Post Market Performance Follow-up for IVDR

The new in vitro diagnostics regulation of the European Union, the IVDR 746/2017, will soon be replacing the existing IVD Directive on May 26^th, 2022. The regulation is set to bring in many drastic changes to the way the IVD medical devices are regulated by strengthening the old requirements and adding many new ones. Post Market Performance Follow-up, or PMPF, is a completely new concept introduced by the regulation. Its counterpart in the medical device regulation, the EU MDR, is the PMCF, or Post Market Clinical Follow up. Both PMCF and PMPF are mandatory requirements that the manufacturers have to comply with if they wish to launch products in the European Union.

The IVDR changes have strengthened the requirements for Performance Evaluations, which are conducted in the premarket phase. Further, it mandates that the performance of devices be continuously monitored throughout the life cycle of the device. Therefore, in the post market phase once a product is launched in the market, we have the PMPF system. This system is an essential and key element of the PMS system and it serves as an important link between PMS and Performance Evaluation.

The PMS system is expected to gather the device’s usage experiences proactively and re-actively, once it is launched in the market. The IVDR mandates a PMS Plan, which is then executed by the manufacturer with the help of other economic operators. The purpose is to determine if there are any corrective actions required by the manufacturer to improve the safety and performance of the device. Similarly, the PMPF process continuously collects all data related to performance of the device in the post market phase, identifies new or emergent risks, and maintains the acceptability of the benefit – risk ratio. This continuous review of the Performance Evaluation ensures it reflects the current state of the art.

Let us consider a new RT-PCR kit for COVID-19. Before this kit gets the CE mark, a complete performance evaluation has already been done, which takes into account the scientific validity, analytical performance, and clinical performance generating clinical evidence for the kit. After it is launched in the market, the Post Market Surveillance and PMPF come into play gathering relevant data regarding the safety and performance of the device. Now, consider that new mutants arise and have now infected the population. Would the old performance data suffice? The PMPF system will now have to re-assess the performance of the kit against the new variants and update the PER accordingly. The new variants have thus served as a trigger for carrying out a PMPF. Ideally, the PMPF plan should define the frequency of carrying out PMPF and any such triggers.

The IVDR’s Annex XIII part B describes in details how PMPF is to be done.

Steps towards a PMPF system as per the IVDR:

• The first step is to create a strong PMPF Plan, and it should be documented as a part of the PMS Plan
• Both plans are a part of the Technical Documentation of the device
• Once the plan is implemented a PMPF report has to be created
• The conclusions of PMPF are to be included in the PER – Performance Evaluation Report

Since this is a newly defined process, those organizations already certified under ISO 13485:2016 will have to integrate the PMS and PMPF plans within the QMS documentation. Since these plans are mandatory, it clearly shows that the regulation has now taken up a proactive stance for these requirements rather than the earlier reactive approach. Manufacturers can document the PMPF plan in multiple different ways. For instance, some may prefer to have the plan in the form of a procedure covering several products or a product family. Others may choose to have a template form to be used for each product. The plan could also be a separate stand-alone document. The method depends on the type of devices to be covered under the plan.

The PMPF aims to:

1. Confirming the safety and performance of the device throughout its expected lifetime
2. Identifying previously unknown risks or limits to performance and contra-indications
3. Identifying and analyzing the emergent risks on the basis of factual evidence
4. Ensuring the continued acceptability of the clinical evidence and the benefit-risk ratio referred to in Sections 1 and 8 of Chapter I of Annex I
5. Identifying possible misuse of the device

The PMPF plan shall include at least:

1. The general methods and procedures of the PMPF to be applied, such as gathering of clinical experience gained, feedback from users, screening of scientific literature, and other sources of performance or scientific data
2. The specific methods and procedures of PMPF to be applied, such as ring trials and other quality assurance activities, epidemiological studies, evaluation of suitable patient or disease registers, genetic databanks, or post-market clinical performance studies;
3. A rationale for the appropriateness of the methods and procedures referred to in points (a) and (b);
4. A reference to the relevant parts of the performance evaluation report referred to in Section 1.3 of this Annex and to the risk management referred to in Section 3 of Annex I;
5. The specific objectives to be addressed by the PMPF;
6. An evaluation of the performance data relating to equivalent or similar devices, and the current state of the art;
7. Reference to any relevant CS, harmonized standards when used by the manufacturer, and relevant guidance on the PMPF, and
8. A detailed and adequately justified time schedule for PMPF activities, such as the analysis of PMPF data and reporting to be undertaken by the manufacturer

The manufacturer must decide the frequency of carrying out PMPF  and document this rationale in the PMPF plan.

• The manufacturer should then analyze the findings of the PMPF and document the results in a PMPF evaluation report
• This will update the performance evaluation report and be part of the technical documentation
• The conclusions of the PMPF evaluation report shall be taken into account for the performance evaluation and in the risk management. If, through the PMPF, the need for preventive and/or corrective measures has been identified, the manufacturer shall implement them

If a manufacturer thinks that a PMPF process is not required for a specific device, then they must provide a justification and document it within the performance evaluation report.

Notified bodies are expected to review the PMPF process, procedures, and reporting when they review the performance evaluation process and also, how the data from the PMPF is used to update the PER and risk management file.

With the IVDR deadline of May 2022 quickly approaching, it’s time for manufacturers to start planning how they will address the new PMPF requirements. The small number of notified bodies approved for the IVDR will create a bottleneck that cannot be overlooked.

The conclusions of the PMPF will be documented in the PER. For the higher risk class devices, such as Class C and D, the PER is expected to be updated at least annually which means that the PMPF report should be updated annually as well. Important updates of the PMPF report shall also be included in the PSUR (Periodic safety update report for Class C and D) and in the Summary of Safety and Performance (SSP), which shall be updated as soon as possible, where necessary.

Thus, it is critical for manufacturers to have a robust PMPF plan since many linked documents also must be updated to remain compliant with the IVDR.