The Shift from IVDD to IVDR—and the Challenges

This article was originally published in LabCompare.

The shift from IVDD to IVDR represents a major change in how the IVD industry is regulated. While the EU Commission maintains that the system’s overall structure and approach remain consistent, manufacturers continue to face significant challenges.

The shift brings a stricter classification framework, clearer definitions of intended use, and higher standards for demonstrating and verifying clinical evidence. These changes reflect the EU’s focus on improving patient safety and market transparency while also introducing new compliance demands that require strategic adjustments from industry stakeholders.

But what does this shift actually mean for manufacturers, and how do these changes affect the regulatory landscape and the way IVD products are developed and brought to market?

The evolution of IVD classification under IVDR

Previously, IVDs were categorized based on a general listing that reflected the technology and scientific understanding available in 1998. Nevertheless, the previous system lacked a risk-based strategy and became outdated, prompting the EU to adopt the classification scheme suggested by the Global Harmonization Task Force (GHTF) in 2008. This new framework, already implemented in many countries worldwide, categorizes IVDs into four risk classes, with specific rules guiding the regulatory conformity assessments required for each device based on its risk level.

Under the new classification system, IVDs are categorized based on their intended purpose and manufacturer claims, reflecting their potential impact on patient health. There are higher-risk categories for devices used for high-risk diagnostics, like blood grouping or cancer detection, and lower-risk categories for devices with less critical implications. Screening devices, for instance, carry distinct considerations compared to those used for diagnosis or monitoring, as the decisions made from these tests pose varying levels of risk.

​​The shift in classification requires that an IVD’s intended purpose extends beyond the simple detection of an analyte to include its clinical function, claims, indications, and the targeted population. In regulatory terms, the shift from a purely analytical intended purpose moves from a simple description like "intended to measure in EDTA plasma" to a more detailed definition that includes the target population, clinical indication, and specific use case. For example, the new description would be "intended to measure in EDTA plasma on the automated analyzer [device name] for human patients aged [age range], for [type of cancer] cancer screening."

Additionally, all combinations of devices—such as those used for automated processes or in combination with other devices for sample collection, preparation, or other parts of the workflow—must be clearly specified.

Finally, the claims must be validated as part of the clinical evidence, which includes scientific validity, analytical performance, and clinical performance, through a performance evaluation process (separate plan and report). The IVDR emphasizes that clinical evidence should be based on sufficient, high-quality data to assess whether the IVD is safe, effective, and achieves the intended clinical benefit. Manufacturers must consider the latest scientific information and minimize foreseeable risks as much as possible, incorporating this into both the design and user information (such as warnings and contraindications). This may also need to be verified through clinical performance or usability studies.

Planning and compliance in IVD development

This change requires structured planning, a thorough understanding of scientific, analytical, and clinical assessment, and testing according to applicable standards. All of this must be documented meticulously so that independent notified body (NB) reviewers can verify it through objective evidence. When demonstrating and substantiating clinical evidence, the planning process is crucial to the lifecycle approach of medical device development and the associated Quality Management System (ISO 13485), as outlined in Guidance MDCG 2022-2.

The IVDR stipulates that the performance evaluation process, as outlined in Article 56 and Annex XIII, must be understood as a continuous process that is regularly updated. This means manufacturers must have a detailed plan in place, with defined responsibilities, methods, and timelines, before performance testing begins. This plan then informs the actual reports. This approach ensures that changes are tracked, allowing adjustments to avoid inefficiencies or unnecessary rework, and ultimately aligns plans with actual results.

Here are a few examples from the IVDR or current standards that require “Plans” and “Reports”:

In theory, the concept of planning, executing, and summarizing is straightforward, especially when QMS procedures are in place to define and control planning, testing, and reporting. However, many IVD manufacturers lack adequate QMS procedures, despite most being required under the IVDD and defined in ISO 13485 for years. Furthermore, this simple concept is often not fully understood, and both planning and post-market surveillance (PMS) are not prioritized by many IVD manufacturers, who have operated with minimal regulatory oversight under the IVDD in the EU for years.

Impact on manufacturers

Under the IVDR, IVDs requireclear verification and documentation of their intended purpose through performance data. This requirement may limit sales, as clinicians are restricted to the specific uses claimed by the manufacturer. Off-label use is allowed, but it shifts the responsibility to the clinician and the validation to the laboratory. As a result, this can lead to significant discussions between sales and regulatory teams as they work to define the intended purpose and ensure alignment with clinical evidence. For combined devices, such as IVD kits used with automated analyzers, the manufacturer must also validate these combinations. If the manufacturer does not, the laboratory is responsible for validating the combination, which adds both costs and time to the laboratory.

Then, the performance evaluation and clinical evidence may require substantial documentation, especially if there has been insufficient planning or if recent state-of-the-art standards have not been properly considered. The proper application of QMS (ISO 13485), Risk Management (ISO 14971), Usability (EN 62366-1), and Good Study Practice (ISO 20916) standards is often the source of nonconformities identified by notified bodies, which can sometimes date back years. These issues cannot be easily resolved if planning documents and procedures are missing or noncompliant.

In summary, the changes in the IVD classification system under the IVDR significantly impact intended purposes and clinical evidence. While medical device manufacturers are familiar with the risk-based classification system under the MDD, many IVD manufacturers are still adjusting to the changes from the IVDD to the IVDR. These challenges often only become apparent when their data is reviewed and assessed by an independent Notified Body. As with many other regulatory processes, good planning and awareness are key to meeting requirements. With proper preparation, CE marking under the IVDR can be more manageable than it may initially seem. IVD manufacturers who have already gathered and documented sufficient data to support their claims and comply with state-of-the-art standards will find the transition from IVDD to IVDR much easier, and in some cases, it may not pose a significant challenge at all.

What’s next?

To comply with IVDR, IVD manufacturers must take a systematic approach to meet evolving regulations. While the transition can be difficult, especially for those unfamiliar with risk-based classification, proper planning and documentation make the process easier. From expert guidance to the use of advanced tools, manufacturers who prioritize regulatory preparedness will be in a better position to meet IVDR requirements, save time and money,  and stay ahead of the competition.

About the author

Oliver Eikenberg is Pure Global's Global QA/RA & IVDR Manager. He brings over 17 years of experience in regulatory affairs for medical devices, along with hands-on expertise in device development, manufacturing, and product management. With a PhD in analytical chemistry and 15 years in R&D, manufacturing, and quality control, Oliver is committed to advancing smart, efficient solutions in the IVDR sector.

Written by Oliver Eikenberg, PhD, Pure Global

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