CER Reviews: Common Issues identified by Notified Bodies

Clinical Evaluations are essential documents required within a Technical File for the successful submission to a Notified Body. They play a major role in achieving compliance with the regulations, and in gaining the ability to place a medical device on the market. Often, Notified Bodies can come back to manufacturers with nonconformities identified in a Clinical Evaluation Report that need remediation prior to the next round of document reviews. Dealing with the feedback effectively or avoiding it altogether can save a manufacturer stress and time.

In this blog, we present 3 of the most common issues found and flagged in Clinical Evaluations by Notified Bodies, and give helpful information as to how to avoid nonconformities in these areas.

Insufficient information on product variants, previous product versions (particularly in software), and predecessor devices

It is vital that it is clear whether there are differences between alternative/ previous versions of a device and the subsequent expected difference between devices with regard to clinical performance and safety. This is especially the case in instances whereby available clinical data on an old version of a device is being used to analyse the safety and performance profile of a current version of a device. Additionally, it is vital that clinical data on a particular version of a device is recognised as applicable to ALL versions of said device and this should be disclosed within the Clinical Evaluation documents with a sufficient justification. For example:

• Device Version 2 is an updated version of Device Version 1, with the only implemented difference the fixing of software bugs as per the Bug Fix document [REF]. Therefore, it is expected that there is no clinical differences between the performance and safety profiles of the devices. This means that clinical evidence on Device Version 1 is applicable to Device Version 2.

OR

• Device Version 2 is an updated version of Device Version 1, which introduces a greater level of functionality due to its new feature as per the Device Update document [REF]. There is a recognised clinical difference between the performance and safety profiles of these devices. This means that clinical evidence on Device Version 1 is not applicable to Device Version 2.

To address this, a comprehensive explanation should be provided explaining the relationship between each of the alternative versions of the device and/ or between the device and its predecessor. This should include a description as to whether both devices are to be placed on the market or if the latest generation is to replace the current generation.

Clinical Evaluation Plan does not clearly identify the Clinical Development Plan for the device under evaluation, i.e., what data is available for the device under evaluation and how will this data be compiled?

A Clinical Development Plan can be tricky to create but is essential to lay out the expected method that is to be used for collecting relevant evidence and data of a sufficient level and quality for use in evaluating the performance and safety profile of a medical device. Within the Clinical Development Plan, it should be determined whether as part of the Clinical Evaluation Report which of the following sources you intend to use data from, and which are not applicable for consideration (with appropriate justification):

• Clinical Investigation
• Expert Panel Consultation
• Clinical Evidence from Scientific Literature (from the Literature Search)
• State-of-the-Art Analysis from Scientific Literature (from the Literature Search)
• Clinical Evidence from Scientific Literature (Manufacturer Held Literature)
• Available PMCF Data
• Available PMS Data
• Vigilance Activities
• Pre-Clinical Evidence and Testing

Issues with the demonstration of equivalence

Using equivalence as a strategy to identify clinical evidence for a Clinical Evaluation can be useful, especially in instances whereby data has been collected on a predecessor device that still remains applicable to newer versions of the same device. It has, however, become more difficult to claim equivalence since the implementation of the EU MDR and the more stringent approach adopted and is one of the main issues (if claimed) that Notified Bodies look out for. To ensure an equivalence assessment between two devices is compliant, MDCG 2020-5 should be used and referred to within both the CEP and CER. If a difference between devices is identified using the criteria in this guidance document, then a justification is required as to why the clinical performance and safety profile between the device’s remains the same; depending on the characteristic, pre-clinical testing or supporting evidence may be required to demonstrate this conclusion.

Manufacturers should consider relying on an expert regulatory compliance partner when drafting Clinical Evaluations to avoid nonconformities or feedback from Notified Bodies, thus avoiding time consuming and stressing processes such as revisions and remediations.

Contact us at hello@imedconsultancy.com to find out how we can help you with your clinical evaluations and more!