For many years, the majority of in vitro diagnostic products in Europe – 80 to 85 percent — were self-regulated. What that meant in practice was that under the In Vitro Diagnostic Directive (IVDD) companies that had a quality management system and met the Essential Requirements, which were determined by the manufacturer. could self-declare for CE marking and then distribute throughout Europe.
But as of 26 May 2022, when the In Vitro Diagnostic Regulation (IVDR) will be implemented, there will be a reversal of that process. In future, 90 percent of products will need to be reviewed by a notified body before they are eligible to be distributed in Europe. This means that IVD companies will have to go through the process of making sure they can fulfill a notified body assessment.
As a result, all documentation has to be a lot more substantial, including more records and evidence. Furthermore, companies will have to go through that review process with the notified body, which takes some time.
Compounding the challenge is the fact that there are only a few notified bodies that can give certification under the IVDR. Whereas in the past there were more than 30 notified bodies that could give certification for IVD products, now there are just six, with a seventh coming on board shortly. Inevitably that will create a bottleneck, with every company needing to work with a notified body to review their product, but not enough people to carry out the reviews.
Potential product withdrawal
The consequences of these requirements mean that some products used by consumers, which had been self-declared under the IVDD, may no longer be available under the IVDR.
There are several reasons for that. It might be because the company decides that the process is too long, that they don’t want to go back and create new data for products that have been on the market for many years, or they might just be in a queue with the notified bodies. As they await a review by the notified bodies, their products might become out of stock, in which case they would no longer be able to supply products to the European market.
From a consumer perspective, that might mean, in some product categories, there will be more limited choices.
For diagnostic companies, there are massive hurdles to overcome with new requirements that they have never had to deal with before, and with which they are therefore completely unfamiliar. These companies will need to create procedures, records and do the actual testing, including clinical and stability testing, if necessary. They will need to navigate areas that, in the past, they could justify under self-declaration, including post-market surveillance, clinical studies, stability and usability.
A further requirement that diagnostic companies are struggling with is maintaining the quality management system, including regular updates to all the downstream work instructions and forms. Since many diagnostic companies have very few resources in their quality and regulatory organization, the work required is typically beyond what they can manage.
How to move forward
With so many changes to manage, diagnostic companies will need to prioritize and be strategic with applying updates. They might also want to assess their product portfolio and decide whether the documentation updates and improvements are worth the trouble for all their products. Instead, they should prioritize those higher class or higher risk devices that are important to the company.
It will also be important to focus on the key changes within the regulations. The top priorities will need to be post-market surveillance and vigilance, since these were the primary drivers behind the IVDR. That will mean putting the structure and the pieces in place to fulfill those requirements for key documentation such as the periodic safety update reports (PSURs) and post-market surveillance plans.
Another priority will be to identify the right economic operators to work with. Under the IVDR, everybody has legal responsibility for the product being distributed, imported, manufactured and beyond. It will be imperative to have the right people in place, and to ensure they can meet the IVDR requirements. Diagnostic companies will need to ask questions such as whether key partners have kept adequate documentation and can carry out the level of diligence that is expected under the IVDR.
Clinical and stability data will also come to the forefront, since diagnostic companies will need to ensure they have suitable clinical evidence to support the product being launched in the European Union. That information can be taken from post-market surveillance studies, from clinical studies, from multiple sources and even literature, but companies need to be able to justify it. Companies that have had products on the market for many years may not have sufficient clinical data and might need to consider doing clinical trials. Some may also have to conduct stability and usability studies to demonstrate that the product usability is appropriate, and the storage conditions are suitable.
Finally, there are a lot more post-market surveillance activities that must be completed and regularly updated and that could mean significant process and resourcing changes.
Companies can take progressive steps by engaging with the notified bodies as soon as possible but should ensure that their Quality Management System is fully aligned before doing so.
About the author: Terrance Thiel (TJ) is senior director and principal consultant for medical devices/IVD and has worked in quality and regulatory affairs in the Australian, US and European medical device and diagnostics industries for more than 20 years