Europe’s Medical Device Regulation: Get to Know the Basics

The regulatory landscape for medical devices in Europe is undergoing some major changes. Published in May 2017, the new European Medical Device Regulation (MDR) (Regulation [EU] 2017/745) and In Vitro Diagnostics Regulation (IVDR) (Regulation [EU] 2017/746) is gradually replacing the Medical Devices Directive and the Implantable Medical Devices Directive in the European market.

Although the MDR officially went into effect 20 days after publication, manufacturers, notified bodies, and those working with them will have a 3-year transition period to fully comply with a deadline of May 26, 2020. Likewise, these entities will have a 5-year transition period for the IVDR with a deadline of May 26, 2022, for full compliance. After these dates, no new applications under the former Directives will be accepted. Despite the lead time, there’s a lot of ground to cover. Proper gap analysis and an operationalized approach is key for making this transition a smooth one.

New MDR, New Opportunities

Why the big change? The MDR came about because of the vastly different interpretations and implementations of the previous Directives, as they were applied as per national requirements. This lack of standardization is believed to have played a role in the PIP silicone breast implant scandal. Under the MDR, regulators hope to ensure greater uniformity and consistent high standards, restoring patient confidence and ensuring their safety.

With much more stringent requirements on all parties concerned and greater oversight, the MDR creates the opportunity for advanced planning and operational applications for manufacturers and their representatives. Clinical research organizations (CROs) like Premier can help manufacturers and notified bodies implement the new regulations.

International CROs are especially poised to meet these needs. By thinking globally, manufacturers and their representatives can apply MDR requirements with a global program and study environment in mind. Identifying and utilizing data found in previously conducted trials elsewhere may, however, help to reduce the workload necessary for providing clinical evidence under the new regulations.

CROs should also explain to clients the advantages of risk-based monitoring approaches and adaptive designs, which are favored under the new MDR. Clinical evaluation-related services, such as report preparation and gap analysis, are likely to be in high demand from both existing and new medical device clients. Detailed planning and focus on the work behind the Clinical Evaluation process is required, with solid transparency on the resulting CER.

If you’re new to the world of European medical device regulations, here’s a quick basic primer of its current regulatory pathways.

What is CE Marking?

CE marking indicates that a product meets the regulatory requirements set forth in Europe. CE certification covers a wide range of products from home appliances to children’s toys. In the context of clinical research, CE marking must also be obtained to bring medical devices and in vitro diagnostic devices to market in the European Economic Area. This market includes all European Union Member States, as well as Iceland, Liechtenstein, Norway, Switzerland, and Turkey.

What are Notified Bodies?

CE marking is designated by a notified body. A notified body is an independent entity responsible for conducting a conformity assessment under Directives — and soon the new Regulation. This process often includes an audit of the manufacturer’s quality system, as well as a review of relevant technical documentation to support the safety and performance claims of the device.

Manufacturers are free to choose which notified body to bring their products to. For example, a manufacturer with a new implantable pacemaker may wish to have a notified body with a long history of assessing similar devices to evaluate their product.

Accreditation Under MDR
There are currently more than 70 notifying bodies assessing conformity under the Medical Device Directives, which includes on-site audits of the manufacturer’s quality system. A major change brought by MDR is the stringent certification requirements for notified bodies. Although potential MDR-accredited notified bodies were first allowed to apply for designation under the MDR and IVDR in November 2017, at the time of writing, none have been approved.

The transition to MDR requires diligence on all existing CE-marked certificates with effective dates varying based on the product. Once MDR is fully implemented, there will be a much greater workload for notified bodies. At the same time, there is likely to be a dip in the number of notified bodies due to the new accreditation process. In fact, some notified bodies are already informing manufacturers that they will not be applying for MDR accreditation. This perfect storm sets up a serious logistical challenge for getting new medical devices to the EU market, also, for arranging re-certification for previously certified devices.

Role of CROs
From an operational perspective, early planning to address this future problem is key. Manufacturers will need to engage in early, effective, and frequent communication with notified bodies. However, notified bodies cannot serve as consultants to manufacturers, which can make troubleshooting applications difficult. However, CROs can work together with both entities to facilitate communication, ensuring regulatory compliance and faster approval. Additionally, with a very different pool of notified bodies to choose from, CROs may be consulted to help clients identify the right notified body for their products.

Brexit’s Consequences
Further complicating this transition period is the UK’s plan to leave the EU, as CE marking can only be given by EU-based notified bodies. If the UK leaves the EU, all UK-issued certificates will become void as of March 29, 2019. Additionally, the current prime minister has indicated that the UK would not seek permanent membership as part of the European Economic Area. If this occurs, there will be serious changes to how medical devices are approved for market in the UK. Companies will likely turn to CROs to properly apply any new UK regulations.

Universal Impact

In addition to changes in notified body accreditation, the MDR will have a major impact on literally every other aspect of medical device development. Some other key changes include:

Clinical Evidence
Much stronger clinical evidence will be needed to demonstrate safety and efficacy. Under MDR, less equivalence data will be allowed. This means manufacturers will need to provide more actual data for high-risk devices, even when similar products have already been approved. For products undergoing recertification, strong post-market safety and performance data will also be necessary.

Pre-market Processes
MDR implements a new scrutiny process that involves stricter early control for high-risk devices. During this process, Responsible Persons and Authorized Representatives should be designated for manufacturers, serving as a liaison to national Competent Authorities. The role of a Responsible Person is analogous to that of a Qualified Person in drug regulations.

Also during the pre-market phase, authorities may re-review technical documentation prior to CE approval of high-risk devices. Article 54 as advised by Dr. Akra – to be verified requires notified bodies to submit new technical review reports, which could potentially impact submission timelines.

Post-Marketing Safety and Vigilance
One focus of the MDR is on increased transparency, which will be accomplished through the establishment of a comprehensive EU medical device database. The MDR also introduces greater traceability through a system using Unique Device Identifications (UDIs). This is another place where planning globally is helpful; similar UDI systems are being adopted in most markets over the next few years, and a single UDI may be used in all of them.

To ensure compliance, CROs will need to evaluate their clients’ post-marketing safety data, along with post-market clinical follow-up strategies and protocols. Likewise, implant cards will need to be evaluated or prepared for implanted devices. Under the Regulations, these wallet-sized cards containing vital medical device information must be given to all patients receiving implants.

Additional Governance and Oversight
To ensure compliance, peer reviews and expert panel evaluation will likely be an important aspect of implementing MDR. A CRO working with a manufacturer may be responsible for putting them together.

Aesthetic device manufacturers who previously did not require medical device CE approval will also need assistance. Under MDR, certain aesthetic devices that, although not covered under the Directives, have the same characteristics and risk profiles as analogous medical devices, hence will need to meet medical device requirements.

Finally, the new risk classification system for in vitro diagnostic medical devices will need to be taken into account. Of special note, Class IIb devices will now require product-specific certificates.

Operationalizing the MDR

The only way for success in the new European medical device market is to embrace these upcoming changes. This means early engagement of operational teams, which allows for a fast-paced environment for study planning. As soon as data becomes available, the appropriate processes should be applied to address gap analysis results. Ultimately, understanding and implementing the new MDR requires the creation of new partnerships between all stakeholders in device development.

Late last year, the European Commission and Competent Authorities for Medical Devices (CAMD) issued a roadmap for MDR/IVDR implementation. The CAMD is a newly formed umbrella group with the mandate to enhance collaboration and improve market surveillance in the single EU device market. This document provides key insights for operationalizing these new requirements over the next few months and years.

Greater Focus on Clinical Evaluation

For those involved in product development, the emphasis on clinical evaluation is likely MDR’s biggest impact — and greatest operational challenge. If you have any questions about MDR clinical evaluations, check out our next post.