When a medical device is placed on the market, it is critical for the manufacturer to demonstrate through appropriate Conformity Assessments (CAs) that the device complies with the Essential Requirements (ERs) as set out in the Medical Devices Directives (MDD). The manufacturer needs to demonstrate that the device achieves its intended purpose, that any known (or possibly foreseeable) risks are minimized and weighed against the benefits of the intended use, and that any claims about the device's performance are supported by evidence.
Any medical device manufacturer that is looking to introduce a new medical device on the European market or to continue selling an existing product in Europe must not underestimate the importance of clinical evaluation to verify the device's clinical safety and performance. In fact, every medical device that is sold into Europe, irrespective of specification, must have an up-to-date Clinical Evaluation Report (CER) as part of its Technical File. Considering the significance of this regulatory requirement, there remains to be a lack of clarity on the approach that manufacturers should adopt when dealing with their CERs as well as the overall requirements manufacturers should follow.
Lack of clarity can result in varying approaches to the CER process by both manufacturers as well as Notified Bodies (NBs), leading to a slew of CERs being misfiled and manufacturers feeling uncertain as to whether their CER process will be considered compliant and their medical devices adequately supported or not (see Figure 1).
With the growing scrutiny that medical device manufacturers are coming under due to the introduction of the new Medical Device Regulation (MDR), proactive implementation of CERs not only enables businesses to keep their products on the market, but also means they can avoid costly recalls and the reputational damage that this can lead to — a very relevant consideration given the speed at which information circulates over social media.
In light of the time requirements and resource drain of having to repeat reviews of clinical data when a deficiency is recorded, it is apparent that clinical data reviews should be carried out efficiently the first time around. This article looks further at what exactly the requirements are for properly documented, up-to-date CERs.
Regulation Roller Coaster
When the new MDR came into force on the May 25, 2017, it placed a greater emphasis on the requirements for supporting clinical data and closely reflected the requirements defined by MED-DEV 2.7/1 Rev. 4, shining a spotlight on the planning of CERs and on the need for a clearly documented process (see Figure 2). Further to a string of highly publicized safety breaches, NBs are under increased pressure to improve their performance in terms of safeguarding public safety.
In 2012, the Joint Plan for Immediate Action reinforced the role of the NB by stipulating the need for unannounced inspections to be increased as well as more focus on improving CAs. The new regulation also aims to provide clarity in terms of definitions and expectations regarding clinical data.
The Heart of the Matter: Clinical Evaluation Reports
Clinical evaluation is defined as the assessment and analysis of clinical data pertaining to a medical device in order to verify its clinical safety and performance when used as intended. However, there are two common misconceptions among manufacturers when it comes to CERs. Firstly, that it is just a one-off task when, in fact, it is an on-going activity that is conducted throughout the product life cycle. Secondly, that it can exist as a stand-alone activity; in reality there are other activities (post-market surveillance and risk management) that are necessarily interlinked and cannot function in isolation.
A common challenge that many manufacturers are facing is underestimating how long it takes to complete a CER; if conducted methodically, it can take up to three months to finalize. Time is much more of a concern to manufacturers that have multiple devices that require new, updated, or revised CERs. With the new MDR and the unannounced inspections by the NBs, manufacturers really can't afford to let time be an issue. Secondly, it is important that the CER is completed by qualified individuals who have the expertise to deal with the clinical data. Ideally, CER writers will have the knowledge of the device and therapy area as well as knowledge of research methodology and critical review skills (See Figure 3). Expertise and familiarity with regard to the CER process itself is also important to avoid noncompliance and overcome gaps in the guidance. If a manufacturer does not have an experienced CER writer in house, it is critical to source the right level of expertise elsewhere.
Maetrics, for example, has developed the following five key areas to help draft and maintain properly documented, up-to-date CERs.
Develop Internal Procedures for the QMS. In order to ensure that the required information is available and can be obtained in the correct format when needed, it is important to develop an understanding of all the inputs to the clinical evaluation, particularly from internal sources, and implement associated procedures.
Develop CER Procedures. Developing a standard operating procedure (SOP) that includes comprehensive and standard templates means that the evaluators are equipped to consistently follow the correct process without reinventing the wheel each time round, ultimately saving time.
Training. Ensuring that CER writers are trained on the CER process and are not relying solely on guidance will remove the likelihood of time consuming revisions during the production phase or after NB review. Developing in-house expertise is essential, whether for writing or for reviewing outsourced CERs. There are training courses available on clinical evaluation and also for other aspects of research methodology if necessary.
Team Approach. To reduce time spent to complete a CER, it is advisable to allocate certain elements of the process to different (appropriately trained) internal or external personnel. For example, when it comes to the data extraction element, this doesn't necessarily need to be carried out by the CER author. It can be completed by someone who has that specific skill set. Looking at the varying skill sets amongst available personnel can reduce time and increase quality; often the author is required to collate data that would more effectively be produced by others, such as equivalent device product data, which would be better provided by the technical team.
Adequate Resourcing. Ensuring that there are enough dedicated staff available (factoring in potential workloads) is critical to help ensure that the time-consuming elements are completed as swiftly as possible. Many companies look to insource or outsource the preparation of CERs by tapping into external expertise — meaning that organizations will be properly prepared and not caught on the back foot with an unannounced NB inspection and other regulatory requirements.
With the constantly evolving regulatory landscape putting increased pressure on the NBs, it is paramount that manufacturers are prepared to increase scrutiny of their CERs and face heightened expectations with regard to the appropriate use of clinical data to support their devices. It is important that manufacturers don't delay and develop a road map for a successful pathway to meet regulatory changes and evolving market needs, by combining the right knowledge, resources, and processes. Ultimately, adopting a proactive approach to CER reporting ensures that medical device manufacturers can reap business benefits to stay ahead in the market.
This article was written by Scott Edwards, Managing Director, Solutions Delivery at Maetrics, Indianapolis, IN. For more information, visit here.