‘The Medical Device and In Vitro Medical Device Regulations represent the most significant change to European legislation for medical devices in over 20 years’ (Hoxey). As of the fifth of May 2017, new MDR and IVDR regulations have been approved and published by the European Commission. The new regulations will replace the directives; MDD, AIMD, and IVDD with two new regulations; The medical device regulations (MDR) and the In-vitro device regulations (IVDR). The medical device regulations are expected to come into effect in mid- 2021. ‘The release of the new Medical Devices Regulation (EU-MDR) in the Official Journal of the European Union in May of 2017 marked the start of a three-year transition period for manufacturers, suppliers, Notified Bodies, and national Competent Authorities to comply with the new Regulations that took effect in May of 2020. The scale of the changes made is significant, putting pressure on all impacted parties to closely examine the MDR, assess the impact it will have on their own organisation, and implement compliant processes and procedures accordingly.’ (The FDA Group, LLC)
This change comes after 25 years and was initiated by scandals such as the PIP Breast Implant Scandal in 1991. ‘These directives, introduced in early 1992, have worked well and helped create the single market for medical devices in Europe. However, the directives had some inherent weaknesses and the changes in technology and medical science demanded changes in legislation. These shortcomings challenged national member states and the interpretation of the directives was not consistent across all national governments. Directive 2007/47/EC modified the MDD and AIMDD in an attempt to address these concerns, but this amendment did not achieve all goals. The scandal involving defective breast implants manufactured by Poly Implant Prosthesis (PIP) in France demonstrated additional structural weaknesses in the system.’ (Loh PhD, RAC (US/EU) and Boumans Msc)
The Medical Device Regulation (MDR) is composed of 10 chapters, 123 articles and 17 Annexes over 175 pages will replace the 23 articles of the Medical Device Directive (MDD) in May 2021. MDD, AIMD and IVMDD certificates will no longer be valid after May 26th 2024 for placing products on the EU market, and after May 26th 2025 for putting products into service in the EU.
The following paragraphs will summarize the main changes that will occur because of the change to the MDR.
Promotes a Shift from the Pre-Approval Stage to a Life-Cycle Approach
The MDR has two dedicated articles to post market surveillance, Article 85; Post-market clinical follow up (PMCF) and Article 86; Periodic safety update report. Post market clinical follow up will allow for the device is reviewed continuously throughout its lifecycle and ensure that the device remains acceptable. The life-cycle approach will allow for more vigilant surveillance, trend reporting and enforcement activities. ‘The lifecycle activities associated with clinical evidence for a medical device include:
- establishing clinical evidence through premarket clinical evaluations or clinical investigations;
- preparing and maintaining clinical evaluation reports (CERs);
- planning and conducting post-market clinical follow-up (PMCF), or documenting a justification why it is not applicable;
- planning and conducting PMS;
- documenting periodic safety update reports (PSUR) for:
- class II and class III medical devices, and
- class C or D IVD devices
- documenting PMS reports for:
- class I medical devices, and
- class A or B IVD devices;
- publishing a summary of safety and clinical performance (SSCP); and
- maintaining the risk-benefit analysis up-to-date based on the latest information’ (Hoxey)
Products will now be classified in a new risk-based classification system A, B, C, and D (lowest risk to highest risk respectively) and classes B through D require an assessment of the technical documentation by a notified body. In Annex VIII there are 22 classification rules. Of these 22 some have had minor changes such as wording, some have relevant changes and additions, some have substantially changed, and some rules are completely new in the MDR. This is mainly due to implantable devices and there is one new rule regarding software. These rule changes have created a more robust system for medical device requirements. ‘Some of the major classification changes include:
- Devices intended for the skin, through an orifice, absorbed or locally dispersed will be Class III
- Nanomaterial devices will become class III
- Total and partial joint replacements become class III
- IVF and ART non-invasive devices may be Class IIa or IIb.
- In vitro contact with cells and/or embryos returning to the body will be Class III.
- Reusable surgical instruments will no longer be self-certified Class I devices, but the newly created Class IR.
- AIMD accessories will be Class III.
- Devices that record diagnostic images will be Class IIa.
- Spinal implants will be Class III.
- Apheresis devices will be Class III.
In addition to classification changes, MDR lists specific types of products that, although not serving a “medical purpose,” will fall under the Regulation addressed in a Common Specification (Article 1, Annex XVI). These include the following items:
- All contact lenses
- All implants for cosmetic or anatomical modification
- Facial and other dermal or mucous membrane fillers
- Invasive laser equipment
- Pulsed light equipment
- Liposuction equipment’ (The FDA Group LLC)
Independent assessment bodies will come under stronger supervision by national authorities. They will need to seek approval for auditing against the MDR during the transitional period. This means there will be less room for outsourcing expertise and more clinical competence and expertise will be required in-house. ‘After reviewing the new MDR, there’s a long list of changes and actions that the industry can expect to unfold. Some of which are;
- Long queuing times at Notified Bodies – because they will be fewer;
- Notified Bodies, which stopped their activities or discontinued certification of certain devices or in certain regions;
- In-depth technical file assessments that have not been experienced so far;
- Unannounced audits;
- Product testing performed by Notified Bodies;’ (Smart-Trial)
As a result of these tighter regulations regarding assessment bodies, they will now be granted more power. Unannounced audits, sample checks, and rotation of notified body staff carrying out assessments will ensure more consistent compliance against the new MDR.
Better Traceability and Extended Eudamed Database on Medical Devices
Following in the FDA’s footsteps the Eudamed database under MDR will allow for better traceability. The new unique device identifier (UDI) will be composed of the device identifier (DI) and the product identifier (PI). Both the product and packaging must be UDI labelled so it can be used over the product’s entire lifecycle, which will enable a swift and effective response to safety problems. The database will also allow for the sharing of non-confidential knowledge. ‘Mandatory Unique Device Identification (UDI) is introduced with the intention to facilitate the traceability of devices. Devices will be allocated a device identifier (DI) and production series or batches will be identified with a production identifier (PI). The Basic UDI-DI must also be referenced in the Declaration of Conformity (DoC). Various databases for clinical investigations, product registration, and vigilance are introduced under the aegis of the EU Commission. Member States will have to issue a Single Registration Number to each EUDAMED user. As this is the gateway into EUDAMED, this is expected to be a complex and demanding process, which may take more time than anticipated.’ (Loh PhD, RAC (US/EU) and Boumans Msc)
Although conformity assessments in the MDR is essentially unchanged, MDR conformity assessments are likely to be, more demanding and a much longer process. This is down to two major changes from the MDD to MDR. In the new Annex I there are additional requirements for safety performance, technical documentation, Quality assurance, clinical evaluation, and post-market surveillance. There are additional requirements on notified bodies to consult with EU bodies and health authorities in Article 52. ‘Although the regulation may have many similarities with the MDD, the devil is in the details. The regulation will change the European regulatory environment as more stringent clinical data requirements, extended data management, more complex conformity assessment procedures (particularly for high-risk medical devices), and product liability and penalties will be introduced. NBs are already signalling they will not be able to process all this extra work, which may lead to compliant devices losing access to the European market.’ (Loh PhD, RAC (US/EU) and Boumans Msc)
The transition from MDD to MDR brings with it uncertainty but a promising development in the European medical device industry. Manufacturers will need to fully understand the requirements set out in the MDR and prepare for the imminent changes approaching. Manufacturers will need to perform gap analysis against their current systems, develop transition plans and allocate appropriate resources before the transition timeline elapses. ‘It might appear that there is plenty of time to implement the changes in vigilance reporting and PMS as they apply after CE marking a device to the applicable Regulation or at the end of the transition period – however, given the magnitude of change involved, it is prudent to start preparing for implementation as soon as possible. Timely preparation and implementation will allow you to understand fully the effect on your internal processes and accommodate external factors outside your direct control.’ (Hoxey)
- Hoxey, Eamonn. The European Medical Devices Regulations What Are the Requirements for Vigilance Reporting and Post-Market Surveillance? BSI, 2017.
- Loh PhD, RAC (US/EU), Evangeline, and Ronald Boumans Msc. UNDERSTANDING EUROPE’S NEW MEDICAL DEVICES REGULATION (MDR 2017/745) New Requirements, Key Changes, and Transition Strategies for Device Companies. July 2018.
- Smart-Trial. Navigating the EU MDR – Strategies for Success. MEDEI Aps, May 2018.
- The FDA Group LLC. THE COMPLETE GUIDE TO EU-MDR TRANSITION. a Playbook for Successful Revision and Implementation. The FDA Group LLC.