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.
Companies face constant pressure to meet the increasing regulatory expectations and demands for information. Data identification through Systematic Literature Review (SLR) supports critical regulatory functions throughout the company, from MDR requirements through IND submissions.
In this session, we review:
Sign up for future webinars here.
This webinar is co-hosted by Criterion Edge and RAPS.
Criterion Edge has the expertise and resources to do literature reviews for many types of documents. Ready for a free consult?
Author: Suzanne Broussard, PhD
The Premarket Notification 510(k) Program is the pathway used by manufacturers of low- to moderate-risk devices that are substantially equivalent (SE) to a device already on the market in order to begin the process of legally marketing in the United States. The Food and Drug Administration’s (FDA) release of 4 updated 510(k) guidance documents on September 13, 2019 was intended to both help streamline the FDA reviewer process and help sponsors save time and resources.
The 510(k) Program is required for any device that does not need a Premarket Approval Application (PMA) and does not meet the specified exceptions. The sponsor must demonstrate that a device is at least as safe and effective, e.g. SE, to a legally marketed device that is not subject to PMA. The 510(k) submitters must receive a SE order from the FDA in order to market the device in the U.S. The SE determination typically takes 90 days, although that time is decreasing. Indeed, faster response times are one of FDA’s anticipated outcomes of these 4 guidance documents. The FDA hopes another outcome will be more guidance for the sponsors to streamline their submission process which will save time and resources. These outcomes are prevalent throughout the document and summarized in the FDA statement that 510(k) submissions “address the recommendations of an FDA guidance document should be easier to prepare by manufacturers and for FDA to review.”
Legally marketing a device based on a claim of substantially equivalent to devices legally marketed prior to May 28, 1976 (preamendments devices) requires the manufacturer to submit a Premarket Notification 510(k). The majority of premarket devices use the 510(k) program; hence, it is important to clarify FDA’s definition of a legally marketed device.
A Legally Marketed Device must fit one of these 4 criteria:
Note that the legally marketed device(s) used for equivalence is commonly referred to as the “predicate.”
The Refuse to Accept Policy for 510(k) Final Guidance Document contains nonbinding recommendations and supersedes the “Refuse to Accept Policy for 510(k)s” issued early in the same year (February 21, 2019). The newest Refuse to Accept (RTA) policy includes an early review that will inform the submitter within the first 15 calendar days after receipt of the 510(k) submission of issues against specific acceptance criteria with information as to the administrative completeness and if not, includes identification of missing element(s). This guidance includes checklists of which items a sponsor should include in their 510(k) submission if they want to ensure their application is reviewed in a timely fashion.
The Abbreviated 510(k) Program is used by the FDA as an optional approach to the traditional 510(k) Program to demonstrate SE in premarket notifications by using guidance documents, special controls, and/or voluntary consensus standards to facilitate review of 510(k) submissions. This review relies on summary reports that “briefly describe and summarize the testing performed to support the submission as recommended in relevant guidance document(s).”
Device manufacturers can choose the Abbreviated 510(k) pathway if the submission relies on one or more of the following:
The FDA provides specific guidance for the general framework of Traditional 510(k)s and Abbreviated 510(k)s in the Final Guidance Document. These formatting guidelines do not apply to Special or other premarket 510(k) submissions. FDA believes that using this Formatting Guidance will conserve both FDA and industry resources as well as facilitate timely 510(k) review.
The Special 510(k) Program is designed to provide an optional and potentially expedited pathway to legally market “well-defined device modifications where a manufacturer modified its own legally marketed device and design control procedures produce reliable results that can form, in addition to other 510(k) content requirements, the basis for substantial equivalence (SE).”
The Special 510(k) Program: Guidance for Industry and Food and Drug Administration Staff provides the FDA’s current thinking and intent on premarket notifications that are appropriate for review as a Special 510(k). This Final Guidance Document describes an optimal pathway for certain well-defined device modification for manufacturers that modify their own legally marketed device and clarifies the types of technological changes that are appropriate for review including changes to design, labeling, and indications for use.
To further help clarify the Special 510(k) Program, the FDA recently held a webinar to discuss the Special 510(k) Program Final Guidance, and to answer questions. It is packed with useful information for those considering filing for the Special 510(k) Program including eligibility factors and examples of devices appropriate and those not appropriate for a Special 510(k). The recording of the webinar can be accessed here.
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.