Written by Kirsten Van Garsse from Qarad (part of the QbD Group) based on an online seminar presentation, made in collaboration with TOPRA and QbD, given on 6 December 2022 by Kirsten Van Garsse and Anne-Sophie Grell from QbD.
February 2023 | Volume 20 | No.2
Medical devices and in vitro diagnostic (IVD) medical devices – even if carefully designed and developed – may be subject to post-market changes. These changes can range from residual risks associated to the device, to its quality, safety, and performance.
There are various factors that can impact a device throughout its lifecycle, such as product and production variability, changes to the device’s use environment or end user, and unanticipated use or misuse. Therefore, it is important for device manufacturers to continuously collect and analyse data on their devices after they have been released to market in a real-use environment. In this way, they can register any unforeseen issues or improvements to further mitigate residual risks, improve quality and safety, and better address user needs.
In Regulation (EU) 2017/746 (IVDR) and in Regulation (EU) 2017/745 (MDR), post-market surveillance (PMS) is defined as “all activities carried out by manufacturers in cooperation with other economic operators to institute and keep up to date a systematic procedure to proactively collect and review experience gained from devices they place on the market, make available on the market or put into service for the purpose of identifying any need to immediately apply any necessary corrective or preventive actions.”
PMS enables data on a device’s quality, performance and safety to be collected in a systematic way. The ultimate goal of the PMS activities is to identify, implement and monitor corrective and preventive actions. The objectives of PMS have been defined in Article 78 (3) of the IVDR, and Article 83 (3) of the MDR, and include functions such as updating the benefit-risk determination, and trend reporting. This implies that the result of PMS activities feed back into other relevant device-related processes such as design and development, change control, risk management, vigilance, and corrective and preventive actions.
it is important for device manufacturers to continuously collect and analyse data on their devices after they have been released to market in a real-use environment.
In PMS, there is a post-market performance follow-up (PMPF) for IVDs, and a post-market clinical follow-up (PMCF) for medical devices. PMPF / PCMF is the part of PMS that focuses on the safety, performance, and scientific validity of the devices. It is the PMS component in which a manufacturer proactively collects and evaluates performance and relevant scientific data from the use of a CE-marked device within its intended purpose.
The objectives of PMPF/PMCF are defined in the IVDR Annex XIII Part 5.1 and the MDR Annex XIV Part B 6.1 and include eg, confirming safety and performance of the device, identifying, and analysing emerging risk or previously unknown risk or side effects. The result of PMPF/PMCF activities feed back into areas including the performance evaluation / clinical evaluation process, and risk management.
For each device, the manufacturer must draw up a PMS plan which is proportionate to the risk class of the device and appropriate for the type of device. This plan should not be confused with the PMS procedure. Although there are common elements that will recur in all PMS plans – such as the references to relevant processes to be used during the PMS activities – there are specific elements that are particular to a device, such as trends to monitor for, similar devices to look at, and indicators and thresholds to be used during data analyses.
In the PMS plan, a manufacturer should also draw up a PMPF / PMCF plan for each device. A well-documented rationale could be provided to demonstrate why PMPF/PMCF is not applicable for a certain device. However, it is important to note that if this approach is taken, then the manufacturer should also consider documenting when this decision will be re-assessed to consider if it is still justified, or which events may trigger the activation of PMPF/PMCF.
The result of the data analyses collected in accordance with the PMS plan, and the conclusions drawn are documented in either a PMS Report (for Class A and B IVDs or Class I medical devices) or a periodic safety update report (PSUR) (for Class C and D IVDs or Class IIa, IIb and III medical devices). For certain devices (Class D IVDs and Class III medical devices) the PSUR will have to be submitted to the notified body (NB) through EUDAMED (after go-live of the fully functional system). The NB will review the document and add its own evaluation to EUDAMED.
The result of the data analyses collected in accordance with the PMPF/PMCF plan and the conclusions drawn are documented in a PMPF/PMCF evaluation report which is considered part of the performance/clinical evaluation report of the device. The main findings of the PMPF/PMCF should also be included in the PMS Report / PSUR.
For each device, the manufacturer must draw up a PMS plan which is proportionate to the risk class of the device and appropriate for the type of device
Responsibility for the PMS is often questioned; however, there is no simple or single answer to that question, since all parties involved with the device production and post-production play a part in this process, and all of these parties are expected to contribute to the PMS process. As per Article 15 (3) of the MDR and the IVDR, the person responsible for regulatory compliance (PRRC) at the manufacturing site is responsible for ensuring that the PMS obligations are met in accordance with Article 10 (9) of the IVDR and Article 10 (10) of the MDR.
The PRRC is thus responsible for ensuring that a PMS system is in place but is not necessarily the person performing the PMS activities. Whoever is chosen to be responsible, must have sufficient authority and capability to push tasks to completion as they will be working with a multi-disciplinary team and will have to source information from nearly all departments within a manufacturer.
In addition, it is paramount to understand that PMS and PMPF/PMCF cannot be done without the involvement of the various economic operators within a device’s distribution chain. As a manufacturer you may sell devices direct to end-users, but importers and/or distributors are often involved. These economic operators hold a wealth of information with regards to a device in the real use environment because the end users to whom they sell devices will interact directly with them and not with the manufacturer.
This means that manufacturers must set up ways to ensure that this valuable information flows back to them. As it is required per the IVDR and the MDR, manufacturers must define processes to ensure the appropriate and relevant information reaches them in a timely and organised manner, allowing them to use this information as input in their PMS and PMPF/PMCF activities.
In conclusion, PMS for a device is comparable to an internal audit for a quality management system. Internal audits are conducted to ensure continued compliance to the requirements of the standard applied and the company’s policies and procedures. PMS aims to ensure that the device is being produced according to plan and that the quality, safety and performance achieved in a real use environment meets the requirements set by the manufacturer. PMS, which includes PMPF/PMCF, are the activities conducted to answer the question: “Is the device that I have designed and developed produced safely as intended, is the device performing as intended, and is it still compatible with the state of the art?”