Preparing for PMCF: Eight Suggestions for Best Practices

The European Medical Device Regulation 2017/745 (EU MDR) regards the post-market clinical follow up (PMCF) as a continuous process that updates the clinical evaluation and is to be addressed in the manufacturer’s post-market surveillance (PMS) plan. The new regulation increases expectation for supporting both data quantity and quality, and also involves significant changes. As a result, its implementation was destined to be a challenge for manufacturers, even with the additional year for implementation; though the MDR deadline was moved from May 2020 to May 2021, many of the pre-pandemic challenges, such as the well-recognized capacity issues among the Notified Bodies, persist.

The EU Medical Device Regulation’s date of application has passed, but activities such as PMCF require a nonstop effort to meet the new regulation’s requirements, and it is therefore vital manufacturers keep up the momentum gained during the EU MDR application phase.

Some manufacturers may have taken the option of renewing their certificate under the Medical Device Directives, but it is important to note Article 120 of the MDR indicates post-market requirements will also apply to MDD-certified devices during the transition period ending in 2024. Especially in the context of the pandemic, cost-effective planning is more essential than ever, so manufacturers are strongly advised to adopt best practices in PMFC activities from the start.

1. Develop a Strategy
PMCF falls under PMS requirements, which is given greater emphasis under the MDR. Consequently, it is vital for companies to develop a strategy, preferably one that is easily adaptable to device-specific requirements and data variations, in order to optimize their chances of achieving full compliance.

To achieve that, companies should weigh all available options, based on a device’s need for data, cost of activity, timeframe of activity, and effectiveness of the activity to collect required data. To build the best rationale for PMCF data, start with a detailed clinical assessment on the device and understand the depth and relevance of data needed through PMCF. It is also important to consider the Notified Bodies’ point of view and potential workload and to plan for minimal feedback and questions.

2. Standardize Processes
The key to ensuring the safety and performance of medical devices throughout their lifecycle is to promptly identify emerging risks and side-effects and to prevent device misuse through complete and thorough data collection. Example areas to standardize processes include:

• Process to enable flow of data throughout clinical and post-market documents: The PMS Plan, PMCF Plan, PMS Report/periodic safety update report (PSUR), and the clinical evaluation plan/clinical evaluation report (CER) all contain overlapping information and data. Aligning on processes for how this data connects and is shared across documents is key for consistency, efficiency, and lifecycle management.
• Process for complaint management and analysis coming from PMCF activities: It is likely complaints may come from PMCF activities if the manufacturer is seeking proactive feedback. Having a process in place in advance to handle those complaints and feed them into the existing complaint management assessment and process is helpful.
• Process to drive downstream document updates: The output of CER updates, PMS Reports/PSURs, and PMCF activities may drive the need to update the benefit-risk assessment, risk management file, and/or label. Defining these processes will help to enable workflow and ensure the activities are happening.

3. Standardize Data Assessment
Companies should also consider adopting a standardized approach to data assessment and identification. This brings many advantages, starting with enabling linear and transparent communication within the company. Clear communication and full assignation of all possible aspects is critical to improving workflows.

It also ensures consistency across all devices, medical indications, and target population, and can help highlight any possible gap in clinical data, as well as facilitating prioritization at later stages. For example, complaint trending methods may vary based on device family, risk classification, or target population. Alternatively, the same complaint trending method may be used but the thresholds for tolerability may be defined differently. Either way, standardizing data-related processes will also make it easier to contextualize and keep track of risk factors, recalls, or changes in specific marketing regions.

4. Review Available Data
When it comes to preparing for PMCF, reviewing data (starting with product portfolios) is one of the first and more important steps to be taken. This will help determine which products to prioritize based on revenue, certificate expiration timelines, available data, likely lifecycle, market strength, and number of devices in need of data remediation. An effective data review should include all departments (PMS, marketing, R&D, and general management) in order to identify, understand, and address all product-specific needs.

Reviewing and assessing product data will therefore determine which devices are closest to meeting PMCF compliance requirements and which have a long way to go, as well as whether carrying out PMCF activities makes commercial sense for all existing product classes or not. Manufacturers can thus gain more insight for any decision to remove (or introduce) products to a market and will not risk a forced withdrawal due insufficient clinical evidence.

After addressing all potential issues, manufacturers should also question the quality and relevance of their data, specifically from the perspective of a Notified Body. This evaluation should include assessing if outcomes appropriately support clinical benefit, if the follow-up extensively covers the product lifetime, variants, and ranges, as well as trying to identify and correct any existing bias.

5. Conduct a Trial Run
Medical device companies should also keep in mind the PMCF is not an isolated process, and as such, it will need to be integrated with PMS, clinical evaluation, and risk management processes. It will also require document updates over time (see standardize processes).

Therefore, it might be a good idea to pilot PMCF processes with a few representative high-priority devices first to test the efficacy of templates and forms, especially across the company. From there, manufacturers can fine tune their strategy for optimal efficiency.

6. Don’t Superficially Define the Term ‘Sufficient Clinical Evidence’
Deciding exactly what “sufficient” clinical data means may cause confusion among manufacturers as its interpretation can be both qualitative and quantitative.

To determine the amount of data required, companies should keep in mind that it varies depending on the risk class of the device, the indication, claims, available data to support the device, and any recent changes in clinical practice or the device itself. Data to be included should therefore be relevant to the intended use of the device, demonstrate clinical benefit, and support the indications and claims. It can be useful to compare it to available submissions for similar devices or treatment to determine whether existing data is sufficient.

7. Do Not Compartmentalize Activities
One of the most common mistakes manufacturers tend to make is failing to align with other departments outside of clinical, such as sales and marketing and general management, from the start of the process.

The scrutiny and clinical evidential basis requirements apply to legacy devices as well as new products so in order to achieve long-term compliance, it is crucial the whole company is up to speed with the regulatory submission process and the costs and processes it implies.

To mitigate side-effects of compartmentalizing activities, all departments should be included in conversations about device priority, submission risk, all available sources of product data, and be part of PMCF decisions. They should also be alerted to the potential business damage that could result from non-compliance or insufficient data.

8. Don’t Omit Details in Documentation
Notified Bodies have also reportedly observed a tendency to not provide enough detail in the documentation, even if the level of detail expected is clearly stated by both Notified Bodies and the Medical Device Coordination Group.

It is critical every decision, even if obvious to the author, is explicitly rationalized and manufacturers document proposed data and justification, the underlying rationale and risks, as well as references (footnotes to EU MDR, guidance, etc.), in order to ensure the amount of PMCF required, together with the associated justification, fits the strategy and presents sound scientific principles, measurable and clean objectives, along with robust statistical planning.

Conclusion
Good planning is now more essential than ever, with the MDR deadline delay bringing the application date closer to the IVDR one, not to mention the shortage of Notified Bodies compared with the high volume of manufacturers choosing to update their medical device certification. This, together with the quality of the submissions themselves, could cause delays and ultimately prevent products from reaching the market.

Following these key principles can help companies start to outline or to integrate a PMCF plan while avoiding common pitfalls. Manufacturers can achieve compliance in a cost-effective and efficient manner. In addition, given the high stakes of non-compliance and additional pressures facing manufacturers, it may be advisable to partner with third party experts with the knowledge and experience in this area to develop and implement tried-and-tested PMCF processes and roadmaps. 

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Celeste Maksim has a Ph.D. in analytical chemistry, a RAC certification, and over a decade of experience in regulated industries including pharmaceuticals, medical devices, and IVD products. Her main focus at RQM+ is building and managing PMS and PMCF/PMPF services.