Mastering PMCF & PMPF: A Practical Guide on Post-market Clinical and Performance Follow-up

Medical device and IVD manufacturers tend to misunderstand what Post-market Clinical Follow-up (PMCF) under the EU MDR and Post-market Performance Follow-up (PMPF) under the IVDR involve, and how these differ from other Post-market Surveillance (PMS) activities. PMCF and PMPF activities do not necessarily equate with clinical or performance studies; neither can they be circumvented on the grounds that there is sufficient safety and performance evidence for the concerned device.
If you feel uncertain about the PMCF and PMPF activities you need for your device, read on.

Key takeaways

• PMCF and PMPF are mandatory to maintain the clinical evaluation or performance evaluation updated throughout the device’s lifecycle. Thus, if there is a Clinical Evaluation Report (CER), the manufacturer needs PMCF; if there is a Performance Evaluation Report (PER), the manufacturer needs PMPF.
• For in-vitro diagnostic devices (IVDs), PMPF is a new requirement under the IVDR. It is however required for “legacy” IVDs, too, even when such devices do not have a Performance Evaluation Report (PER).
• To ensure compliance, manufacturers must understand the difference between “generic” and “specific” PMCF/PMPF activities, and be aware of the overlaps between Post-market Surveillance (PMS) activities and “generic” PMCF/PMPF activities.

Content

What are PMCF according to EU MDR and PMPF according to IVDR? 

To clear any misunderstanding, let’s start with the legal concepts in the EU MDR (Reg. 2017/745 on medical devices) and IVDR (Reg. 2017/746 on in-vitro diagnostic devices).

• Post-market CLINICAL follow-up (PMCF) under the EU MDR “shall be understood to be a continuous process that updates the clinical evaluation referred to in Article 61 and Part A of this Annex and shall be addressed in the manufacturer’s post-market surveillance plan.” [EU MDR Annex XIV, Part B, point 5]
• Post-market PERFORMANCE follow-up (PMPF) under the IVDR “shall be understood to be a continuous process that updates the performance evaluation referred to in Article 56 and Part A of this Annex and shall be addressed  in the manufacturer’s post-market surveillance plan.” [IVDR Annex XIII, Part B, point 4]

Simply put, PMCF or PMPF activities constitute the means of keeping continuously up-to-date either the Clinical Evaluation Report (CER) for non-IVDs or the Performance Evaluation Report (PER) for IVDs.

PMCF and PMPF shall be regarded as an extension of the clinical evaluation or performance evaluation process throughout the device’s lifecycle, just like the device’s risk management process has a continuous post-market phase.

Are PMCF and PMPF new requirements at all?

Although PMCF was already required under the former Directives (MDD and AIMDD), it could be easily waived as both Directives indicated:

“Where post-market clinical follow-up as part of the post-market surveillance plan for the device is not deemed necessary, this must be duly justified and documented.”

This was further encouraged by the fact that, based on the only guideline available at the time (MEDDEV 2.12/2), PMCF activities were understood to be post-market clinical trials only.

PMPF is a new requirement. It was not mentioned in the previous IVDD.

Some manufacturers assume that this is no different under the EU MDR because Annex III also indicates that the PMCF Plan must be included within the PMS Plan “or a justification as to why a PMCF is not applicable”. This assumption is wrong, as explained in chapter When are PMCF or PMPF activities required?

Conversely, for IVDs, it is indeed a new requirement. PMPF was not mentioned at all under the former IVDD, and there was no MEDDEV guideline on this topic. The IVDR has clearly introduced the requirement for PMPF activities as the means to update the Performance Evaluation Report (PER), in an analogous manner as for PMCF activities under the EU MDR. 

When are PMCF or PMPF activities required?

Under the EU MDR, PMCF is always required if:

• The device is a Class III or implantable device. EU MDR Art. 61(11) leaves no room for other options.

“For class III devices and implantable devices, the PMCF evaluation report and, if indicated, the summary of safety and clinical performance referred to in Article 32 shall be updated at least annually with [clinical data obtained from the implementation of the PMCF Plan & PMS Plan].”

• There is a Clinical Evaluation Report (CER). According to EU MDR Annex XIV part B, PMCF is the means for keeping the CER up-to-date. And, there are very few instances when a CER is not required. Even when the manufacturer relies on the exception in EU MDR Art.61(10), i.e. clinical data not being appropriate to demonstrate conformity with the General Safety and Performance Requirements, the manufacturer must compile a CER to document the justification.

This is very similar under the IVDR. PMPF is always required if:

• The device is a Class C or Class D IVDs. IVDR Art. 56(6) leaves no room for other options.

“The performance evaluation report for class C and D devices shall be updated when necessary, but at least annually,  with the [data obtained from the implementation of the PMPF Plan & PMS Plan].”

• There is a Performance Evaluation Report (PER). According to IVDR Annex XIII part B, PMPF is the means for keeping the PER up-to-date. There is no exception for compiling a PER under the IVDR.
  Now, because most “legacy” IVDs do not have PER, as it was not a requirement under IVDD, the situation is a bit particular: MDCG 2022-8 recognizes that PMPF requirements still apply but exempts the manufacturer from retrospectively generating a PER. See also Do PMCF and PMPF apply to “legacy” devices?
  

Last, PMCF activities under the EU MDR are also needed in the following special cases:

• For products without a medical purpose listed in EU MDR Annex XVI (so called “Annex XVI products”), PMCF is explicitly required per EU MDR Art. 61(9) and in consideration of the corresponding Common Specifications, Reg. (EU) 2022/2046.
• For Custom-made devices, even though they are not CE-marked, PMCF is required in EU Annex XIII, point 5: “The manufacturer shall review and document experience gained in the post- production phase, including from PMCF as referred to in Part B of Annex XIV, and implement appropriate means to apply any necessary corrective action”. Now, PMCF activities must be adapted to the fact that there is only one unit of a given Custom-made device.

Do PMCF and PMPF apply to “legacy” devices?

For “legacy” devices, guidance documents MDCG 2021-25 for non-IVDs and MDCG 2022-8 for IVDs, on the requirements in the new Regulations apply, share the same logic and some of the same wording. They clearly indicate that all Post-market Surveillance (PMS) requirements in the EU MDR and IVDR apply to “legacy” devices, and that includes PMCF and PMPF.

That means that manufacturers must collect and evaluate clinical/performance data for “legacy” devices throughout the post-market phase, following the requirements of PMCF and PMPF in the EU MDR/IVDR. However, there is no requirement to upgrade the technical documentation adopting the structure and contents of EU MDR/IVDR Annexes II and III. In the case of IVDs, it means that the manufacturer does not need to retrospectively generate a Performance Evaluation Report (PER) in line with the IVDR.

How should this be implemented?

Manufacturers of “legacy” devices should start by preparing a PMCF or PMPF Plan (see What types of activities do PMCF or PMPF entail?), and then collecting the data in a PMCF or PMPF Report, with the same periodicity required for devices CE-marked under the EU MDR or IVDR.

All Post-market Surveillance requirements in the EU MDR and IVDR apply to “legacy” devices, and that includes PMCF and PMPF.

Now, whereas templates exist for PMCF Plans and Reports under the EU MDR, nothing is specifically available fo IVDs. Therefore, IVD manufacturers need to extrapolate the existing templates and guidelines using common sense. See also What guidelines should manufacturers consider for PMCF and PMPF?

Non-IVD manufacturers can integrate the results of each successive PMCF Report into the existing “legacy” CER. As to IVDs, given that there is no requirement to retrospectively generate a PER under the IVDR, manufacturers could simply keep updating the resulting PMPF Report throughout the transitional period in a manner that forms a useful basis for the first PER that shall be created for the submission to the Notified Body as part of the technical documentation for IVDR certification.

What guidelines should manufacturers consider for PMCF and PMPF?

If you have not found guidelines on PMPF, do not search any further. There are no specific guidelines under the IVDR yet.

For the time being, IVD manufacturers can only extrapolate the existing guidance documents issued by the Medical Device Coordination Group (MDCG) for PMCF, namely:

• MDCG 2020-7, Guidance on PMCF plan template
• MDCG 2020-8, Guidance on PMCF evaluation report template

These documents are both templates and guidelines. Even if MDCG documents are not legally binding, they provide interpretation of legal requirements and, indirectly, represent the views of the European Commission. They also form the basis of regulatory expectations from Notified Bodies and competent authorities. As such, manufacturers have little choice but to follow them.

In addition to the MDCG guidance documents for PMCF under the EU MDR, the old guideline MEDDEV 2-12/2 on PMCF studies, which was issued under the former Directives, tends to be still followed by Notified Bodies in the absence of an equivalent guidance document from MDCG. See also, Are clinical/performance studies always needed for PMCF or PMPF?

What types of activities do PMCF or PMPF entail?

As a first step, manufacturers must prepare a PMCF or PMPF Plan, where the activities that are deemed necessary are duly planned.

The aim of such activities should be to:

1. confirm the safety and performance, as well as, for IVDs, the scientific validity, throughout the expected lifetime of the device, 
2. ensure the continued acceptability of the benefit-risk ratio and 
3. detect emerging risks on the basis of factual evidence.

The structure is given by the guidance and template MDCG 2020-7 for PMCF Plans. For IVDs, in the absence of something specific for PMPF, manufacturers should extrapolate this template.

• Section A – Manufacturer contact details
• Section B – Medical Device description and specification
• Section C – Activities related to PMCF: general and specific methods and procedures
• Section D – Reference to the relevant parts of the technical documentation
• Section E – Evaluation of clinical data relating to equivalent or similar devices
• Section F – Reference to any applicable common specifications, harmonized standards or applicable guidance documents
• Section G – Estimated date of the PMCF evaluation report

The core of the PMCF Plan is Section C, where all the activities planned must be listed on a tabular form and further described.

The manufacturer must determine and justify the “general and specific methods and procedures” that are appropriate for the concerned device. Here is where the difficulties really start because there is no guidance. Even Notified Bodies appear to have different expectations.

EU MDR Annex XIV, Part B, section 6.2 and IVDR Annex XIII, Part B, section 5.2, give some basic ideas as to what type of PMCF/PMPF activity should fit where:

• “General methods and procedures” include, for example: gathering of clinical experience gained, feedback from users, screening of scientific literature and of other sources of clinical data or, for IVDs, performance or scientific data.
• “Specific methods and procedures” include, for example: 
  • For non-IVDs: evaluation of suitable registers or PMCF studies.
  • For IVDs: ring trials, and other quality assurance activities, epidemiological studies, evaluation of suitable patient/disease registries, genetic databanks, or PMPF studies.

It is important for manufacturers to differentiate “registries” from other publicly available databases (e.g. EUDAMED or competent authority databases on device safety).

Medical device registries are well described in IMDRF/Registry WG/N42FINAL:2018:

“An organized system that continuously and consistently collects relevant data in conjunction with routine clinical care, evaluates meaningful outcomes, and comprehensively covers the population defined by exposure to particular device(s) at a reasonably generalizable scale (e.g. international, national, regional, and health system) with a primary aim to improve the quality of patient care.”

Registries exist mostly for implantable devices and are usually maintained at national level by clinical specialties (e.g. orthopedics, cardiovascular). IMDRF advocates for an international system that would cross-link existing national registries (e.g. coordinated networks) and Total Product Life Cycle (TPLC) platforms (e.g. UK Beyond Compliance for orthopedic implants). Relying on data from registries is useful for “Nest” studies that use registry data as Real-World Evidence (RWE) to test a research hypothesis.

What about surveys? Where do they fit? It depends on the type of survey.

• High-quality surveys could correspond to PMCF studies (i.e. prospective studies with specific clinical/performance endpoints that are quantifiable, and with statistically calculated sample size), and would definitely fit under “Specific” PMCF/PMPF. And, obviously, follow-up surveys of pre-market studies are PMCF/PMPF studies.
• Low-quality surveys that are typically retrospective, with random sample sizes and focusing mostly on usability aspects or on identifying off-label use, would fit under “General” PMCF/PMPF. Note that marketing-oriented customer satisfaction surveys are not PMCF/PMPF surveys.

The easiest way to determine where the survey fits is by considering the level of clinical evidence it corresponds to. This can be done by following the hierarchy of 8 types of clinical evidence (1 being the highest quality and 12 the lowest) in Appendix III of guidance document MDCG 2020-6. High-level surveys rank at level 4 and low-quality surveys at level 8.

In brief, “General” PMCF/PMPF activities are always expected if there is a CER/PER. “Specific” PMCF/PMPF can be simplified or avoided based on the device risk and with due justification. For example, absence of “specific” methods can be justified for low-risk devices and well-established technologies. Some Notified Bodies even consider that “specific” PMCF/PMPF activities can be waived for devices with known long-term safety and performance, no trends identified, sufficient clinical/performance data to support claims, and acceptable risk-benefit ratio. In any case, the justification for not conducting “specific” PMCF/PMPF activities must be well grounded.

The results of a PMCF/PMPF Plan must be documented in a PMCF/PMPF Report. Just like for the plan, the only guidance and template available is for PMCF Reports, MDCG 2020-8., which IVD manufacturers should also consider.

Last, in case the outcome of PMCF/PMPF activities reveals the need for updates to the PMCF/PMPF Plan (e.g. different types of general/specific activities, changes in study objectives, extended timelines), manufacturers should consider the need to report the modified PMCF/PMPF Plan to their Notified Body. BSI, for example, has published a statement with their expectations on notification of substantial changes in PMCF/PMPF Plans prior to their implementation and their interpretation of what such substantial changes are.

How do PMCF or PMPF overlap with PMS?

The type of data to be proactively monitored for PMS activities does overlap with the type of data to be gathered in PMCF/PMPF activities. For example, the proactive screening of relevant scientific literature appears both under PMS and PMCF/PMPF.

But that is not all because the description of “generic methods and procedures” for PMCF/PMPF includes all clinical experience gathered in the post-market phase, which is basically a full overlap with the reactive monitoring of PMS data. This is depicted below.

How to solve this conundrum?

It is not recommended to duplicate the reported data unnecessarily, as it is always a source of potential inconsistencies, particularly upon subsequent updates.

“Reactive” PMS data should always be reported as PMS data, since this is the essence of the PMS requirements in Annex III of the EU MDR and IVDR as well as in guidance document MDCG 2023-21 on how to prepare a Periodic Safety Update Report (PSUR). The corresponding sections in the PMPF/PMCF Reports should merely cross-reference the PMS Report or PSUR with a brief conclusion and highlighting any findings relevant for the CER/PER.

Conversely, because PMCF/PMPF is the proactive collection of clinical data to keep the CER/PER up-to-date, it makes better sense to report “proactive” PMS data that relates to clinical aspects in the PMCF/PMPF Report and cross-reference them in the PMS Report or PSUR with a brief conclusion. This is even more important where “specific” PMCF/PMPF activities are not deemed necessary.

Also, let’s keep in mind that there might be “proactive” PMS data that does not correspond to clinical data. For example, cybersecurity monitoring in the post-market phase that must be part of the PMS activities, per MDCG 2019-16.

Are clinical/performance studies always needed for PMCF or PMPF?

No. And that, even if there is no specific guidance as to when PMCF/PMPF studies are mandatory under EU MDR/IVDR.

MDCG 2020-6 (on sufficient clinical data for legacy medical devices under EU MDR) still points to the old MEDDEV 2.12/2 (rev.2), which in turn indicates that:

“[The] decision to conduct PMCF studies must be based on the identification of possible residual risks and/or the lack of clarity in long term clinical performance that may impact the benefit/risk ratio of a medical device.”

According to the old MEDDEV 2.12/2, PMCF studies “may have been justified” in case of:

• Novel technology / significant device changes
• Unknown long-term safety or performance / Delayed occurrence of clinical events
• High risks (device-related, anatomical locations, target populations)
• Newly identified risks (e.g. interactions, unstudied subpopulations, lifetime discrepancies)
• Initial CE-marking based on equivalence

This is also the expectation of Notified Bodies under the EU MDR/IVDR, including for “legacy” devices.

Pre-market vs. post-market studies as part of PMCF/PMPF

When the manufacturer considers conducting a study as part of the PMCF or PMPF activities, it is important to determine the implications of the type of study. The study objectives and design determine the type and extent of regulatory requirements. 

Specifically, manufacturers need to consider the following aspects:

• Is the study being conducted in accordance with the device’s instructions for use (IFU)?
• Does the study involve additional and invasive/burdensome procedures?
• Is the study somehow being conducted beyond the intended purpose?

Per EU MDR Art. 74 and IVDR Art. 70, as well as guidance document MDCG 2021-6 on clinical investigations (no equivalent guidance under IVDR yet):

In brief, PMCF/PMPF studies conducted according to the IFU are considerably less burdensome than pre-market studies. However, national differences exist within the EEA and manufacturers should always consult the local authorities for specific requirements.

Note that, contrary to pre-market studies, adverse events occurring during PMCF/PMPF studies are subject to Vigilance reporting (i.e. as serious incidents) except “where a causal relationship between the serious adverse event and the preceding investigational procedure has been established” [EU MDR Art. 80(6)], in which case the requirements for adverse event reporting in pre-market studies apply.

How Decomplix can help

Decomplix offers consultancy services in all regulatory and quality assurance matters relative to medical devices. We can support your company in fulfilling all PMS and PMCF/PMPF requirements under the EU MDR/IVDR, and ensuring compliance in the most efficient manner. 

If you wish to discuss your needs with us, please contact us for a non-binding quote.

Further reading

• Post-market Surveillance (PMS) for medical devices under EU MDR and IVDR
• Medical device and IVD Vigilance in EU and Switzerland
• Clinical Evaluation of medical devices under the EU MDR
• “Legacy” medical devices and IVDs under EU legislation
• Annex XVI and EU MDR – Guide to regulation of products without intended medical purpose