Post-Market Clinical Follow-up – Clinical follow-up of medical devices

Post-market clinical follow-up (PMCF) plays an essential role in the product life cycle of a medical device, which many manufacturers only realised with the introduction of the Medical Device Regulation (EU) 2017/745 (MDR). PMCF helps to continuously monitor and improve the clinical performance and, above all, the safety of medical devices even after their market launch. This important process is based on various methods, best practices and regulatory requirements that every manufacturer should be familiar with.

The meaning of “PMCF” and underlying requirements

With regard to the regulatory requirements and the origin of the “Post Market Clinical Follow-Up” (à PMCF), the MDR should of course be mentioned first and foremost:

• Article 61 of the MDR demonstrates the inextricable link between PMCF and the clinical evaluation that is also required,
• Annex XIV, Part B of the MDR specifies the requirements for post-market clinical follow-up.

Clinical follow-up after a medical device has been placed on the market is a continuous process aimed at achieving this:

• update the clinical evaluation of the device in accordance with the provisions of Article 61 MDR and Part A of Annex XIV MDR.
• form an integral part of the Post Market Surveillance Plan (à PMS) in the form of a summary. The manufacturer must prepare the PMS during the marketing phase and also keep it up to date.

During clinical follow-up, the manufacturer actively collects and analyses clinical data resulting from the actual use of the device. This refers to situations in which the device is properly labelled in accordance with the applicable conformity assessment procedures and is intended for use in or on the human body.

The main objective of this activity is to confirm the safety and performance of the product over its expected lifetime. The (newly) identified risks are also continuously assessed to ensure that they remain acceptable. At the same time, clinical follow-up aims to identify new potential risks at an early stage. This is done on the basis of comprehensive and relevant evidence to enable an appropriate response from the manufacturer.

In order to fulfil the required systematic approach, the data collection must be planned accordingly and the results documented; for this purpose, the manufacturer prepares both a plan and a report on the clinical follow-up. The MDCG documents 2020-7 “Guidance on PMCF plan template” and 2020-8 “Guidance on PMCF evaluation report template” are very helpful here, as they provide detailed information on the design and content of the PMCF plan and PMCF report. However, Annex XIV of the MDR also provides valuable guidance on the required content of the PMCF plan, specifically Part B of the Annex, point 6.2.

The manufacturer must address the following aspects:

1. a) the general methods and procedures for post-market clinical follow-up shall include merging acquired clinical experience, obtaining feedback from users, reviewing scientific literature and other sources of clinical data.
2. b) specific methods and procedures for post-market clinical follow-up include, for example, the evaluation of appropriate registries or post-market clinical follow-up studies.
3. c) the suitability of the methods and procedures described in sections a) and b) must be justified.
4. d) reference shall be made to relevant sections of the clinical evaluation report referred to in Section 4 and to the risk management referred to in Section 3 of Annex I.
5. e) the specific objectives that shall be achieved by the post-market clinical follow-up must be defined.
6. f) evaluation of clinical data on similar or equivalent products.
7. g) references to applicable guidelines, harmonised standards and other relevant guidelines on post-market clinical follow-up and, where applicable, to applied Common Specifications.
8. h) a detailed and adequately justified timetable for the post-market clinical follow-up activities to be carried out, including data analysis and reporting.

Differentiation between PMS and PMCF – what is the respective focus?

Post-Market Surveillance (PMS) and Post-Market Clinical Follow-up (PMCF) are two different concepts in the field of medical device surveillance after placing on the market. While both concentrate on the surveillance of medical devices in their marketing phase, their focus is on different aspects:

• Post-market surveillance (PMS) mainly focuses on monitoring and evaluating the safety and performance of medical devices in the real-world environment after their market launch, focussing on the medical device itself. This includes the continuous monitoring of complaints, adverse events, recalls, quality problems and other safety-related aspects in the context of vigilance that may occur in connection with the use of the product. The focus here is on collecting and analysing data on similar products/the corresponding product group from relevant authority databases, including reports/feedback from users (beyond complaints) as well as feedback and reports on adverse events from other sources, such as large-scale registers.
• PMCF, on the other hand, emphasises the ongoing evaluation of the clinical performance (“Clinical Claims”) and benefits (“Clinical Benefit”) of the product in a real-world setting, with a focus on the patient. This includes conducting specific clinical studies or other investigations to gather additional clinical data that can help confirm the safety and performance of the product. The purpose of PMCF is to evaluate the clinical performance of the product over its entire life cycle, identify potential risks in clinical use and to ensure that the product continues to meet the requirements for safety, performance and effectiveness and, overall, continues to demonstrate a positive benefit-risk ratio. The focus here is particularly on possible residual risks; if these change in terms of probability of occurrence/severity, the manufacturer must react accordingly. This activity does not necessarily mean conducting a study.

In principle, the topics of “PMS/PSUR“, “PMCF”, “Clinical evaluation“, “Vigilance” and others should be recognised as having a different focus, although they are often based on the same underlying data. And in case of doubt, corrective measures in the field can also lead to similar consequences, but with different causes in the background. The combination of these contents within the technical documentation must therefore be customised for the respective products and manufacturers.

The PMCF investigation – the ideal solution

The Post-Market Clinical Follow-up (PMCF) investigation can be considered the “silver bullet” for post-market clinical follow-up. The manufacturer can

• actively shape the issues that interest him with regard to the clinical application of his medical device,
• define the clinical endpoints,
• design the study in such a way that a sufficiently large study population is included
• collect other relevant data

Nevertheless, it is important to note that the medical device is used within the scope of its intended purpose. Article 74 of the MDR specifies this in more detail and distinguishes further subordinate scenarios: Provided that subjects/patients are not subjected to any additional invasive or burdensome procedures to those performed under normal conditions of use of the device as part of this trial, only a procedure in accordance with Section 15 of the German Professional Code for Physicians (Berufsordnung für Ärzte) is applicable with regard to the planning and performing of the PMCF investigation; in other words, the requirements of the MDR do not provide any explicit regulations for this case. Nevertheless, the essential requirements of ISO 14155 must be taken into account during planning and implementation. The German medical device law (Medizinprodukterecht-Durchführungsgesetz MPDG) confirms this view in Section 47 (3): no special statutory regulations are envisaged, i.e. a procedure in accordance with Section 15 of the Professional Code for Physicians is to be applied.

However, if the study objectives include additional invasive or burdensome procedures,

• Article 62(4)(b) to (k) and (m),
• Article 75,
• Article 76
• Article 77 and
• Article 80(5) and (6)
• and the relevant provisions of Annex XV of the MDR

apply. Conversely, this means that in this case the competent authority does not have to grant authorisation to conduct the investigation, only an obligation to notification applies. However, this notification requirement becomes an authorisation requirement if the investigation uses the medical device outside its intended purpose. Articles 62 to 81 and Annex XV of the MDR therefore apply in full.

Do you still find it difficult to differentiate between PMS and PMCF? Or does your collected data indicate the need for a PMCF study? Get in touch with us! We will help you to analyse the data and find the right approach for your product.

Please note that all details and listings do not claim to be complete, are without guarantee and are for information purposes only.