It is strongly advised that manufacturers adopt a proactive attitude towards their CERs and take the appropriate steps required to successfully present a compliant CER when their Notified Body (NB) requests to review their Technical File.
However, developing a clear, methodical and comprehensive strategy for getting CERs up to scratch is often unclear to professionals who are not CER specialists.
As the regulatory landscape continues to evolve, the requirements for manufacturers also change, making it more of a challenge for medical device producers to be confident in their approach to CERs. The lack of proficient CER experience during times of regulatory change will lead to various interpretations of CER guidelines being adopted, which means different approaches to CER compliance will be followed.
To help manufacturers attain compliance and prepare for future regulatory challenges, it’s important to highlight common sources of non-compliance, clarify requirements and address gaps in clinical evaluation guidance.
CERs: the business case
Why are up-to-date CERs important? The business case is simple. Good practice and the proactive implementation of CERs within organisations ensures that businesses are able to continue trading their products on the market. They also help to avoid costly recalls and the subsequent reputational damage associated with a lack of compliance, as well as expensive remediation efforts.
Not to mention that having to repeat reviews of clinical data in response to deficiencies is also extremely time-consuming — and it creates a distinct drain on company resources. Therefore, completing CERs efficiently and effectively the first time around is key.
Implementing an efficient and proactive strategy to manage the process of getting CERs into shape has multiple benefits, such as improving the synergy between risk management and post-market surveillance (PMS) activities.
Maintaining up-to-date CERs, facilitated by ongoing monitoring of relevant published literature and PMS data, is an extremely effective way of ensuring that there are minimal updates to make when the CER comes under review and less time is spent reviewing and preparing numerous documents from scratch.
This proactive approach with CERs doesn’t just reduce the level of admin that manufacturers have to deal with; it can also help the business to gain efficiencies that can be applied to more than one product and may involve combining multiple products under a single CER.
Adopting this analytical approach to CER management can help to rationalise product portfolios and reduce time-to-market for any new devices, as well as speed up and improve overall product design at the R&D stages. Therefore, efficient and proactive management is central to increasing the company’s bottom line and growing profits.
The evolving landscape of medical device regulation
In 2002, it came about that manufacturers did not always have clinical data to hand when required … and that the NBs did not always verify the adequacy of clinical data with respect to device characteristics and device performance.
It was also noted that the wording in the Medical Devices Directive and the MEDDEV guidance documents led to doubts regarding interpretation. Multiple attempts were made to address this through various amendments and iterations, with the most recent in June 2016 (MEDDEV 2.7/1 Rev. 4) now defining a much more systematic and robust approach.
On 25 May 2017, the new MDR came into force, marking the start of a 3-year transition period. The MDR closely reflects MEDDEV 2.7/1 Rev. 4 regarding the requirements needed to support clinical data. NBs are themselves coming under increased pressure following a plethora of publicised safety breaches within the industry. Therefore, the pressure is on for NBs to improve their overall performance to safeguard the public.
Specifically, NBs are now required to increase unannounced inspections and limit their activities to devices wherein they have proven competence. This means that NBs will continue working to improve their processes and skill sets — meaning more frequent and rigorous assessments are to be expected. The new regulation also attempts to avoid differences in interpretation by providing clarity in terms of definitions and expectations with regard to clinical data.
David Egbosimba, Solutions Delivery Manager, Maetrics
CERs: defined
Whenever a new medical device is placed on the market, the manufacturer must have demonstrated — through the use of appropriate conformity assessment procedures — that the device complies with relevant Essential Requirements (ERs).
It is expected that the manufacturer will be able to demonstrate that the device achieves its intended performance and that any known foreseeable risks are minimised. Ultimately, clinical evaluation is defined as the assessment and analysis of clinical data pertaining to a medical device to verify its clinical safety and performance when used as intended.
If manufacturers have not already done so, they should be assessing their existing clinical evaluation reports without delay to check whether they correspond to the new regulatory obligations.
Getting CERs right
When looking at the clinical evaluation of a new device, the available data will typically be limited. The evaluation will be based on the best available data at the time; however, the best indication of safety and performance will only be obtained once the device is in use. With the increasing lifespan of devices on the market, there will be increased need for clarity regarding the risk/benefit profile of the device.
This means that the CER must be updated periodically to take account of new information, so the risk/benefit assessment remains as up to date as possible and the safety and performance claims for the device continue to be supported.
The first challenge for manufacturers is to ensure that they treat the maintenance of their CERs as an ongoing cyclical activity. It’s not just a one-off task, but should instead be conducted throughout the lifecycle of the device. A methodical best-practice CER can take up to 3 months to complete, depending on available resources and expertise, so it is crucial that manufacturers plan accordingly.
Manufacturers need to develop an understanding of the required inputs for clinical evaluations, particularly from internal sources (product information, PMS and risk management data) and implement associated procedures to ensure that the required information is available and can be obtained at the right time in the right format.
To facilitate the CER process next time around, manufacturers should develop standard operating procedures (SOPs) that include comprehensive and standard templates to help follow the correct process each time.
Involve the experts
Ensuring that the right level of expertise is available to complete the CER cannot be underestimated. The CER needs to be completed by qualified and accredited individuals. CER writers are expected to possess knowledge of the device and therapy areas, as well as research methodology and critical review skills, all of which will help to avoid non-compliance and overcome gaps in guidance.
If the required level of expertise is not already available in house, then it’s important that manufacturers invest in training programmes for existing employees or procure appropriate expertise from outside the business. Knowing that CER writers are not relying solely on guidance will remove the likelihood of time-consuming revisions during the production phase or after NB review.
There is a plethora of training courses available on clinical evaluation and for other aspects of research methodology to develop in-house expertise.
Allocating dedicated staff to complete this process can help to avoid backlogs derived from conflicting workloads. Many manufacturers with additional resource requirements insource or outsource the preparation of CERs, with many consultancies providing this service.
The key to success is combining external expertise and resources with internal processes to provide timely data inputs. With a partnership approach to maintaining compliance, organisations never need to be on the back foot with NBs and regulatory requirements.
Owing to the changing regulatory landscape and increased pressure on NBs, manufacturers need to be ready for increased CER scrutiny, including heightened expectations concerning the appropriate use of clinical data to support their devices.
Combining the right knowledge, resources and processes, medical device manufacturers can tackle their CERs without delay, ultimately achieving improvements to their products that will increase safety and reap maximum business benefits … keeping them ahead in their market.
