By Celeste Maksim (Ph.D., RAC), RQM+
The European Medical Device Regulation 2017/745 (EU MDR) has increased expectations for data quantity and quality by reinforcing previous requirements. The regulation imposes new requirements for clinical evaluation for some Class III and implantable devices, narrowing equivalence routes and placing greater emphasis on postmarket clinical follow-up (PMCF). The aim of PMCF is to confirm the safety and performance of a device throughout its expected lifetime; to monitor known side effects and analyze emergent risks; to ensure that a device’s benefit-risk ratio remains acceptable; and to identify possible device misuse or off-label use, where the device is used differently from manufacturer instructions. Though “clinical benefit” is emphasized throughout the regulation, it is unaccountably absent in the definition of PMCF, which can be found in Annex XIV, section 5 of the regulation.
Whether manufacturers were able to meet the May 2021 deadline or are working toward the May 2024 deadline (having renewed their certificates under the Medical Device Directives), it is imperative that they have appropriate processes in place. According to Article 120 of the MDR, postmarket requirements will apply to MDD certified devices throughout the transition period ending in 2024.
This article first provides a summary of three best practices developed through practical experience with medical device manufacturers and then offers an overview of common issues observed in notified body submissions.
Best Practice #1: Strategy Development
It is advised that manufacturers begin by assessing all possible options for their PMCF compliance strategy and ensure the solutions adopted are appropriate to the residual risks identified through the clinical evaluation; not every device requires an RCT or large observational study. There must be rigorous justification for the decisions made and measurable objectives for the solutions adopted. There should be a documented process that includes an activity timeline, available budget, risk class of the device, quality of data needed to provide sufficient evidence, and whether a general or specific PMCF activity is required to provide the data needed (most devices will require both specific and generic PMCF activities). While notified bodies cannot legally offer consultancy or advise on how to achieve compliance, there are ethical opportunities to interact with them, for example, to clarify the intent of questions or meaning of nonconformities raised.
From an organizational standpoint, it may be helpful to divide responsibilities within product teams. Resources per device can then be allocated and prioritized in order of certificate expiration timeline, gap analysis, likely life cycle, sheer volume of devices requiring data remediation, and the product’s role within larger therapeutic systems. PMCF activities may reveal that pursuing MDR compliance for certain product classes does not make commercial sense. The earlier you begin your preparations, the sooner you can take that view and establish a proactive plan for compliance, rather than invest effort and subsequently withdraw products under pressure.
Best Practice #2: Data and Process Standardization
Manufacturers must be clear on processes for PMCF data assessment, what data is available for each device, medical indication, and target population. Process standardization ensures that areas are not missed when dividing workload, that processes are consistent across devices, and that information is presented consistently for effective comparison. Once this is complete, the data can be added into a wider risk framework to support postmarket monitoring, including, for instance: complaint trends, complaint severity measures, adverse events, recalls, field safety corrective actions, field safety notices, sales data, changes in specific marketing regions, and political risk or hazard legalities.
Best Practice #3: Data Quality Review
Once data has been collected using the standardized approach, manufacturers should identify the residual and emerging risks and where additional clinical evidence may be required to support continuing compliance. It is useful to map these residual risks against identified PMCF activities to confirm the activity is appropriate and that data collected through the activity will address the particular area of residual risk. From there, companies will need to decide the most effective way to collect the required data. Businesses should also interrogate their data quality and relevance once all data has been collated to ensure they can provide the level of evidence that a notified body would expect for the relevant risk class for each of their devices. For instance, manufacturers should consider whether their follow-up data is representative of a device over the course of its entire product lifetime, particularly for devices such as implants. They should also be wary of any bias within their collected data that could need correcting and discuss the limitations of the activity in the PMCF report.
3 Common Pitfalls (With Solutions)
One of the principal difficulties frequently encountered by companies in their PMCF compliance journey is determining what qualifies as “sufficient clinical evidence.” Manufacturers should realize that the term “sufficient” here has both qualitative and quantitative interpretations. For instance, some businesses make the mistake of including literature that may be relevant to their product but does not include findings on relevant outcomes; data must be relevant to the intended use of the device. How much clinical evidence is required will largely depend on the risk class of the device, the indication, claims, available data to support the device, and any recent changes in clinical practice. A good gauge for checking whether a device has sufficient clinical data is to compare outcomes achieved with other state-of-the art treatment options.
The second most frequently encountered PMCF compliance pitfall is a reluctance to put enough detail into the documentation, as well as a reluctance to provide detailed data stratification that shows exactly how much data is available for each device variant, combination, treatment indications, patient population, etc. Documentation should include justifications for why the proposed level and type of clinical data are acceptable based on the risks, intended performances, and clinical benefits associated with the device. It should also provide references to the EU MDR or relevant guidance to support the rationale for the type of data included. Feedback from notified bodies shows that too many companies are not taking this to the required depth. Any decision for no specific PMCF activity needs to be carefully justified, even if the reasons seem obvious to the authors.
Another common mistake among manufacturers is failing to align with other departments outside of clinical, such as sales & marketing or general management, early in the process. Non-regulatory specialists may not see the need to spend on compliance for highly established products, and so it is important to stress that MDR scrutiny applies to legacy devices as well as new products. All departments should be informed on device priority, submission risk, and all available sources of product data and should understand the potential business damage from poor data quality and non-compliance. Without buy-in from other business units, it may be challenging to procure the necessary resources to fulfill PMCF activities to the required level.
Even with the additional year to prepare for EU MDR compliance, many of the pre-pandemic challenges remain, such as the limited number of notified bodies authorized to validate compliance. The capacity issue was exacerbated in 2020: As many manufacturers took advantage of the opportunity to recertify their medical devices under the outgoing directives, the number of MDD certificates due to expire in 2024 rose by 37%.1 This volume of applications, as well as the sheer number of devices requiring certification and the quality of the submissions themselves, are contributing to this issue. Furthermore, with the IVDR deadline close on the heels of the EU MDR, good planning is essential to ensure PMCF activities pass notified body review without major difficulties. By following the advice outlined in this article, you will be better equipped to carry out your PMCF plan efficiently and cost-effectively.
For more guidance on staying on track for EU MDR compliance, download the dedicated PMCF white paper from RQM+ here.
About The Author:
Celeste Maksim (Ph.D., RAC) is senior manager, PMS & PMCF Services, at RQM+.
She has a PhD in analytical chemistry, a RAC certification, and more than a decade of experience in regulated industries, including pharmaceuticals, medical devices, and in vitro diagnostic products.
- Med Tech Dive, MDR is live. Here are 5 things to know on where the rule stands, 25th of May 2021