The Rev 4 is emphasized moreon the scientific outlook of the clinical evaluation, the competence and independenceof the clinical evaluators, and the need to make this a living document thatmust be updated regularly or whenever there is a safety or clinical performanceissue.
Rationale to the clarifications and new requirements in the clinicalevaluation process are as follows: Rationale to the clarifications and new requirements:1. Clarification on frequency of updatingCER report: Section 6.2.3 states that the CER needs to be updated atleast annually if the device carries significant risks or is not yet wellestablished, and every2 to 5 years for lower risk and well established devices with a justification. CER needs to be updated when newinformation or relevant changes viz., changes in clinicalsciences, materials sciences or other sciences related to the device underevaluation; the data available from clinical investigations, PMCF studies,registries or other systematic studies; the total number of devices used so farin the market, risks and uncertainties or unanswered questions, in the mediumor longterm, that would influence the frequency of updates; design changes orchanges to manufacturing procedures; manufacturer receiving new informationfrom PMS that has the potential to change the current evaluation. 2.
Inclusion of additional two new stages: Section6.3 explains additional 2stages which are: stage 0 – scoping, plan and stage 4 – finalizing the CER. It emphasizeson :1. being compliant with the essential requirements (ER1, ER3, ER6) onperformance and safety of the device along with risk benefit profiles.2. considering all the contents of information materialssupplied by the manufacturer (including the label, IFU of the device, availablepromotional materials, including accompanying documents possibly foreseen bythe manufacturer).3.
residual risks/uncertainties/unansweredquestions which can be either acceptable for CE marking or required to beaddressed during PMS. 3. Newrequirement: Expertise andexperience of CER authors and evaluators: Section 6.4 introduces specific requirements for the expertise andexperience of CER authors and evaluators, including a relevant higher educationdegree qualification and professional experience.
Only very few of the past authors qualify as future authorsdue to new and stricter qualification requirements. So the single author willhave a hard time to comply with the requirements alone. It can be expected thatwe will witness a shift from one author to a team of authors, each withspecific skills to complement the overall requirements. 4. Concerningcurrent knowledge/the state of the art: Section 8.2 states that copies of the full textpapers and documents to be obtained for the appraisal stage. This section ismore detailed in establishing and documenting the state of the art.
This also includesestablishing the safety and performance of the device, it’s claimed equivalent,and any benchmark or other similar devices, as well as the risks and benefitsof other available treatment options. 5. Documentation of appraisal plan: Section9.2 points out that anappraisal plan must be documented in the CER. This is done to ensure systematicand unbiased appraisal of the data. 6. Scientific validity of data: Section9.
3.1 and Appendix7 and 7.2 emphasizes on the demonstration of thescientific validity of data, including statistical considerations, adequacy ofdisclosure of data, study design for pre and post market investigations.
Thisis done to address factors which could affect the scientific validity ofdifferent types of datasets including literature searchand retrieval methods, data appraisal and weighting, and the analysis of dataand demonstration of conformity. 7. Essential factors while selecting pivotaldata: Section 9.3.
2 emphasizes on the factors essential while selectingpivotal data and other data the different aspects to be taken intoconsideration when determining relevance to the subject device. 8. CV & declaration of interest: Section11 mentions that the clinical evaluators should provide theirCV and their declaration of interests to the manufacturer. The clinicalevaluation report should be dated and version controlled to enhance the effectivenessof the CER. 9. Clinicalevaluation requirement: Appendix 2 explains the keyconsiderations relating to device risk and procedure to determine if they havesufficient clinical evidence by the manufacturers. 10.
PostMarket Surveillance (PMS) and Post Market Clinical Follow-up (PMCF): Appendix12 highlights the requirement for Notified Bodies to ensurethat PMCF is planned and appropriately justified. 11. Equivalentdevices data: Appendix A12.2.3mentions a new requirement which will require a manufacturer to have a contractin place allowing access to data for competitor devices with which equivalenceis claimed. UpshotFailure to properly executeany of the key requirements listed above is likely to invalidate CER.
Implementationperiod has not been decided for Rev 4. However,it is expected that the all the CER reports are prepared and updated (older) inaccordance with the REV 4. Broader expectations are being laid on the NB andthe expertise requirements of the evaluators. Therefore, MEDDEV 2.7/1 is helpful formanufacturers and notified bodies, if seen from the perspective that itprovides a smooth transition from nice to have to must have. The focus of clinical evaluation at various stages of productlifecycle is precise and updating it frequently is mandatory, alarming theimportance of medical device clinical investigations.