The Medical Device Regulation (EU-MDR) transition period has started and time for the medical device industry to have their clinical data and documentation in compliance with EU-MDR is rapidly running out. Are they getting ready, are you prepared?
Racing against an impending deadline, currently approved CE-marked product portfolio clinical strategies are being analyzed, prioritized and updated. The industry will be looking closely at their clinical evaluation reports (CERs) of each of their products raising the following questions: Is the classification still valid under EU-MDR? What sources of clinical evidence were used in the CERs? Is the justification for not performing a clinical investigation and/or not implementing post market clinical follow-up (PMCF) still valid, and sustainable under the EU-MDR?
For new emerging technologies (i.e., Class III implantable) that will be CE-marked under the EU-MDR, clinical investigations shall be performed. When devices are designed by modification of an approved device, or are based on clinical data from an equivalent device for which equivalency has been shown, only then will an exemption be acceptable. When exempt, a contractual agreement allowing full access to the technical documentation is required between manufacturers.
Equivalence Route is Less Accessible
Scientific literature to demonstrate equivalence of current CE-marked devices or future EU-MDR devices is made less accessible, especially for class III and implantable devices.
If a competitor’s equivalent device(s) form the foundation of current or future class III devices, manufacturers are reconsidering if they want to continue with the equivalence route. If the manufacturers have not contractually arranged full access to the technical files of these equivalent devices, they face noncompliance. Competitors may in all capitalistic reality be unwilling to grant such access. Therefore, initiating comparative clinical investigations, PMCF studies or other pro-active PMS activities (e.g. registries) to obtain clinical data of their own device would limit the manufacturer´s dependency on equivalence.
Clinical Investigations to Increase in Quantity and Quality
Results of clinical investigations and/or PMCF studies that were already performed in the past or that are currently ongoing/being planned, will be very valuable for medical device manufacturers. A critical re-evaluation of these results in all cases is necessary to bring their CERs to the required level of compliance. Compliance with ISO 14155 (Medical Device Good Clinical Practice, GCP) when conducting clinical investigations is indispensable. Measures to prevent any form of clinical trial bias should be considered and where possible implemented. Considerations for conduct bias include randomization, independent monitoring/auditing, biostatistical power, data collection methods that do not bias data integrity and objective endpoints.
Clinical data collected in clinical investigations that lack sufficient ISO 14155 compliance are at risk of providing insufficient clinical evidence. Data collected with low scientific value are a waste of patients´ benefit, time, money and may not be accepted by Notified Bodies moving forward. Historic trial data will be re-evaluated by Notified Bodies under a magnifying glass regarding GCP compliance. Remember, there is no grandfathering of medical devices under the MDR so all historic trial data is needed to keep current CE Marked devices on the market.
Impact on Investigator Sponsored Research (ISR)
The increased demand for GCP clinical investigations has been regulated in the EU-MDR. ISR may increase to meet industry´s low supply of its own device data from the past, present and future.
Justifying the application of a potential preventative or curative intervention, medical need must be evaluated in terms of the magnitude of the intervention´s benefits vs. its adverse effects. For devices, the latter often are quite difficult to precisely quantify because of sample size limitations. EU-MDR may help investigators achieve a greater sample size from the entire product cycle, from bench to bedside.
Editor’s Note: Clinlogix is a Global Clinical Research Organization working to improve human quality of life by supporting and accelerating innovation in the life science industry. Its full suite of clinical research services supports the regulatory and clinical development pathway of medical devices from proof of concept/discovery, early feasibility/first-in-human, through pivotal and the post-marketing/safety surveillance of client products. The company delivers this global expertise by way of its regional office locations in the US – Spring House, Pennsylvania, Europe – Mainz, Germany, South America – Medellin, Colombia, and Asia – Tokyo, Japan.