IVDR: a small update of IVD regulations

14 Apr 2023 8min read

The new In Vitro Diagnostic Regulation (IVDR) came into effect on 26 May 2022 and regulates the making available of IVDs onto the market in the EU and EEA. While the EU Medical Device Regulation (MDR) has been very impactful for medical device manufacturers, the transition to the IVDR for IVD manufacturers is likely to be significantly more so, due to the way IVDs were classified from a risk perspective under the In Vitro Diagnostic Directive (IVDD). The following article provides a brief overview of the IVDR, including how it differs from the IVDD and the new challenges it has introduced for IVD manufacturers.

What is the IVDR?

Since 1998, in vitro diagnostics (IVDs) have been regulated for use in the EU and EEA (the CE mark) through compliance with the IVDD, which specifically addressed the safety, quality and performance of IVDs. High-profile device failures involving devices such as breast and hip implants drove the European Commission to review and fully revise the directives for both medical devices and IVDs, resulting in the transition to more stringent regulations aimed at improving patient safety, namely the MDR and IVDR.

The introduction of the IVDR

One of the most significant impacts of the IVDR is that fact that the need for an independent body to review technical data before a device is placed on the market has increased. These independent assessments are performed by Notified Bodies (NBs), who are accredited agencies whose roles are to ensure manufacturers have fulfilled requirements of the regulations.

Under the IVDD, NB involvement was limited to devices specifically listed in Annexes II List A (highest risk) and List B (lower risk), or those classed as a self-test for lay-person use. Examples provided in the IVDD lists included HIV, Hepatitis, blood grouping (List A), Rubella, PSA and self-testing for blood glucose (List B). NB involvement was also only required under the IVDD for approximately 20% of IVDs on the market and the vast majority of IVD manufacturers were able to CE mark their devices though a self-certification route in accordance with Annex III of the IVDD. The new IVDR requires the majority of products to be scrutinised by a NB potentially greater than 80% of IVDs.

Compliance to the IVDR applies to products that are already on the market, as well as new products being brought to the market. As this is such a huge undertaking, it will not happen all at once. Instead, a phased approach has been determined. Table 1 outlines the timetables set by the IVDR.

Table 1: Timeline for IVD registration under the IVDR

IVDD vs IVDR: differences and challenges

Implementing the IVDR will introduce a range of new challenges to IVD businesses. One of the most significant of these is the transition to a rule-based regulatory classification process.

Under the IVDD, classification was defined through the application of Annexes II and III. In comparison, under the IVDR, use-based rules are applied to derive the risk posed by a device. This is aligned with the approach taken for medical devices.

The IVDR classification system has four classes, i.e. A to D, D has been defined as carrying the most risk, down to A with the least risk. Table 2 outlines the different classes and examples of devices that sit within each class.

Table 1 Timeline for IVD registration under the IVDR

Table 2: Risk-based classification of IVDs

Useful reference: MDCG2020 – 16 Rev 1 Guidance on Classification Rules for in vitro DiagnosticMedical Devices under Regulation (EU) 2017/746

There is a provision within the IVDR to allow legacy devices (those placed on the market under the IVDD) to remain on the market during the transition window defined in Table 1. There are, however, significant restrictions imposed on any changes to the device in order to continue marketing during the transition, and any of the following key device changes would drive transition to the IVDR:

Any change in the intended purpose
Any significant change in the product, including:
o Changes to product design
o Changes to software
o Changes to ingredients or materials
o Changes to sterilisation, or changes to packaging that could impact sterilisation.

There is a Medical Device Coordination Group (MDCG) document (MDCG 2022-6) that provides guidance to indicate the types of change that would be considered significant. While this is a guidance document only, many NBs follow these and expect manufacturers to as well.

The rollout of the new IVDR

The actual transition process itself will require the involvement of a Notified Body for all but Class A non-sterile devices, which will remain as self-certified by the legal manufacturer. In a vast number of cases, legal manufacturers are submitting to an NB for the first time against the new requirements of the IVDR. The manufacturer will be required to undergo a QMS audit and submit a full technical documentation, including clinical evidence (scientific validity, analytical and clinical performance data) to support the intended use and clinical benefit of the products. As a result, manufacturers can expect much higher costs and increased time to get their product to market, or indeed removal of products from market if they fail to meet IVDR requirements.

In addition, one of the perhaps unforeseen issues with the IVDR rollout is the relatively low number of NBs that are approved to review products against the IVDR (only 6 as of January 2023). There is therefore a significant risk of a bottleneck developing for IVDs waiting to get to market and there is potential for a significant number of IVDs not gaining registration under the IVDR before the deadline for conformity.

To counter this, the European Commission generated a proposed amendment seeking to delete the ‘sell off’ clause contained within the IVDR, thereby allowing devices legally placed on the market after the end of the transition period under the IVDD to continue being sold until their actual expiration date. This proposed amendment passed successfully through the European parliament in February and was approved unanimously on the 7th of March 2023 by the European Council.

This will ensure that safe and effective IVDs that would have otherwise been removed from the market can continue to be made available until their actual expiry date.

The table below shows a summary of key new IVDR requirements as well as some of the potential challenges facing the manufacturers.

Meeting the IVDR requirements – an example

Let’s consider an example medical device on the market and the steps needed to meet the IVDR requirements.

A patient presenting with a persistent cough and fever would have a battery of tests ordered by their healthcare professional, one of which would be for the detection of Tuberculosis (TB). Under the IVDD, detection of TB would be a self-declared CE marked test, with minimal regulatory burden. Whilst manufacturers are obliged by the IVDD to generate a technical file for their self-certified products, many don’t, and often these companies do not have an ISO 13485 QMS.

Under the IVDR, the same test would be categorised as Class C. This change means that a manufacturer would now need to implement a QMS and submit technical documentation for review by an NB or undergo a Type Examination where the NB would review technical documentation, testing of the IVD and assessment of how the IVD was manufactured. Clearly, this is a significantly greater effort and commitment for IVD companies placing products on the market.

Read more about the different IVDR conformity assessment routes.

Ensuring compliance with IVDR

The objective of the IVDR is to ensure a greater level of regulatory scrutiny for IVDs. This can only be a benefit for end users as it will help to ensure safety and efficacy in all IVDs. However, its implementation may have the unintended consequence of temporarily limiting the availability of the IVDs in Europe while stakeholders adjust to the new regulation. It is essential that IVD manufacturers give adequate resource and time to ensuring that their IVD products are compliant with the IVDR in a timely manner. The level of effort that will be required should not be underestimated.