THE SKINNY: The Council of the European Union adopted the proposed new European Medical Device Regulation (EU MDR) in March 2017 and passed by Parliament in April 2017. It is expected to be published in the Official Journal of the European Union in the upcoming weeks, making the application date mid-2020. The EU MDR will replace the Medical Device Directive (Council Directive 93/42/EEC) and the Active Implantable Medical Device Directive (Council Directive 90/385/EEC). Among the vast changes occurring with this transition from directive to regulation are the new requirements surrounding clinical evidence. If you found the clinical portion of your technical documentation to be challenging in the past, you need to prepare for some additional hurdles.
~ Note: This post is just a taste of the detail we'll explore during our R&Q Intelligence Series webinar on EU MDR April 25th at 1:00pm EST. All registrants will have access to the slides and recording from the session.
The intent, equivalence, and clinical risks
The intent of the new requirements is respectable. Historically, the European Commission’s approach to medical device governance was seen by some as laissez-faire in comparison to its regulatory agency counterparts in countries such the United States, Canada, Japan, Australia, and Brazil. One of the key objectives of the new EU MDR is to ensure a high level of health and safety protection for EU citizens. Making clinical investigation and evaluation requirements more stringent is aimed at improving health and safety through transparency and traceability.
Using clinical justifications based on device equivalence has been a standard practice for decades. With the advent of the MDR, equivalence is going to be less accepted, particularly for higher risk devices. Even with lower risk devices, equivalence arguments may be harder to make and you can expect to be challenged by your notified body. You will be expected to show that the device has the same technical, biological, and clinical characteristics, and demonstrate that you have sufficient access to the data on that equivalent device. For implants and Class III devices that includes an agreement to access technical documentation for the equivalent device.
In the past, it was common to have risk management files and clinical evaluations as separate, stand-alone documents. The EU MDR expects risk management and clinical evaluation be interdependent processes, calling for careful alignment of the risk management system with the clinical evaluation. The expectation is that clinical risks will be addressed in clinical investigations, clinical evaluations, and post-market clinical follow-up.
Eudamed, the European database on medical devices, will become a public tool. Up until the EU MDR’s debut, the Eudamed database was an information repository exclusively accessible to national competent authorities and the European Commission. The EU MDR is now mandating use of this web-based portal for economic operators and notified bodies to provide data related to various Articles of the MDR including clinical investigations and summaries of safety and performance for Class III and implantable devices. The database is expected to be ready by the application date in mid-2020 and could experience delays. If it is not finished on time, manufacturers will have 6 months to populate the database after it is fully functional and a notice has been published.
Clinical evidence is not a new requirement. Under the MDD, lower risk devices were required to have clinical evaluation reports (CERs) and higher risk devices needed clinical data. CERs are still required (EU MDR Annex XIV, Part A) but the content and acceptability is changing. In addition to CERs, a public summary of safety and clinical performance (EU MDR Article 32) is now required for certain types and classes of devices. This summary is expected to consider diagnostic or therapeutic options addressed in the CER and diagnostic/therapeutic alternatives. Class III and implantable devices are expected to have clinical data derived from clinical investigations that were conducted under the supervision of a sponsor. Those clinical studies need to follow Good Clinical Practices (GCPs) such as those outlined in ISO 14155:2011 and the Medical Association Declaration of Helsinki on Ethical Principles for Medical Research Involving Human Subjects. And don’t forget that any data produced by the clinical study must be done in accordance with Article 8 of the Charter of Fundamental Rights of the European Union which governs personal data protection. One exciting change will be the ability to submit a single application for a study that covers multiple member states but the implementation of that rule doesn’t occur until after ten years after entry into force (2027). The new EU MDR is chock full of clinical investigation requirements.
The bar has been raised
The bar has been raised on not just the requirements surrounding clinical evidence, but the level of examination now expected. For example, the regulation outlines a clear expectation for notified bodies to provide a clinical evaluation assessment report (CEAR). However, for some specific types of devices, an analysis of the notified body’s CEAR by “expert panels” will be obligatory. It is further expected that the Competent Authorities be notified of any device that receives a certificate post-conformity assessment involving an expert panel so that Common Specifications can be developed for specific, higher risk devices.
But expert panels are not just going to be reviewing CEARs. They are expected to be busy with voluntary consultations by manufacturers to provide input on clinical development strategies and clinical investigation proposals prior to having their clinical data reviewed as part of conformity assessment.
The EU MDR is setting the stage for busy times ahead and clinical evidence plays a big role. While some requirements of the MDD carried over into the MDR, it is safe to say that the clinical support piece needs to be re-evaluated sooner rather than later.
- CERs need to be reassessed considering limitations on equivalent devices, state of the art and updated to withstand a higher level of scrutiny from the Notified Body level and above. Updates to CERs may also trigger updates to Instructions for Use; make sure they are in alignment.
- Clinical investigations must be conducted within the constructs of the new legislation (EU MDR Annex XV) and recognized ethical principles. They must also align with the clinical evaluation plan.
- Post-market clinical follow-up (PMCF) will no longer be a “check-the-box” activity. As a matter of fact, Annex XIV Part B of the EU MDR is dedicated to PMCF. Notified Bodies will be looking for “living” PMCF plans and reports.
- The summary of safety and clinical performance must be updated “at least” annually which means a more frequent assessment could be expected.
The EU MDR will apply by mid-2020 (three years after it is entered into force). Product certificates to the MDD will no longer be issued after the full application date but existing certificates will be honored until the expiry date up to four years after the full application date. However, given the guarantee that all clinical support documentation is going to need to be re-evaluated and revised to meet the new legislative criteria, coupled with the realization that Notified Bodies are going to be inundated, we need to embark on clinical compliance now.
For the entire scoop on the EU MDR, register for our R&Q Intelligence Series webinar on April 25th.