The European Union’s new in vitro diagnostics regulation (IVDR) creates significant hurdles to certification of in vitro diagnostic devices (IVDs). Chief among these is that notified body (NB) review will be required for about 90 percent of all IVDs, up from about 10 percent today. The only exceptions will be devices in the lowest of the four risk categories, Class A, which includes only products for general lab use, lab instruments and specimen receptacles.

On 26 May 2022, any IVD device sold in the EU – and likely the UK and countries around the world that embrace EU standards as well – must be certified under the new IVDR rules. In addition to scientific and analytic validity, the IVDR requires that most tests in Class B and above demonstrate clinical performance before certification. Post-market monitoring of scientific, analytic and clinical performance will also be required for most IVDs, and will need to be reported at least annually for Class C and D devices (1).

In all cases, demonstrating clinical performance will require making a case that the IVD test results are clinically useful. This generally requires showing that a test generates information that can lead to some clinical benefit, such as guiding specific treatment decisions that may have a clinically significant impact, or assessing risk of developing a disease or condition. Often, this will require clinical testing before certification.

Here we address a few questions about how manufacturers can prepare for the complex challenges the IVDR presents.

When should I start preparing for the IVDR?

As soon as possible. While five years may seem like a long time to get ready, complying with the new IVDR will entail significant lead time, particularly in preparing the clinical studies and evidence that will be required to certify many new and existing products. For organisations that have not previously done clinical trials, developing this capability will require a great deal of time and resources.

In addition, review of certification applications by NBs will take time. This must be allowed to avoid delaying market entry for new IVDs or disrupting market availability of existing ones. Keep in mind that since they have not reviewed many IVDs before, NBs also must develop the capacity to do so. The earlier you get your applications in the NB queue, the smoother the process will go.

How complicated is clinical testing for IVDs?

Clinical tests for IVDs differ from those of pharmaceuticals or therapeutic devices primarily in their end points. Where drugs and devices generally can be evaluated based on how they directly affect a disease or condition, IVDs and other tests must be evaluated based on how the information they provide affects treatment decisions.

In essence, the test endpoint is two steps removed from the clinical endpoint it influences, and the connection between the test and the clinical impact must be made across these two steps. Specifically, the test result must be shown to be relevant to the clinical condition in question, and to be necessary to guide the treatment decision.

For example, a gram test for a bacterial infection could be shown to be relevant to the condition itself and necessary for choosing an appropriate antibiotic. Similarly, various antibody tests could be shown to identify specific viruses or cancer stages, and for guiding the appropriate vaccine or chemotherapy treatment.

Clinical tests for IVDs should be based on precise definitions of how the test relates to the condition and the treatment decisions made around it. It may be helpful to consult with clinical research organisations experienced in developing such tests to ensure they meet regulatory and payer requirements for demonstrating acceptable clinical performance.

Clinical testing sounds expensive. Will it be worth the investment?

The best way to tell whether your products are worth the investment needed for clinical testing or even just NB review based on existing evidence is to conduct a “gap analysis” of your pipeline and existing product portfolio. For each product, determine what category in which it will be certified under the IVDR, and what additional evidence, clinical testing, production process, technical file documentation, labelling or other changes will be required to conform.

Then estimate the cost of these changes, assess how they will affect profitability, and reconfigure your portfolio accordingly. Your analysis may well indicate that it’s time to drop marginal products with a lot of competition and focus on preparing packages for new, more profitable, IVDs with strong evidence showing they support clinically beneficial treatment decisions.

IVD clinical test costs can be reduced by adopting strategies such as:

  • Incorporating adaptive design elements that allow alteration of clinical tests based on accruing data. This can help refine tests quickly and may accelerate development by combining trial stages.
  • Automated data collection using electronic health records, which can reduce data collection costs while broadening the scope of data collection, especially for post-market surveillance.
  • Risk-based monitoring of trials and post-market surveillance, which can help spot device performance issues early, enabling quick corrections to bring trials and the entire development process back on track.

ICON’s IVD experts can help you quickly assess your portfolio for product viability under the new regulations, and move forward creating the clinical evidence needed for certification, and the real-world evidence for post-market surveillance and performance assessment required to conform with the new regulations.

For a consultation on how your organisation can efficiently adapt to the new European regulatory requirements, schedule a meeting with ICON’s Medical Device and Diagnostic Research group leaders.


(1). REGULATION (EU) 2017/746 OF THE EUROPEAN PARLIAMENT AND OF THE COUNCIL of 5 April 2017 on in vitro diagnostic medical devices and repealing Directive 98/79/EC and Commission Decision 2010/227/EU. Official Journal of the European Union, May 5, 2017.