Karen Hill

	Big changes are coming to European Union legislation for medical and in vitro diagnostic devices. Launching a major transition effort to the new regulations now is critical for remaining in the 27-country EU market-and will give organizations a competitive edge over the next three to five years. This transition effort should include assessing the financial viability of your pipeline under the new rules, expanding data collection capabilities, and locking in soon-to-be-scarce notified body resources.

	The new regulations replace earlier EU directives and add stringent new requirements for CE Marking of new and existing devices. On May 26, 2020, any new medical device certified in the EU must comply with the new requirements of the Medical Device Regulation (MDR). On the same date in 2022, any new in vitro diagnostic device must be certified under the new In Vitro Diagnostic Device Regulation (IVDR). In 2024, any device sold, and in 2025 any device put into service, must comply with the new regulations.

	While the deadlines seem far off, significant lead-time and resources will be needed to meet the new requirements. Among these are:

	â     Certification for about 90% of IVDs, up from about 10% today

	â     Reclassification of some medical devices, requiring certification for the first time for some types, and recertification under different rules for others

	â     Increased clinical data reporting for certification and recertification for most devices, and pre-approval clinical studies rather than equivalency statements for many new implants

	â     Post-market surveillance and performance assessment for most devices

	â     Unique device identifier numbers on labelling

	â     Increased liability for defective devices for manufacturers and distributors, meaning more insurance and greater scrutiny of outsourced production

	Additionally, the new rules change the role of notified bodies (NB) and what types of devices they may certify. Fewer NBs are likely to be available to review devices above Class I, or IVDs above Class A. As the deadlines approach, NB processing for both new and existing product applications likely will slow, possibly delaying market entry in some cases.

	Getting ahead of the curve is essential to protect existing revenues and market share, and presents an opportunity to grow.

	New clinical testing requirements for new and existing products will be expensive and time-consuming. So, will it be worthwhile?

	Conducting a “gap analysis” of the existing pipeline and product portfolio will help with this decision. The goal is to identify the additional costs and resources needed to certify or recertify products under MDR or IVDR.

	The first step is determining what risk class each product will be certified in under MDR or IVDR. Then determine what, if any, additional clinical testing, production process, technical file documentation, labelling or other changes will be required to conform.

	In most cases more clinical testing will be needed. This may be challenging for makers of IVDs, most of which did not require clinical testing under previous EU rules.

	IVDR introduces a new, risk-based classification system, from A through D. It requires clinical testing for all IVDs above the lowest-risk Class A-which includes only products for general laboratory use, lab instruments, and specimen receptacles. As a result, about 90% of IVDs will now need clinical testing, compared with about 10% today.

	IVD manufacturers that have not done clinical testing before will have to develop the capability to do so. Further complicating the issue, the clinical evidence required for IVDs is more complex than for most medical devices. In addition to documenting that the test itself is valid, it must show that the test is necessary for making a medical decision that can significantly affect treatment decisions and patient outcomes. Developing this evidence will take time, money and expertise, adding cost to development programs.

	MDR requires clinical testing for most medical devices, including a proactive post-market surveillance program. Also, it entails clinical testing for re-certification of devices already on the market, if the current clinical data does not meet the new requirements. This will increase the cost of introducing new devices and maintaining legacy devices.

	Next, the second step of a gap analysis is to assess the cost of these changes and how they will affect profitability, allowing manufacturers to reconfigure portfolios accordingly. An analysis may indicate it’s time to drop marginal products with ample competition and focus on preparing packages for new, more targeted and profitable devices.

	There are many opportunities in testing as well. MDR and IVDR require uniform performance data reporting to a central database, making it easier for insurers and health system buyers to compare product performance head-to-head. As a result, any product that can show a clear performance edge could gain a decisive market advantage. Insurers, national health plans and other payers require this kind of real-world evidence to approve coverage of new devices and tests. Given growing payer preference for data submitted early to certify under MDR and IVDR could give organizations a market edge.

	However, it could expose the weakness of certain offerings, and is important to consider in deciding which portfolio and pipeline projects to pursue.

	Tailoring products to defined needs of specific patient populations and indications, and developing clinical test strategies that clearly demonstrate effectiveness for these populations, will help to gain and press market advantage under MDR and IVDR.

	The new EU regulations will create backlogs with Notified Bodies and may result in delayed certification reviews. This lag is caused by the MDR and IVDR change in the role of NBs, and their relationships with manufacturers, national competent authorities and EU officials.

	Previously, NBs functioned as consultants, helping manufacturers meet CE Mark requirements. Now they will act as the primary enforcers of the new regulations. Among other responsibilities, they will be tasked with reviewing clinical data submissions, submitting clinical evidence packages to expert panels, and conducting occasional unannounced inspections of manufacturer’s facilities, suppliers, and subcontractors.

	Furthermore, NBs will be designated by the European Commission to evaluate any device above Class I or IVD above Class A. The designation process begins in November 2017 and is scheduled to last six months. However, given the volume and complexity of the task, and the European Commission’s limited resources, it could take significantly longer, delaying the date on which some NBs can begin reviewing products.

	NBs will be restricted to evaluating only specific categories of devices for which they show expertise. As a result, there will be fewer NBs available to approve some devices, particularly those in higher risk classes. This could delay approvals. So, if a manufacturer currently uses NBs not redesignated for their devices, they will need to find new ones.

	The greater volume of data NBs must review will lengthen reviews, and will make them more expensive. The bottleneck created by fewer NBs with higher workloads could lead to long waits before reviews even begin.

	Therefore, the best strategy is to move early. Assess NB needs based on the types of devices produced. Ensure prospective NBs are or will be designated to review specific products. Coordinate a development plan with NBs to ensure timely access. This strategy will not only ensure products get to market and remain there, but also could result in slower competitors losing out at the back of the queue.

	Beyond jumping on certification planning and securing NB resources early, several other strategies can help keep medical and IVD device development on schedule, while meeting the new clinical testing and performance reporting requirements. These include:

	â     Integrating performance testing with early stage development. For example, parallel open-label testing of devices in broader populations for clinical and economic outcomes, such as the impact of a device on the use of other medical services, alongside any narrower clinical study needed for CE approval

	â     Incorporating adaptive design elements into clinical trials that may accelerate development by combining trial stages, and may enable a continuous learning development process in which data from earlier device versions support applications for new variations

	â     Automated data collection using electronic health records, which can reduce data collection costs while broadening the scope of data collection, especially for post-market surveillance

	â     Risk-based monitoring of trials and post-market surveillance, which can help spot protocol deviations or device performance issues early, enabling quick corrections to bring trials and the entire development process back on track

	MDR and IVDR have profound implications for device manufacturers that will affect every aspect of development, production, distribution and follow up. While a complex undertaking, developing an action plan that addresses these issues early will pay big dividends in the end.

 is Senior Manager, Regulatory Affairs, both with the Medical Device and Diagnostics Research division of ICON plc.

	1. Regulation (EU) 2017/745 Of The European Parliament And Of The Council of 5 April 2017 on medical devices, amending Directive 2001/83/EC, Regulation (EC) No 178/2002 and Regulation (EC) No 1223/2009 and repealing Council Directives 90/385/EEC and 93/42/EEC. Official Journal of the European Union, May 5, 2017. http://eur-lex.europa.eu/legal-content/EN/TXT/?uri=CELEX:32017R0745

	2. Regulation (EU) 2017/746 Of The European Parliament And Of The Council of 5 April 2017 on in vitro diagnostic medical devices and repealing Directive 98/79/EC and Commission Decision 2010/227/EU. Official Journal of the European Union, May 5, 2017. http://eur-lex.europa.eu/legal-content/EN/TXT/?uri=CELEX:32017R0746

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The EU is launching a major transition within their legislation for medical and in vitro diagnostic devices. This transition is important and should include assessing the financial viability of the pipeline, expanding data collection, and locking in soon-to-be-scarce notified body resources.

Karen Hill

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