EU MDR Clinical Evaluation Requirements – Understanding the CER
A critical component of the Technical File Submission for the CE Marking /conformity assessment process, Clinical Evaluation Reports are essential to sell or distribute medical devices in Europe. However, many manufacturers struggle to comply with European CER requirements as there is a significant lack of clarity regarding key requirements and best practices for creating these reports.
What is a CER?
A CER documents the assessment and analysis of clinical data pertaining to a medical device to verify the clinical safety and efficacy of the device. Clinical data analysis based on either a clinical investigation of the device under evaluation or existing clinical studies for equivalent devices comprises a CER. The goal, of course, is to establish that any risks associated with the intended purpose of the device are acceptable when weighed against the benefits it offers users.
Which Medical Devices need a CER?
Under the new European Medical Devices Regulation (EU MDR 2017/745), CERs will be required for all classes of products. The depth and extent of evidence needed however shall be proportional to the nature, classification, intended purpose and risks of the device under evaluation, as well as to the manufacturer’s claims pertaining to the device. To illustrate, low risk, well-established products like thermometers may not need a clinical investigation. However, these devices must still comply with safety and efficacy requirements and perform all of the Post Market Surveillance (PMS) activities outlined in the regulation.
How to prepare a Clinical Evaluation Report (CER)?
In line with MEDDEV. 2.7.1 Rev.4, the CER should cover all assessments of benefit and risk of possible relevance for the use of the device, when used in accordance with the intended purpose given by the manufacturer and the specific claims made about the clinical efficacy and safety of the device. The clinical evaluation should be thorough and objective, emphasizing the significance of risks that remain after mitigation strategies have been employed by the manufacturer and should account for both favorable and unfavorable data.
Here are some of the elements that should be included in the CER scoping process, though some of these apply only to “new” devices getting CE Marking for the first time.
- General information pertaining to the device such as the device and manufacturer name, CE Marking status of the device, where the device is marketed outside Europe
- Intended use and Indications for use
- Technical device description & specifications, including images as they exist
- Overview of intended claims
- Current state of the device
- Clinical evaluation comprising a summary of clinical data, analysis and review
- Risk management documentation- Assessment of performance, safety, and conformity to claims & standards
In general, one must consider the risk management files and demonstrate compliance to appropriate standards such as IEC 60601-1 (electrical safety) and EN 62366 (usability). It is important to ensure consistency with relevant clinical data and describe the merit and limitations of any data cited or included in the evaluation.
Read More on Completing an EU MDR Clinical Evaluation Report
Are additional clinical investigations required?
Unfortunately, there is no hard rule that determines whether the clinical data collected is enough to meet the General Safety and Performance Requirements (GSPR) of the EU MDR. An in-depth gap analysis must be conducted to decide if additional clinical investigations will be required. Factors such as long-term device performance, safety under extensive use and rare complications which may lead to safety risks or affect the performance should be also be considered during the evaluation.
Is the CER a one-time activity?
Though the CER needs to be completed prior to market launch to support safety and performance of the device, it is a lifecycle activity which continues well into post-market. All of the post-market processes including surveillance and vigilance activities feed into the CER and are used to determine the overall acceptability of the device basis its risk/benefit analysis. Any notable changes that impact the initial data should be recorded and the CER should be updated accordingly. Failure to do so could risk conformity with the Medical Devices Directive/MDR.
How will Europe’s new Medical Device Regulation (EU MDR) Impact CERs?
The main impact can be broadly explained in terms of more stringent requirements for CERs, such as the grounds of establishing equivalence with another device, the quality of data and processes considered in the clinical evaluation, and increased post market surveillance Stricter Criteria for establishing equivalence: A uniform review of sales literature from comparable products and services can contribute to an extensive and useful product review. A literature review of devices having similar technical, biological & clinical specifications may help identify equivalent devices and will also provide an understanding as to the current state of the art. Manufacturers must demonstrate that the device under evaluation is substantially equivalent in terms of safety and effectiveness to the aforementioned equivalent devices (technically termed predicates).
Greater emphasis on clinical investigations
The EU MDR has raised the bar on not just the need for clinical evidence and evaluation, which may necessitate modification in CER processes and collection of additional data from clinical investigations, but also the expected level of scrutiny. Most often, manufacturers submit literature reviews containing existing clinical studies for equivalent devices. Now with the EU MDR, the use of scientific literature as a sole means for clinical assessment will become strictly regulated. Pre-market clinical studies though time consuming and more expensive are essential for new technology and indications. Additional data generated from PMS post-market surveillance activities and post-market clinical studies, such as post-market clinical follow-up (PMCF) should be included in the CER, organized and developed in a uniform and smoothly reproducible process.
Enhanced examination of CERs by Notified Bodies (NBs)
Manufacturers will be required to re-evaluate the CERs across their portfolios, which is especially important in cases where the initial CE marking was supported with limited clinical data. High risk device manufacturers such as class III or implantable devices should compile and submit a summary of safety and clinical performance on the European Data Bank on Medical Devices (EUDAMED) database. However, even for lower risk devices, a clinical study is required if clinical data is not available in the published literature, or if the device has a novel feature.
With the implementation of the EU MDR, the tune is set to change towards heavier post-market surveillance requirements, among others, meaning more emphasis on risk management, post-market clinical evaluation, and ensuring conformity to new specifications through the device lifecycle. With this understanding, manufacturers can reduce time to market for new entrants, save valuable time & money by optimizing clinical evaluation processes, appropriate for that device, and reduce risks of recalls and lawsuits