The In Vitro Diagnostic Regulation (IVDR 2017/746), provides a harmonised regulatory framework to ensure the safety and performance of devices in the European Union (EU).

In contrast with current directives, the new IVDR classification system requires most IVD devices to be subject to verification and certification by notified bodies (NBs). This new classification system presents an enormous change, as broadening scope of the rules means that approximately 80 to 90 percent of all IVDs will now require conformity assessment by an NB, compared to only 10 to 20 percent of devices undergoing this process under the IVDD. 

With dramatically increased workloads for NBs and reference laboratories, significant bottlenecks and delayed product reviews should be expected. This will be particularly relevant for IVDs classified as high-risk, because these devices will require a greater amount of attention and documentation. With the need to prove compliance to a NB prior to CE marking further complicating the IVDR transition process, an increased burden on IVD manufacturers may result in a higher cost of regulatory compliance if they do not have a thoughtful strategy in place. Here we discuss how to develop a regulatory and clinical evidence outcomes strategy for high risk IVDs.

Understanding the new risk-based classification system

Under IVDR, IVDs will fall into one of four classifications from class A (low risk) to class D (high risk). These classifications are defined by the intended purpose of the device, which must be clearly specified by the manufacturer on the device label, the performance evaluation or in promotional or sales materials. Failure to clearly communicate this information, or ambiguous claims around the uses of the device, may lead to higher classification. This is important to note because different device classifications under the IVDR have different documentation requirements.  

To help manufacturers better understand the nuances of this updated classification system, a new guidance was published in November 2020 providing information on how to classify an IVD prior to placing it on the market. Careful review of guidances in conjunction with IVDR is critical because if an NB does not agree with the manufacturers classification, a dispute process may be initiated. Important information that is often omitted include design specifications, final quality control inspections, legacy information and promotional materials. If feedback is not addressed within three rounds of review, the device application can be rejected and will be reported to EUDAMED. With these challenges in mind, classification of devices should be one of the first steps in each manufacturer's transition strategy. 

Developing a regulatory and clinical evidence outcomes strategy 

In addition to understanding the new classification requirements, manufacturers can prepare for regulatory submission by performing a portfolio assessment and gap analysis to address new requirements for each device and determine how to best prioritise resources moving forward. This portfolio assessment should include review of profitability, marketability and patient need for each product. Additionally, a gap analysis of current documentation can help manufacturers determine additional needs. 

Once these processes are complete, technical documentation should be created or updated in preparation for regulatory submission. Under IVDR, it is useful to note that although every product will require technical documentation, it will not require its own technical file. Manufacturers of high-risk products can save time and resources by combining multiple products with the same classification, analyte or dedicated assay systems. For example, an assay, calibrator and control may have different SKUs, but if they are dedicated they can be combined into one technical file rather than three technical files. 

In addition to technical documentation, high-risk devices will require a greater amount of clinical evidence than other IVD classifications. Due to the up-classification of many devices, manufacturers may be required to perform clinical testing on devices that previously did not require it. To aid in the process of collecting clinical evidence, manufacturers should develop a performance evaluation plan (PeP), which specifies the characteristics and the performance of the device, as well as outlines the processes and criteria to generate the clinical evidence. In addition to the PeP, a performance evaluation report (PER) should be assembled, which should be inclusive of the clinical evidence summary and the following three attachment reports:

  1. Analytical Performance Report, which presents evidence that the IVD performs as designed
  2. Clinical Performance Report, which presents evidence that it performs as designed in a clinical setting
  3. Scientific Validity Report, which focuses on the analyte, or target, and its clinical uses

This report will need to be continually updated. IVD manufacturers that have already begun these assessments will be well-prepared for the transition.

Finally, once technical documentation and clinical evidence are gathered, all materials should be submitted directly to a NB. A direct working relationship can ensure improved efficiency in gaining approval and ultimately maintaining market share under IVDR. 


Current trends are proving that IVD developers must move faster to comply with IVDR by the deadline. Manufacturers who have not begun preparations will need to adopt a strategy to address gaps in meeting the new regulation. To help navigate the complexity of this transition, it can be useful to involve top management in compliance efforts, as well as seek external expertise. To learn more about how to develop an effective transition strategy, read our whitepaper: The IVDR journey.

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