Most manufacturers will have to revisit all technical files and the quality systems for all their devices, they will need to generate additional clinical and performance evidence.Gert Bos
The stricter rules are especially tougher for advanced molecular diagnostics and lab-on-chip assays used in the clinic to help identify a patient’s pathology. But also coming under scrutiny for the first time will be DIY pregnancy kits or at-home nutrigenetic tests that have not been covered by the current regulations. Outraged by the scandal over breast implants that fraudulently used industrial-grade silicon and with on-going concerns for metal-on-metal hip implants, the European Parliament launched a total overhaul of the directives for awarding the CE Mark for medical devices and in vitro diagnostics (IVDS) devices.
The reform movement in Brussels has resulted in nothing less than an upheaval of the landscape for manufacturers. For example, all IVDs will need to be recertified, including products already on the market. And where the current EU directives allowed a self-certification of the vast majority of tests, the new IVDR now requires 80 percent of all assays and reagents to undergo a strict level of independent scrutiny that runs up the supply chain to include subcontractors and software associated with the product.
While there is a five-year transition period provided in the new laws, that may not be enough for many manufacturers, according to Gert Bos, the Executive Director at Qserve Group, a medical device consulting firm based in Amsterdam. He also is the past-President of the European Association of Notified Bodies for Medical Devices. The notified bodies are the gatekeepers for access to the EU market, independent companies accredited by a Member State to assess whether a product to be placed on the market meets the preordained standards. ‘Most manufacturers will have to revisit all technical files and the quality systems for all their devices, they will need to generate additional clinical and performance evidence,’ Bos wrote in a detailed guide entitled, Dos and Don’ts: How to prepare for and implement the upcoming In Vitro Diagnostic Regulations (IVDR).
The white paper was co-authored by Erik Vollebregt, a partner at Axon Lawyers in Amsterdam, an expert on EU regulation and the author of the widely followed blog, Medical Device Legal. With permission of the authors, this article extracts highlights from the white paper. ‘The IVDR will bring about extremely significant changes. Most critical is the full revision of the classification system into a rule- based risk classification matrix. In contrast to the current situation, this means the vast majority of products will need to be evaluated by the notified bodies.’
As the result of greater scrutiny since 2013, the number of notified bodies has been dramatically reduced, a critical issue for manufacturers. Bos estimates that, by the end of 2016, there will be from 40 to 45 certified notified bodies remaining from approximately 80 before the 2011 breast implant scandals that provoked the reform movement for EU regulations. ‘Manufacturers must be aware that they may need to change a notified body as a result of this development, and act accordingly if their current notified body is not able to support the manufacturer anymore,’ he cautions.
In addition, he said that the administrative burden will increase substantially for manufacturers as a result of registration requirements and the implementation of a Unique Device Identification (UDI) system. ‘Consequently,’ he wrote, ‘manufacturers must take a proactive approach to the new regulation, plan and budget for the transition of existing devices in a timely and detailed way, and allocate resources for this effort.’
IVDR shares many new features with the upcoming EU Medical Devices Regulation (MDR) proposal, such as new supply chain requirements and the implementation of a central database (EUDAMED)
Here are the four major developments specific to the IVDR field highlighted by Bos and Vollebregt.
- Extension of the concept of in vitro diagnostic devices to include tests of ‘indirect medical purpose’ and ‘prediction’ to include nutrigenetic tests and lifestyle tests, which are not covered by the current IVD Directive.
- IVDs will no longer be subject to the list-based system currently in the IVD Directive, but to the risk classes developed by the Global Harmonisation Task Force (GHTF), dividing the landscape of IVDs into risk classes from A (low- risk) to D (high public and high patient risk) with seven classification rules. With notified bodies having to perform conformity assessment on all but class A devices, the landscape is dramatically changing in terms of files to be reviewed and audits to be performed pre- and post-market.
- The conformity assessment routes for IVDs are amended to fit the new classification logic. IVDs that do not fit any of the other classification rules fall into class B and have to be certified by a notified body. This is a major change compared to the IVD Directive, which allows such IVDs to be self- certified. As a consequence 80 percent of all IVDs will need to be certified by a notified body under the IVDR, as compared to 20 percent currently under the IVD Directive.
- Clinical performance studies will be required to support the CE mark under the IVDR. As a consequence IVD manufacturers will need to produce significantly more clinical evidence. The IVDR will contain rules for interventional clinical performance studies and other clinical performance studies that largely overlap with the clinical studies regime in the MDR proposal.
It is crucial for manufacturers of IVDs currently on the market to plan the generation of additional clinical evidence well, and timely assess what clinical evidence will likely be required, how long it will take to generate this and plan ahead for notified body slots for conformity assessment. In short, the clinical performance evaluation will include not only the classic clinical performance and analytical performance, but also scientific validity. With this change, the first steps towards manufacturers becoming fully responsible for the clinical utility of their devices are initiated.
Gert Bos is an influential voice for European regulatory issues. For many years he served as the President of the Notified Body association TEAM- NB, and as Vice Chair of the Medical Notified Body Forum. Until 2016 he was the Head of Regulatory and Clinical Affairs of British Standards Institute for Medtech. Currently he is the Executive Director and Partner at Qserve consultancy.