Jo-Ann Fabila Gonzales, Director, In Vitro Diagnostics & Quality at Precision for Medicine, offers an overview of the changes coming and strategy to prepare for them
In 2017, the European Union (EU) published the In Vitro Diagnostic Regulation (IVDR) that will be fully implemented as of May 26, 2022. That deadline is fast approaching, and time is running out for IVD manufacturers to prepare for these major changes in the IVD approval process. These new regulations include stricter certification procedures, with the vast majority of products necessitating review by notified bodies (NB), as well as being subject to clinical evidence requirements and post-market surveillance and vigilance requirements for both currently existing products and IVDs being newly introduced to the EU market.
Under the current EU In Vitro Diagnostic Directive (IVDD), about 80 percent of IVDs are allowed to be self-certified, making entry into the EU market a far lower hurdle than what is required in the United States by the Food and Drug Administration (FDA).
That is about to change as the IVDR is much more closely aligned to FDA requirements and will require that about 80 percent of products be reviewed by a NB and that clinical evidence will be needed for many IVDs that currently only have analytical data. While there are definite advantages to a similar regulatory framework in the US and EU – streamlining the process of bringing a regulated IVD to the global market – the IVDR also presents significant challenges for manufacturers.
The IVDR transforms the device classification structure from the current two-class approach to a four- class, risk-based system that goes from Class A to D, with A representing the lowest risk and D the highest. Products now classified under List A and B (the highest risk classifications and those requiring NB review under the IVDD) will fall into Class D, and products that currently only require self-certification by the IVDD, will be placed into Class C, B or A, depending on their risk level. All but Class A products will need to undergo NB review.
Additionally, products not previously identified under the IVDD, such as companion diagnostics and standalone software products, are now included within the IVDR classification system.
Given the limited number, five at the time of publication, of EU-certified IVDR NBs and the huge increase in products that will need to be reviewed by them, as well as changes in the types of data and documentation required for a far more comprehensive review process, time is quickly running out for manufacturers who have not already engaged an appropriate NB.
For those choosing an NB for the first time, the European Association for Medical Devices of Notified Bodies (TEAM NB) is one resource available that includes current updates of NBs that have received or are seeking certification to the IVDR. Keep in mind, that the NB needs to match the type of classification of your product, have experience in your product area and have the resources to conduct the required reviews in a timely manner. This is particularly important given the tight time constraints for companies who are late in beginning the premarket review process.
In addition to the new NB requirement, the IVDR also stipulates that manufacturers have a designated employee who will be responsible for regulatory compliance.
The IVDR requires far more clinical evidence than previously needed to support the CE mark, including not only the usual clinical and analytical performance data, but also scientific validity. Because of these changes, manufacturers need to perform a gap analysis to determine the evidence currently available for their product(s) and the data necessary for meeting IVDR requirements. If your IVD has already gained FDA approval/clearance, you should have everything you need for the IVDR technical documentation. Your concerns will primarily be focused on addressing the gaps to the new clinical evidence requirements.
For manufacturers whose products have only been approved or are only seeking approval in the EU, the challenge to interpret and address these new demands is significant. If you have multiple products for IVDR review, a gap analysis can help prioritize IVDs according to the quality of existing evidence and the level of effort and resources needed for new studies to produce additional supporting data. When deciding on the initial products to submit for review, it is a good idea to begin with currently marketed IVDs, especially those with a robust post-marketing surveillance program. Surveillance data collected on these products can be used to support the clinical evidence report and can help create a template and tested process for future IVDs planned for the EU market.
The need for manufacturers to focus their efforts on a limited number of products is particularly relevant considering the COVID-19 pandemic potentially causing delays and impacting study timelines.
While presenting challenges, the EU regulatory changes will offer greater opportunities for global commercialization given how closely aligned they will be to US regulations. In the long run, this should be good news for IVD innovators since it will help harmonize the development processes and enable more shared data across submissions. Rather than initially launching an IVD in the EU, manufacturers can now think globally about their product launches, and develop and execute plans for producing required evidence in parallel for both EU and US approvals.
