MEDDEV 2.7.1 Rev 4 – Demystifying the new requirements
MEDDEV 2.7/1 is a guiding document for clinical evaluation of medical devices and it is titled as “Clinical Evaluation: A Guide for Manufacturers and Notified Bodies under Directives 93/42/EEC and 90/385/EEC”. MEDDEV 2.7/1 revision 04 (guideline for clinical evaluations) is available for guidance since 1st July 2016. It proposes more comprehensive guidelines than the earlier version, but also put forth some stringent requirements from the previous one.
Despite the fact that the new revision is lengthier and more comprehensive, in reality most of the changes are offered to enhance guidance, and to explain current requirements, rather than to introduce a series of exclusive new requirements. Requirements are therefore enhanced from the earlier version, MEDDEV 2.7/1 revision 3 published in 2009. The earlier version however observed the guidelines of the Global Harmonization Task Force (GHTF) to synchronize with the requirements and processes internationally. The new revision 4, conversely, incorporates detailed elements that somehow suggest a localization of requirements for Europe.
Frequency of updates to the Clinical Evaluation Report (CER)
Under the revision 4; Clause 6.2.3 requires the Clinical Evaluation Report to be updated at least yearly for new or high risk devices. On the contrary for lower risk established devices, CER will be updated every two to five years. The guidelines mandates a reasonable rational for the frequency of updates. Moreover the CER now needs to be updated for all medical devices of any risk category, whenever new evidence from the Post Market Surveillance (PMS) influences the CER or its outcomes.
Credentials of CER Authors and Evaluators Required!
Clause 6.4 of the guidelines; presents particular requirements for the proficiency and experience of CER authors and evaluators, together with a higher education degree and relevant professional experience of five years, or ten years’ relevant professional experience if a degree is not needed as a requirement for the task. Valid Justifications should be available whenever there are deviations. All evaluators are also required to make a declaration of interest.
CER Objectives to be structured as Specific & Measurable
Revision 3 of MEDDEV 2.7.1 mandates the companies to maintain documentation related to the scope and objectives of the CER and to describe objectives under the domain of performance, safety, and risk endpoints as per the Essential Requirements. However the connection between scope, objectives and endpoints was somehow missing in the text and was only implicitly available in evaluation checklist incorporated as Appendix F, the Clinical Evaluation Checklist for Notified Bodies.
MEDDEV 2.7/1 Revision 4 enhances the requirement for the objectives of the CER to be specifically connected to performance, safety, and clearer risk versus benefit endpoints using a process based approach PICO (Populations/diseases or conditions, Interventions, Comparator groups/controls, Outcomes/endpoints). The detailed guidance on objectives is provided in Section 7 and Appendix 5.2
Establishing the state of the art
MEDDEV 2.7/1 Revision 4 – Clause 8.2 offers more comprehension as per developing and documenting the state of the art and available treatment alternatives. This means incorporation of the performance and safety of the device, its stated equivalence, and reference to similar devices, together with the risks versus benefits analysis of other treatment alternatives offered.
Scientific validity of Clinical data
The current version of MEDDEV 2.7.1 emphasizes more on proving the scientific validity of data with statistical concerns. MEDDEV 2.7/1 Section 9.3.1 talks about factors which can influence the scientific validity of different data sets’ types. Furthermore, simplifying and descriptive detail is offered all over the guidance document for each part of the clinical evaluation procedure. Section 8 and Appendix 5 elaborates the elements which could influence the completeness, objectivity, neutrality and substance of data, including literature search and retrieval methods. Section 9 and Appendix 6 elaborates data appraisal and data weighting details. Section 10 and Appendix 7 elaborates the analysis of data and demonstration of conformity.
Equivalence was just a text note in Appendix F of MEDDEV 2.7.1 Revision 3. It has been enhanced considerably in Revision 4. In appendix 1; the mandatory elements for prove of equivalence are explained comprehensively. The criteria which are biological, clinical, and technological are uninfluenced, but more details are provided in terms of how this should be documented and details about elements which could influence the prove of equivalence.
Specifically, Revision 4 mandates that the outcomes of design variations and the design changes’ are monitored for its impact on clinical performance and safety. Such impacts have to be explained in detail, for this reason; comparative illustrations should also be prepared. Finally each individual device with which its equivalence is claimed must meet all three above discussed equivalence criteria.
Access to data for equivalent devices
MEDDEV 2.7.1 Revision 4 also mandates that the Notified Body to check the manufacturer’s access to data on the equivalent devices as per Appendix A12.2.3. It is reflected as a momentous part for this Regulation. Because of this addition; manufacturers should have a contract with other companies permitting access to data for devices in which equivalence is sought.
The need of Clinical Investigation
The current MEDDEV 2.7.1 Appendix 2 explains key factors concerning the device risk and how companies should define if they have adequate clinical evidence.
Risk versus benefit Analysis
The new revision in Appendix 7; offers comprehensive assistance on the analysis of data to prove medical device safety and performance. Appendix 7.2 elaborates the risk-benefit profile, incorporating the assessment of benefits and risks and assigning numeric values to these elements, and the evaluation encompassing the big picture of device’s risk-benefit profile. The significance of post-market data, and elements which could influence the statistical validity of the evaluation of this data, are also incorporated with an overview.
Post Market Surveillance (PMS) and Post Market Clinical Follow-up (PMCF)
In the Revision 4, the gaps between PMS, PMCF and clinical evaluations are bridged. Appendix 12 emphasizes the need for Notified Bodies to check whether that PMCF is well planned or not. Moreover the notified bodies will also need to prove frequency of PMCF demonstration which should be reasonable with the data collected and conclusions available in the CER.
Way forward for Medical Devices Manufacturers in Europe
The latest MEDDEV revision 2.7/1 Rev. 4 can be reflected more enlightening, but also more strict in terms of requirements as well. The clinical evaluation process trails a product lifecycle methodology and should incorporate evaluation of clinical usability statements for the anticipated users. However, the most important transformation in this revision, the proof of “equivalence” between predicate and applicant device, is much stringent and may result in extensive clinical trials with greater population of patients, in combination with higher prospects for the scientific validity of clinical data and comparison assessment with treatment alternatives.
Since no transition period is being provided for published MEDDEV Revision 4 guidance document, companies are recommended to discuss with Notified Bodies about how they will begin performing gap assessment, and when to fulfill these new MEDDEV requirements to fill identified gaps with the requirement for new resources. TS Quality & Engineering can help companies in planning and preparing the new MEDDEV revision.