MEDICAL DEVICE REGULATION (MDR)
In general the new Regulations devices, improve traceability and transparency and define stricter requirements to clinical evidence and post-market surveillance. The MDR now also regulates devices for cosmetic purposes such as colored contact lenses and cosmetic implant devices. The introduction of Unique Device Identification should improve traceability, and transparency is created by the European Databank of Medical Devices (EUDAMED) where all mandatory regulatory documentation on each device is kept and updated. Manufacturers must re-certify devices in accordance with the new regulations and update their technical documentation accordingly with special attention to higher clinical requirements for class III and implantable devices. A shift of focus from a mere pre-market perspective towards a life-cycle approach also includes stricter requirements regarding post-market surveillance, post-market clinical follow-up and vigilance.
This brings us to the Clinical Evaluation, which lies at the basis of CE mark approval and the life-cycle approach. It is defined as “a systematic and planned process to continuously generate, collect, analyze and assess the clinical data pertaining to a device in order to verify the safety performance, clinical benefits of the device when used as intended by the manufacturer.” The Clinical Evaluation process is described in a MEDDEV (MEDical DEVices) guidance document. MEDDEVs promote a common approach to be followed by manufacturers and notified bodies that are involved in conformity assessment procedures. Although these MEDDEVs are not legally binding, it is expected that their guidance be followed, ensuring the uniform application of the various elements of the directives/regulations. MEDDEV 2.7/1 rev. 46 is the guidance document with regards to Clinical Evaluation and is prescriptive on the process, the required qualification of the evaluators and the contents of a Clinical Evaluation Report (CER).
The CER should “describe the intended clinical benefit and provide evidence of safety and performance” where performance is defined as “the ability of a device to achieve its intended purpose as stated by the manufacturer.” This report describes the risk profile of the device based on the technical documentation and provides an appraisal of all available clinical data related to safety and performance. Any evidence gaps and residual risk need to be addressed in Post-Market Clinical Follow Up (PMCF) studies to demonstrate long-term performance safety. The results from the intensified surveillance are laid down in the Periodic Safety Update Report (PSUR, mandatory for Class IIa/b and III) and Summary of Safety and Clinical Performance (SSCP, for implantables and Class III). These documents must be uploaded in EUDAMED, which allows public access to the SSCP.
Although European market approval of new devices can still be obtained by referring to clinical data of predicate equivalent devices, the MDR explicitly lists criteria by which equivalence can be claimed from a technical, biological and clinical perspective. The equivalence under the MDD was less well defined. Under the MDR, the predicate device must have a similar design, use the same materials and come in contact with the same tissues and body fluids, and be used for the same clinical indications. If a device does not meet these criteria, manufacturers need to generate their own clinical evidence with appropriate clinical investigations.
CE Marking requires Notified Body involvement for most medical device classes and is related to implementation of a Quality Management System, which must include plans pertaining to Clinical Evaluation, Post-Market Surveillance (PMS) and Post Market Clinical Follow-up (PMCF). For non-sterile Class I devices, manufacturers can conduct the conformity assessment themselves and basically self-certify. For Class I devices that are sterile, measuring or reusable surgical instruments as well as for all higher device classes, oversight of a Notified Body is required. In the end, it is the Notified Body that issues a CE Marking Certificate and ISO 13485 Certification. Only with these certificates in place the manufacturer can prepare a Declaration of Conformity and put the CE Mark sign on their products and labelling.