The In Vitro Device Regulation (IVDR) comes into force on 25 May 2022, which means companies must start complying with the regulations. While we’re seeing many companies have aspects in place, there are many issues that they may not have considered.
For example, if you’re using a biomarker assay in your clinical study, has it been CE marked? With combination products, have you tested them appropriately within the context of your study and included the relevant validation data? While the process is different to that for drug products with conditional requirements based on intended use or classification, you do still need to start with the end in mind and you need to get your plans in place early to get your product on the market. For sponsors from outside the EU seeking to conduct trials in Europe, there are a number of complex considerations.
Key considerations
First if you’re using marketed medical devices in EU clinical studies, you will need to ensure the device you intend to use is IVDR compliant from the outset, and, if your trial is ongoing, any device used under transitional arrangements will need to be certified as IVDR compliant (or face changing the device mid study, thereby creating a host of requirements such as an equivalence study between the old and new devices to show the old data is still valid).
Second, if you want to use a non-CE marked experimental device as part of your study, you will have to show that the product could be CE marked (would meet the performance requirements), and that will require interaction with the notified bodies as well as clinical evaluations to show the device is compliant.
And third, if you as an IVD manufacturer want to register your device, you likely will need to conduct clinical evaluations, which may require having an EU legal representative if these are conducted in the EU.
Other important questions to consider include:
- When will you have enough data to be able to go through the clinical trial process?
- What does that mean for the validity of the data in earlier studies that are relying on this as a biomarker
- How will this impact those conversations with the regulators about the strength of that biomarker as an endpoint?
You can spend a lot of money on a new innovation, biomarker and a wonderful artificial intelligence solution that analyses it all for you, but if you haven’t taken the appropriate regulatory advice, and made sure that it fits with the regulation for the territory that you want it to operate in, you can’t use any of that data.
Northern Ireland: A complex new market
Following Brexit, Northern Ireland finds itself in both the EU single market and UK National market, which means that for a particular device the regulatory requirements are based on where the device may be marketed. Products to be marketed elsewhere in the EU (e.g. Ireland, France, Germany, etc.) will require CE marking. Devices to be marketed in the UK will require UK Conformity Assessment (UKCA) marking and devices to be marketed across both EU and UK markets will require both. Companies have a short window to deal with this complexity since there is a transitional regime in place allowing UK recognition of CE marking until June 2023 for devices where the requirements of the two systems remain aligned. If a device is only to be used in Northern Ireland, there is a further marking available, CE UK (NI), under which UK notified bodies certify a product as meeting EU standards. These different requirements make the process a lot more messy and mean companies must spend more time planning.
Additionally, these requirements are under continuing political review as the controls involved in implementing the “Northern Ireland Protocol” aspects of the UK/EU Brexit agreement continue to cause disagreement within and between local and national legislatures.
Not surprisingly, these complex arrangements have led to product shortages in NI as the country tries to navigate the different import processes.
Plan your IVDR process now
Even for those companies that have an existing IVD product in the EU that is also sold in the UK, there are issues to address, because all products sold in the UK will have to either gain or show the UKCA mark by June 2023. That means manufacturers will have to consider the logistics of products that are manufactured and labelled this year, but which may still be on the shelves in June 2023.
For all current and prospective IVD companies, and all companies using IVD’s in clinical studies, the coming into full effect of the IVDR means a lot of careful planning and thinking through of processes. If this applies to you, or will in the next 12-18 months, you need to speak with a regulatory expert sooner rather than later to get your plans in shape before it’s too late.
In all EU markets, the IVDR does involve change, with new thinking and new requirements that must be considered when conducting compliance testing and clinical evaluation.
“If you’re hoping to take a product to the market in the next 12 months, you need to be speaking with a regulatory expert now.”