EMERGO BY UL SUMMARY OF KEY POINTS:

• The European Medical Devices Regulation (MDR) will tie post-market clinical follow-up (PMCF) data more closely to post-market surveillance and clinical evaluation report requirements.
• Medical device companies’ PMCF studies will have to include specific components identified in the MDR.
• Approvals for PMCF studies will need to be obtained by Ethics Committees and, in some cases, Competent Authorities.

Requirements for manufacturers to provide clinical data obtained via post-market clinical follow-up (PMCF) are set to both increase and intensify under the European Medical Devices Regulation (MDR), necessitating additional planning by companies planning to certify or gain re-certification under the new Regulation.

In the new European regulatory context, PMCF is required in conjunction with post-market surveillance (PMS, see Annex III) and clinical evaluation reporting (CER) obligations, as well as with risk assessments and reassessments. PMCF studies previously addressed under MEDDEV 2.12-2 guidance are now included in the MDR and the need to conduct PMCF is furthermore reinforced and expanded upon in the MDR. Article XIV, part B of the Regulation defines PMCF as “...a systematic approach to obtain additional information on the performance and safety of a medical device…” that has already obtained CE Marking when used in clinical settings. Manufacturers should develop PMCF plans including all PMCF activities for the expected lifecycle of their devices. Article XIV Part B section 6.2 of the MDR lays out specific components manufacturers should include in the PMCF plan.

PMCF study design and planning

To meet MDR requirements, device manufacturers should design and run PMCF studies with three major goals in mind:

• Confirming device safety and clinical performance
• Ensuring continued acceptability of identified risks
• Detecting emerging risks on the basis of factual evidence

In addition, according to MEDDEV 2.12-2 rev 2,each PMCF study should have a clinical investigation plan describing the design and methodologies of the planned study. The clinical investigation plan should include amongst others:

• the study population and inclusion/exclusion criteria;
• rational and justification of the chosen study design;
• study objectives, related study endpoints, statistical considerations;
• the number of subjects involved and the duration of patient follow-up;
• the data to be collected;
• methods of quality control of data where appropriate. (NOTE: ref. MEDDEV 2.12/2 rev.2. This MEDDEV will be superseded in the course of 2019 by a different document issued by the newly established MDCG.)

Approvals from Ethics Committees (ECs) are required for PMCF studies, while Competent Authority approvals are generally not needed—however, approval processes are not uniform across all European Union Member States, so manufacturers should consider these requirements on a country-by-country basis to ensure compliance.

Instances in which Competent Authority approval does become a requirement include those studies with a CE Marked device in which planned study assessments deviate from clinical practice, such as those involving additional invasive or burdensome procedures. Also, any planned off-label use of a CE Marked device will trigger Competent Authority approval requirements and may disqualify such a study as a PMCF, unless cleared with the Competent Authority and NB prior to its start.

PMCF documentation requirements including potential Conflict of Interest disclosures

Manufacturers undertaking PMCF studies should prepare all required documentation for submission to regulators for approval. These requirements include PMCF investigational plans; patient informed consent forms; device Instructions for Use and CE certificate; and usually study site qualification documents such as doctors’ CV. Increasingly, a statement confirming the absence of a Conflict of Interest is demanded by the reviewing institutions. If there is a potential CoI, then the intended investigator should detail what that is or could be, and justify his participation.

Closing Note about the context of the PMS and PMCF

A prerequisite for the proper planning, budgeting and execution of the PMS and PMCF plans and activities is a proper understanding of these terms and their respective context, their input and outflow interfaces as well as the documents resulting from the information gained. This set of documents includes the Periodic Safety Update Report (PSUR), the Summary of Safety and Clinical Performance (SSCP where applicable), and of course the risk management files and CER updates as well as the labeling and IFU. Several of these documents will be in the public domain, and therefore should be drafted with utmost care for the intended audiences.

Aleksandra Klimaszweski is Manager of Clinical Affairs at Emergo Clinical BV.

Additional European MDR and PMCF regulatory resources from Emergo by UL:

• European PMCF study support for medical devices
• European CE Marking strategy for medical device companies
• Whitepaper: Understanding Europe’s new MDR
• Webinar: Conducting a medical device PMCF study