Chris Rule, Contributing Writer11.17.15
The clinical evaluation report (CER) increasingly has become a key topic in the medical device regulatory world, particularly given the scandals including Poly Implant Prostheses’ (PIP) use of cheaper, industrial-grade silicone in breast implants, toxic debris from metal-on-metal hip implants and transvaginal mesh causing tissue erosion. Following these scandals, CERs have been thrust into the public eye and, as a result, now are coming under increased scrutiny.
The 2007 amendment to the European Union’s Medical Device Directive (MDD) resulted in every medical device sold into Europe requiring an up-to-date CER as part of its technical file. This did little, however, to clarify issues surrounding standards and compliance. Confusion remains as to what a CER should contain, how to set it out and what the standard for clinical data should be.
The issue only will become thornier with the introduction of the new medical device regulation (MDR), resulting in CERs becoming one of the most important elements of a product’s technical file. While the MDR currently is undergoing review and not expected to come into effect until 2018 at the earliest, manufacturers will need to ensure they are clear and concise on the current requirements that keep them up-to-date with the latest regulations and themes of the MDR.1
The lack of clarity has led to a variety of approaches being taken by manufacturers and notified bodies (NBs) when it comes to the CER process, leading to uncertainty in what is considered compliant. Recent scandals have highlighted the weaknesses in terms of the MDD’s content and, more notably, its implementation. In the European market, the vital importance of understanding and correctly implementing the requirements for clinical evaluation is paramount. This will help keep medical device manufacturers ahead of the game and ready for impromptu reviews of their technical files by notified bodies.
Even if a medical device already has a CE mark, manufacturers must still be wary as product technical files are not static; content continually must be reviewed and updated. So despite NBs passing their CER, manufacturers can’t rest on their laurels and think they are in the clear.
Ensure High Standards
Medical device manufacturers often are required to remediate their files when NBs scrutinize their product technical files. Quite often, and increasingly, many manufacturers maintain their files to a certain extent but are finding out that their CERs fail to hold up under more intense inspection as they are either out of date or not up to the required standard of increasingly taxing NB evaluations, leaving manufacturers feeling confused. This is particularly poignant for those that “passed” the CER last time or upon its initial review.
Update Regularly with New Evidence
When a medical device is brand new, there often is little, if any, clinical evidence to support the product. After a few years in the marketplace, a large body of clinical evidence becomes available, and it is essential that this is included in the CER. Original CERs often are based on literature reviews of equivalent products, components and compounds, but must be regularly updated and maintained as new evidence becomes available that is directly relevant to each particular device. Additionally, postmarket surveillance data and risk management activities should be included. NBs will expect to see CERs being constantly updated as new information becomes available.
This process isn’t only for new products, however. Updating and keeping information fresh applies to devices that have been in the marketplace for a number of years. This is due to advances in technology, data collection and medical innovation, which have resulted in a better understanding and improved knowledge of medical device performance. Facts from 10 or so years ago, for example, have become questionable as new clinical data gradually has emerged. A good example is the clinical evaluation of a cigarette. Many years ago they were deemed as good for our health. When it became clear that cigarettes were causing illness, a filter was then added as a way to inhale the smoke while reducing the risk of illness. At that point in time, data supported the use of the filter; however the full, long-term effects of smoking remained unknown.
Equally, risk management and clinical evaluation should be closely linked. While risk management activities should identify risks that need to be addressed in the CER, clinical evaluation can help identify, quantify and modify previously identified risks, so combining both is essential.
Prepare for Intense Scrutiny
As mentioned, previously passed CERs—even ones for which advancements in technology, data collection and medical innovation have had little impact—increasingly are likely to receive recommendations for improvement and non-conformity. As public pressure has mounted due to scandals such as the PIP case, the business case for viewing CERs as a fundamental part of a product technical file, especially where clinical data for the device is unavailable, is extremely strong.
Create an Ecosystem
Alongside this, it is vital that CERs combine to create an ecosystem including risk management, vigilance and postmarket surveillance activities, rather than coexisting as individual and separate silos. From our own experience, we find that many medical device manufacturers urgently need to readdress how they maintain and update their CERs in the future, particularly if they find it difficult to navigate through an unclear and complex regulatory environment.
Handle the CER Process
CERs outline the scope and context of the clinical evaluation of a medical device, including the actual clinical data, appraisal and analysis stages of evaluation. CERs are required when bringing a medical device to market, and are essential in demonstrating the product achieves its intended purpose while minimizing any foreseeable risks or adverse events.
Time Implications & Required Expertise
Manufacturers also need to be aware of the time implications a complete CER poses. Quite often, they underestimate how long it takes to conduct a thorough CER. Carried out systematically, a CER can take up to three months to finalize, although it will take less time for an update. This amount of time can be a major problem for all manufacturers, and especially if a medical device requires a new, updated or revised CER. Nevertheless, with unannounced NB inspections becoming the norm, medical device companies need to ensure that time no longer is a hindrance to compliance.
Additionally, CERs must be completed by qualified, experienced and accredited individuals. Therefore, authors are expected to possess the required knowledge of the device, as well as the regulatory knowledge, and an understanding of research methodology. The skills required to complete this include systematic and critical review skills.
It is vital to ensure the right expertise is available when it comes to the CER process. Failing to do so can lead to a risk of noncompliance. Any lack of understanding can sabotage a product’s ability to go to market, which will negatively impact a business’s reputation. If experienced researchers or CER writers are unavailable in-house, it is important that manufacturers develop or acquire appropriate expertise to minimize the risks.
* * *
Processes must be established and maintained in order to ensure that CERs are always up to the required standard, accurate, regularly updated and complete. CERs must be ready to pass inspection from NBs at any moment. Failure to prepare can be financially damaging, time consuming, and perhaps most important of all, detrimental to business reputation. If a full schedule isn’t already planned, a complete review of all product CERs is needed to keep them in line with today’s expectations, especially with new medical device regulations becoming effective.
Reference
Chris Rule is manager, Solutions Delivery, at Maetrics, a global life-science consulting firm based in Indianapolis, Ind., that helps clients with critical enterprise compliance, performance improvement, risk management, information technology and organizational change. He is an experienced regulatory and quality professional with an engineering background. As the clinical evaluation lead and subject matter expert, he brings a hands-on approach and strong interest in new and evolving technologies to Maetrics clients. Together with his team, Rule has produced a white paper on the changing landscape of CERs. Download the CER white paper for free at www.maetrics.co.uk/white-papers/uncategorized/clinical-evaluation-of-medical-devices/
The 2007 amendment to the European Union’s Medical Device Directive (MDD) resulted in every medical device sold into Europe requiring an up-to-date CER as part of its technical file. This did little, however, to clarify issues surrounding standards and compliance. Confusion remains as to what a CER should contain, how to set it out and what the standard for clinical data should be.
The issue only will become thornier with the introduction of the new medical device regulation (MDR), resulting in CERs becoming one of the most important elements of a product’s technical file. While the MDR currently is undergoing review and not expected to come into effect until 2018 at the earliest, manufacturers will need to ensure they are clear and concise on the current requirements that keep them up-to-date with the latest regulations and themes of the MDR.1
The lack of clarity has led to a variety of approaches being taken by manufacturers and notified bodies (NBs) when it comes to the CER process, leading to uncertainty in what is considered compliant. Recent scandals have highlighted the weaknesses in terms of the MDD’s content and, more notably, its implementation. In the European market, the vital importance of understanding and correctly implementing the requirements for clinical evaluation is paramount. This will help keep medical device manufacturers ahead of the game and ready for impromptu reviews of their technical files by notified bodies.
Even if a medical device already has a CE mark, manufacturers must still be wary as product technical files are not static; content continually must be reviewed and updated. So despite NBs passing their CER, manufacturers can’t rest on their laurels and think they are in the clear.
Ensure High Standards
Medical device manufacturers often are required to remediate their files when NBs scrutinize their product technical files. Quite often, and increasingly, many manufacturers maintain their files to a certain extent but are finding out that their CERs fail to hold up under more intense inspection as they are either out of date or not up to the required standard of increasingly taxing NB evaluations, leaving manufacturers feeling confused. This is particularly poignant for those that “passed” the CER last time or upon its initial review.
Update Regularly with New Evidence
When a medical device is brand new, there often is little, if any, clinical evidence to support the product. After a few years in the marketplace, a large body of clinical evidence becomes available, and it is essential that this is included in the CER. Original CERs often are based on literature reviews of equivalent products, components and compounds, but must be regularly updated and maintained as new evidence becomes available that is directly relevant to each particular device. Additionally, postmarket surveillance data and risk management activities should be included. NBs will expect to see CERs being constantly updated as new information becomes available.
This process isn’t only for new products, however. Updating and keeping information fresh applies to devices that have been in the marketplace for a number of years. This is due to advances in technology, data collection and medical innovation, which have resulted in a better understanding and improved knowledge of medical device performance. Facts from 10 or so years ago, for example, have become questionable as new clinical data gradually has emerged. A good example is the clinical evaluation of a cigarette. Many years ago they were deemed as good for our health. When it became clear that cigarettes were causing illness, a filter was then added as a way to inhale the smoke while reducing the risk of illness. At that point in time, data supported the use of the filter; however the full, long-term effects of smoking remained unknown.
Equally, risk management and clinical evaluation should be closely linked. While risk management activities should identify risks that need to be addressed in the CER, clinical evaluation can help identify, quantify and modify previously identified risks, so combining both is essential.
Prepare for Intense Scrutiny
As mentioned, previously passed CERs—even ones for which advancements in technology, data collection and medical innovation have had little impact—increasingly are likely to receive recommendations for improvement and non-conformity. As public pressure has mounted due to scandals such as the PIP case, the business case for viewing CERs as a fundamental part of a product technical file, especially where clinical data for the device is unavailable, is extremely strong.
Create an Ecosystem
Alongside this, it is vital that CERs combine to create an ecosystem including risk management, vigilance and postmarket surveillance activities, rather than coexisting as individual and separate silos. From our own experience, we find that many medical device manufacturers urgently need to readdress how they maintain and update their CERs in the future, particularly if they find it difficult to navigate through an unclear and complex regulatory environment.
Handle the CER Process
CERs outline the scope and context of the clinical evaluation of a medical device, including the actual clinical data, appraisal and analysis stages of evaluation. CERs are required when bringing a medical device to market, and are essential in demonstrating the product achieves its intended purpose while minimizing any foreseeable risks or adverse events.
Time Implications & Required Expertise
Manufacturers also need to be aware of the time implications a complete CER poses. Quite often, they underestimate how long it takes to conduct a thorough CER. Carried out systematically, a CER can take up to three months to finalize, although it will take less time for an update. This amount of time can be a major problem for all manufacturers, and especially if a medical device requires a new, updated or revised CER. Nevertheless, with unannounced NB inspections becoming the norm, medical device companies need to ensure that time no longer is a hindrance to compliance.
Additionally, CERs must be completed by qualified, experienced and accredited individuals. Therefore, authors are expected to possess the required knowledge of the device, as well as the regulatory knowledge, and an understanding of research methodology. The skills required to complete this include systematic and critical review skills.
It is vital to ensure the right expertise is available when it comes to the CER process. Failing to do so can lead to a risk of noncompliance. Any lack of understanding can sabotage a product’s ability to go to market, which will negatively impact a business’s reputation. If experienced researchers or CER writers are unavailable in-house, it is important that manufacturers develop or acquire appropriate expertise to minimize the risks.
* * *
Processes must be established and maintained in order to ensure that CERs are always up to the required standard, accurate, regularly updated and complete. CERs must be ready to pass inspection from NBs at any moment. Failure to prepare can be financially damaging, time consuming, and perhaps most important of all, detrimental to business reputation. If a full schedule isn’t already planned, a complete review of all product CERs is needed to keep them in line with today’s expectations, especially with new medical device regulations becoming effective.
Reference
Chris Rule is manager, Solutions Delivery, at Maetrics, a global life-science consulting firm based in Indianapolis, Ind., that helps clients with critical enterprise compliance, performance improvement, risk management, information technology and organizational change. He is an experienced regulatory and quality professional with an engineering background. As the clinical evaluation lead and subject matter expert, he brings a hands-on approach and strong interest in new and evolving technologies to Maetrics clients. Together with his team, Rule has produced a white paper on the changing landscape of CERs. Download the CER white paper for free at www.maetrics.co.uk/white-papers/uncategorized/clinical-evaluation-of-medical-devices/