The In-Vitro Diagnostic Medical Device Regulation (EU) 2017/746 (IVDR) overhauls the existing regulatory regime provided for by the In Vitro Diagnostic Medical Device Directive 98/79/EC (IVDD), a piece of legislation that was introduced in 1998. Not only will the IVDR bring about changes that are expected to have a profound and lasting impact on the IVD industry in the long term, but a number of factors are also conspiring to make the transition from the IVDD to the IVDR potentially very disruptive for manufacturers.
26 May 2022 – The road to IVDR
The IVDR was published on 5 May 2017 and entered into force on 27 May 2017 alongside the MDR. Although the primary focus during the legislative process was on the MDR (as a result of device related incidents such as the PIP breast implants scandal and problems related to Metal-on-Metal hip implants for example) and both Regulations share a similar structure and themes, the IVDR does provide for various in-vitro device (IVD) specific changes, particularly in the way in which IVDs will now be classified.
Perhaps in recognition that the IVDR would bring about more far-reaching structural changes to the way that IVDs are regulated as a result, and also that reform of the regulation of IVDs was perhaps not required as urgently as medical devices, the transitional period provided for in Article 110 of the IVDR was five years, as opposed to three years for the MDR. As a result, we have now entered the fifth and final year of the IVDR transition period as originally provided for.
Meanwhile, the three-year transition period provided for in Article 120 of the MDR was subsequently extended to four years in order to relieve the added pressure on stakeholders created by the COVID-19 pandemic. This necessary delay of the MDR coming into full effect on 26 May 2021, has arguably resulted in the focus remaining on the MDR at the expense of the IVDR, which remains on track to come into full effect on 26 May 2022 despite growing calls for that date to be delayed.
Changes and challenges
An overview of some of the key changes and challenges for manufacturers brought about by IVDR can help us to understand why such a postponement might be welcomed.
The IVDR provides for a new regime for the classification of IVDs under Article 47 and Annex VIII that creates a new set of risk categories (A, B, C and D). The net effect of these new rules is that whereas under IVDD, roughly 20% of IVDs required third party conformity assessment by a notified body in order to be placed on the market, it is estimated that over 80% of IVDs will now require the involvement of a notified body in order to be placed on the market. The significance of this development is highlighted when considered alongside the lack of ‘grandfathering provisions’ in the IVDR, thus creating a very significant increase in the demand for conformity assessment services. Similar to the MDR, the IVDR also makes provision in its classification rules for various special categories of IVD such as software, single-use IVDs, companion diagnostics and genetic tests.
Alongside creating a surge in demand for conformity assessment services through revised classification rules, the IVDR also makes provision for stricter initial requirements for organisations seeking accreditation as notified bodies for the purposes of the IVDR, as well more oversight of notified bodies once accredited. This has led to a corresponding decrease in supply of conformity assessment services. At the time of writing, there are only four notified bodies accredited to provide conformity assessment services under the IVDR. Moreover, not all notified bodies are necessarily accredited to provide conformity assessment services in respect of all of the categories of IVD regulated under the IVDR, so certain manufacturers with a varied portfolio of IVDs may therefore be required to source conformity assessment services from different notified bodies depending on the IVD type.
Manufacturers of the +80% of IVDs that are expected to require the involvement of a notified body will also need to carefully evaluate existing clinical and performance data for their devices before making this available to their new notified body for review. This will be required for Class B, C, and D IVDs (and some Class A IVDs also). More specifically, Article 56 of the IVDR also requires manufacturers to compile a performance evaluation report (PER) for each device, as well as a performance evaluation plan, scientific validity report, analytical performance report and clinical performance report (See Chapter VI & Annexes II and XIII).
Like the MDR, the IVDR provides for an enhanced focus on post-market surveillance and vigilance, with a general increase in requirements accompanied by a reduction in reporting timelines. This requires manufacturers to return to their established post-market surveillance processes to ensure that IVDR-ready plans and reporting systems are in place (see Article 10(9) and Chapter VII). Under the heading of vigilance, IVD manufacturers are also required to report and analyse serious incidents and field safety corrective actions and carry out trend reporting and analysis on vigilance data. Article 15 of the IVDR also makes provision for the appointment of a Person Responsible for Regulatory Compliance (PRRC) who has responsibility for ensuring that these and other obligations (such as ensuring that the conformity of the devices is appropriately checked in accordance with the quality management system under which the devices are manufactured, and that the technical documentation and the EU declaration of conformity for devices are drawn up and kept up to date) are met by the manufacturer.
The IVDR also contains enhanced requirements regarding information to be supplied with IVDs on labelling and as part of instructions for use (See Annex I, Chapter III). These detailed requirements need to be carefully considered in order to identify and implement any necessary changes to the labelling and packaging of devices. For example, labels for IVDs shall now be required to bear the Unique Device Identifier (UDI) carrier code which is another new feature of the IVDR (see Article 24 and Annex I).
Owing to an increased focus on traceability and transparency across the supply chain, both the MDR and the IVDR also contain various provisions referring to the establishment of EUDAMED as well as the UDI system. EUDAMED has been designed as a sophisticated European database that will be used by economic operators and competent authorities to submit and store information on the manufacture, distribution, certification and postmarket surveillance of devices. IVD manufacturers therefore need to become familiar with the various modules making up this system (as they continue to become operational) in order to ensure that they are prepared to use this system once it becomes fully operational. Article 25 of the IVDR also provides for a UDI database in respect of IVDs which cross refers to the same system being implemented in respect of medical devices under Article 28 of the MDR.
Will the IVDR be postponed?
Although calls have been increasing for a delay to the implementation date of the IVDR, stakeholders must continue to plan on the basis that the IVDR will come into force on 26 May 2022. The MDCG has also recently published a joint implementation and preparedness plan for the IVDR which acknowledges the serious challenges involved in achieving full implementation of the IVDR on time. This plan lists two sets of ‘essential’ (Set A) and ‘high priority’ (Set B) actions:
Set A (essential)
- Contingency planning and monitoring
- Availability of notified bodies
- EU reference laboratories
Set B (high priority)
- Common specifications
- Guidance for notified bodies
- Performance evaluation and expert panels
- Companion Diagnostics
- In-house devices
It is important to note that this document is drafted on the basis that implementation on 26 May 2022, although challenging, is achievable. Further detail and analysis of the actions identified in the MDCG implementation plan is addressed in more detail elsewhere in this edition of the Review.
In such a challenging environment, manufacturers need to do everything they can to stay up to date on new developments while also working to execute on IVDR transition strategies for their devices. There are a number of practical steps that can guide this process:
- Carefully consider the classification of devices and what certification under IVDR will require. If involvement of a notified body is required, begin or continue work to secure these services urgently
- Clarify what information will be required for ongoing performance evaluation
- Actively monitor for new guidance being published by MDCG and ensure familiarity with guidance issued to date
- Review labelling, packaging and instructions for use to ensure compliance with enhanced requirements under the IVDR
- Become familiar with the operational modules of the EUDAMED database and the UDI system
- Take steps to identify and appoint a suitably qualified PRRC
As work intensifies to ensure that all stakeholders are fully ready for IVDR, the path to full implementation is likely to demand many creative solutions and difficult decisions by all involved as the clock continues to count down to 26 May 2022.