News Updates
- Benefits of Integrating Patient Engagement with Diversity, Equity, and Inclusion in New Medical Product Development: A Call for Action
- Drug Shortages in the Global South: A Proposed Parallel Tech and Reg Transfer Framework
- Fair Pay for Patient Engagement: Navigating the Evolving Landscape of Remuneration
- Industry’s Window to Express Interest in Africa Continental Product Evaluation Pilot Closes End of February 2024
- The Importance of Regulatory Due Diligence During the Acquisition Process
New EU Medical Devices & In Vitro Diagnostic Regulations
Transition and Impact: The New EU Medical Devices and In Vitro Diagnostic Regulations
Introduction
The EU Commission has just finalized the new Medical Devices Regulation (MDR) and In Vitro Diagnostic Regulation (IVDR). The regulations will likely enter into force this summer as there are still some formalities that must be completed before publication.
These two regulations will provide a new regulatory framework for medical devices in the EU for the coming decades. They initially started as modest mid-life updates to the three EU medical devices directives but were considerably revised following a political move for more centralized and premarket controls on higher risk medical devices.
The regulations will cause important changes for all companies in the field and will harmonize a number of things that are currently not yet harmonized or harmonized informally by means of the MEDDEV guidances or other interpretative notices, or dealt with quite differently between Member States.
Common Features
The IVDR shares the majority of its new features with the MDR proposal. There is so much overlap that the Commission considered integrating the proposals into one text, but in the end decided against it because of the different nature of the devices concerned. The most important and imminent change under both regulations is that all medical devices currently on the market have to be re-assessed in accordance with the MDR and IVDR standards, and that this must happen before the transitional periods end. There are some limited exceptions (discussed below) but, generally speaking, companies should plan to revise the CE marking of every medical device that they currently have on the market within three (MDR) or five (IVDR) years from now. The EU will not provide grandfathering, so devices that have not been CE marked under the new standards by the end of the transitional periods can no longer be placed on the market.These new regulations will also introduce the EUDAMED database, the IT backbone for the EU medical devices regulatory framework. This database will unite all information currently spread out over various national competent authorities and contain systems for Unique Device identification (UDI) and registration of all manufacturers and authorized representatives, which provide the basis for databases containing all CE certificates, vigilance information, market surveillance information, and clinical investigations information The regulations will impact the entire medical device supply chain, as opposed to the current regulation of the manufacturer only at EU level.
Both regulations can and must be significantly amended by delegated and implanting acts to make them fully operational. For example, the functioning of and interaction with EUDAMED as well as the specifics of EU UDI must be further specified in implementing and delegated acts. The regulations also contain a regime for parallel imports and repackaging based on case law in the field of medicinal products.
All notified bodies will lose their notification by the end of the transitional period and thus have to re-apply for notification under the MDR and/or IVDR. The MDR and IVDR notification is subject to much more rigorous scrutiny than the notification under the current directives used to be; thus, it may be that a company’s notified body will not be re-notified under the MDR and/or IVDR, the consequence of which is that the company will need to transition to another notified body for its MDR or IVDR certificates.
Both regulations require a lot of administrative transition work. They prescribe, for example, a mandatory technical documentation format that is different from many currently used technical files. Also, there is a mandatory declaration of conformity format that may be different from the current declaration of conformity used by the company.
The MDR and IVDR will centralize the EU regime for clinical investigations for medical devices, which up to now was full Member State competence. The system put in place is much inspired by, and similar to, the EU Clinical Trial Regulation. There is a strong emphasis on postmarket clinical data, which is reflected in the obligation of manufacturers to establish a post-market surveillance plan and a post-market clinical follow-up plan, with (trend) reporting requirements that increase with the risk class of the device. Finally, the regulations contain a regime for advertising of medical devices and product liability provisions in addition to those under the EU Product Liability Directive.
The Medical Devices Regulation (MDR)
The MDR integrates the Medical Devices Directive and the Active Implantable Medical Devices Directive. It has a significantly extended scope, covering, for example, products for cleaning, sterilization and disinfection of medical devices, plus a broader concept of accessories and products with a risk profile similar to medical devices but not having a medical intended purpose, such as invasive laser equipment. The Commission also proposed to include products manufactured utilizing non-viable human tissues or cells, or their derivatives, closing a long-standing regulatory gap.The MDR features a number of new instruments, such as an EU-level borderline products decision mechanism, a scientific advice procedure for high-risk devices and an EU level review of clinical evaluation for certain high-risk devices. Other novelties are the regime for hospital-produced devices and the reprocessing regime for single-use devices.
The MDR will require companies to invest significantly in additional clinical data for existing and new devices, compared to current requirements, under the MEDDEV guidance on clinical evaluation. Additional clinical data must be presented in the newly-prescribed technical documentation format, which will require companies to completely overhaul their current technical files.
While existing conformity assessment procedures do not significantly change, more conformity assessment procedures are added (for example, for so-called substance based devices – devices that are absorbed or dispersed in the human body). The classification rules do change considerably for some devices, such as substance-based devices, standalone software and devices containing nanomaterials. These devices can fall in (sometimes much) higher risk classes than currently under the Medical Devices Directive.
The In Vitro Diagnostics Regulation (IVDR)
Apart from the new elements shared with the MDR proposal described above, like the new supply chain regime and a central database EUDAMED, there are a number of major developments in the IVD field. The IVDR contains a number of novelties, such as a regime for diagnostic services provided at a distance, a regime for hospital developed test and a regime for companion diagnostics.IVDs will no longer be subject to the list-based system currently in the IVD Directive but to the risk classes developed by the Global Harmonization Task Force (GHTF), dividing the landscape of IVDs into risk classes A (low risk) to D (high public and high patient risk) with seven classification rules. This is a major change because the conformity assessment routes for IVDs are amended in the sense that IVDs that do not fit any of the other classification rules now have to be certified by a notified body.
Under the IVD Directives, such IVDs fall into the category that can be self-certified, but under the IVD Regulation these IVDs must be certified by a notified body, because they end up in class B rather than A (the risk class that can still be self-certified). Combined with the new risk classification methodology, this will lead to a quantum leap increase of IVDs that require notified body certification compared to the current situation. While currently only 20% of the IVDs are notified body certified, this will increase to about 80% under the IVDR. This means that the majority of IVDs that have been on the EU market as self-certified will have to be certified by a notified body under the IVDR. Updating the technical documentation and underlying (clinical) performance data will be a challenge for many manufacturers, who will be required to produce significantly more clinical evidence for their IVDs by means of clinical performance studies. The IVD Regulation will provide for a regime regulating the conduct of interventional clinical performance studies and other clinical performance studies where the conduct of the study, including specimen collection, involves invasive procedures or other risks for the study subjects. The clinical performance studies regime is largely similar to that under the MDR, which is in turn inspired by the EU Clinical Trials Regulation.
It is crucial for manufacturers with IVDs on the market to assess what clinical evidence will likely be required, how long it will take to generate this evidence, and to plan ahead for notified body slots for conformity assessment before the expiry of the transitional period.
Transitional Regime
Companies need to prepare to deal with all the changes described above in a proactive and timely manner to avoid having certificates suspended or revoked because they were unable to comply with the new legislation in time.The transitional regime is centered around the transitional period of three years under the MDR and five years under the IVDR. During the transitional period, the notified bodies will still be able to grant certificates under the medical devices directives. However, these certificates are limited in the period of time that they can overrun the end of the transitional period: four years maximum for medical devices and two years for IVDs. In addition, devices on such overrunning certificates may not change anymore past the end of the transitional period. In addition, devices that are placed on the EU market during the transitional period may still be sold off for another five years after the expiry of the transitional period.
A big problem that arises is that, as a result of the re-notification process for notified bodies, it will be at least half way through the transitional periods before companies will be able to apply for new CE certificates under the new regulations. It is expected that this will create a bottleneck that will adversely affect companies.
Conclusion
All devices currently on the market will need to be transitioned into the new regulations and a lot will change. This will require not only a lot of work in gap assessment and remediation, but also careful planning to not get stuck in the bottleneck for certification at the end of the transitional period. Companies should start preparing soon, to have the required additional clinical data and amended documentation ready in time for assessment under the new regulations, and to avoid not being able to place devices on the market after expiry of the old certificates.
This article originally appeared in the April 2017 Global Forum - read the entire issue.
To learn more about the regulatory environment in the EU, plan to attend sessions in the Regulatory Track at our DIA 2017 Global Annual Meeting.