Medical Devices Regulation
Medical Device Regulation (MDR) & In-Vitro Diagnostic Devices Regulation (IVDR)
The EU’s Medical Device Regulation (MDR) 2017/745 and Regulation 2017/746 on In-Vitro Diagnostic Devices (IVDR) were officially published on 5 May 2017 and came into force on 25 May 2017.
Regulation (EU) 2017/745 is a regulation of the European Union on the clinical investigation and sale of medical devices for human use.
It repealed Directive 93/42/EEC, legislation for medical devices, and Directive 90/385/EEC, which concerns active implantable medical devices, on 26 May 2021.
- One of the biggest challenges for manufacturers implementing the new MDR & IVDR regulations has been the insufficient number of notified bodies that have been designated.
- While manufacturers have addressed some of the near-term challenges of the new regulations they still face significant uncertainty and a range of issues.
- One major concern is the fact some Notified Bodies are still in the process of obtaining designation to the new MDR and IVDR.
- The danger for device makers is that not enough Notified Bodies will have received the proper designation prior to the expiration of the current CE Mark certifications for device manufacturers. Medical devices are defined by the Medical Devices Directive (MDD), Active Implantable Medical Devices Directive (AIMDD), and In Vitro Diagnostic Medical Devices Directive (IVDD).
- If this occurs then the affected manufacturers and their respective devices will no longer be able to be legally marketed in the EU, potentially causing supply shortages for healthcare providers and patients.
- The NANDO (New Approach Notified and Designated Organisations) database provides information on notified bodies responsible for assessing the conformity of goods which are placed on the market in the EU.
- At the end of June 2022 there are a total of 30 Notified bodies who have obtained designation under the new MDR and IVDR. The list of Notified Bodies can be found via the following link; NANDO list June 2022
The Medical Device Regulations 2017/745 are focused on improving patient safety. The objective is to make use of the existing experience with previously sold devices as well as carry out a comprehensive device assessment before and after distribution on the EU single market.
- The lack of follow-up post-market approval and the requirement for continuous clinical assessment were not mandatory.
- The inability to keep pace with technology development particularly as it relates to hybrid devices and medical software was also a concern.
- MDD was based on directives as opposed to regulations.
This resulted in conflict between the directive and the laws of individual countries. This led to inconsistency in how MDD was implemented across the various EU member states.
- Under MDD the focus of Notified Bodies was initial premarket assessments and subsequent approvals.
- This led to Notified Bodies being perceived as partners to the industry rather than being the gatekeepers for safety and quality.
With MDR liability for failures of devices now transcends not only the original manufacturer but also other companies in the supply chain and distribution network.
MDR Content Overview
- Is four times larger than the previous MDD.
- Gives greater attention to device safety with the word safety appearing 290 times in the MDR, but only 40 times in the MDD.
- MDR has forced device manufacturers to significantly update clinical data, compile pre and post-market surveillance, strengthen technical documentation, and revise labelling for all devices.
The emphasis previously fell on pre-marketing efforts and clearances under MDD and IVDD. The MDR focuses on a life-cycle approach to devices and includes standards for Unique Device Identification (UDI), Post-Market Surveillance (PMS) reporting, and thorough clinical evaluation prior to market introduction.
This encourages a life-cycle approach to medical device regulation and is more in line with the strategy used by the US FDA.
The European Union region has a population of approximately 450 million people, and its residents are living longer than previous generations. This creates new issues for medical device companies and regulators as they assess the risks associated with adverse events and failures.
This is one of the major reasons the new regulations put greater emphasis on the product life-cycle than just getting a device to market.
MDR repealed Directive 93/42/EEC, which covers medical devices, and Directive 90/385/EEC, which relates to active implantable medical devices. The MDR originally allowed for a transition period of three years however due to the global outbreak of Covid-19 the full implementation of the MDR was extended and came into force on 26 May 2021. Regulation 2017/746 (EU IVDR) on In-Vitro Diagnostic Devices (IVDR) was agreed upon and entered into force in May 2017 and had a staggering transitional period.
Regulation (EU) 2022/112 amended Regulation (EU) 2017/746 and facilitated longer transitional periods regarding the validity of certificates issued by notified bodies. Regulation (EU) 2022/112 also allows manufacturers to market and put into service in-vitro diagnostic medical devices that were lawfully placed on the market pursuant to the same IVDD. Safety and performance requirements set out in the IVDR and their respective application date of 26 May 2022 remain unchanged.
Medical Device Classification
Under MDR the classification of medical devices is a risk-based system which considers the potential risks associated with the devices while also assessing the vulnerability of the human body. Utilising this approach different criteria can be used or combined in various ways in order to determine classification. For example, the degree of;
- Potential toxicity
- Length of time the device is in contact with the body
- Part of the body affected by the use of the device
- If the device requires energy as part of its operation.
In addition, the MDR also sets out special rules for certain devices such as;
- Substance-based devices
- Devices that contain nanoparticles
- Those which contain a medicinal product
Using these criteria an extensive range of different medical devices can then be assessed and classification determined. These are referred to as the ‘classification rules’ and are set out in Annex VIII of Regulation (EU) 2017/745 on medical devices (MDR).
- The release of MDCG 2021-24 by the Medical Device Coordination Group (MDCG) had significant implications for manufacturers of specific devices such as spinal implants.
- The device industry expected the majority of spinal implants that do not preserve motion to be classified as Class IIb. However, the MDCG guidance categorised all fusion devices, motion-preserving implants, as well as components such as hooks and other devices placed in the disc space as Class III.
What does this mean?
- For device manufacturers, this means a more intense application process, closer scrutiny from notified bodies, and a significant resource investment into reclassification.
Regulation 2017/746 (EU IVDR)
- Has many common aspects and requirements with the Medical Device Regulations 2017/745.
- This has resulted in important changes and requirements for IVD manufacturers.
- The IVDR introduces a rules-based classification system for IVDs which utilises four different classes based on risk from class A (low) to class D (high).
Changes in Risk Classification:
- A significant change for IVD manufacturers is the change in risk classification.
- With the implementation of the IVDR, 84% of the in-vitro diagnostics currently marketed in the EU will see a change in classification and require Notified Body certification.
- This will result in a 12-fold increase in in-vitro devices requiring certification compared to the previous IVDD.
- The IVD manufacturers will be significantly impacted since they will need to do a gap analysis to ascertain which devices should be placed in a different class, how this will affect conformity assessment processes, and whether more clinical evidence is required.
Introduction to the new Basic UDI-DI system
Before placing a device on the market, the manufacturer has to assign a Basic UDI-DI to the device and input it into the UDI and Device Registration module of EUDAMED.
To allow manufacturers time to transition to the new system, the new Regulations allow for products to be placed on the market after the general application dates of the new Regulations (and until 26 May 2024 at the latest) by virtue of valid Directive certificates. These legacy devices are not subject to UDI obligations but they should be registered in the EUDAMED database.
The Basic UDI-DI is an EU approach for linking devices to their regulatory documentation and it is intended to uniquely identify the product model throughout the entire life cycle of the product. The implementation of the new UDI system will;
- Enable easier traceability of medical devices.
- Significantly improve the effectiveness of the post-market surveillance activities for devices.
- Allow for enhanced scrutiny by competent authorities.
The use of UDI aims to minimise the risk of medical errors and prevent the marketing of falsified devices. Other benefits of UDI include;
- Improved procurement
- Waste disposal policies
- Greater stock control by health organisations and other economic players.
The new UDI requirements will apply to all medical devices except custom-made devices and investigative devices.
Transitioning from MDD/AIMDD to MDR/IVDR
Under MDR/IVDR, a device manufacturer’s quality management system and related obligations under Article 120(3) MDR allows for devices to be placed on the market or put into service until 26 May 2024 provided they are covered by valid certificates under the MDD/AIMDD.
This is dependent on manufacturers continuing to comply with either of those Directives and that there are no significant changes in the design and intended purpose of the device.
While continuing to maintain the quality management system approved under MDD/AIMDD, in accordance with the first subparagraph of Article 120(3) MDR, device manufacturers must ensure all relevant requirements set out in Chapter VII MDR relating to;
- Post-market surveillance market surveillance vigilance, registration of economic operators, and;
- Of devices that apply in place of the corresponding requirements in those Directives.
According to Article 120(3) MDR, the notified body’s activities in principle should be a continuation of the previous surveillance activities under the Directives, as notified bodies designated under the MDD or the AIMDD are not designated to conduct assessments under Article 52 of MDR.
In the framework of their surveillance activities, notified bodies need to consider the new requirements resulting from the transitional provisions
About Medical Devices
The term ‘Medical Device‘ represents all products that are marketed for use in;
- Diagnosing illnesses
- Preventing illnesses
- Monitoring illnesses
- Treating illnesses
Medical Devices also deliver their principal intended action by physical means. Medical devices cover a wide range of products and include many thousands of devices used each day by healthcare organisations and patient end-users.
- Orthopaedic implants
- Heart valves
- Dialysis machines
- Wound care products
- Blood glucose monitors
Under MDR manufacturers of devices of drug-device combination and who are marketing these combination products as a “medicinal product” are compelled to seek a Notified Body Opinion (NBOp).
There is an ever-growing number of drug-device combination products being placed on the market which require NBOp. These include;
- Drug-eluting stents
- Pre-filled nebulisers
- Pre-filled pens
- Prefilled syringes
- Transdermal patches
Similar rules apply to combination products under IVDR. The regulatory environment will change as a result of companion diagnostics becoming under the IVDR’s purview.
Companion diagnostics will be subject to a high level of clinical surveillance because they fall within the new IVDR classification’s second risk category, class C. This is especially true for pharmaceutical companies that create their own companion diagnostics.
Types of Medical Devices outlined in the legislation
- General medical devices
- Active implantable medical devices
- In-vitro diagnostic medical device
According to MDR Article 51, devices are divided into the following classes I, IIa, IIb and III, considering the intended purpose of the devices and their inherent risks.
Under MDR a manufacturer must conduct a conformity assessment. This is the process where a manufacturer must demonstrate the requirements of the MDR relating to a device have been fulfilled. Demonstrating conformity is in the first instance the responsibility of the manufacturer.
For the majority of device classifications, the conformity is assessed by a notified body. The higher risk and classification of the device, then the greater the involvement of a notified body in conformity assessment.
A manufacturer must ensure, regardless of the classification of the device, that the general safety and performance requirements are satisfied under MDR Article 5, MDR Annex I.
This includes carrying out the necessary clinical evaluations (MDR Article 5 (3), MDR Article 61, MDR Annex XIV.
For implantable devices and class III devices, a premarket clinical investigation is compulsory, with some exceptions such as modifications of an existing device, demonstrated equivalence to CE-marked device, placed on the market under Directive 90/385/EEC or Directive 93/42/EEC for which sufficient clinical data is already available, and specific exemptions laid down in Article 61(6)(b).
The European MDR is a taste of how the regulatory environment for medical devices will be changing over the next decade.
The newly published ISO 13485:2016 and the MDSAP Program are already pushing for greater standardization and stronger post-market surveillance requirements, along with process-oriented risk management and a life-cycle approach to device management.
If you could like to discuss medical device regulations, please contact AQF today.