In three days’ time (on May 26, 2022), the EU Regulation on In-vitro-Diagnostic Medical Devices (the “IVDR”) becomes applicable in Europe. But what will this mean for companies who sell in-vitro-diagnostic medical devices (“IVDs”) in the UK?
Following the UK’s exit from the EU, the IVDR will not become effective within Great Britain (i.e., England, Scotland and Wales), but it will apply to Northern Ireland. Companies operating in both the EU/Northern Ireland and Great Britain will therefore need to be aware of the different obligations applicable to IVDs between these jurisdictions.
The IVDR will replace the existing EU IVD Directive (the “IVDD”), but will not change the fundamental principles of how IVDs are regulated. IVDs will be still be subject to a system of self-certification, notified body assessment (in certain instances) and CE marking. Most notably, under the current system, ~90% of IVDs are self-assessed for conformity and self-certified by the IVD’s manufacturer. By contrast under the IVDR, the new classification rules mean that this will be flipped to require ~90% of IVDs to be subject to notified body assessment. This creates practical issues for manufacturers, since there are currently only seven notified bodies who are authorized to conduct conformity assessments under the IVDR.
Following calls from industry (triggered by the lack of notified body capacity) and also challenges caused by COVID-19, the European Commission has extended the transitional periods under the IVDR to allow companies (in certain instances) to continue to place IVDs on the EU market for a longer period, provided they comply with the IVDD. However, regardless of any applicable transition periods, IVDR requirements that attach to the “manufacturer” of the IVD, including those relating to post-market vigilance and registration, and significant new obligations on other economic operators, such as importers and distributors of IVDs, will still apply from May 26, 2022.
Key changes under the IVDR include:
- Classification. Instead of a “list-based” approach to IVD classification, IVDs will now be classified according to a “risk-based” approach by reference to specific implementing and classification rules. IVDs will fall into one of four categories (Classes A, B, C and D), with Class A presenting the lowest risk and Class D the highest. Only Class A devices (which include reagents and specimen receptacles) can be self-certified. All others will need to be assessed by a notified body.
- Performance Studies. Given the up-classification of IVDs, it is hardly surprising that the IVDR brings increased expectations as regards clinical evidence to support their performance. Under the outgoing IVDD, manufacturers wishing to carry out performance evaluations would need to register the study, but there was no requirement that a regulator and/or ethics committee approve it (although some Member States had implemented such requirements). The IVDR replaces these rules with a regime governing so-called performance studies, which reflects more traditional methods of regulating interventional clinical research. It shifts the focus and much of the regulatory burden away from the manufacturer and onto the sponsor of the performance study. Interventional performance studies will require both regulatory authorization and ethics committee review, and must comply with a standard of good clinical practice found in ISO 20916:2016. Sponsors will be able to seek regulatory and ethics committee review in multiple Member States once the EUDAMED database is fully operational.
- Companion Diagnostics (“CDxs”). For the first time, notified bodies will need to engage with medicines regulators when assessing CDxs. CDxs are IVDs that support the safe and effective use of a specific medicines, by identifying patients that are suitable or unsuitable for treatment. Before a notified body can issue a certificate of conformity for a CDx under the IVDR, it will need to seek a scientific opinion from the European Medicines Agency (“EMA”) and/or a national competent medicines authority to assess the suitability of the CDx for the relevant medicine. CDxs are playing an increasingly important role in personalized medicine. These new rules are therefore not only relevant for IVD manufacturers, but also for pharmaceutical companies. Once the EUDAMED database is fully operational, it will be interoperable with the EMA Clinical Trial Information System (“CTIS”), so that the review and approval of clinical trials involving a CDx can be coordinated with the review of the application for the companion performance study.
- Economic Operators. Additional players within the IVD supply chain will now be regulated under the IVDR, with specific obligations applying to IVD importers and distributors.
- Distance Selling. Under the IVDD, there was scope to avoid EU IVD rules by shipping samples for testing outside the European Economic Area (“EEA”), e.g. in a Clinical Laboratory Improvement Amendments (“CLIA”) approved laboratory in the U.S. However, the IVDR will apply to IVDs used outside the EEA to provide diagnostic or therapeutic service to persons in the EEA. This means that entities involved in distance sales of IVDs into the EU market, and those that offer services into the EU market, will need to consider the IVDR.
- Health Institution Exemption. Unlike in the U.S., under the EU device rules, there is no CLIA-type exemption for laboratory-derived tests. Instead, there is a far more limited exemption that provides that IVDs produced in a health institution for use with patients it serves do not need to be CE marked. These rules become more detailed under the IVDR, meaning that health institutions have additional obligations to satisfy before being able to benefit from the exemption.
- EUDAMED Database. Although not yet fully operational, the EUDAMED database will improve the transparency and coordination of information regarding IVDs (and medical devices more broadly). Members of the public and healthcare professionals will be able to access information about IVDs available on the EU market, including information about relevant economic operators. It will also allow for coordinated review and approval of performance studies.
- Traceability. A new unique device identifier (“UDI”) system will apply to IVDs, which aims to enhance the traceability of IVDs across the supply chain.
For more information on the changes being implemented by the IVDR, join Covington’s webinar entitled “In the Dawn of the EU IVDR: New Laws Apply for In-Vitro-Diagnostics and Companion Diagnostics” on May 25, 2022, which will be hosted by our colleague Dr. Dr. Adem Koyuncu.
Implications for companies supplying IVDs in the UK
The IVDR will apply in the EEA (including all EU Member States, Norway, Iceland and Liechtenstein), but has not been adopted under UK law for Great Britain. With the exception of Northern Ireland, the UK will continue to follow the existing rules set out in the IVDD, as implemented under the UK Medical Devices Regulations 2002. This means that from May 26, 2022, the IVD rules in EEA/Northern Ireland and Great Britain will diverge.
The UK has introduced a transitional period to allow IVDs that comply with the EU rules to be placed on the market in Great Britain until June 30, 2023. However, after that date, such IVDs will need to bear a UKCA mark. The UK Medicines and Healthcare products Regulatory Agency (“MHRA”) is currently reviewing industry responses to a consultation on the regulation of devices in the UK and is expected to publish further guidance and/or legislation this year. It is yet to be seen how this will alter the UK landscape for device regulation. Until the MHRA issues further guidance, companies operating across Europe and the UK will need to carefully consider their regulatory strategies to ensure that IVDs supplied to the market are compliant with the rules in each of (i) the EEA, (ii) Northern Ireland, and (iii) Great Britain, as applicable. The Covington Team is on hand to help guide companies through this complex landscape.