What are the Clinical Evaluation routes under the EU MDR?

By Kamiya Crabtree, Regulatory Medical Writer at Mantra Systems Ltd.

Clinical evaluation under MDR, outlined in Article 61 and Annex XIV, is a systematic process of assessing clinical data to demonstrate conformity with the General Safety and Performance Requirements (GSPR) outlined in Annex I.?

Manufacturers have different options for how to carry out clinical evaluations. The most suitable option depends on factors such as the risk level of the device, its background, and the available data. Let’s break down these options.?

Clinical Investigation?

Manufacturers may need to collect new clinical data, particularly when existing evidence is insufficient to demonstrate that a device is safe and effective. This route involves the prospective collection of clinical data through a scrupulously designed and conducted clinical study. Clinical investigations are especially crucial for high-risk devices (Class III and some Class IIb), devices incorporating novel technologies, or those where equivalence with another device cannot be determined. The collected data must meet the regulatory requirements outlined in Annex XV of the EU MDR, ensuring reliability and relevance for the device’s intended purpose.?

Clinical investigations are necessary for implantable devices and Class III devices unless they can show that they are similar to an existing device or use existing data, as stated in Article 61(4).?

Equivalence Route?

For devices that are substantially similar to an existing device, the equivalence route allows manufacturers to use clinical data from the equivalent device to demonstrate conformity. However, access to sufficient data on the equivalent device is required, which can present challenges, notably if the equivalent device is manufactured by a different company. The equivalence route is most viable for devices with a well-documented history of use and similar intended purposes.?

Equivalence must be established with robust evidence for all three parameters: technical, biological, and clinical characteristics according to Article 61(3).?

Literature Review?

A literature review is a viable route when existing clinical data from scientific publications can sufficiently demonstrate a device’s safety and performance. This approach is particularly suited to well-established devices with extensive published data supporting their use. The process involves critically appraising and analysing the quality, relevance, and applicability of the data in relation to the device’s intended purpose. Despite its feasibility, the literature review must be rigorous and comprehensive to withstand regulatory scrutiny.?

The literature review must focus on data relevant to the device’s intended purpose and align with clinical endpoints according to? Article 61(3).?

Post-Market Clinical Follow-Up (PMCF)?

Post-market clinical follow-up (PMCF) is an ongoing process designed to gather and evaluate clinical data after a device has been placed on the market. PMCF activities ensure the continuous monitoring of a device’s safety and performance during its lifecycle, addressing any residual risks and collecting additional evidence as needed. PMCF data can supplement clinical evaluations, particularly for high-risk devices, novel technologies, or devices with limited pre-market clinical data. Annex XIV of the EU MDR provides detailed requirements for implementing PMCF plans and reporting.?

PMCF is mandatory for implantable and Class III devices unless appropriately justified otherwise according to Article 61(6).?

Well-Established Technology (WET) Devices?

For devices classified as well-established technology (WET), clinical evaluation can rely heavily on existing data and literature. These devices are characterised by a long history of safe and effective use. While this route may reduce the need for new clinical investigations, manufacturers must ensure robust post-market surveillance to maintain compliance. WET devices are subject to specific criteria under the EU MDR, and any claims of safety and performance must be substantiated with high-quality evidence.?

WET devices must be clearly identified and justified as such, with supporting evidence according to Article 61(8).?

Article 61(10)?

When demonstrating conformity with GSPRs using clinical data is not considered appropriate, manufacturers must provide a sufficient justification. This justification should be based on the results of the manufacturer's risk management process and a thorough consideration of the specific interaction between the device and the human body, its intended clinical performance, and the manufacturer's claims. The manufacturer must document in the technical documentation, as specified in Annex II, why it considers the demonstration of conformity with GSPRs based solely on non-clinical testing methods, such as performance evaluation, bench testing, and pre-clinical evaluation, to be adequate.

This approach will be considered only for low-risk devices that do not provide a direct clinical benefit. Such devices are those that lack a positive impact on an individual’s health, as defined by meaningful, measurable, and patient-relevant clinical outcomes. These outcomes include those related to diagnosis, improvements in patient management, or contributions to public health.

Selecting the Appropriate Route?

When choosing the right method for clinical evaluation, manufacturers must consider several factors, including the device's risk level, novelty, intended purpose, and the availability of clinical data. Their strategy should align with these considerations while meeting the stringent requirements of the EU MDR. Regardless of the approach taken, the evaluation process must remain transparent, thoroughly documented, and capable of demonstrating that the device is safe, effective, and compliant with the GSPRs.

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