MDR: What You Need To Know

The introduction of the new medical device regulations in May 2020 will bring significant changes to the way that we work with medical devices. Our medical device team has been working with many companies to support them for the changeover from the MDD to MDR. During the course of our interactions with these clients, there are many topics that are being raised time and again.

In this ‘long read’ we will look at the changes that the new medical device regulations will bring, what constitutes a medical device, the new role of the PRRC and more.  An edited version of this article also appears on this website.  This article is our most comprehensive look at the new device regulations.

What Are The Changes in MDR?

The advent of the new Medical Devices Regulation (MDR 2017/745) in May 2020 is a cause of much concern for manufacturers and others in the devices sector.  The new regulations will bring about many changes compared to the current regulatory framework.

Firstly, what is the MDR?

Medical Devices Regulation (MDR)(EU) 2017/745 repeals the existing medical device directives that were first put in place in 1993.  The new regulation was published on May 5th, 2017 and will come into force on May 26th, 2020.

Why Are We Moving from MDD to MDR?

The Medical Devices Directive (93/42/EEC) was in force for all members states of the EU (there are currently 28 including the UK), the members of the European Economic Area (Iceland, Lichtenstein and Norway) and two countries with bilateral trade agreements with the EU (Switzerland and Turkey).

• Directives are transposed into national legislation by each Member State and this meant that the directive was open to interpretation by each participating member state and, as such, it was not uniformly implemented across all participating countries.  Furthermore, the 1993 Directive has not kept pace with the seismic changes in medical technology.
• Regulations are directly applicable in all Member States and do not require transposition into national law. The new regulations have been introduced to enforce uniformity and to address the developments in device capability and technology.  The scandals in Europe involving device manufacturers in recent years have also added to the need for a more robust regulation of medical devices.

What Are the Most Important Changes?

The new MDR presents a significant development in device regulation.  Some of the main changes affecting manufacturers are highlighted below, but this list is not exhaustive.

• Product scope expansion to include products that do not have a medical purpose.
• Enhanced roles of economic operators to include manufacturer, authorised representative, distributor and importer.
• The issue of liability is much enhanced in the new regulations.  EU Authorised Representatives will be held jointly and severally liable for devices.
• The requirement for manufacturers to appoint a responsible person (RP) who is responsible for compliance with MDR.
• More rigorous clinical evidence / clinical evaluation requirements.
• Increased focus on post-market surveillance.
• An overhaul of Eudamed, the European electronic database for medical device information.
• Introduction of UDI system – Unique Device Identifiers – to enhance traceability

The Increased Role of Clinical Data in Medical Device Regulations

Perhaps the most significant change from the MDD to the MDR is the increased focus on clinical evaluation, access to data and post-market surveillance.  This places a greater burden upon manufacturers and their representatives, and it is something that we, at Acorn Regulatory, are helping our clients with.

The MDR only allows comparison under equivalence with one device. Using the equivalence approach to clinical evaluation will be much more difficult to achieve as manufacturers must have contracted access to the full technical documentation of the product with which they claim equivalence. There is an increased responsibility on manufacturers to document the effectiveness, safety and quality of their own devices.

What Is A Medical Device?

The scope of Regulation (EU) 2017/245 (MDR) has changed to include a broadening of the range of products that are subject to the new requirements.

Article 1 of MDR 2017/245 indicates which type of devices are required to comply with these new regulations.

Article 2 of the MDR 2017/245 defines the term “medical device” as any “instrument, apparatus, appliance, software, implant, reagent, material or other article” intended to be used for any of the following medical purposes:

• Diagnosis, prevention, monitoring, treatment or alleviation of disease, disability or injury, where prevention of disability and injury is excluded
• Investigation, replacement or modification of an anatomical, physiological or pathological process
• Providing data via in vitro examination of samples derived from a human body
• The MDR also identifies particular types of products that also qualify as medical devices:
• Products intended for cleaning, disinfection and sterilization of medical devices
• Devices for the control and support of conception

Products manufactured utilising nonviable human tissues or cells (and their derivatives) will now also be regulated under MDR.

Annex XVI of MDR 2017/245 lists groups of products that, even though they have no intended medical purpose, are required to meet MDR requirements.

These include devices used for aesthetic and cosmetic purposes, such as coloured contact lens, dermal fillers, equipment used for liposuction etc.

Accessories (which are products that are intended to enable a device to be used in accordance with its intended purpose or to assist the medical functionality of the medical device) are also covered under MDR 2017/245 (similar to the MDD 93/43/EEC).

However, as some products are now added to the definition of a medical device, it is now important to note that their accessories will also now be covered under the scope of the MDR.

Taking all this broadening of scope into account, means that certain devices who were previously not covered under the MDD 93/42/EEC, now fall under the remit of MDR 2017/245.

In particular, there are now manufacturers, who previously were not subject to the requirements of MDD 93/42/EEC who are now subject to MDR 2017/245.

What Is Risk-Based Classification of a Medical Device?

• Classification of Medical Devices is based on risk as outlined in Annex VIII of MDR 2017/245.
• While the structure of the rules under MDR 2017/245 remains as per MDD93/42/EEC, there are now a number of additional Special Rules under MDR which mean there are now 22 rules in total.
• Devices classification range from Low Risk (Class 1) to High Risk (Class III).
• Active Implantable Device manufacturers should also note that MDR now covers Active Implantable devices and these are subject to the requirements of Class III devices.
• As a manufacturer is it important to consult the regulations directly to determine whether your medical device is covered under the new MDR 2017/245.

Some Questions To Consider When Preparing for MDR

1. Are you a device manufacturer that is now covered under the new MDR 2017/245 and are trying to understand what is required under MDR 207/245?
2. Or are you a device manufacturer trying to determine whether your device falls under the scope of MDR 2017/245?
3. Or are you trying to determine how to classify your medical device under MDR 2017/245?
4. Are you aware of your responsibilities under EU MDR? Do you have the resources and systems in place to fulfil your obligations under the new Regulations?

The MDR & The Authorised Representative

The MDR provides detail on the additional roles responsibilities of various Economic Operators in the medical device supply chain. This was examined in our recent article featured on the Acorn Regulatory website. You can read the brief Economic Operators article by clicking here. In this article we look in more detail at the role of Authorised Representative required for manufacturers based outside of Europe.

It was established in the Directives to act as a contact point within Europe who could act on behalf of the manufacturer. The scope of the role of Authorised Representative has been expanded under MDR compared to previously, and details may be found in Articles 11 and 12 of Regulation (EU) 2017/745.

What Is An EU Authorised Representative?

The authorised representative is defined as ‘any natural or legal person established within the Union who has received and accepted a written mandate from a manufacturer, located outside the Union, to act on the manufacturer’s behalf in relation to specified tasks with regard to the latter’s obligations’ under the Regulation.

The existing MEDEV on authorised representatives has essentially been incorporated into the Regulation and there is also an article that describes the process to change an authorised representative.

What’s New?  The Authorised Representative’s Obligations under 2017/745

• The manufacturer must be based outside of the EU and there is a new requirement for there to be a written mandate to define the designation of authorised representative and for this to be signed and accepted by both manufacturer and authorised representative.
• The authorised representative must verify the declaration of conformity, conformity assessment, technical documentation, registration requirements and manufacturer obligations.
  keep available a copy of the declaration of conformity, technical documentation and certificates.
  establish systems for provision of information to CAs and manufacturers; CAPA; registration; complaint handling; establishment, maintenance, termination of mandate; person responsible for regulatory compliance.
• In addition, the Regulation stipulates that the authorised representative is legally liable for defective devices in the event that a manufacturer established outside the Union has not complied with its general obligations

What Is the Role of the PRRC under MDR?

The role of QP is a familiar one for those working in the pharma sector, however this is the first time in European medical devices legislation that a person is required to be appointed by a manufacturer to take specific responsibility for regulatory compliance of devices.

The requisite expertise is also detailed in Article 15 and involves either:

(a) a formal qualification such as a degree in law, medicine, pharmacy, engineering or other relevant scientific discipline and at least one year of professional experience in regulatory affairs or in quality management systems relating to medical devices or

(b) four years of professional experience in regulatory affairs or in quality management systems relating to medical devices

The five main responsibilities of the person responsible for regulatory compliance are to ensure that:

1.  The device conforms to the manufacturers quality system prior to release.
2.  The technical documentation and EU declaration of conformity are properly maintained.
3. The post-market surveillance obligations are complied with including post market surveillance plan, post-market report and periodic safety update report as applicable.
4. The reporting obligations are fulfilled for serious incidents, field safety corrective actions and trend reporting.
5. The statement referred to in Section 4.1 of Chapter II of Annex XV is issued in the case of investigation.
   devices.

There is a provision within MDR that allows micro and small enterprises to outsource the PRRC role and to have an appropriately qualified person permanently and continuously at their disposal rather than having that person within their organisation.

The definition of micro and small enterprises comes from Commission Recommendation 2003/361/EC and relates to number of employees and turnover/balance sheet figures. A small enterprise is defined as an enterprise which employs fewer than 50 persons and whose annual turnover and/or annual balance sheet total does not exceed EUR 10 million. A microenterprise is defined as an enterprise which employs fewer than 10 persons and whose annual turnover and/or annual balance sheet total does not exceed EUR 2 million. The outsourced PRRC must then be listed as a critical supplier on the manufacturers’ quality system and an agreement must be in place between both parties.

Carrying Out A Clinical Investigation Under MDR

MDR Articles 62-82 and Annex XV cover the requirements of Clinical Investigations. 

Clinical investigations form part of the overall Clinical Evaluation of a device and are required for certain devices classes. 

Class III devices and Implantable devices require a Clinical Investigation – (with exceptions are per Article 61 (4) and (6) ) 

Clinical Literature Evaluation is required for all classes of devices under MDR, however, proving equivalence to another device is now much harder to establish under MDR and therefore, clinical evaluation of the literature as the sole source of clinical evidence is much harder to establish and so a Clinical Investigation may also be needed for Class IIa and IIb devices.  

Current MEDDEVs

The current MEDDEVs relevant to this area are:  

• 2.7/4  Guidelines on Clinical Investigations – A guide for manufacturers and Notified bodies 
• 2.7/2 Guidelines for Competent Authorities– for making a Validation/Assessment of a Clinical Investigation Application 

• 2.7/3 Guidelines for Medical Devices – Clinical Investigations; Serious Adverse Event Reporting 

These are used in conjunction with the MDD 93/42/EEC but have very similar Clinical Investigation requirements to the requirements of the MDR with some additional requirements including: 

Introduction of a Sponsor:

Article 2 (49) Sponsor means ‘any individual, company, institution or organisation which takes responsibility for the initiation, for the management and setting up of the financing of the clinical investigation’. Under MDR this means that investigators initiating clinical studies will be responsible for meeting MDR clinical study requirements. 

• Article 62 Legal representative must be appointed, who is responsible for ensuring compliance with sponsors obligations 
• Annex XV New restrictions regarding appointment of a monitor who is independent of Investigational site 
• Article 80 – inclusion of requirement for sponsor to report to all Member states in which clinical investigation is conducted, without delay ‘any serious adverse event that has a causal relationship with the investigational device, the comparator or the investigation procedure or where such causal relationship is reasonably possible’ 
• Annex XV –policy regarding follow up and management of any deviations from the Clinical Investigational Plan at the investigational site and clear prohibition of the use of waivers from the Clinical Investigational plan 

It should be noted that ISO 14155:2011 (Clinical Investigation of Medical Devices for Human subjects – Good Clinical Practice’ aligns closely with the new MDR. 

This standard contains detailed information about the procedure and content of a clinical investigation plan. 

Clinical Master Plan

If a clinical investigation is required under MDR, the type, structure, and parameters of it must be defined within the overall Clinical Master Plan. 

The clinical study structure must be based on the objective (e.g., demonstrate the performance); the need to demonstrate equivalence through prospective human clinical investigation (this can be with literature as the control); and finally, the risk and “innovative level.” 

Manufacturers must consider the definition of Clinical Evidence in Article 2 (51) in their selection of the study structure that will provide useful results: 

clinical evidence’ means clinical data and clinical evaluation results pertaining to a device of a sufficient amount and quality to allow a qualified assessment of whether the device is safe and achieves the intended clinical benefit(s) when used as intended by the manufacturer; 

Using A Clinical Research Organisation

The use of a Clinical Research organisation (CRO) is recommended for data quality purposes.  If a post-market clinical follow-up study (PMCF) is required, the analysis, trending updating of reports may necessitate a manufacturer to obtain outside assistance for this work.  The purpose of the PMCF is to verify the safety and performance profile that the study sponsor acquired through the selected group of users and patients in the pre-CE-Marking study. 

In conclusion, it is important that manufacturers should decide as early as possible whether to conduct a Clinical Investigation. The decision should be based on reasonable scientific and defendable grounds and in full consideration of the requirements under MDR, with additional support and expert input if necessary. 

Conformity Assessment Routes Under MDR 2017/745

Conformity Assessment assessment routes under MDR 2017/745 have not significantly changed under MDR 2017/745 compared to MDD 93/42/EEC however, the timeline to CE marking might now be longer, particularly if there is the involvement of expert bodies e.g the MDCG (Medical device co-ordination group).

The number of requirements of GSPR’s (Annex I- General Safety and Performance requirements) has increased under MDR compared to the number of Essential Requirements under MDD. Common specifications requirements have also been introduced for some devices.

Medical Devices are required to be in compliance with the relevant GSPRS (Annex I). Compliance with EN harmonised standards and Common specifications (CS) presumes compliance with the GSPR’s.

Summary of Conformity assessment routes under MDR 2017/745:

Class I

For Class I devices (with the exception of Class Im (measuring), Class Is (sterile) and Class Ir (reusable)), the ‘self-certification’ route is acceptable with a requirement to maintain Technical documentation according to Annex II and Annex III.

However, for Class Im, Class Is and Class Ir, a limited QMS (Quality Management system) must be in place to control the production (Annex XI Part A) or to control the special characteristics (Annex IX Chapter I). The involvement of an NB (Notified Body) is required to assess this QMS

Class IIa

Class IIa devices may undergo conformity assessment under Annex IX (Full QMS) or undergo assessment under Annex XI (Production Control) together with Technical documentation as per Annex II and III.

Conformity assessment under Annex IX (Full QMS) requires an NB audit of QMS and NB assessment of the Technical Documentation/Design Dossier.

Conformity assessment under Annex IX requires an NB audit of Production Quality Assurance for the ability to produce and test the device.

Class IIb

Class IIb devices categories are

• Class IIb implantable
• Class IIb active device intended to remove or administer medicinal substances
• Class IIb devices not included as any of the above.

For Class IIb devices, that are not active or intended to remove or administer a medicinal substance, conformity assessment via either of the following routes may be considered.

• Class IIb implantable – Annex IX Chapter I (QMS) and Section 4 (Technical documentation for every device without expert review)
• Class IIb non-implantable – Annex IX Chapter I (QMS) and Section 4 (Technical documentation for representative device without expert review)

Or

• Annex X (Assessment based on Type-Examination) and Annex XI-Part A (Production Quality Assurance)

Or

• Annex X (Assessment based on Type-Examination) and Annex XI-Part B (Product verification)

For Class IIb devices that are active and intended to administer or remove a medicinal product, the following conformity assessment routes may be used:

• Annex IX Chapter I (QMS) and Section 4 (Technical documentation for every device with expert review)

Or

• Annex X (Assessment based on Type-Examination) and Annex XI-Part A (Production Quality Assurance)

Or

• Annex X (Assessment based on Type-Examination) and Annex XI-Part B (Product verification)

Class III

For Class III devices the following Conformity assessment routes may be used:

• Annex IX (Assessment based on a QMS and assessment of full Technical documentation)

An expert panel will also be required to evaluate Class III implantable devices

Or

• Annex X (Assessment based on Type-Examination) and Annex XI-Part A (Production Quality Assurance)

Or

Annex X (Assessment based on Type-Examination) and Annex XI-Part B (Product verification)

There are additional requirements in Annex IX for devices incorporating medicinal product, devices incorporating animal or human tissues/cells or for devices introduced into the human body through bodily orifices or applied on the skin and intended to be absorbed or local dispersed.

EUDAMED

Under MDR, CE mark Certificates will be required to be registered in EUDAMED (European Electronic database). This database will be accessible by the EU Commission, Competent Authorities and the MDGC.

Conformity assessment routes under MDR have not significantly changed since MDD however, timelines for CE marking may be increased due to additional scrutiny by Competent Authorities or expert panels via the EU Commission or the MDGC.

Also, there are also additional requirements for the GSPR’s under MDR compared to the Essential Requirements of the MDD.

Some devices may be required to be reclassified under the list of classification rules that have now changed under MDR.

The impact of MDR not only impacts Medical Device manufacturers but also Competent Authorities, Notified bodies as well as the Economic operators involved with the device.

Regulation (EU) 2017/745 on medical devices (MDR) now has increased requirements on specific Post Market Surveillance (PMS) and Post-market clinical follow-up (PMCF) requirements.  In this article, we look at the requirements for manufacturers.

Post Market Surveillance under Medical Device Directive (2017/745)

Currently, manufacturers are required, under MDD (93/42/EEC) to comply with the requirements of PMS by having an up to date systematic procedure that is used to review experience gained from devices in the post-production phase and to implement appropriate means to apply any necessary corrective action.

However, PMS and Post-market clinical follow-up activities under the new MDR now have more complex requirements and manufacturers will need to maintain more robust Post Market Surveillance procedures and perform more post-market clinical follow-up studies in order to meet the new MDR requirements.

The definition of Post Market Surveillance in the MDR (Article 2 Section 60) is what drives the PMS requirements and is defined as ‘all activities carried out by manufacturers in cooperation with other economic operators to institute and keep up to date a systematic procedure to proactively collect and review experience gained from devices they place on the market, make available on the market or put into service for the purpose of identifying any need to immediately apply any necessary corrective or preventive actions.’

What are the requirements of Post Market Surveillance under MDR (2017/745)?

Under MDR, PMS contains both proactive and reactive elements and the Medical Device and manufacturers need to consider the following activities –

• Post Market Surveillance
• Risk Management
• Clinical Evaluation Plan and report
• Post-market surveillance plan and report
• Post-market clinical follow up (PMCF) plan and evaluation report
• Periodic Safety Update report (PSUR)
• Summary of Safety and Clinical Performance (SSCP)
• Vigilance

The PMS and Periodic Safety report/Periodic Safety update report are required to be part of the Technical Documentation as specified in Annex II and III of MDR (2017/745) and, specific timelines regarding the update of the Periodic Safety Update Reports and their availability to Competent Authorities and Notified Bodies (depending on Classification of device) are detailed in the new MDR.

The increased requirements regarding Post-market clinical follow-up (PMCF), requires additional planning by manufacturers to adequately cover these in their PMS System. A specific PMCF plan is required for describing the activities. Post-market clinical follow-up is a continuous process that is part of clinical evaluation and forms a link from evidence collected in the premarket stage with Post Market data collected when the device is in regular use.

Integration into Quality Management System (QMS)

Manufacturers are required to incorporate PMS activities into their Quality Management System (QMS) – and these activities need to link with many elements of the QMS, including  Design and Development, Management Review, etc.

It is also important to note the Post Market Surveillance, Risk Management and Clinical Evaluation all feed into each other.

What are the impacts on Medical Device Manufacturers?

There are many impacts on manufacturers, who in the past may have relied on their complaint and feedback systems to satisfy post market surveillance requirements.

Since the timeline for implementation is fast approaching (May 2020), manufacturers need to assemble resources and systems to perform the additional required tasks to satisfy MDR post market surveillance requirements.

These now include:

• requirements for resources for performing the collection and evaluation of
• data, and writing of reports
• the requirement for resources to perform documentation updates (risk, clinical evaluation, technical documentation)
• consideration of the impact on other economic operators

Note that the resources are not limited to Regulatory and may include Quality Assurance, Clinical affairs, Service, Sales and Marketing, Service and other Economic Operators.

Get The Medical Device Regulations Whitepapers

The new medical device regulations (MDR) will come into force in May 2020.  In advance of the deadline, companies across the world are working to ensure that their devices will comply with the new regulations.  For many companies there is still much work to do. Also, companies are still actively seeking further information about the regulations and how they will be applied.

Click the cover image to download the whitepaper.

Our first MDR whitepaper looks at a range of issues including:

• The responsibilities of the Person Responsible for Regulatory Compliance
• The impact that the new MDR will have on the role of the EU Authorised Representative
• and most importantly, the whitepaper will look at what actually constitutes a medical device. The new regulations have widened the definition of what is actually a medical device and this change is bound to have significant impact on manufacturers.

Our second medical device regulations whitepaper looks at:

• What will happen to Unique Device Identifiers under MDR?
• Post-market surveillance
• Eudamed and MDR

The second whitepaper can be downloaded by clicking here.

Our third MDR whitepaper covers the following issues:

• Clinical investigations under MDR
• Clinical evaluations under MDR
• Conformity assessment routes

The third whitepaper can be downloaded here.

We Can Help You To Prepare for MDR

Acorn Regulatory can help you to manage your MDR responsibilities.  Our team of medical device experts has a wealth of experience gained in industry and with national health authorities.

If you would like to talk to a member of our expert team, then please complete the form below or contact us on 00353 52 61 76706.