects and the performance of the device. Numerous tools or points to consider are suggested on how to appraise the pertinence of the data, the methodological quality and the scientific validity, with also the development of an appraisal plan to ensure systematic and unbiased appraisal of the data.
- Emphasis on the demonstration of the equivalence of the devices: Annex A1 is entirely dedicated to the demonstration of equivalence. This goes in line with the regulatory authorities which want the equivalence criteria to be more stringent. The approach is not revolutionized per say, but the methodology must be straightforward and reliable because it is one of the weaknesses we can encounter in the CER. The criteria (clinical, technological, biological) are unchanged, but more information on how this should be documented and factors which could affect the demonstration of equivalence is provided. For instance, the manufacturing methods have to be taken into consideration (it implies that they have to be known for the devices taken as reference). Any difference between the MD and the equivalent MD should be discussed and the impact on safety and performance data should be evaluated. Equivalent Medical Device must be CE marked, used within the same indications as mentioned in the IFUs. If they are not CE marked, exceptions are possible, but the regulatory status of the MD must be specified in the report with a justification of the choice of MD and an analysis of the impact onto the evaluation.
- New requirement: Access to information on equivalent Medical Device: the Notified Body, during its evaluation of the CER, has to assess and document the level of access to the technical and clinical data from an equivalent device that the manufacturer has. This is aligned with the new Medical Device regulations which will require the legal manufacturer to have access to the Technical Documentation and other pertinent information of the equivalent device taken as reference.
- Clarification on the risk/benefit: Annex 7 specifies that the Medical Device must have a risk / benefit ratio at least equal to the alternative medical solutions. If this comparison to the state of the art is not available at the time of pre-commercialization, this should be clearly noted in the IFUs. The place of MD in the therapeutic strategy should be clearly documented in the CER.
- Clarification on the Post-Market activities: Finally, the CER must conclude, based on potential identified gaps, the need to initiate clinical investigations or implement other appropriate measures. Appendix A2 explains where clinical investigations must be carried out. The assessment should highlight the residual risks and unresolved issues that need to be assessed thru the post marketing clinical follow-up (PMCF).
In conclusion, this new revision 4 of 2.7.1 MEDDEV does not fully change the clinical evaluation process but includes much more detailed information. However, we should not underestimate the impact of some changes in the light of the upcoming new Medical Device regulations, such as evaluating the device against the state of the art and alternative treatments or accessibility of the information on equivalent devices and more stringent criteria for the demonstration of equivalence.
Many details are provided in the new revision 4 and the manufacturers are highly recommended to perform a gap analysis of their current CER and procedures.The clinical evaluation approach requires more than ever a rigorous methodology that can (and should) only be done by qualified persons.
|ABOUT THE WRITER|
Anne Le Rouzo
West Coast Regional Director & Certification Project Manager at LNE/G-MED North America.
Anne Le Rouzo received her Bachelor’s Degree in Microbiology and Biochemistry from University Paul Sabatier of Toulouse and her Engineering Degree in Food Industry from ENSAIA Engineering School of Nancy. Prior to joining LNE/G-MED, Anne worked for 15 years in the Medical Device Industry specialized in orthopedic implants as a Regulatory Affairs and Quality Assurance Director. At LNE/G-MED, Anne is a Senior Design Dossier Assessor and Lead auditor. Her main fields of qualification include Cardiovascular and Neurovascular Devices, Orthopedic, sutures, and more high-risk and innovative devices, as well as transversal fields of qualification including sterilization.