By Dr. Catarina Carrao
In September 2019, Concept1, a Novartis dry powder inhaler for chronic obstructive pulmonary disease (COPD)1, was the first device to be certified under the new Medical Device Regulation (MDR). According to Rule 20 of the MDR, the inhaler is now a Class IIa device, which requires a Notified Body (NB) review, and an updated post-market surveillance (PMS) control2.
At around the same time, also Biotronik, a cardio- and endovascular medical technology company headquartered in Berlin, Germany, announced that it was the world’s first manufacturer to receive MDR certification for a Class III (highest risk) medical device, and enter a new phase of regulation for all their products3.
There is an increasing number of conformity assessments being reviewed by NBs, covering a range of medical implantable and non-implantable devices, including Class IIa, IIb and class III. As of June 2020, 14 institutions have been designated as NBs. As such, more products are expected to follow these initial certified products, and to be amongst the first to access markets under the new legislation.
With an increasing number of medical devices on the market, there is also an increasing number of incidents associated with them, with Post-Market Surveillance (PMS) an essential feature for all manufacturers. Throughout 2019, the European Commission (EC) has published new guidance clarifying manufacturers’ obligations under the Medical Device Vigilance System, established by the Medical Devices Directive (MDD) and updated with the new MDR. These documents have been developed to provide information to manufacturers in order to assist them identifying incidents and complaints associated with medical devices, and help them determine if a type of incident is reportable to the Competent Authority or not5. The new guidance expands issues covered by the MEDDEV 2.12-1 rev. 86, including Manufacturer’s Incident Reports (MIR), and field safety actions / notices, and device-specific vigilance reporting recommendations.
The “Manufacturer Incident Report (MIR) template for Serious Incidents (MDR/IVDR) and Incidents (AIMDD/MDD/IVDD)” had its first version published by the EC in December 2018; and, since then, it has been revised twice7. The latest version (v7.2) has become mandatory from the 1st of January 2020, for all manufacturers certified under the MDD 93/42/CEE directive8. The new template is intended to pave the way for an effective, efficient and transparent vigilance information exchange between manufacturers, Competent Authorities and NBs in the European Union (EU)9.
The new MIR v7.2 template comes coupled with the MIR Helptext 2020, which contains supporting information structured in six annexes (A-F), useful for filling in the five distinct sections of the MIR form, and employs a three-level coding system to help familiarize the user with what is expected in terms of the reporting procedure10. The annexes are helpful
for manufactures to understand the brand-new terms and definitions used, and, they revise the codes that will replace the "text" sections that were previously used to fill the older versions of the incident reports. Companies have interpreted that the new MIR v7.2 form is only applicable once they are audited and certified under the new MDR, but the truth is that the new MIR is live and ready to use for all medical devices11.
The updated template integrates the new requirements for incidents reporting under the European regulations (EU 2017/745-74612) and, it also reinforces the use of the harmonized nomenclature (coding and terminology) for the description of events, their causes, and their effects on medical device users recommended by the International Medical Device Regulatory Forum (IMDRF) for incidents that involve medical equipment13.
The new documents also suggest the method of reporting that should be used: Individual Incident Reporting, Periodic Safety Reports or Trend Reports. In this last case, if the manufacturer notices a significant increase in the incident rate of events, it must already communicate this trend, and any corrective actions, to the responsible Competent Authority (aka, authority of the country in which the manufacturer or the European representative is based)5.
The guidance also distinguishes between Field Safety Corrective Actions (FSCAs) and Field Safety Notices (FSNs). FSCAs are undertaken by manufacturers to reduce health risks posed by devices already on the European market, and FSNs are communications sent by manufacturers to consumers and users in relation to FSCAs5. Furthermore, the guidance states that manufacturers should initiate FSCAs in all markets in which the devices are commercialized and that FSN content should neither downplay the level of risk stemming from an incident, nor advertise products or services. These should be “uniform and consistent” for all European Economic Area member states, including Switzerland and Turkey where such notices are to be distributed14. In addition, the EC also released Device Specific Vigilance Guidance documents on Cardiac Stents, Cardiac Implantable Electronic Devices (CIED) and Breast Implants, which offer specific support to the manufacturers of these types of equipment on how to determine if an incident is reportable in a MIR or not15.
Other changes in the new template include the addition of the EUDAMED DI (European Database on Medical Devices) as an alternative to Basic-UDI-DI in all kinds of medical equipment, including legacy devices16. It also introduces the concept of the Single Registration Number (SRN) of the economic operator, which will be applied greatly under the new MDR regulations. SRN is a unique code that is assigned to manufacturers, authorised representatives or importers, after they have registered with EUDAMED (distributors don’t need SRN)17. SRNs will enable the companies to comply with both the product registration requirements, and any other obligations (e.g. submission of clinical trial dossiers, post-market surveillance and vigilance). SRNs will also be needed to apply to a NB for a conformity assessment. The Commission recently concluded, that it will only be possible to make EUDAMED operational once the entire system and its different modules have achieved full functionality, and have been subject to an independent audit. Due to this, EUDAMED will only launch in May 2022, with the basic-UDI-DI system in place16.
This delay should be viewed by the manufacturers as an opportunity to complete the MDR preparations, and take a breath. But, not to slow-down or postpone implementation in internal IT and Quality Management Systems (QMS)18. On the contrary, this is the time to reinforce PMS approaches.
In today’s real world, market surveillance methods should be part of any medical device manufacturers QMS and need to be planned, set up, documented and continuously updated to confirm and monitor the benefit-risk profile of medical products19. Proper data collection going back four years can be broken down by product, by year, and by country in order to carry out trend analysis after an incident is investigated11. In the end, a brand new, streamlined process with better analytical abilities for PMS will serve to confirm and monitor the benefit-risk profile of the medical device, and will make it easier to submit Periodic Safety Update Reports (PSUR) for inspection to the NBs, as part of the obligatory MDR regular updates.
Even though it won’t be easy, now is the time to get moving. Later, when these reports will be made available to patients, users and Competent Authorities via the EUDAMED, not only patients will benefit from the new regulations, but also manufactures will see the advantage of the new incident report guidance, in terms of proper market and post-market data collection / analysis.
Dr Catarina Carrao gained a PhD in Biochemistry from Northeastern Ohio Medical and Pharmacy University and an M.Phil in Biochemistry at the University of Beira Interior. She has worked as a researcher at Max F. Perutz Laboratories,Yale Cardiovascular Center at Yale University School of Medicine, and the Center Cardiovascular Research (CCR) at Charité Medical University.
1. Altman P, Wehbe L, Dederichs J, Guerin T, Ament B, Moronta MC, Pino AV and Goyal P. Comparison of peak inspiratory flow rate via the Breezhaler®, Ellipta® and HandiHaler® dry powder inhalers in patients with moderate to very severe COPD: a randomized cross-over trial. BMC Pulm Med. 2018;18:100-100.
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5. EuropeanCommission. Additional Guidance Regarding the Vigilance System as outlined in MEDDEV 2.12-1 rev. 8. 2019;14th February 2020. 6. EuropeanCommission. Guidance document - Market surveillance - Guidelines on a Medical Devices Vigilance System - MEDDEV 2.12/1 rev.8. 2013;14th February 2020. 7. EuropeanCommission. Manufacturer incident report 2020 (MIR). 2017/745-746. 2019. 8. EurLex. Council Directive 93/42/EEC of 14 June 1993 concerning medical devices. 93/42/EEC. 1993. 9. Thema-med. EUROPEAN UNION: Latest version of the Manufacturer incident report (MIR) 2020. 2019;13th February 2020. 10. EuropeanCommission. Helptext MIR 2020. 2019;13th February 2020. 11. ProcessStream. Leadership Q&A: a race to the EU MDR deadline with Mickey Huber. 2019;14th of February 2020. 12. EuropeanUnion. Regulation (EU) 2017/745 of the European Parliament and of the Council of 5 April 2017 on medical devices, amending Directive 2001/83/EC, Regulation (EC) No 178/2002 and Regulation (EC) No 1223/2009 and repealing Council Directives 90/385/EEC and 93/42/EEC (Text with EEA relevance. ). (EU) 2017/745. 2017. 13. IMDRF. IMDRF terminologies for categorized Adverse Event Reporting (AER): terms, terminology structure and codes. 2017;14th February 2020. 14. Eisenhart S. European Commission clarifies medical device vigilance requirements. 2019;14th February 2020. 15. EuropeanCommission. Guidance MEDDEV. 2020;14th February 2020. 16. EuropeanCommission. European database on medical devices (EUDAMED). 2020;13th February 2020. 17. Swissmedic. Single Registration Number (SRN). 2020;13th February 2020. 18. Eudamed.eu. Eudamed delay – a positive move. 2019;14th February 2020. 19. Catherine. Getting your Post-Market Surveillance (PMS) up to Speed with the EU MDR. 2019;14th February 2020.
