Commercialising IVDs – The complex path towards access to early diagnosis

Early diagnosis through the use of in vitro diagnostics (IVDs) plays a critical role in patient outcomes and in supporting the healthcare system as a whole. IVDs are defined in the new EU IVDR legislation as: “Any medical device which is a reagent, reagent product, calibrator, control material, kit, instrument, apparatus, piece of equipment, software or system, whether used alone or in combination, intended by the manufacturer to be used in vitro for the examination of specimens, including blood and tissue donations, derived from the human body”.

Such devices help to provide patients with a better understanding of their condition and how it might be managed and changed with treatment over time. Early interventions also result in lower treatment costs for health systems, preventing chronicization of diseases and the resulting impact on healthcare resources and budgets.

The importance of early diagnosis has really been spotlighted in the aftermath of the COVID-19 pandemic. National health services have been left with depleted staff resources and long waiting lists for surgeries that, in many cases, are long overdue. The impact of the pandemic led to a slow-down in treatment and diagnosis of diseases, with the result that patients who could have been treated with medication and therapy may now require longer treatment or even surgery.

Certainly, there is a need for national and international institutions to do as much as possible to improve access to IVDs. Arguably, public understanding and appreciation of IVDs has never been higher – the COVID-19 pandemic introduced the concept of IVD testing to a huge percentage of people. However, the backdrop to this increased awareness is a scene of regulatory upheaval, as manufacturers in the UK and EU wrestle to comply with changing legislation. These regulatory changes represent both an opportunity to address the issue and a risk for approval bottlenecks in this critical area.

The IVD picture in the EU

In May 2022, the regulatory landscape governing IVD devices within the EU changed. This date saw the introduction of the In-Vitro Diagnostics Regulation (EU) 2017/746 (IVDR), which further tightened control and scrutiny.

Within the EU IVDR, IVDs have been divided into four classes, based on both their intended purpose and its inherent risks. The four classes are: Class A (low individual risk and low public health risk), Class A Sterile subclass, Class B (moderate individual risk and/or low public health risk), Class C (high individual risk and/or moderate public health risk), and Class D (high individual risk and high public health risk).

To date, a vast number of IVDs have not yet transitioned to meet the tighter regulatory requirements of the IVDR. On 23rd January 2024 the EU proposed an extension to the transitional provisions for certain IVD devices, postponing deadlines once again.ⁱ

The transitional provisions would be amended as follows:

• Legacy IVDs Class D (IVDR) must comply by 31st December 2027
• Legacy IVDs Class C (IVDR) must comply by 31st December 2028
• Legacy IVDs Class B and Class A sterile (IVDR) must comply by 31st December 2029

However, it’s important to note that this extension doesn’t mean that manufacturers can afford to relax their compliance efforts. Certain conditions must be met to be eligible for extension, such as having applied to a Notified Body at least two years before the compliance date (i.e., September 2025, September 2026 ,and September 2027, respectively, for Class D, Class C, and Class B and A Sterile devices). As of today, there are in fact only 12 appointed Notified Bodies for IVDs in Europe, so, ensuring that one takes on a new device is not an easy feat.

Estimates suggest that the entire certification process could take up to 18-24 months, depending on risk class, status, and maturity of the technical documentation and QMS, as well as the availability of a Notified Body.

IVDs in the United Kingdom

Early diagnosis is a topical theme for UK industry experts and government departments. In the latest bid to spot disease before it becomes more complex and expensive to treat, the NHS has recently announced NHS staff will be given the latest artificial intelligence (AI) technology to diagnose and treat patients more quickly, thanks to a new £21 million fund.ⁱⁱ

In terms of the here and now for IVDs, regulation is also shifting in the UK. On 1st August 2023, in a significant reversal of policy, the UK Government announced that it will indefinitely recognise the EU’s Conformité Européenne (or CE mark) with respect to a range of manufactured goods placed on the UK market. Previously, post-Brexit, the UK planned to phase out the CE mark and replace it with its own UKCA mark.

However, further confusion lies in the fact that the indefinite extension of CE mark recognition does not cover medical devices, nor IVDs. The MHRA confirmed this position in a follow-up announcement and restated its existing plan to recognise the CE mark for medical devices and IVDs until 2028 and 2030, respectively, at which point manufacturers will be required to use the UKCA mark. A further update is expected in due course. Manufacturers are left wondering what the conformity assessment picture will look like over the next few years.

Clearly, the international scenario concerning IVD development and access is complex, with frequent changes and pushbacks. Manufacturers are tasked with keeping up to speed with these latest developments, and in this environment the role of the regulatory consultancy in informing, advising, and supporting manufacturers takes on significant importance.

As healthcare moves towards a more proactive form of prescribing that aims to “detect and contrast” early on, IVDs are no longer seen as simple tests, but as tools to protect the healthcare system and society from a range of known and new pathogens. Safely commercialising these devices in the shortest time possible enables diseases to be caught at the early stages, to the benefit of individual patients and the broader health service.