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The Medical Device Regulation (MDR) has heightened the standards for clinical evidence, yet ambiguities persist regarding specific requirements. This article delves into the clinical evaluation routes outlined by the MDR, focusing on scenarios where limited clinical evidence suffices for conformity demonstration.

The MDR reinforced the rules on clinical evidence by increasing the requirements for clinical data that can be used as proof of conformity. At the same time, the regulation often remains vague about the exact requirements. For example, the MDR requires that the demonstration of conformity with the relevant general safety and performance requirements (GSPRs) is based on clinical data that provides “sufficient clinical evidence”. However, it is the manufacturer's responsibility to specify and justify the required level of clinical evidence based on the device's characteristics and intended purpose. The regulation provides little guidance on determining the appropriate level of clinical evidence, but it defines certain cases in which a lower level of clinical evidence is justified. These include legacy devices, devices that fall under the definition of well-established technologies, and devices for which clinical data are not deemed appropriate to demonstrate compliance with relevant GSPRs. The following elaborations provide a more detailed examination of these cases.

Legacy devices

Legacy devices are medical devices previously CE marked under Directives 93/42/EEC (MDD) or 90/385/EEC (AIMDD). Generally, the MDR requirements for clinical evaluation and clinical evidence are fully applicable to legacy devices, but a lower level of clinical evidence may be justified for devices already established on the market. The MDCG guidance document 2020-6 was created to support manufacturers and notified bodies in assessing what level of clinical evidence is appropriate for legacy devices.

In contrast to new devices first placed on the market under the MDR, data from post-market surveillance (PMS) activities are available for legacy devices. Depending on their quantity and quality, PMS data can play a substantial role in the demonstration of compliance of a legacy device with relevant GSPRs. Further, other sources of low-level clinical evidence, such as non-clinical data or the state of the art evaluation, may be used to support the performance and safety of a device. For some legacy devices, the combined evidence provided by these data sources may be sufficient to demonstrate GSPR compliance, particularly if they are low-risk and standard of care devices (see also information on well-established technologies below).

MDR Article 61(6a) specifies when Class III and implantable legacy devices may also be exempt from the requirement to perform clinical investigations. Such exemptions require compliance with relevant common specifications and a clinical evaluation based on sufficient clinical data. The application of Article 61(6) must be justified in the clinical evaluation report.

Well-established technologies

Even though MDCG 2020-6 primarily focuses on required clinical evidence for legacy devices, it also provides some general guidance transferable to new devices that undergo the initial CE certification under the MDR, such as a suggested hierarchy of clinical evidence. According to this hierarchy, cumulative evidence from lower-level sources may be sufficient to conform with relevant GSPRs for devices that fall under the definition of well-established technologies (WET).

MDR Article 61(6b) provides a list of Class III and implantable devices that are as WET devices exempt from the requirement to perform clinical investigations, namely sutures, staples, dental fillings, dental braces, tooth crowns, screws, wedges, plates, wires, pins, clips, and connectors. As for legacy devices, prerequisites for such exemptions are compliance with common specifications where these exist, and the fact that the clinical evaluation is based on sufficient clinical data.

Whether the definition of WET can be extended to devices not listed in Article 61(6b) is controversial. The MDR states that only the Commission can modify the list of devices that are considered WET devices through delegated acts. However, the MDCG 2020-6 outlines specific criteria to help identify when a device qualifies as a WET device. According to this guidance, all devices meeting these criteria may be considered well-established technologies. The guidance document further specifies that the evaluation of the state of the art and similar device data are not regarded as clinical data under the MDR, but can be considered supportive of confirmation of conformity to the relevant GSPRs for WET devices. Again, it needs to be clarified from an official side whether this only applies to legacy devices since the authors of this article are aware of new devices having successfully received the CE mark under the MDR using this justification.

Devices for which clinical data are not deemed appropriate

Article 61(10) sets out a potential clinical evaluation route that allows GSPR conformity to be demonstrated solely based on non-clinical data. This route is only applicable for devices where clinical data collection is not deemed appropriate and cannot be used to justify a lack of clinical data for devices where clinical data collection would be feasible. No official guidance on application of Article 61(10) has been issued or announced. Based on publicly available information provided by Notified Bodies, the current understanding is that Article 61(10) cannot be applied if a device is claimed to provide direct clinical benefits, or if there are measurable clinical performance or safety outcomes directly attributable to the device.  Therefore, it is primarily suitable for devices that achieve their intended medical purpose through a purely technical performance that can be sufficiently demonstrated based on pre-clinical data.

Even if Article 61(10) is applied, a clinical evaluation according to MDR Article 61 and Annex XIV still has to be conducted. A thorough justification for the application of this article needs to be presented under consideration of the risks associated with the device, the interaction between the device and the human body, the intended clinical performance, and potential claims. Importantly, implantable and Class III devices are not eligible for clinical evaluation under the Article 61(10) route. Finally, all claims regarding safety and performance of the device must be substantiated with non-clinical data such as performance and pre-clinical evaluation, bench testing, compliance with common specifications or standards, and PMS data for legacy devices.

Conclusion – consider device specific factors when planning clinical evaluation

Manufacturers must specify the required level of clinical evidence that they consider sufficient for GSPR conformity demonstration for each device individually as part of the clinical evaluation process. MDR Article 61 describes several routes allowing conformity demonstration based on limited clinical evidence. The applicability of these routes depends on various device-specific aspects and should be carefully evaluated during the initial clinical evaluation planning. However, some open questions remain regarding the interpretation of MDR Article 61 and related MDCG guidance documents.

Kathrin Abegg, DVM PhD
Team Leader Medical Writing ISS AG

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