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FDA Watch: EU’s New IVD Regulations Could Drive More Firms to Seek FDA Approval

by Ron Shinkman | Dec 5, 2024 | Essential, FDA-lca, Lab Industry Advisor

Although the timelines have been extended several times, IVDR complexity has created a concerning bottleneck in the approval process

The European Union (EU) is the second-largest market for laboratory businesses behind the United States. Its rules for approving and regulating laboratory tests and equipment are undergoing the biggest changes in decades—and these could over the longer-term make more lab companies seek initial regulatory approvals in the US.

The most dramatic revision is coming to the overall regulatory framework for laboratory approvals. The European Commission has developed a new framework called the In Vitro Diagnostic Regulation (IVDR), which is replacing the In Vitro Diagnostic Directive (IVDD). The latter was developed in 1997 to provide guidelines for how laboratories were to sell or use their products in the EU, covering not only tests, test platforms, and test systems, but also reagents, calibrators, and any other instruments used in testing. The IVDD covered all 27 EU nations, along with Iceland, Norway, and Lichtenstein, as does the IVDR.¹

Why is the IVDD being replaced?

The overhaul was sparked by “growing concerns about the safety and performance of in vitro diagnostic devices on the market, and the new regulations aim to ensure that these devices are safe, reliable, and perform as intended,” says Candice Vendettuoli, head of quality assurance and regulatory affairs at the British firm Abingdon Health, which manufactures and distributes rapid test solutions and provides consulting services to labs.

Vendettuoli adds that the IVDD framework “was considered outdated and not fully equipped to handle advancements in medical technology and the increasing complexity of in vitro diagnostics.”

The overhaul of regulations is also connected to mishaps tied to medical devices that required more regulatory scrutiny. Though not relating to diagnostic tests, the biggest of those issues involved silicone breast implants developed by the French company Poly Implant Prothèse (PIP). In 2000, the U.S. Food and Drug Administration (FDA) declined to certify the company’s saline implants over concerns about uneven manufacturing processes at its main factory. Though those saline products were different than the silicone implants later found to have issues, both product lines were manufactured in the same facility.²

The following year, some 30,000 women in the EU began receiving implants filled with industrial-grade silicone rather than the medical-grade version of the substance.³ Within several years, those implants began rupturing at double the rate of other kinds of breast implants available in Europe, causing serious medical conditions in many recipients.⁴ The founder of the company, Jean-Claude Mas, was eventually sentenced to four years in prison for causing bodily harm.⁵

IVDR vs IVDD

The IVDR regulations (157 pages) are much more involved than the IVDD regulations they are replacing (43 pages).^6,7 And, according to Jama Software, IVDR essentially turns the EU’s regulatory paradigm on its head. Under IVDD, roughly 20 percent of medical devices in the EU market needed to follow strict certification protocols. Under IVDR, that ratio will change to about 80 percent of medical devices requiring some sort of certification.⁸ Moreover, there is no grandfathering of tests or devices that were approved under IVDD.

“Overall, the IVDR aligns more closely with the FDA’s regulatory framework in terms of rigor and requirements, but the specific processes and pathways differ, impacting how manufacturers approach market entry in the EU versus the US,” Vendettuoli says.

IVDR product classes

Like IVDD, IVDR stratifies medical devices by the risk they pose to both the individual patient and the public at large.⁹

Class A products are low risk to both patients and the public and include products for general laboratory use such as reagents and specimen receptacles.

Class B is a moderate risk classification for the patient and low risk for the public. It covers the handful of tests not covered by the new IVDR rules, as well as self or home test kits such as those for pregnancy or cholesterol levels.

Class C devices are considered high risk to patients and moderate risk to the public. They include tests for infectious diseases, cancer, genetic testing, and companion diagnostics.

Class D devices are both high risk to patients and the public. Their focus is primarily on testing for infectious and transmissible diseases with a high risk of contagion. Examples include blood screening tests for infections such as Ebola or HIV.

Class D devices must comply with the IVDR by December 2027; Class C devices by December 2028; and Class A and B sterile devices by December 2029. The deadlines have been extended numerous times, including an update issued by the European Commission earlier this year.¹⁰

IVDR challenges

Vendettuoli noted that some labs have been struggling with the impending transition.

“Despite these extensions, there is still concern that some tests may be removed from the market due to non-compliance with IVDR,” she says. “Smaller manufacturers may struggle with the costs and complexity of meeting the new requirements, potentially leading to a reduction in the availability of certain tests.”

Costs and time frames are also expanding. A spokesperson for the Novacyt Group, a British company with several laboratory businesses under its management, says it spent nearly $60,000 and a year to get IVDR approvals for a cystic fibrosis test and a DPYD genotyping assay—a time frame and cost significantly longer and higher than under the IVDD process. These were the first straight IVDR approvals for the company. The DPYD approval was also complicated by the fact that the Association for Molecular Pathology issued new clinical guidelines for DPYD testing during the process.

Another issue is that under the IVDR, the number of notified bodies—independent organizations that evaluate the efficacy and safety of devices—has been reduced to 12 in all. Under the IVDD, there were about 22 notified bodies in operation.¹¹

“The limited number of notified bodies has created a bottleneck in the certification process, leading to delays and increased pressure on both manufacturers and notified bodies,” Vendettuoli observes. She adds that an evaluation of a Class D device can take the better part of a year, and even lower-risk devices require thorough evaluations.

Currently, Novacyt is undertaking a review of all its products and their pathways to IVDR certification.

“There is a concern in the EU that products will come off market,” the Novacyt spokesperson says, adding that “we have had to review the value of the products versus the cost and resources required for IVDR to ensure that we only take products through that will be worth the investment.”

The European Parliament is concerned about the issue. In late October, it adopted a resolution calling for swift revisions not only to the IVDR, but to add more notified bodies to the approval process out of fear that some devices may fall out of the market.¹²

IVDR: A push toward FDA approval?

Partly as a result, Vendettuoli believes the changes may push more laboratory companies to obtain approval of their devices from the FDA first.

“Bringing new IVDs to the EU market will now involve more time, effort, and cost. As a result, manufacturers might reconsider their strategies and potentially prioritize the US market, where the FDA’s 510(k) process, despite being stringent, offers a clearer and sometimes quicker pathway for certain types of devices,” she says.