This article was originally published in Today's Clinical Lab.

The regulatory landscape for in vitro diagnostic (IVD) manufacturers in the European Union is evolving, bringing about significant changes. The latest amendment to the In Vitro Diagnostic Regulation (IVDR), EU 2024/1860, took effect on July 9, 2024, introducing a series of important updates. These include the phased introduction of the EUDAMED medical device database, new supply chain obligations, and revised transitional provisions for IVDs.

The IVDR, which replaced the former In Vitro Diagnostic Directive (IVDD), set forth stringent requirements for the development, manufacturing, and distribution of IVDs within the EU. Initially, all IVD manufacturers were expected to comply with these new regulations by May 26, 2022. However, the reality of this transition has proven challenging for many companies, leading to the introduction of several amendments designed to provide more time for compliance. The latest amendment, EU 2024/1860, extends the transition period for legacy devices by an additional three to five years, depending on the device's risk class.

Manufacturers might view this as just another extension, possibly leading them to slow down or pause their transition efforts, believing there will be less scrutiny from competent authorities or notified bodies (NBs). However, understanding the limitations, deadlines, and specific requirements of this amendment is essential for manufacturers who wish to continue operating within the EU market without facing severe regulatory and business risks.

Key questions IVD manufacturers need to consider for EU 2024/1860

To fully grasp the implications of the IVDR Amendment EU 2024/1860 and to prepare adequately, manufacturers should ask themselves the following questions:

• Do I fully understand the limitations for legacy devices under the amended transition timelines?
• Am I aware of what constitutes significant changes in design and intended purpose that could invalidate these amended timelines?
• Do I know what I need to prepare to have a quality management system (QMS) that meets IVDR Article 10(8) requirements by May 2025, including economic operator controls, risk management, performance evaluation, post-market surveillance (PMS), and vigilance?
• Do I know what I need to prepare for lodging the formal application with the NB and then signing an agreement with the NB starting in May 2025? (The deadline depends on the risk class of the IVD device; see Table 1 below).
• Do I understand the required supply chain controls for my economic operators, critical subcontractors, and crucial supplies?
• Is my resource planning adequate to ensure a timely transition to IVDR compliance?
• Do I understand the consequences, costs, and business risks of failing to comply with these requirements?

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Table 1: IVD manufacturers need to be aware of various upcoming deadlines to comply with EU 2024/1860.

If the answer to any of these seven questions is not a clear “yes,” this could have a significant impact on your business in the EU.  

For instance, if by May 2025 your QMS fails to include the necessary procedures outlined in Article 10(8), the amended timelines may no longer apply to your device. Similarly, if the intended purpose of your product is not fully defined according to Annex I, Section 20.4.1(c), NBs will not accept your application. This is true for software and systems. If your product does not meet and maintain compliance with state-of-the-art standards, it may no longer be considered compliant with the IVDD.

You may ask yourself, "Who will be responsible for ensuring my QMS complies with Article 10(8) by May 2025?" The competent authority has the power to perform unannounced inspections, and it will certainly review your compliance when you submit your application to the NB for CE marking. Even if your submission is after May 2025, the digital documentation systems used by most manufacturers make it easy for auditors to trace back and verify what was implemented by that deadline.

Meeting these amended deadlines also means accounting for potentially lengthy NB review timelines. The amendment indicates an average NB review time of 18 months. However, this can vary significantly based on the quality of your documentation. This is why it’s essential to plan your internal activities and timelines to ensure your IVD complies with IVDR requirements.

This effort may involve significant documentation efforts, including the creation of general safety and performance requirements, performance evaluation plans and reports, PMS plans and reports, and post-market performance follow-up plans, and reports. In fact, it may even require new analytical testing or even clinical performance testing to demonstrate the clinical evidence.

NBs have already warned that delaying applications will result in submissions being placed at the end of the review queue, increasing the risk of delayed assessment. They have also indicated that if applications for legacy devices are submitted too close to the cut-off deadline, they may not be able to process them in time. Consider the perspective of the NBs: They need to manage their resources effectively, which requires predictable numbers of IVD submissions to plan accordingly.

As a consequence, the deadlines for submitting applications and signing agreements with the NBs are crucial for manufacturers of legacy devices aiming to take advantage of the extended transition periods. In fact, from a business standpoint, these deadlines should be treated as internal milestones.

A strategic approach to navigating new regulations

In navigating the complexities of the IVDR, particularly with the recent EU 2024/1860 amendment, it’s safe to say that strategic preparation is key for IVD manufacturers. In my 25 years of work experience in the IVD field, I have frequently discussed with manufacturers what constitutes an adequate level of regulatory information and how to strike a balance between meeting regulatory requirements and managing business needs.

My consistent advice as a consultant is to first conduct a brief analysis of the company's current situation and the level of documentation it has implemented. Many IVD manufacturers have not yet been audited by NBs, and due to the sheer volume of new regulatory interpretations, there is often a significant gap between what manufacturers believe they have in place and what is required to demonstrate IVDR compliance.

The old 1-10-100 rule, commonly used in design to demonstrate the costs of poor design or inadequate controls, applies here as well. Failure to comply with regulatory requirements can result in costs that are 10 to 100 times higher than anticipated. The additional costs associated with extended NB review times and higher hourly fees—recently reported to be between €300 and ~€400 per hour—underscore the importance of thorough preparation.

To mitigate these risks, manufacturers should view the deadlines for lodging applications and signing agreements with NBs as critical internal milestones. After all, these are not just administrative requirements but key aspects of maintaining the market position in the EU.

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