Changes in European In-Vitro Diagnostic Device Regulation Will Begin to Impact IVD Manufacturers; New Regulation Structure Will Increase Cost and Evidence Burden to Enter Market

The new In Vitro Diagnostic Regulation (IVDR) is poised to bring about a substantial transformation in the regulatory landscape for in vitro diagnostic medical devices within the European market. Firstly, it greatly broadens the scope of devices falling under its purview, now encompassing high-risk devices designed for use within a single healthcare institution, diagnostic services, including internet-based services, genetic testing, and tests that provide insights into a patient’s predisposition for specific diseases or susceptibility to certain medical treatments. This expanded scope reflects the evolving nature of diagnostic technologies and their increasing importance in healthcare.

Another fundamental change introduced by the IVDR is the reclassification of in vitro devices. It establishes a classification structure consistent with that of the Global Harmonization Task Force (GHTF), categorizing devices into risk classes ranging from Class A for low-risk devices to Class D for those posing the greatest risk to patients and the public. Instead of relying on predefined lists, the regulation provides specific rules for classifying devices based on their level of risk, offering a more flexible and comprehensive approach to device categorization. Looking at specifics on classification, Class D includes devices related to general life-threatening conditions and transmissible agents in blood and biological materials for transplantation, posing a high risk to the wider population. It also covers blood grouping or tissue typing with specific markers. Class C encompasses high-risk IVD devices with a lower risk to the broader population, including infectious disease and cancer testing, companion diagnostics, and genetic screening. Class B serves as the default class for IVD devices not covered by other rules, typically representing lower risks to patients and the population. It includes self-testing devices for pregnancy, fertility, cholesterol, and urine analysis, as well as controls without assigned values. Class A is for laboratory devices, instruments, and specimen receptacles, covering less risk-intensive aspects of IVD testing. Importantly, laboratory developed tests, which previously did not require device registration are also covered under the new rules.

The IVDR also emphasizes accountability within device manufacturing organizations. It mandates the identification of a person responsible for regulatory compliance, someone who oversees all aspects of compliance with the new regulation. This individual’s qualifications must be documented relative to the required tasks, ensuring a focused and responsible approach to regulatory adherence.

Notably, the IVDR significantly amplifies the role of Notified Bodies in the approval process. Notified bodies are independent organizations designated by an EU country to perform a set of assessments on products that are regulated by certain CE Marking directives or regulations. With the application of the IVDR’s risk classification scheme, nearly 70 percent of all in vitro diagnostic devices will now be subject to Notified Body review, a stark contrast to the less than 15 percent currently. Simultaneously, the regulation tightens the requirements for designating and monitoring Notified Bodies under the IVDR, enhancing scrutiny and oversight in the certification process. Under European regulations, notified bodies are required to be located in the EU and can led to significant added expense. Typical charges for a notified body often charges $3,000-$4,000 per technical documentation examination day for Class III devices.

Moreover, the IVDR mandates the implementation of unique device identification (UDI) mechanisms, providing a robust means to trace specific devices throughout the supply chain. This requirement is expected to enhance manufacturers’ ability to track and recall IVDs promptly in cases where safety risks are identified.

The regulation also introduces more stringent requirements regarding technical documentation and clinical evidence. Manufacturers will need to provide increased detail in their technical documentation and conduct clinical performance studies, offering evidence of safety and performance commensurate with a device’s assigned risk class. Post-market clinical data collection and retention are also mandated as part of ongoing safety risk assessment, contributing to a more comprehensive approach to device evaluation.

Lastly, the IVDR eliminates any “grandfathering” provisions, necessitating the recertification of all previously approved in vitro diagnostic devices in accordance with the new requirements. Manufacturers with currently approved devices are granted a five-year window to demonstrate compliance with the IVDR’s stringent new standards, emphasizing the regulation’s commitment to ensuring the safety and efficacy of in vitro diagnostic devices in the European market.

The transition to the IVDR presents significant challenges for device manufacturers due to the complex development process and new regulatory requirements. Previously approved devices are not exempt, requiring re-evaluation and re-approval. Transition timelines vary based on device class and conditions, but the IVDR allows devices compliant with previous legal requirements to remain on the market without disposal if they meet certain criteria. For example, devices placed on the EU market prior to 26 May 2022 will need to transition to the new guidance by 25 May 2025. Those without a notified body will need to transition between 2026 and 2028 (depending on risk structure – for class D, C, and B devices). Manufacturers must also adapt to the stricter requirements imposed on Notified Bodies.

Similar changes to the new IVDR guidelines have been proposed in the United States for years but continuously stalled due to industry pushback. However, the U.S. FDA recently has indicated its intentions to propose new guidance on the regulation of laboratory developed tests following the failure of Congress to pass the Verifying Accurate Leading-edge IVCT Development (VALID) Act in December 2022. Included in these initiatives were the launch of a pilot program in June 2023 titled Oncology Drug Products Used With Certain In Vitro Diagnostic Tests: Pilot Program, which allowed for registration of certain companion diagnostic tests following the initial drug/device approval.

The new In Vitro Diagnostic Regulation (IVDR) is set to reshape the regulatory landscape for in vitro diagnostic medical devices in the European market. It significantly expands the scope of covered devices, encompassing high-risk devices, diagnostic services, genetic testing, and tests revealing patient predispositions. The transition poses challenges for manufacturers, necessitating re-evaluation of previously approved devices and adherence to new regulatory timelines. Overall, these changes are poised to bring added expense and regulatory burden to in-vitro diagnostic device manufacturers in coming years looking to sell in-vitro diagnostic products into the EU market and could limit the number of companies that choose to sell into the EU, especially for smaller companies or for smaller, more specialized test indications.