Delay and Implementation of the EU MDR - MedTech eBook
Discover the challenges of EU MDR implementation and impacts of the delay on the medical device industry - MedTech Summit
The Delay and Implementation
of the EU MDR
The challenges of implementation and impacts of the delay on the medical device industry
July 2020
The EU MDR Delay and Compliance
At the start of 2020, medical device companies were preparing for the EU Medical Device Regulation (MDR) date of application in May. However, in April 2020, with the unprecedented spread of COVID-19, the EU Commission took the step of postponing the date of application to 26th May 2021. This gave Medical Device, Software and Combination Product manufacturers an extra year to ensure their processes and products meet the increasingly stringent regulatory requirements.
Here in this interactive eBook, MedTech Summit takes an in-depth look at what the delay means for the medical device industry and how well prepared manufacturers are for EU MDR implementation, as well as exploring different aspects of the regulation.
Jump to any article using the contents on the following page, or at any time using the Contents menu in the top left. There you can also download this eBook as a PDF.
Medtech insiders representing every aspect of the industry look at what the EU MDR delay means for medical device manufacturers, Notified Bodies, Competent Authorities and the EU Commission.
Many manufacturers are now investigating the possibility of replacing the paper Instructions For Use with electronic IFU. European Regulatory Affairs consultants Qarad looks at the challenges, requirements and benefits of implementation of eIFU.
The Manufacturer Incident Report (MIR) template aims for effective and transparent vigilance information exchange between manufacturers, Competent Authorities and Notified Bodies in the EU. This whitepaper looks at MIR under the EU MDR.
With confirmation of the EU MDR delay due to COVID-19, MedTech Summit brought together four industry insiders to discuss the update and the impacts it will have on industry.
Over the course of 2020, we have conducted numerous studies of the industry. Here we look at how the survey respondents view the EU MDR implementation and subsequent delay.
Article 117 of the EU MDR has provided an amendment outlining specific requirements for drug device combination medical products. This whitepaper offers advice to prepare drug device combination product manufacturers for the new regulations.
What does the EU MDR deadline delay mean for the medtech industry?
EU MDR Deadline To Be Postponed
On Friday the 3rd April 2020, the EU Commission released the highly anticipated statement regarding the postponement of the EU Medical Device Regulation (MDR) date of application. Just two weeks later, on 17th April, European Parliament voted on this with 693 in favour, with just 1 vote against it (and 2 abstained), advancing this proposal to the European Council for final sign-off. So long as this is law before the original MDR date of application, the new deadline will be the 26th May 2021 offering Medical Device, Software and Combination Product manufacturers one more year to ensure their processes and products meet the increasingly stringent regulatory requirements.
"This will relieve pressure from national authorities and industry and it will allow them to focus fully on urgent priorities related to the coronavirus crisis,"
Stefan de Keersmaecker, European Commission spokesperson
The widespread and ongoing need for ventilators, assistive devices, technology and vaccines were a primary reason for the extension of the EU MDR. As Vice-President for Promoting our European Way of Life, Margaritis Schinas, says:
“Shortages or delays in getting key medical devices certified and on the market are not an option right now. The Commission is therefore taking a pragmatic approach and delaying the entry into application of new EU rules on medical devices, so we can have our medical industries pouring all their energy into what we need them to be doing: helping fight the pandemic.”
Vice-President for Promoting our European Way of Life, Margaritis Schinas
The recognition of the necessity to accelerate certain products to market highlights a key challenge of the increasingly stringent regulations which, at this moment in time, would increase timelines from concept to market and delay patients from receiving potentially life-changing treatments.
Regulators in some countries have already relaxed regulations in order to get devices onto the market quickly in the effort to reduce the devastation of COVID-19, and the delay of the EU MDR will bring further relief.
Under the increasing social and organisational pressures brought about by this global pandemic, and with many teams dispersed as some tackle the corona virus on the front-line and others do their part remotely, the industry consensus it that this postponement was absolutely necessary in light of these current circumstances.
Beyond freeing up resources to help combat COVID-19, what is hoped is that this additional year will increase awareness and provide the opportunity for manufacturers producing patient-crucial (but not necessarily profitable) devices to recognise the patient value of their product, and that some sort of regulatory oversight will be developed across Europe to ensure minimal product fallout across the sector.
What Does It Mean For The Medtech Industry?
Medical Device Manufacturers
- Medical device, combination product and software manufacturers will have more time to prepare for the EU MDR compliance deadline. This increases the time opportunity for companies to survive the new regulations and maintain healthy competition.
- Our recent EU MDR & IVDR Compliance report showed 67% of respondents were planning on using their entire MDD certificate time to get EU MDR ready. The one year extension gives Medical Device manufacturers more time to secure more products under EU MDD extension certificates and/or EU MDR CE marking, for products that may have otherwise been dropped.
- Industry will have more time to seek further clarification on regulations, attend events, work with peers and benchmark with guidance.
Notified Bodies
- With a limited number of designated Notified Bodies under the EU MDR, this extension provides a lifeline for many Notified Bodies that had yet to achieve this status.
- With vast numbers of products being submitted for review as the industry compete to meet the regulations, this will give Notified Bodies additional time to process applications and provide the necessary feedback to ensure more products achieve timely compliance.
- A chance to expand and take on new products? Currently it is hard to predict how many Notified Bodies will be designated by May 2021, however an ideal picture would see those designated processing applications efficiently and expanding to take on new clients and product types.
Competent Authorities
- Competent Authorities will now have more time to process more product submissions. This should reduce the fallout of products when the EU MDR date of application comes in to play.
The EU Commission
- The deadline postponement allows for more time for the EU Commission to address industry concerns and confusion. E.g. An opportunity to providing additional guidance documents for manufacturers to follow and implement.
Patients
Originally the EU Commission brought in the new medical device regulations "to ensure better protection of public health and patient safety". Ultimately this was deemed necessary to protect end users following some major adverse events that highlighted flaws in the previous regulations. However, the extension of the EU MDR is just as crucial to public health and patient safety as it is to manufacturers, as it:
- Increases the likelihood of compliance for a larger number of product lines that patients heavily rely upon.
- Provides more time for the industry to assess the medical device landscape and identify gaps in the market to ensure patients have the products they need.
Implementing a Compliant Solution for the Electronic Distribution of Instructions for Use
Qarad - European Regulatory Services
Implementing a Compliant Solution for the Electronic Distribution of Instructions for Use
For a long time, paper Instructions For Use (IFU) have been the norm in the medical device industry. However, many manufacturers are now investigating the possibility of replacing the paper IFU with electronic Instructions For Use (eIFU), provided to the user online. Such a web-based solution has many advantages, but presents challenges in complying with all regulatory requirements and dealing with its major impact on internal processes. Outsourcing the project to an experienced partner can greatly reduce the efforts for the implementation of an eIFU solution.
Electronic Instructions For Use as the Norm
The advantages of eIFU cannot be underestimated. By replacing the paper IFU with their digital versions, manufacturers significantly reduce their economic and environmental costs, while customers enjoy an improved customer-experience.
Traditionally, paper IFU are known for their small fonts and unattractive appearance as a consequence of fitting a lot of information in many languages on the smallest possible paper or booklet. Though everyone got used to this unattractive, non-user-friendly and hardly legible format, providing users with access to IFU online to print once or to consult on smartphones, tablets, computers or intranet would significantly enhance the user experience. The limitations on font and lay-out do not apply to the digital format. Digitizing documentation offers room for improving design and layout and allows users to only select those languages of interest to them, eliminating the need to browse through pages upon pages of information in a language not their own.
From an operational perspective, the electronic distribution of IFU has many merits. If IFU are no longer printed, the industry saves money on large amounts of paper and on printing. Removing the paper from the boxes will also allow companies to reduce the box sizes, thus saving money on product packaging and increasing the storage capacity of the warehouse. Moreover, leaving out paper IFU from the box impacts the packaging process. It eliminates the need for having the right IFU at the right time, eliminates the step of adding the IFU to the box and eliminates the errors that may occur in those steps. It also makes the in-process controls to verify whether the right document went into the right box obsolete. Furthermore, in case of IFU related nonconformities, the manufacturer is no longer faced with the physical replacement of the paper IFU in the packages.
The concern for patient risk may be a reason companies are not implementing eIFU yet. How can patient safety be ensured when clear working instructions are not provided with the product? Contrary to the expectations, for many medical devices (MD) and in vitro diagnostics (IVD), eIFU actually have characteristics that help to improve patient safety. The improved legibility of the IFU and the absence of constraints on the volume of information provided, reduce the occurrence of user error. In a professional environment, a clear indication how to obtain the eIFU enables users to access the right document at any time. Moreover, the electronic version allows regular, instant updates to the instructions and it eliminates the risk of a paper document getting lost once the package is open.
These numerous advantages are creating a shift towards eIFU to become the future norm in the MD and IVD industry. Nevertheless, current regulations still limit the use of eIFU to all medical devices.
The first objective of regulations is to ensure the safety of patients, users and other persons. Therefore, the electronic distribution of IFU is the subject of European regulations and guidance and is also regulated in other territories.
Patient safety can only be guaranteed if eIFU are used in the right setting and under appropriate conditions. It is important to understand the regulatory framework in which eIFU can be used. In this article, the focus is put on the European eIFU regulations.
First of all, replacing the paper instructions by eIFU is not allowed for all MD and IVD. eIFU are only accepted for devices to be used by a healthcare professional. All devices intended for lay people require a paper IFU to be supplied together with the product. For IVD used by healthcare professionals, eIFU can be provided instead of paper IFU, except for point-of-care devices. The regulators fear that the user in a point-of-care setting might not have easy access to the eIFU at the time of use of the IVD. Furthermore, special rules also apply for IVD instruments and software.
For MD, the regulations are even more restrictive. There are five clearly defined types of MD for which IFU can be made available online (see table below). All others still require a paper copy to accompany the device.
Only for professional use!
- Exception: Point-of-care
- Special cases:
Only for professional use!
- Active implantable MD & their accessories
- Implantable MD & their accessories
- Fixed installed MD
- MD and accessories with built-in system visually displaying IFU
- Stand-alone software
Second, even with an electronic system in place to provide eIFU, some users may still want a paper copy of the IFU. Therefore, a compliant eIFU solution must also provide the users with a way to obtain a paper copy upon request. For IVDs, the manufacturer must provide a free telephone number which the user can call to request the paper IFU to be sent to him via mail, fax or email. For medical devices, the regulation does not specify how a copy must be provided. It does clearly state, though, that the paper version must be provided to the user within 7 days from the request, and this without any charges to the user.
Third, uploading documents to a digital platform may appear quite straightforward, but the platform itself must comply with certain requirements as well. From a functional perspective, the website must work properly. Retrieving an IFU from the website should be self-explanatory in a language easily understood by the end-user. Access to the IFU should be quick and easy. The content of the instructions from the eIFU website, should be identical to the paper IFU and in a read-only format such as pdf. Moreover, the system must be secured and as such be hosted in an environment protected against hardware and software intrusion. This is also important to ensure permanent access to the website.
From a regulatory perspective, more restrictions apply to an eIFU platform. For instance, privacy regulations do not allow to capture personal data of the users downloading eIFU without their consent. However, regulations do not only restrict the use of eIFU. The new European MD and IVD Regulations clearly recognize the increasing importance of eIFU and state that the manufacturer has to make IFU available and keep them up to date on their website. This applies to all the devices, but except for the product groups described above, should be done in addition to the paper IFU accompanying the product. Manufacturers could consider meeting this requirement as an opportunity and first step to remove paper when possible, provided that they immediately use a web platform that meets the regulatory requirements for eIFU.
The decision to shift towards eIFU should not be made lightly. It has a significant impact on the manufacturer’s quality management system and will have to meet Notified Bodies’ expectations during audits.
A switch to the electronic distribution of IFU influences many quality system processes. The web platform itself will require full validation and the risk for patients and users has to be assessed. This risk assessment needs to focus on the risks associated with eIFU compared to paper versions, taking the use of the product, the environment of use and other end-user’s needs into consideration.
The implementation of an eIFU solution will have an impact on procedures and instructions in the management of eIFU and label content, the inventory management of labeling, the packaging process, logistical process, the ERP system and will trigger the creation of new procedures for the management of the web platform itself. Although this will initially take some effort, it will considerably reduce the work load of these processes. It will for example facilitate the process of introducing a new version of the IFU, since it will a.o. not impact the destruction and replacement of obsolete inventory. Paper IFU would require to be reprinted and if it concerns an immediate correction of an IFU boxes in stock must be reopened and IFU replaced. This is very labor-intensive compared to the electronic alternative.
Notified Bodies will verify whether the eIFU solution has been properly validated, whether risk assessment has been done, quality system processes and operational instructions have been adapted and labelling modified.
Manufacturers that use eIFU must inform the user on how to obtain the instructions for their products. It is recommended to do so via the product’s labeling.
Clear instructions must be provided on how to obtain the respective IFU, including a unique reference to identify the correct version of the document. This identifier has to be defined by the manufacturer and could be the reference number, UDI, GTIN or any other unique identification assigned to the product. As mentioned before, whenever the IFU have been revised, a clear indication must also be added to alert the customer that the document has been changed. Last but not least, a customer must be provided with the option to obtain the IFU on paper upon request as alternative for the eIFU. The necessary information on how to request that paper copy should be included on the label as well, or communicated by other means.
It clearly takes a significant effort to implement an electronic system for the distribution of IFU, that complies with the different regulatory, functional and operational requirements. However, the investment will quickly create a return by savings in direct costs and by increasing the efficacy of the processes related to IFU management. The implementation of an eIFU solution becomes considerably less burdensome by working with a reliable supplier, who not only offers a ready-to-use, fully compliant eIFU solution, but who also understands the full context of an implementation project and provides the manufacturer the necessary support in e.g. validation, risk assessment, labeling etc… With such a partner, the manufacturer is not alone and what first looked impossible, suddenly becomes a solution within reach.
Qarad is the pioneer in eIFU and is still global leader. Its eIFU solution complies with all regulatory requirements and has all the functionalities that manufacturers expect built-in. Qarad assists its customers by providing risk assessment and software validation documentation, by giving recommendations in handling labeling changes, notified body change requests, etc… Qarad not only provides a platform, but also facilitates its implementation, reducing the manufacturer’s resource needs.
Qarad was founded in 2000 to offer expert consultancy on IVD regulations and quality management systems. Based on this expertise, Qarad’s first compliant eIFU solution was developed in 2008. Since then, it continuously improved to meet changing and new regulatory requirements and increasing customer demands.
Qarad is an ISO 13485 and ISO 27001 certified company and it applies EN IEC 62304 for the development and life cycle management of the eIFU platform.
Qarad’s eIFU solution has been developed by regulatory experts focusing on compliance and risk management. The solution is fully compliant with EU and FDA regulations and is familiar to notified bodies. This will definitely facilitate the eIFU implementation process.
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- MEDDEV 2.14/3 Rev.1 IVD Guidance: Supply of Instructions For Use (IFU) and other information for In-vitro Diagnostic (IVD) Medical Devices.
- Commission Regulation (EU) No 207/2012 of 9 March 2012 on electronic instructions for use of medical devices.
- Regulation (EU) 2016/679 of the European Parliament and of the Council of 27 April 2016 on the protection of natural persons with regard to the processing of personal data and on the free movement of such data, and repealing Directive 95/46/EC (General Data Protection
- Regulation)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
- Regulation (EU) 2017/746 of the European Parliament and of the Council of 5 April 2017 on in vitro diagnostic medical devices and repealing Directive 98/79/EC and Commission Decision 2010/227/EU
- ISO 13485:2016 Medical devices - Quality management systems – Requirements for regulatory purposes
- ISO/IEC 27001:2013 Information technology - Security techniques – Information security management systems - Requirements
- IEC 62304:2006 Medical device software – Software life cycle processes
Manufacturing Incident Reports (MIR) under the EU MDR
By Dr. Catarina Carrao
Manufacturing Incident Reports (MIR) under the EU MDR
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.
Medical Device Vigilance System: The New PMS Cop
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.
MIR: Live and Ready to Use
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.
MIR v7.2: Reports, Field Actions and Notices
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.
EUDAMED and SRNs: Delayed to May 2022
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.
Leverage PMS to Promote a Safe Benefit-risk Profile of Your Product
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.
About the Author
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.
2. Brennan Z. Novartis Inhaler is First Device to be Certified Under MDR. 2019;14th February 2020.
3. Biotronik. BIOTRONIK Obtains the World’s First MDR Certification for a Class III (Highest Risk) Medical Device. 14th February 2020.
4. Brennan Z. Ireland’s NSAI Designated as 11th Notified Body Under MDR. 2020;14th February 2020.
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.
Video Panel Discussion: Update on the EU MDR Delay and Impact on Industry
Video Panel Discussion: Update on the EU MDR Delay and Impact on Industry
With confirmation of the EU MDR delay due to COVID-19, MedTech Summit brought together four industry insiders on 30 April 2020 to discuss the update and the impacts it will have on industry, featuring: Gert Bos, Executive Director & Partner at Qserve Group, The Netherlands, Annabelle Bruydonckx, Counsel at Simmons & Simmons LLP, Belgium, James Whitehead, Patient Safety Medical Device Lead at AstraZeneca, UK, and Vladimir Murovec, Supervising Associate (Healthcare & Life Sciences) at Simmons & Simmons, Belgium.
The Industry View of EU MDR Implementation and Delay
Over the course of 2020, we have conducted numerous studies of the industry. Here we look at how the survey respondents view the EU MDR implementation and subsequent delay.
The Industry View of EU MDR Implementation and Delay
Over the course of 2020, MedTech Summit and Informa Connect Life Sciences have conducted numerous studies of the industry, surveying medical device professionals from across Europe and beyond. Here we look at how the respondents view the EU MDR implementation and subsequent delay.
In February 2020, before the true scale of COVID-19 was apparent and before the extension to the EU MDR deadline, 265 medical device professionals responded to our survey around EU MDR compliance, implementation and preparedness.
What was clear was that many felt their company was not prepared for implementation, and many were extending their certificates under the existing Medical Device Directive (MDD), potentially up until May 2024.
How prepared do you think your company
is for EU MDR implementation? (Feb 2020)
Just 17% of medical device professionals thought that their company was 'fully prepared' for EU MDR implementation before the delay.
Of those not fully prepared for implementation, a lack of guidance dominated the reasons why (selected responses):
- "A lot of procedures still need to be updated and some require guidance docs that are not yet available."
- "There is a sense of confusion, compounded by Brexit."
- "The lack of guidance and Notified Body experience."
- "My company initially underestimated the effort to become MDR compliant AND there is a clear lack of guidance from the Competent Authorities."
- "Discussions about some interpretations, guidances which are not written or published, timelines which are not realistic anymore."
- "Incomplete standards."
- "Insufficient time to prepare due to Notified Body withdrawal causing other more immediate issues."
- "Lacking people, IT resources and legal consultation."
- "There are many unknowns; we have actions in place and believe we have covered off the elements required, but with interpretation issues in the mix, who knows?!"
- "Still finalising some aspects of PMCF and technical file templates."
- "Notified Body uncertainty and hence ability to plan."
- "Our Notified Body is not yet designated to the EU MDR."
- "UK govt (MHRA) guidance delayed. Lots of minor issues, but in house manufacture a key one."
"Companies feeling the pressure to be EU MDR-compliant wanted more guidance from the European Commission than they were getting, as well as more time and resources, including capacity at Notified Bodies. Around a third of respondents wanted to see more Notified Bodies in place, reflecting the fact that the number of Notified Bodies designated to work under the EU MDR was far below what industry had expected.
Specific comments from respondents also highlighted concerns about the Notified Bodies’ frequent struggles to find enough resources to certify all companies. They feared that Notified Bodies are unprepared, with an insufficient number of auditors and a lack of understanding about how long it will take to gain CE marking under the EU MDR."
- Philip Greenfield, Editor-In-Chief, Medtech Insight
Which of the following do you need more of to be fully prepared for EU MDR implementation?
"While a vast majority of companies felt they were prepared for the new regulatory environment to some degree, three quarters were extending their certificates under the existing Medical Device Directive (MDD), potentially up until May 2024, and most were planning to use the entire MDD certificate time to get MDR-ready." - Philip Greenfield, Editor-In-Chief, Medtech Insight
What proportion of your products have you
extended your MDD certificate for?
*Excluding 'Not Applicable' (63)
67% of respondents are planning on using their
entire MDD certificate time to get EU MDR ready
*Excluding 'Not Applicable' (70)
In April 2020, following the global outbreak of COVID-19, we conducted a second study around the response of the medical device industry to the crisis and the impacts that delaying the EU MDR Date of Application (DoA) would have.
Many of the 178 medical device professionals that responded saw the delay of the EU MDR as a positive move, offering manufacturers and Notified Bodies more time to prepare for the change, or else believed that in the long term, the delay will have minimal impact. question.
Reaction to the EU MDR delay post-COVID-19
What do you think the long term impact will be from delaying the EU MDR by a year in light of COVID-19? (Selected Responses)
"A few more manufacturers may be ready to go if they get an additional year to prepare."
"Allows more Notified Bodies to be approved for MDR designation. Allows companies to be more prepared."
"Both industry and the regulators will have more time to to put plans in place for compliance."
"No major impact. It was already very difficult to meet the timeline for Notified Bodies, authorities and companies. I think this delay will only bring a more realistic timeline."
"Hopefully all companies can focus on getting their MDR documentation and registrations ready. And hopefully we can have all the necessary NBs certified in time for the new MDR DoA."
"It will allow more companies to comply in time as there are delays and change in processes in the industry at the moment. It will likely have a positive impact on industry that has invested already in meeting compliance but is facing delays and unlikely to cause any long-term negative impact on the regulatory compliance."
"Minimal - most manufacturers on the MDR pathway need to forge ahead as if no change. Manufacturers that are still in the implementation stage will get some relief. Manufacturers utilizing MDD certificates until May 2024 will continue as planned. Biggest relief will be for NB and CA to be better prepared by May 26, 2021."
"The Notified Bodies will have more capacity for COVID-19 related devices / tasks. With regard to quality requirements, I think there will be no long term negative impact as MDR will be coming anyway."
"None. Companies which are not prepared by now will not be prepared in one year. Neither the quantity of Notified Bodies nor the quantity of qualified employees of the Notified Bodies will increase rapidly as everybody is focusing on COVID-19."
"Since the preparation for MDR was a difficult and costly process for many manufacturers, the delay may be financially advantageous for some manufacturers and help them to survive difficult times."
"It might decrease the pressure on companies directly dedicated to the investigation of COVID-19, and will allow them to dedicate their efforts to this real problem across the world. Highly safe medical devices have been developed till now with the current legislative framework."
"Lets get the right products made correctly and appropriately with CE and reg approval asap, not cut corners. Work on making the process easier and smoother, not removing reg approval completely."
"MDR aims to ensure the manufacture of safe and effective devices and motivates for innovation. There is a risk that this group of manufacturers, who are not capable or not willing to meet these requirements, have now enough time to prevent the success of the MDR."
"More devices and hopefully more Notified Bodies."
"This may not be long enough and will need to be reviewed again."
"Very little if the companies impacted by the EU MDR have been working since 2017 (like they should have been) to become compliant. For those companies that haven't been working towards compliance, it gains them a year to hustle and get compliant products."
"The impact of COVID-19 is probably much bigger than the MDR delay. This delay was needed anyway, so now the process can run smoother."
Does delaying the EU MDR DoA solve the issue of needing more respiratory devices/tests to hit the market or raise new challenges?
Respondents were conflicted when asked about the effectiveness of delaying the EU MDR DoA in solving the issue of needing more respiratory devices and tests to hit the market in response to COVID-19. The majority said it would raise as many challenges as it would solve the issues.
Should regs be eased to allow for non-medical manufacturers to help with the shortage of PPE and respiratory devices?
And finally, away from the EU MDR, we also asked the industry for their opinion on whether regulations should be eased to allow for non-medical manufacturers to help with the shortage of PPE and respiratory devices. The response was a resounding yes, with 70% agreeing.
Article 117: Preparing Drug Device Combination Product Manufacturers for the EU MDR
By Dr. Catarina Carrao
Article 117: Preparing Drug Device Combination Product Manufacturers for the EU MDR
By Dr. Catarina Carrao
The European Medicines Agency (EMA) has seen an increase in the number of scientific advice requests and Marketing Authorisation Applications (MAAs) for devices where a medicinal product incorporates, either in an integral or non-integral manner, a medical device component1. Such devices have clear benefits for patients with regular long-term dosing requirements in outpatient settings, either by self-administration or with the support of a lay caregiver. This reduces not only the burden on patients, but also on healthcare systems.
Previously, there were no clear regulatory requirements for such types of medical devices. But, to ensure that such components do not escape regulatory scrutiny, Article 117 of the European Union (EU) Medical Device Regulation (MDR) has provided an amendment outlining specific requirements for drug device combination medical products.
Drug-Device Combination Product Manufacturers Seek Notified Body Opinion
Article 117 finds itself within Chapter X (10) of the Final Provisions of the new MDR. This article is of high impact to market authorisation holders who provide medicinal products integral with administration devices, known as Drug-Device Combination (DDC) products2.
Article 117 requires that the MAA for an integral DDC device should include a declaration of conformity, or relevant certificate, issued by a Notified Body (NB) 3. If the product dossier does not include the results of the assessment of conformity, then the manufacturer will be required to provide an opinion from a NB on the conformity of the device part, in relation to the relevant requirements of Annex I (MDR 2017/745) 3.
The NB is an entity designated by an EU Competent Authority to assess the conformity of medical devices before being placed on the market. Companies are free to choose the NB they engage with; the only criterion is that the NB must be designated to carry out the conformity assessment procedure for the particular medical device type(s) for which a certification is sought3. As such, applicants can check the NANDO
website (New Approach Notified and Designated Organisations), by clicking on ‘Legislation’, and then select the relevant Directive/Regulation to search for a NB designated for the product types and technical competences needed4. The guideline even goes the extra-mile and contains a proposed template for the NB opinion on the conformity of the device in relation to the relevant safety and performance requirements of the new regulation5.
Article 117 only applies to medicinal products that form an integral product with a medical device - also known as integral DDC. These are devices necessary for the administration, dosing or use of a specific human medicine5; and, can fall into two categories:
1. Devices that incorporate a substance as an integral part; that, if used separately, would be considered a medicinal product (according to
Article 1(8) MDR);
2. Devices intended to administer a medical product, envisioned exclusively in that given combination; and, which are not reusable (according to Article 1(9) MDR)1.
As such, if a medical device is used to administer a medicinal product, and it is placed on the market in such a way that the device and medicinal product form a single product, intended exclusively for use in the given combination and not reusable, then Article 117 applies3.
For example, pre-filled syringes, pre-filled pens, nebulizers pre-charged with a specific drug, patches for transdermal drug delivery and pre-filled inhalers are all integral products which are not reusable. On the other hand, an example of a combination product which is not an integral product, is a vial containing a drug solution with an (empty) co-packaged syringe.
As always, there is an exception to the rule, which falls in the case of combined Advanced Therapy Medicinal Products (ATMPs), where the guidelines are clear that Article 117 does not apply (Article 2(1)(d) of Regulation EC 1394/2007) 3.
According to the EMA, integral DDCs currently authorized for sale in the EU, or those whose applications which will be submitted prior to the MDR enforcement date (26th May 2021), will not be impacted by Article 117 requirements6. But, such products may become subject to those requirements if manufacturers make substantial modifications to the device components of their products (e.g., addition, full parts replacement or design changes) 3.
After the 26th of May 2021 all MAAs for integral DDCs must demonstrate that the device part meets the relevant requirements of the regulation. As such, if the device component has CE marking, then the manufacturer is expected to provide a Declaration of Conformity, or the NB certificate, allowing the manufacturer to affix CE marking to the device3.
In the case the product file does not include at least one of those documents, and the device component is a risk classification of sterile class I, measuring class I, class IIa, class IIb or class III medical device, then the applicant must provide an opinion from an NB on the conformity of the device part with the relevant general safety and performance requirements set out in Annex I of MDR 2017/745.
In November 2019, the EMA released an update on the guidelines based on a stakeholder public consultation. It focusses on aspects relating to the implementation and applicability of the requirements of Regulation EU2017/745 to medicinal products with an integral medical device, and it is meant to be a living document. The questions and answers are being updated continuously, and will be marked by “NEW” or “Rev.” with the relevant date upon publication until the final date of enforcement of the new MDR7.
To smooth the procedures, there is a strong recommendation from the agencies for the EU certificate or declaration of conformity or NB opinion to be already included as part of the dossier of the initial MAA for the medicinal product. The absence of such documents could result in additional clock stops during the procedure, as these are fundamental for the adoption of a positive opinion by the Committee for Medicinal Products for Human Use (CMPHU) and market approval.
General Safety and Performance Requirements (GSPRs): The Track for Approval
NBs will require Technical Documentation that provides evidence and scientific data to support the product claims; and, expectations of which Technical Documentation to include are detailed in Annex II of the MDR8. The information that is usually needed by NBs to support a conformity assessment for medical devices includes:
- Risk Management Documentation
- Safety and Performance Data including clinical data
- Functionality Testing (accuracy of dosage, performance of device)
- Instructions for Use/Training for Users - Usability/Human Factor Testing
- Compatibility Testing
- Sterilization Validation, Sterility Test Data
- Packaging Validation Testing
The submitted scientific data must demonstrate conformance to the appropriate General Safety and Performance Requirements (GSPRs), found in Annex I of the EU MDR (not all GSPR’s will be applicable to integral drug-device combination products)8. Based on the data provided, NBs will assemble a report that concludes whether the device meets, or does not meet, all the relevant requirements. If the NB concludes that requirements are not met, the manufacturer should work with the NB to obtain a positive opinion. NB reports will not include quality management certification8.
- Identify a Notified Body intending to be EU MDR designated for their specific technology
- Assess which GSPR’s are applicable to their products
- Obtain scientific data that demonstrates conformance to the applicable GSPRs
- Assemble Technical Documents to support the medical device components
To meet the deadlines in time, and efficiently manage compliance timelines and expectations, planning is of the upmost importance. Manufacturers should take into account NB liaison and procedures, as well as the level of device risk and, therefore, the level of scrutiny required for market approval. To ensure patient safety, avoid any interruption to the market, and, by that a negative impact on the company’s reputation; maybe, seeking advice and practical support from a third-party specialist might be the way to go.
Most medical device developers already follow the design and development methodology ISO 13485, though pharma developers will now need to register their products under medical device regulations when they previously didn’t. The requirements listed in Annex I of the EU MDR and needed for compliance with article 117 will represent only a small proportion of the total number of physical and performance characteristics of the intended medical device.
Most developers have prepared and keep an up to date “checklist” listing each of the general safety and performance requirements, a short summary of how the requirements are fulfilled, or explanation for why the requirement is not applicable. So, on the most part, the information is already in the hands of the manufactures and just needs to be delivered to the NBs upon the MAA.
About the Author
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.
- EMA. Guideline on the quality requirements for drug-device combinations EMA/CHMP/QWP/BWP/ 259165/2019. 2019;18th February 2020.
- Keene A. EMA ISSUES Q&A REGARDING IMPACT OF MDR, ARTICLE 117. 2019;18th February 2020.
- EMA. Questions & Answers on Implementation of the Medical Devices and In Vitro Diagnostic Medical Devices Regulations ((EU) 2017/745 and (EU) 2017/746). 2019;18th February 2020.
- European Commission. Nando (New
Approach Notified and Designated Organisations) Information System. 2020;18th February 2020.
- EMA. Consultation on draft guideline on quality requirements for medical devices in combination products. 2019;18th February 2020.
- EmergoByUL. Europe’s MDR and combination products: Clarifications for drug-device product oversight. 2019;18th February 2020.
- EMA. Human regulatory: medical devices. 2020;18th February 2020.
- NetworkPartners. WHAT YOU NEED TO KNOW EU MDR ARTICLE 117. 2019;27th February 2020.
