Five Lessons Learned Since MDR’s Implementation

The European Union’s (EU) Medical Device Regulation (MDR 2017/745) took effect May 26 (date of application), whereby all device manufacturers must be in compliance with certain aspects of the regulation if they intend to sell in the EU. Companies with a CE certificate under the Medical Device Directive (MDD) before the date of application are not required to conform with all aspects of the MDR until their CE certification expires or a significant change occurs in accordance with MDR Article 120(3). For some manufacturers, there may be an additional three years of breathing room, with the final deadline for full compliance on May 26, 2024 (based on the CE certificate expiration date or if they are leveraging the second corrigendum for the Class I reusable devices).

Lesson 1: Companies with an existing MDD certificate should pursue MDR certification ASAP.
Even companies with extra time to obtain MDR certification, the changes under MDR are significant and time-consuming; therefore, they should begin to address the requirements early. There are lengthy lead times to submit for MDR review with a Notified Body (not to mention some Notified Bodies are not yet MDR certified), and review times are prolonged over the “newness” of the process. In addition, all manufacturers will be submitting for MDR review during the same time frame, so companies would be wise to submit ASAP.

There were previously more than 50 Notified Bodies certified under MDD, but less than half are currently certified under the MDR. Estimated review times are nine to 24 months, depending on the Notified Body and point of contact. If there are questions from the Notified Body or additional testing or evidence is requested, the process is further extended, as the back and forth between the manufacturer and Notified Body is, at the moment, glacially slow.

Since the MDR certification process can be quite lengthy, it is in the manufacturer’s best interest to start the process now so they have their MDR CE certificate in hand before their MDD certificate expires. The same is true for manufacturers with a new device that must be reviewed under MDR before CE marking.

Lesson 2: The clinical evidence burden is not going away.
Under MDR, clinical evidence is required “of a sufficient amount and quality to allow a qualified assessment of whether the device is safe and achieved the intended clinical benefit(s), when used as intended by the manufacturer” (MDR Article 2(51)). Common gaps in this evidence include insufficient data on all devices/variants, indications, and/or anatomic locations, unanswered questions on long-term safety and performance, or instances where data are only available on the equivalent comparator.

MDR has tightened the equivalency standards, making it more challenging for manufacturers to obtain or maintain device CE marking via data on an equivalent comparator. Similar to the MDD, MDR requires that technical, biological, and clinical equivalence are demonstrated; however, per Article 61(3), “it shall be clearly demonstrated that manufacturers have sufficient levels of access to the data relating to devices with which they are claiming equivalence in order to justify their claims of equivalence.” For manufacturers with a legacy product that used an equivalence route of conformity with no potential internal equivalent comparators, obtaining “sufficient levels of access” to device data is challenging because it requires collaboration between two competitors. These manufacturers must collect data now to support safety and performance on their device under MDR. The same is true for manufacturers with a new product that falls into a well understood category of device class. If there is not a viable  equivalent device, a pre-market study might be necessary even if there are no substantive unanswered safety and performance questions for the device class as a whole. Because there are no data on the specific manufacturer’s device, safety and performance cannot be demonstrated per MDR. Note: There are opportunities for well-established technologies to use common specifications to support an initial application; however, no common specifications have yet been released.

Lesson 3: Brexit opens doors?
With the U.K. leaving the EU, MHRA is transitioning to a new approval system, specifically the UKCA (UK Conformity Assessed) marking. While the CE mark can be leveraged for existing products until June 30, 2023, new devices will require the UKCA mark in the U.K. The U.K. is currently working under MDD, so external equivalence may still be a viable path for manufacturers planning to enter the U.K. market.

Lesson 4: There is flexibility in PMCF and pre-market data.

For devices without sufficient clinical data to demonstrate conformity with the relevant General Safety and Performance Requirements (GSPRs), or if circumstances exist where a PMCF study is indicated, the path forward can be burdensome. Since the requirements for devices to claim equivalence are fairly non-existent for manufacturers without an internal equivalent comparator, a pre-market study and/or post-market clinical follow-up activity(ies) is likely required. The design of these clinical activities can be flexible, depending on the existing level of evidence, device and technology history, and risk classification.

There are many different activity types sufficient to meet MDR requirements if companies can adequately address unanswered safety and performance questions. PMCF activities can include retrospective data collection, observational or registry studies, and even user surveys for more well-established technologies with well-understood risk/benefit profiles and sufficient clinical evidence. In fact, observational studies provide manufacturers a proactive method to address the MDR PMCF requirement for identifying possible systematic misuse or off-label use. Post-market clinical follow-up activities are time-consuming to design and conduct, so if a manufacturer determines additional data are needed to support a legacy device under MDR, trials should be initiated immediately to ensure data are properly collected and synthesized before submitting for CE certification under MDR.

Accordingly, for devices marketed outside of Europe, where retrospective data may be available for collection (such as the U.S., Australia, or Canada), these data could be collected to support a pre-market CE mark application. The data must support safety, performance, and any intended clinical benefits or claims related to device use.

Lesson 5: Don’t forget the CER, PMS, SSCP, Risk File, Cybersecurity, etc.

Most medtech professionals are very familiar with the added burden of CERs under both MEDDEV 2.7/1 Rev 4 and the MDR. All devices, including Class I products, require a CER. Obtaining and synthesizing all cross-functional input and available data on the respective devices can initially be a months-long endeavor; however, once the CER has been built under adequate processes, future updates will be much more manageable.

Formal and methodical literature searches are necessary to obtain any articles related to the subject and/or equivalent device, as well as the current knowledge and state of the art for the relevant clinical conditions and treatment options. The state of the art discussion should include benchmark/similar devices and a quantitative assessment of the risks and benefits for each relevant treatment option. Formal search protocols should be detailed to allow for search reproducibility, including search terms, date ranges, and inclusion/exclusion criteria. These searches must demonstrate that data were adequately captured on the safety and performance parameters and therapeutic options without bias. Each CER is accompanied by a Clinical Evaluation Plan that identifies the relevant GSPRs and parameters to determine acceptability of the risk-benefit ratio, intended purpose, intended target group(s), intended clinical benefit(s), methods for examining device safety, data appraisal and analysis plan, and clinical development plan.

Another area expanded under MDR is the requirements for post-market surveillance (PMS) and vigilance/trend reporting. “The post-market surveillance system shall be suited to actively and systematically gathering, recording and analysing relevant data on the quality, performance and safety of a device throughout its entire lifetime, and to drawing the necessary conclusions and to determining, implementing and monitoring any preventive and corrective actions…The technical documentation shall be updated accordingly” (MDR Article 83). Required documentation includes PMS Plans, PMS Reports/Periodic Safety Update Reports, Post-Market Clinical Follow-Up (PMCF) Plans, and PMCF Evaluation Reports for each device or device family. Additional requirements encompass reportable events (“serious incidents”), specifically what events must be reported and their disclosure timeline. Under MDR, manufacturers must have proper procedures and systems in place to demonstrate compliance. These surveillance requirements took effect May 26, 2021.

Besides the added PMS expectations, what was once sufficient for existing documents under MDD may no longer be adequate under MDR. For legacy products, an MDR review should be considered a new certification review and all documents will be re-evaluated for conformity with the GSPRs. Documentation that often falls short under current standards are the Risk Management File, Usability Engineering File, and Cybersecurity. These include risk management plans and reports for each device and/or device family, in alignment with EN ISO 14971, with clear traceability between the risk management and other technical documents (IFU, PMS, and CER).

Additionally, the MDR addresses expectations about the generation of the Summary of Safety and Clinical Performance (SSCP). The SSCP must be updated in conjunction with the processes for the CER/PMS/PMCF. There must be two sections: one for healthcare professionals and one for patients. Once the European Database on Medical Devices database goes live (expected May 26, 2022), the SSCP will be available to the public. 

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Hannah Irwin supports MCRA’s Regulatory Affairs department with drafting, compiling, reviewing, and maintaining regulatory submissions, focusing on Clinical Evaluation Reports. She helps draft and submit regulatory documents to the FDA on medical device submissions and handles strategy, analysis, and development of medical devices as it relates to Notified Body and FDA approval. Before joining MCRA, Irwin worked in clinical and regulatory affairs for a medical device company and performed research for a biotech company.

Michelle McDonough leads the International Regulatory team for MCRA with significant expertise in assisting clients in remediating files to meet the new European Medical Device Regulation. Michelle develops and implements strategies for international and U.S. regulatory submissions for orthopedic, spinal, and cardiovascular client companies including 510(k)s, PMAs, IDEs, pre-submissions, technical documentation, and clinical evaluation reports, as well as, the management, design, and implementation of pre- and post-market clinical studies.