February 22, 2023
By Rachel Paul and Evangeline Loh
We’re rapidly approaching the two-year anniversary of the European Medical Devices Regulation (MDR) Date of Application (DoA) (26 May 2021). MDCG 2022-21 (December 2022) was published just in time to provide guidance.
Recital 74 of the MDR advances the import of the manufacturer’s post-market surveillance (PMS) system, PMS Plan, and assessing and reporting that data (Article 10(9)(i), Article 10(10), Chapter VII, Section 1 PMS, Articles 83-86, Annex III). For manufacturers with Class IIa, IIb, and III medical devices, one of the crowning jewels is the Article 86 Periodic Safety Update Report (acronym part of Article 86(1) PSUR).
What is Article 86 on PSUR?
The PSUR is essentially the living record (lifetime of the device) of the PMS assessment for higher-risk devices (Class IIa-Class III devices). Article 86(1), (a)-(c) establishes the contents of the report and the timeframes for reports:
“(a) the conclusions of the benefit-risk determination;
(b) the main findings of the Post-Market Clinical Follow-up (PMCF); and
(c) the volume of sales of the device and an estimate evaluation of the size and other characteristics of the population using the device and, where practicable, the usage frequency of the device.”
“Manufacturers of class IIb and class III devices shall update the PSUR at least annually.”
“Manufacturers of class IIa devices shall update the PSUR when necessary and at least every two years.”
Overview of MDCG 2022-21
MDCG 2022-21 is a compendium of 40 pages that articulates the consensus guidance on PSUR. The guidance is extensive and provides counsel on many topics, including managing expectations with legacy devices. A trifecta of reminders: Article 86 is the law, this is guidance; in-vitro diagnostic devices (IVDs) are not part of this guidance; and Class I medical devices are only subject to PMS Reports (Article 85). This guidance does not include PMS Reports, though may in the absence of other relevant guidance, provide useful suggestions on how information could also be presented in PMS Reports.
The first 14 pages is organized into sections. There are three figures and five annexes. The figures represent flow diagrams: assessment of PSUR requirement, MDR compliance PSUR based on classification, and legacy devices PSUR based on classification. These are a little redundant, though if you like graphic representations, these do guide the user.
The five annexes include: template for PSUR, template for presentation of data, presentation and assessment of collected PMS, summary tables for PSUR requirements MDR compliant and legacy devices, PSUR web form (specifically for manufacturers of Class III devices or implantable which need to be in EUDAMED (Article 86(2)).
Some of the highlights from the text:
PSURs already compiled
The guidance describes that PSURs already drafted or in the process of being prepared when this guidance was published should not be expected to have followed this guidance, as long as those PSURs comply with the legal requirements. There is no guidance on what is considered “in the process of being prepared”.
Annex III 1.1(a) of the MDR provides the elements to be considered in the PMS Plan in order to prepare the summary of data as required in the PSUR. The guidance highlights the fact that the PSUR should be generated as a stand-alone document that can be assessed independently from the supporting documentation. There is no aim to duplicate all data and reports but to summarize all results and conclusions.
New devices terms
Besides the terms of legacy devices and old devices previously defined in other MDCG guidances, one new term is defined by the guidance: “leading devices.” Leading device is related to grouping.
Lifetime of the device (and shelf life)
The MDR emphasizes lifetime of the device. And, our review of manufacturer’s MDR Notified Body (NB) reviews indicate that the majority of manufacturers are not sufficiently documenting and defining lifetime. Section 3.2.1 discusses lifetime of the device. It is made very clear that a PSUR is required throughout the lifetime of the device. Included examples describe shelf-life and intended use, and also remind manufacturers to some extent that lifetime of the device is shelf life plus intended period of use.
A PSUR should be compiled per device (including different variants or sizes) and, where relevant, for a category or group of devices (implying multiple Basic UDI-DIs or device families). A justification for grouping should be provided. Grouping within one PSUR is only possible for devices certified by the same NB. The leading device is the highest-risk or one of the highest-risk class device assigned by the manufacturer and this leading device drives the schedule of that PSUR.
Terms are introduced related to timing
The concept of annually and every two years is explained in Section 1.2 terminology: for legacy devices, this is one or two years respectively from the MDRDoA. Section 5.1 describes that for MDR certified devices, annually and every two years should start at the device MDR certification date. Section 5.1 also introduces the terms: data collection period, first PSUR, first PSUR update, PSUR preparation and issuance timeline, and schedule for PSUR. Manufacturers do have time to assess the data after the data collection period, before the PSUR is submitted/issued. There is no guidance on what is a reasonable preparation and issuance timeframe. The submission in EUDAMED (only for MDR certified Class III and implantable devices, not legacy devices) should occur with due diligence/without undue delay after the end of the issuance timeline.
There is also an interesting consideration about Article 120(3) and MDR certification of legacy devices related to timing. If there are no significant changes in design or intended purpose of the legacy device, the schedule continues (initial PSUR schedule for the MDD compliant device). If there is a significant change of the legacy device, a new schedule is started (based on the MDR certification date of this device) because the device should be considered as a “new” device.
Annex I template for PSUR
The sections proposed in the format: PSUR cover page, executive summary, description of the devices covered by the PSUR and their intended uses, grouping of the devices, volume of sales, size and other characteristics of the population using the device, PMS: vigilance and CAPA information, PMS: information including general Post Market Clinical Follow-up (PMCF) information, specific PMCF information, and summary of findings and conclusions of the PSUR.
Further subsections are envisioned for some of the sections to help organize the report. There is interesting discussion related to volume of sales and the note that this indicator needs to be consistent in the report. The estimate of the number of patients exposed may need to factor usage frequency.
Section on general PMCF methods
The MDR Annex XIV, Part B 6.2(a) stated that general methods of PMCF could be gathering of clinical experience gained, feedback from users and screening of scientific literature. Guidance on the PMCF Plan and PMCF Evaluation Report were published in 2020, MDCG 2020-7 and MDCG 2020-8 respectively. However, Annex I of this new guidance provides more examples of what constitutes general methods of PMCF. There is a clarification that feedback and complaints from users, importers, and distributors, can be part of this provided this was not reported in the vigilance section (so excluding serious incidents, field safety corrective actions (FSCAs) and trend reports). Other types of general PMCF could include public databases and registry data, PMCF study data from similar devices, or a manufacturer’s Summary of Safety and Clinical Performance (SSCP), real world data from electronic health records or digital health monitoring devices. The guidance also describes that findings should be discussed in comparison to similar devices (devices with same intended purpose).
Annex II template for presentation of data and Annex III presentation and assessment of data
The tables in Annex II are examples only. This Annex needs to be reviewed for examples. The regions of EEA+TR+XI and worldwide was proposed in Annex I as the units for the provided data. There are also references to the International Medical Device Regulators Forum (IMDRF) guidance on Adverse Events in Annex I, II, and III, for the manufacturer to use the terminology as presented in this IMDRF guidance. Annex II explains that this is the EU plus the EFTA, Turkey (TR) and Northern Ireland (XI). Annex III also needs to be reviewed. There is the comment in Annex III that worldwide data is comprehensive and includes EEA, TR and XI.
The guideline is a fascinating read and helps address many outstanding questions.