As of today, the 26 May 2022, the in vitro diagnostic Medical Devices Regulation (EU 2017/746) (IVDR) applies across the EU.
Those working in the industry will be aware that the implementation of the IVDR has been far from straightforward, and that there is still a lot of work to be done. In this post, we provide an overview of the current status of the transitional provisions, identify recently published guidance, and briefly consider the position in the UK and Switzerland.
Overview of the IVDR
The IVDR replaces the in vitro diagnostics Medical Devices Directive (IVDD). While the IVDR reinforces key elements of the previous regime, there are many important differences, in particular more rigorous rules on the classification of IVDs and the provisions governing performance evaluation and performance studies.
Under the IVDD, manufacturers must categorise their IVDs as either a device for self-testing or other device. This categorisation is based on risk, and impacts the conformity assessment procedure that must be followed to place an IVD on the market. In contrast, the IVDR introduces a rule-based classification system whereby IVDs are classified into one of four classes: A, B, C or D. Class A is the lowest risk, and Class D is the highest. As would be expected, more stringent rules apply the higher the classification of the IVD.
Under the IVDR, significantly more IVDs have to be placed on the market with the involvement of Notified Bodies, with estimations indicating that the proportion of such IVDs will rise from just 20% of IVDs currently on the market, to at least 80% under the IVDR. Since there are only seven Notified Bodies currently authorised to undertake conformity assessments under the IVDR, this has created significant delays and practical issues for manufacturers wishing to place IVDs on the EU market under the IVDR, which have only been exacerbated by the COVID-19 pandemic.
Transition periods and timing
As noted in a previous blog, the Commission recognised these difficulties for IVDs that are already on the market, and in January 2022, extended the transition periods for certain IVD under the IVDR, to allow manufacturers and Notified Bodies more time to process IVDs through the IVDR conformity assessment procedure. The details of this “progressive rollout” of the IVDR are set out in our previous blog, but in summary, the date of application has been extended depending on the classification of the IVD under the IVDR, provided that the device continues to comply with the IVDD, and that there are no significant changes in the design and intended purpose of the IVD. In addition, the requirements of the IVDR regarding post-market surveillance, market surveillance, vigilance and registration of economic operators and devices must be complied with from 26 May 2022. The extended transition period does not apply to Class A IVDs (non-sterile), which is estimated to be around 20% of the market, or new IVDs that are not already on the market under the IVDD prior to 26 May 2022.
The Commission rolling plan sets out information on the progress of implementing acts and actions that the Commission is planning to adopt to assist with the interpretation and implementation of the IVDR, plus an update of the expected timelines. Further, a joint implementation plan for the IVDR was endorsed by the Medical Device Coordination Group (MDCG) in March, and outlines the essential and high-priority actions that were to be completed before the date of application of the IVDR. As part of this, a number of guidance documents have recently been published by the MDCG. Arguably, publishing such guidance in the month in which the IVDR becomes applicable causes difficulties for manufacturers, but the guidance is nevertheless welcomed by industry. In particular, the following have been published:
- MDCG 2022-10, Q&A on the interface between Regulation (EU) 536/2014 on clinical trials for medicinal products for human use and the IVDR, which is particularly relevant to companion diagnostic products, discussed below.
- MDCG 2022-9, Summary of safety and performance template.
- MDCG 2022-8, Application of IVDR requirements to ‘legacy devices’ and to devices placed on the market prior to 26 May 2022 in accordance with the IVDD. ‘Legacy devices’ refer to IVDs placed on the market or put into service after 26 May 2022 and until the end of the relevant transition period.
- MDCG 2022-6, Guidance on significant changes regarding the transitional provisions under the IVDR, which is particularly important for companies seeking to rely on these transitional provisions to continue to place products on the market from today. For example, this guidance sets out the scope of significant changes, and what changes may be permissible to still benefit from the provisions.
Key issues for specific products
Some of the most common questions that we receive on the IVDR relate to companion diagnostic products and laboratory developed test. These are, arguably, products for which there are some of the most significant changes under the IVDR, and we set out some further information below:
- Companion diagnostics (CDx) are defined in the IVDR as a device that is essential for the safe and effective use of a corresponding medicinal product to identify, before and/or during treatment, either (i) patients who are most likely to benefit from the corresponding medicinal product, or (ii) patients likely to be at increased risk of serious adverse reactions as a result of treatment with the corresponding medicinal product. The IVDR introduces specific rules for CDx, including that the Notified Body must obtain a scientific opinion from a national competent medicines authority and/or the European Medicines Agency (EMA) to assess the suitability of the CDx for the medicine in question prior to granting a certificate of conformity. Performance studies involving CDx (as well as other subgroups of performance studies) will be subject to additional requirements, and the aim is for the EUDAMED database to be coordinated with the EMA Clinical Trial Information System for the review and approval of clinical trials involving CDx and the relevant performance study under the IVDR. Both pharmaceutical companies and IVD manufacturers will therefore need to be aware of these requirements. The guidance noted above is also important in this regard.
- Lab Developed Tests (LDTs), or in-house tests, were not generally regulated by the IVDD. However, under the IVDR, these tests, including devices manufactured and used only within health institutions in the EU or EU based laboratories, are included within the scope of the legislation. Many requirements of the IVDR, including the requirement to obtain a CE mark, do not apply to in-house IVDs, provided that specific conditions are met. These include that the IVD is not transferred to another legal entity; that the health institution justifies in its documentation that the target patient group’s specific needs cannot be met, or cannot be met at the appropriate level of performance, by an equivalent IVD available on the market; and that relevant general safety and performance requirements are met. If these conditions cannot be met, the LDT is subject to the full regulatory regime as set out in the IVDR, including the requirement to undergo conformity assessment and be CE marked. These conditions are considerably more onerous and far reaching than under the IVDD, and there have been significant concerns raised about the continued availability of such tests in the EU. As such, LDTs are subject to some of the longest transition periods under the updated IVDR.
What about the UK and Switzerland?
While the IVDR now applies in the EU, that is not the case in countries that historically had regimes aligned with the EU.
- In Great Britain (England, Scotland and Wales), following the UK’s departure from the EU and the end of the transition period on 31 December 2020, the IVDR does not apply. Instead, the previous UK legislation that implemented the IVDD, the Medical Devices Regulations 2002, remains applicable. Further, a new route to market and accompanying mark, the ‘UKCA’, has been introduced to enable manufacturers to place medical devices and IVDs on the market in Great Britain. The requirements for this route to market are based on the provisions in EU law as currently implemented in the UK. The EU CE mark will continue to be recognised on the Great Britain market until 1 July 2023. The position in Northern Ireland is different, and the rules for placing medical devices and IVDs on the Northern Ireland market align with the rules in the EU; this is causes some complications for companies as they seek to comply with both regimes. Further, as noted in a previous blog, the UK government is currently consulting on changes to UK law on medical devices and IVDs.
- In Switzerland, despite ongoing political discussions, a notice to stakeholders in relation to the status of the EU-Switzerland Mutual Recognition Agreement (MRA) for IVDs was published on 24 May 2022. The MRA provides for recognition of conformity assessment certificates between the EU and Switzerland based on equivalence of the IVDD and corresponding Swiss legislation. However, since no update has been made to the MRA to include the IVDR, the part of the MRA covering IVDs ceases to apply as of today, 26 May 2022. This means that Swiss manufacturers will be treated as ‘third country’ manufacturers, and, among other things, must appoint an Authorised Representative designated in the EU. The notice also confirm that certificates issued under the MRA by conformity assessment bodies established in Switzerland will no longer be recognised as valid in the EU, even when they were issued before 26 May 2022.