Author: Suzanne Broussard
Post-market clinical follow-up (PMCF) requirements have increased under the newest Medical Device Regulations (MDR) 2017/745. All medical devices will be required to meet these standards, and the deadline is here. The possible 1-year extension for the application of MDR might give manufacturers a little wiggle room to achieve compliance, but not much.
The European Commission (EC) states in a nutshell that one of the reasons for the new regulations is to strengthen post-market surveillance requirements for manufacturers.
The goals for these new regulations are to:
The EC considers these newest regulations as providing extremely important improvements to modernize the current system and, therefore, medical device manufacturers need to make every effort to be compliant or risk further delays in obtaining a CE marking for their device.
In a recent post, we discussed one of the most challenging areas in the CER: Defining Measurable Safety and Performance Endpoints.
The PMCF plan must establish processes that proactively and systematically collect information from a variety of sources. These sources include serious incidents, Periodic Safety Update Reports (PSUR), field safety corrective actions, inputs on non-serious injury, undesirable side-effects, trend reports, literature, databases, registers, feedback and complaint sources form users, distributers and importers, as well as publicly available information on similar medical devices (MDR 2017/745, Annex III).
The PMCF plan should document the method in which the PMCF should be performed. Therefore, the PMCF plan needs to specify the methods and procedures that will be used by the manufacturer to proactively collect the clinical data and the data’s subsequent evaluation. The plan’s aims are to:
Choosing the post-market data to be collected in the PMCF plan is not an easy or straightforward task. The plan must include pertinent parameters to ensure the device is safe and effective. However, including too many or irrelevant variables may result in low response rates and/or missing data. The manufacturer should also consider that some data will be visible to the public. Indeed, one of the goals of the new regulations is to introduce transparency into the system to keep the general public informed, allowing patients to be more engaged in making their healthcare decisions.
The PMCF plan plays a central role under MDR 2017/745 since it lays the groundwork for the PMCF studies that subsequently interface with PSUR, Summary of Safety and Clinical Performance (SSCP), risk management files, CER updates, labeling, and IFU.
The data acquired through the application of the PMCF plan can provide strong evidence as to the safety and efficacy of the device and details about the clinical risks associated with use. Analysis of these post-market clinical data in combination with clinical literature is a powerful tool for manufacturers to improve product performance and support claims to regulatory agencies.
Getting these done is very time consuming and requires significant expertise, especially since the PMCF plan is an integral part of the quality system under MDR. The level of specificity necessary for the methods and protocols is intense.
The PMCF Plan must, at the very least, include the following:
At Criterion Edge, we understand how important the PMCF plan is to the success of your device’s new or annual CER and, thus, ultimately compliance with regulatory authorities and marketing in the European Union. Our experienced medical writers can provide guidance and expertise on the PMCF plan or any other aspect of your CER. If your organization needs expertise or just some breathing space for your medical writers, please reach out to us to chat.
Author: Suzanne Broussard
Performing a methodologically sound literature review in the early stages of product development, as well as in the later stages, can help reduce most of the inadequacies highlighted by the European Commission in section A6 of MEDDEV 2.7/1 revision 4. Section A6 provides examples of studies that lack scientific validity for the demonstration of adequate clinical performance and/or safety.
Here are the seven areas highlighted in section A6 of MEDDEV 2.7/1 revision 4 that manufacturers tend to have the most problems in proving scientific validity:
In a recent post, we talked about one of the most challenging areas of the CER: Defining Measurable Safety and Performance Endpoints
The first deficiency listed, “lack of information on elementary aspects,” can obviously be improved using a robust systematic literature review. Defining the evaluation criteria is the first step in performing a methodologically sound systematic literature review, and these sections would then fall into place. For example, one criterion would define the clinical study methods, while other criteria might include clearly defining results to be included, undesirable side effects, and the intended-to-treat population. A scientifically sound approach and well-organized data management plan can bring all the clinical data together and allow for a thorough understanding of where the device is in the process of obtaining an CE marking.
Less obvious is how a methodologically sound systematic literature review can help with some of the other CER deficiencies. Let’s look at the three points in a devices lifecycle in which clinical evaluation is undertaken: development of the medical device (section 6.2.1), initial CE-marking (section 6.2.2), and updating the clinical evaluation (section 6.2.3).
The systematic literature review can be an effective tool early in the development of the medical device for gap analysis and determining State-of-the-Art. Once all the clinical evidence is gathered it is much easier to see if the publications and report documents have conclusive preliminary data or if further clinical data is required before moving forward with CER submissions. And, closely evaluating the complied data makes it easier for manufacturers to note statistical methods in the supporting data, and the potential of bias.
Of course, not all inadequacies can be addressed with a systematic literature review, such as improper collection of mortality and serious events data that rely on a different process for review. It is always important to collaborate with your organization’s regulatory authorities or a regulatory specialist to make sure you are complying in these areas.
Following leading practices and presenting clinical data in a straight-forward manner helps manufacturers be in good position to help regulatory agencies not to have to say No to your CER submission. Lack of organization and transparency can create a cycle of generating responses to regulatory agencies and delays getting devices to market.
Systematic literature reviews can help you find gaps in information that may be needed for inclusion in the CER, as well as putting your best foot forward by strongly providing sufficient clinical evidence for the evaluation of safety and performance of the device. Regulatory agencies expect this level of compliance. We can help you meet the challenge. We are experts in this area. Check out our recent webinars to better understand the process.
At Criterion Edge, we are experts at generating methodologically sound systematic literature reviews and state-of-the-art reports to ensure your CER is ready for review by notified bodies. And, we can help ensure the scientific validity is adequate and document the methods we use for data collection. Talk to us about running a systematic literature review for you.
Author: Suzanne Broussard
All medical devices sold in Europe must have a Clinical Evaluation Report (CER), and specific and measurable safety and performance endpoints are paramount for an acceptable CER. However, many small medical device manufacturers are struggling to adequately define and subsequently document measurable safety and performance endpoints, especially in the literature review, to support an evidence-based evaluation.
The newest regulations for medical devices, Medical Device Regulation (MDR) 2017/745 and MEDDEV 2.7/1 revision 4, set high standards for confirming safety and performance when using the device according to the manufacturer’s Instructions for Use. Regulations under the old MDR and MEDDEV were not as demanding, and manufacturers are not accustomed to the current systematic process of CER evaluations.
These relatively new requirements for clinical evaluation extend to manufacturers trying to get new products into the European market, as well as those that are already selling medical devices. Safety and performance are central components of the evidence-based evaluation process for obtaining and maintaining CE Marking for MDR 2017/745 and MEDDEV 2.7/1 rev 4, and medical device manufacturers are expected to be in full compliance by May 26, 2020. For manufacturers that already have products on the market, the CER must be updated throughout the product lifecycle.
For more information on the role of CERs in obtaining CE Marking for legal marketing in the European Union (EU), see Criterion Edge’s article What role does the CER play in getting a Medical Device Approved for Marketing in the EU?
Systematic literature reviews (SLRs) are a big part of the CER. The ultimate goal of the CER is to provide sufficient clinical evidence that the device achieves its intended purpose and is safe and effective. MEDDEV 2.7/1 rev 4 Section 4 defines evidence-based as:
Note that this list is comprised primarily of endpoints that need to be generated by performing methodologically sound systematic literature reviews.
Clearly setting safety and performance objectives in the review of scientific literature proves to have its own special challenges. Conducting systematic literature reviews requires expertise, people, and time.
A systematic literature review is much different than an internet–based literature review for a scientific manuscript. It requires a clear and methodologically sound search strategy coupled with a robust literature search. Every decision needs to be documented.
There are many circumstances in which using experts in some areas of CER preparation can fill in gaps where expertise may be needed, or time is of the essence. To determine if hiring a consulting expert to facilitate timely and expert CER development, ask your organization these questions.
Does your team meet all the criteria for preparing the clinical evaluation?
Does your team know how to document the methods used to generate systematic literature reviews?
Are they familiar with what aspects to consider when determining relevance?
Do they have the time to perform systematic literature reviews?
Criterion Edge is an expert at CER preparation, generating a systematic literature review, and determining state of the art of medical devices based on systematic literature reviews. As leaders in this area, we have given 3 webinars for our customers; one we sponsored for the Regulatory Affairs and Professional Society (RAPS) community. These webinars can be accessed on our main page or by following these links:
In addition, our whitepaper State of the Art: Best Practices and Literature Review Using DistillerSR provides detail on how we perform systematic literature reviews and document all processes.
We share these resources to help medical device manufacturers develop strong CERs with measurable endpoints that ultimately make the review process smoother and get products to market faster.
“These rigorous principles for performing systematic literature reviews are now mandated by global regulatory authorities.”Laurie Mitchell, President Criterion Edge
At Criterion Edge, we are experts at preparing CERs and can ensure your reports and systematic literature reviews are methodologically sound, and safety and performance are measurable. Our medical writers are experienced at setting measurable objectives for safety and performance and performing methodologically sound systematic literature reviews. Contact us for more information on how we can help your organization with preparing CERs and systematic literature reviews.
Author: Suzanne Broussard
Clinical evaluation is an integral part of technical documentation mandated for regulatory compliance of medical devices sold in the European Union (EU); therefore, having a well-designed and clearly written clinical evaluation report (CER) is paramount for manufacturers of both existing and new medical devices.
This is especially true with the passing of Medical Device Regulation 2017/745 (MDR). The MDR directive places stricter regulations on medical device safety and performance.
Not only are new devices seeking regulatory compliance impacted, devices on the market prior to the initiation of the MDR directive are also affected as every device must be re-submitted for CE marking before the end of the May 2020 transition period. This effect will require manufacturers to update the CER for each device to current MDR standards in order to be in regulatory compliance.
A survey of medical device manufacturers revealed that 78% of respondents do not sufficiently understand MDR, while 58% do not have a strategy in place to correct gaps in their clinical data or a process for collecting the data needed (KPMG & RAPS).
With so little time left to meet the MDR May 2020 transition deadline, consider hiring a professional to help your organization prepare the CER document.
The CER documents a device’s entire clinical evaluation process and is required to achieve regulatory compliance for marketing in the EU. Essentially, the CER outlines the assessment and the clinical data that determine if evidence sufficiently verifies the clinical safety and performance of the medical device. Furthermore, the CER is considered a living document and must be updated on an ongoing basis throughout the devices’ life cycle.
The MEDDEV guidance document 2.7/1 revision 4 outlines the stricter regulatory requirements placed on medical device manufacturers. Several key differences exist between the previous EU Medical Device Directives (MDD) and MDR, including the data requirements to determine device equivalency and clarification on the risk/benefit profile.
For a detailed gap analysis of the differences in the requirements for device equivalency and risk/benefit profiles between the previous and the current standards see our white paper Gap Analysis Report: MEDDEV 2.7/1 Guidance and Risk/Benefit Profile.
Establishing and describing the state of the art for each medical device is central to the clinical evaluation because it establishes a reference standard that is used to determine if the device’s safety and performance are compatible with current treatment options. This information is used throughout the clinical evaluation process and is documented in the CER.
Criterion Edge’s Founder and President Laurie Mitchell outlines steps for developing state of the art to comply with MEDDEV 2.7/1 revision 4 in the white paper “State of the Art: Best Practices and Literature Review Using DistillerSR.”
Manufacturers have a lot at stake. Having experienced CER writers that can integrate the complex regulatory requirements with the device’s specific characteristics and can present the information with clarity can save both headaches and money. Pulling together the CER document requires a thorough understanding of the regulations’ meaning and, as importantly, the ability to apply the MDR regulations to each device’s specific situation.
The role of the clinical evaluator is so pivotal that expected qualifications for the clinical evaluation authors and evaluators are outlined in the MEDDEV 2.7/1 rev 4 guidance document right along with the stricter standards for device equivalency, risk/benefit justification, and scientific validity of data.
“The clinical evaluation should be conducted by a suitably qualified individual or a team.”
The list of qualifications to consider when choosing a clinical evaluator to author the CER is clearly stated in section 6.4 of the MEDDEV 2.7/1 rev 4. Foremost on this list are the author’s and evaluator’s qualifications and experience, including an advanced degree, documentation experience, and knowledge of the device being evaluated, research methodology, information management, regulatory requirements, and medical writing.
All of these requirements can be difficult to find in-house. Poorly organized or incorrect CER documents can hold up the compliance process delaying obtaining a CE mark or result in removal from the market during subsequent inspections.
Professional CER writers at contract regulatory agencies such as Criterion Edge can help manufacturers on multiple levels:
At Criterion Edge, our clients enjoy our transparency in the services we provide as our candid scoping includes a time frame for delivering the CER and detailed information on gaps in compliance. All of our writers have experience writing CERs and are up to date on current regulations. Providing a comprehensive analysis and subsequent solutions sets us apart from other vendors. Contact us if you would like to have a conversation about what we can do to help with your writing and regulatory needs.
Author: Douglas McGarvey
Criterion Edge chats with regulatory authorities and other medical device and pharmaceutical industry experts to share their viewpoints on topics that impact our industry. With this expert advice, we aim to keep you informed about current developments and encourage discussion among those of us who work in large and small medical device, pharmaceutical, or biologic companies, CROs and other industry groups. Our goal is to offer up-to-date and reliable information to help you navigate the regulatory landscape and gain a better understanding of critical issues that affect our industry.
NOTE: This forum is not meant to provide legal advice or official policy for any participant. It is simply provided as a discussion between Criterion Edge and various experts for the purpose of sharing the thoughts and opinions of participants.
We spoke with an expert from a major European notified body about how companies can prepare for revision 4 of MedDev 2.7/1 and upcoming changes in MDR rules. We discussed how these new regulations affect both new and existing products. Our expert says that the new MDR regulations pose serious implications for clinical evaluation reports based on literature review.
In the future, it will not be acceptable to build a clinical evaluation report (CER) based on literature instruction. This is a significant change! To put this in context, some 80% of products placed on the European market today are based on literature research. Industry experts think that that number will shrink to about 10% following the new MDR requirements.
For a new product, a literature review will no longer be sufficient to establish equivalency with an existing product. Manufacturers must establish equivalence between the medical device and its equivalent comparator. This requires comparison of devices for clinical application, biological compatibility features and technical parameters. In order to prove that these features are the same for the two products, companies will need to have access to the technical documentation of the equivalent product. It’s not sufficient to simply bring the other product to the laboratory and test it. Manufacturers will need to have two sets of technical documentation. Otherwise, the product equivalency will not be accepted.
For ongoing/annual updates, clinical literature will continue to be important. However, since there is no grandfathering of certificates, every new product will basically get to the European market in the first place based on MDR.
Once the MDR changes are in effect, the certification of many existing products will no longer be valid. Even if an organization certifies today, the certification will not be grandfathered into the new system. Every organization will need to go through the new certification process based on the new rules that go into effect in May 2020. It’s important to note the limited timeframe for the new certification process, so companies need to plan ahead.
With regard to current CERs, companies will need to revise and update all clinical reviews. First, they will need to update all of the initial CERs to meet Rev 4 of the guidance document, which is actually very close to the MDR requirements.
Crucially, it will not be acceptable to just focus on safety in order to update the report. It will be necessary to go back and prove the clinical safety of the product in the first place and then to provide updates. This is a major issue for both small and large companies.
Many companies will need to perform clinical studies and, in many cases, retrospective clinical studies. They’ll need robust programs for post-market clinical surveillance (PMCS) and post-market clinical follow-up (PMCF). With the changing rules, manufacturers will need to take a proactive, not a reactive approach, to stay compliant. Companies will need to have a very strong PMCF plan, which is different from requirements in MedDev revision 3.
Significantly, companies will need to proactively collect PMCF data. Then, depending on the product classification, they will need to produce two yearly reports with clinical data – a Product Safety Update Report (PSUR) and a Summary of Safety and Clinical Performance (SSCP). The data posted in those reports will come from the company’s post-market follow-up activities.
The Commission is creating guidance documents to clarify what it wants to see in these reports. But this reporting is not the same as a regular CER update. The two efforts must be done in conjunction with each another.
But writing the annual reports is just the beginning – evaluation of the reports is also necessary. Companies must upload the annual reports to Eudamed, the European Databank on Medical Devices, and the manufacturer’s notified body will review those reports each year.
Current discussions among notified bodies suggest that the Eudamed databank will be available by the end of the transition period or the month prior to the implementation in May 2020.
For further guidance, the Notified Body Operations Group (NBOG), a membership organization of European notified bodies, may be publishing papers with their interpretation of the regulations.
‘Ask the Expert’ is published by Criterion Edge, Inc. Criterion Edge, Inc. is a regulatory writing company that provides outsourced writing services to the pharmaceutical and medical device industries. The company’s expertise in regulatory writing best practices, honed over decades, produces superior deliverables and provides budget, resource and timeline flexibility for regulatory managers. We empower companies to deliver superior health care solutions. To learn more about how we do this, click here to contact us.
Join our President, Laurie Mitchell, on April 29, 2020, at 11AM PST / 2PM EST to align your CER with some key MDR requirements. This live webinar will help you assess your CER and identify possible gaps for mitigation before submission.
Attendees are eligible for a free consultation and scan of their CER (or CER template). Spots are limited – click to register for this free webinar.