The European Union’s Medical Device Regulation (MDR) and In Vitro Diagnostic Regulation (IVDR) will replace the Medical Device Directive (MDD) and In Vitro Diagnostic Directive (IVDD) beginning with the MDR that takes effect May 26, 2020. The IVDR compliance deadline is May 26, 2024. The new regulations are intended to increase the transparency and stringency of the approval and usage of medical devices while also improving patient safety and outcomes.
Under the new regulations, medical devices and in vitro devices must receive a CE Marking (the symbol for European conformity) certificate by the set deadlines. With the MDR compliance deadline quickly approaching, medical device manufacturers the world over are seeking greater insight and information on how they can bring their devices into compliance.
Apsalys, a life sciences quality and compliance consultancy company based in France and a value-added reseller partner of MasterControl, recently conducted a Q&A with MasterControl subject matter experts Alex Butler and Bryant Headley to gain greater clarification on issues surrounding the MDR/IVDR.
Butler: The MDR is four times longer than MDD and the word “safety” appears 290 times in the new regulation as opposed to 40 times in the MDD. That should give you some idea of the breadth and depth of the MDR and, therefore, the sizable changes that come with it. Key changes that interest me are that most companies will need to update legacy products to the new standards and provide more clinical evidence with stricter guidance around equivalency standards. The definition of a medical device is also expanded to include non-medical devices and cosmetic devices that weren’t previously regulated. These are good changes, and though the industry is struggling with the implications, I think we can all get behind better safety and performance standards.
Headley: The EU MDR impacts medical device manufacturers in the following areas — introduction of a unique device identifier (UDI) system; general safety and performance requirements; technical documentation; classification rules; conformity assessment procedures; and clinical investigation. There’s also increased requirements for premarket and postmarket regulatory obligations, more dialed-down risk management requirements, new Notified Body (NB) accreditation obligations, and new conditions for quality management system (QMS) compliance. There’s no doubt the changes with the MDR are substantial.
Butler: Yes, and there’s a lengthy process to update each manufacturer’s product. Gap assessments must be done on the current CER and plans implemented to meet the new requirements. CER authors must be proficient in many disciplines — development, clinical, regulatory and postmarket. Single-disciplined individuals or departmentally-siloed reporting will not suffice under the MDR. CERs need to tie the whole story together.
Headley: Also, the documentation approved by the NBs in the past is not accepted any more. The level of the technical documentation has started to increase, and the NBs are asking for far greater detail than previously required under the MDD. We’re already seeing the effects of this as no more than five or six NBs have designated against the MDR to recertify devices even though the European Commission expects there to be 20 MDR-designated NBs by the end of 2019. This potential shortage of NBs is something to keep an eye on.
Butler: There are much stricter guidelines around equivalency. Equivalency without supporting clinical evidence has been misused in the past to get products to market faster. This has had devastating results in terms of device safety and efficacy for patients and customers. It will be almost impossible to leverage a competitor’s clinical data under the MDR.
Headley: And where equivalency requirements were less defined under the MDD, the MDR specifies that clinical data provided by a manufacturer must be an equivalent or similar device. The new regulation also identifies specific criteria for evaluation of an equivalent device to be used as clinical evidence. Section 3 of Annex XIV of the MDR requires that a device a manufacturer claims equivalency for needs to share the same technical, biological and clinical characteristics; so greater evidence must be submitted. And by and large, devices that lack a CE Marking will not be accepted for equivalency under the MDR.
Butler: Companies need to plan for and report how they will address PMCF. This means negotiating with an NB to make sure the plan meets new standards. This also implies changes to the clinical evaluation reports. Manufacturers will also need to design and run PMCF studies to confirm device safety and clinical performance, ensure continued acceptability of identified risks, and detect emerging risks of the basis of factual evidence.
Headley: Under Annex XIV (Clinical Evaluation and Post-Market Clinical Follow-up) of the MDR, PMCF data will have to be provided for high-risk medical devices when the long-term safety and performance data is not yet available or in situations where certification by the European Commission is dependent on equivalence. As such, a company’s clinical evaluation and risk management procedures will have to be revised to reflect the new requirements.
Butler: Unique device indicators (UDI) will be placed on the labels of all devices and provide device traceability under the MDR. The purpose of the UDI is so that serious incidents and safety corrective actions in the field can be reported. For implantable devices, an implant card with warnings, information about the expected device lifetime and necessary follow-ups will be required.
Headley: Also, the UDI enables data to be tracked to a specific device so that in the event of recall, each device affected can be speedily located and action taken. The UDI was created by the U.S. Food and Drug Administration (FDA) to be able to track and monitor devices throughout their life cycle.
Butler: The IVDR completely overhauls the classifications framework of the new regulation. It significantly increases the number of IVD devices IVDR covers and expands the scope of compliance. By far the biggest change is that the IVDR mandates NBs to review 80-90 percent of IVDs sold in Europe compared to the 10-20 percent of IVDs required under the IVDD. There are also no grandfathering clauses, and all IVDs must be certified against the IVDR by May 2022. Also of note, software as a medical device (SaMD) and apps are now considered IVDs and fall under the IVDR.
Headley: And instead of naming specific IVD devices or medical conditions, the IVDR categorizes the risk classification of a device by its intended purpose. The classification designation also takes into account the risk of the IVD to public health in addition to the risk to an individual, which is quite a departure from the IVDD. NBs will need to review all of the four classes of IVDs under the IVDR, including conformity assessments of Class B, C and D devices. As for Class I non-sterile/non-measuring devices, companies are now required to report data about their devices to the European Database on Medical Devices (EUDAMED). They will have to set up a QMS for these devices, but certification of the QMS is not mandated.
Butler: There will be more stringent requirements and greater management responsibility. A gap assessment will need to be done for a company’s existing QMS and new MDR-compliant requirements for a QMS. Manufacturers will need to ensure that devices in production remain in conformity and that changes to device design or harmonization standards must be quickly addressed. The new QMS requirements also serve to further remove the organizational walls between quality, regulatory and clinical. These departments will need to function as one with clear management responsibilities outlined.
Headley: I think it’s safe to say that the MDR will have a considerable impact on a company’s QMS. Quality managers should do a gap analysis based on the new regulations to make sure their systems are fully compliant. Manufacturers will also need to assess the impact of the MDR changes early during R&D, design development and design scale-up to ensure that the manufacturing and commercialization of the products comply with the new regulation. Finally, companies will also need to review their core quality processes, such as quality assurance, risk management and postmarket expectations, and fine tune them where necessary to meet MDR compliance.
Butler: Manufacturers will need to get executive support and make clear mandates across the organization that this new holistic approach to regulations and quality is how your organization plans to do business going forward. I don’t think it’s enough to hire out consultants to transition to the MDR, though you probably need to do just that. But success with the MDR means internalizing these standards. Organizations should view the MDR transition process as an opportunity to improve all business processes.
Headley: We’re down to the wire here. With all the technological and regulatory changes, manufacturers will need to rely more on digital tools to provide them with the level of quality and compliance management they need to keep up with the MDR. Make sure all your data is up to date and accurate, particularly when it comes to clinical studies documentation. Device companies doing big business in Europe should have started training and performing internal gap analysis by this point. If the manufacturer has little opportunity in Europe, they must evaluate the return on investment and reset their strategy for the EU market.
For more analysis and information on EU MDR/IVR, read the new industry brief, “EU MDR: How to Prepare for the Upcoming Changes in Regulation.
Alex Butler is manager of medical device solutions at MasterControl. He oversees development and continuous improvement initiatives for several of MasterControl’s core products, including Regulatory Excellence (Rx), Development Excellence (Dx) and Supplier Excellence (Sx). He has also had a prominent role in the conception, design, and development of MasterControl’s highly anticipated Checklist and validation software. Butler has an extensive background in medical device technology and innovation with over eight years in product development, strategic planning, quality assurance and process improvement. Prior to MasterControl, he functioned as product development manager for Opal Orthodontics, where he was directly involved with the development, quality and compliance, risk management and launch of several Class II medical devices.Bryant Headley is a life sciences industry professional with over 20 years’ of experience in regulated and regulatory government organizations, including the U.S. Food and Drug Administration (FDA). As MasterControl’s customer success executive/government liaison, he serves as a regulatory industry expert as well as facilitates sales and customer service with government entities such as the FDA, the VA, Department of Defense and Department of the Treasury. Headley has held several high-level positions with various government offices including the FDA, the U.S. Department of Veterans Affairs (VA), the Department of Defense and the Department of the Treasury. With the FDA, he served as a business program manager tasked with reframing the agency’s deployment of the MasterControl QMS. Headley was also a program manager and certified ISO 9001 trainer with the U.S. Department of Veterans Affairs (VA). Headley earned a bachelor’s degree in management with an emphasis in health care from Wayland Baptist University and a master’s degree in project management from the George Washington University.
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