In Vitro Diagnostic Products

In the post-COVID-19 era, healthcare grapples with staff shortages and treatment delays, emphasising the need for early diagnosis. While regulatory changes pose challenges, EU extensions provide relief

In the aftermath of the COVID-19 pandemic many national health services have been left with depleted staff resources and long waiting lists for surgeries that in many cases are long overdue. In addition to this, the two-year slow-down in treatment and diagnosis of diseases caused by the pandemic have led to many conditions going undiagnosed or untreated during lockdown with consequent chronicisation of diseases that could have been treated more successfully if detected and countered early on. Many more patients that could have been treated with medication and therapy now require surgery.

In this context, early diagnosis plays a critical role in patient outcomes, ensuring patients understand how their symptoms will change over time and how this can be changed with treatment. Targeted interventions can also be started earlier, before potentially irreversible damage has occurred, helping to slow or reverse the disease process.

In vitro diagnostics (IVDs), described in the new EU IVDR 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’, play a critical role in supporting the healthcare system with early diagnosis. In addition to better outcomes, early intervention also results in lower treatment costs for health systems, making it imperative for national and international institutions to do as much as possible to improve access to IVDs. The regulatory upheaval in the UK and EU with the introduction of a new regulatory framework in the UK and IVDR are both an opportunity to address the issue and a risk for further bottlenecks in this device area.

With some variation, levels of spending by governments on IVD testing during the pandemic were consistently higher across the board: in the UK, NHS Test and Trace (NHST&T) spent £10.4bn on IVD testing in 2020 and 2021, up from £850m in 2017, while Denmark spent 0.5% of its GDP on testing in 2021. So while on the one hand the interest and awareness of the benefits that earlier testing through IVDs can bring, there are also other factors at hand, such as regulatory change, that are putting the brakes on this acceleration.

The regulatory landscape in Europe is experiencing revolutionary change with the introduction of the EU MDR and EU IVDR. Since the 1990s, in vitro diagnostic medical devices (IVDs) have been regulated by an EC Directive (IVD Directive (EC) 98/79). Since May 2022, the In Vitro Diagnostics Regulation (EU) 2017/746 (IVDR) fully applies and demands, among other things: greater transparency; enhanced harmonisation and standardisation; more regularity scrutiny; increased obligations and oversight of economic operators and notified bodies; more stringent criteria for clinical evidence and performance evaluation; and heightened traceability across supply chain through Unique Device Identification (UDI).

Within the EU IDVR, 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) and 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). On 23 January 2024 the EU has proposed an extension to the transitional provisions for certain IVD devices, postponing deadlines once again. Specifically, the proposal amends Article 110 IVDR and grants additional time to certify legacy devices under the In vitro Diagnostic Medical Devices Regulation (EU) 2017/746 (‘IVDR’).

The transitional provisions would be amended as follows:

• Legacy IVDs Class D (IVDR) must comply by 31 December 2027

• Legacy IVDs Class C (IVDR) must comply by 31 December 2028

• Legacy IVDs Class B and Class A sterile (IVDR) must comply by 31 December 2029.

However, it’s important to note that manufacturers need to meet certain conditions to be eligible for extension, such as having applied to a Notified Body (NB) at least two years before the compliance date (ie, September 2025, September 2026 and September 2027 respectively for Class D, Class C and Class B and A Sterile devices).

Therefore, this extension doesn’t mean manufacturers should pause their compliance activity, especially with current limited NBs availability. 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 NB. As of today, there are in fact only 12 appointed Notified Bodies for IVDs in Europe, so ensuring that a NB takes on a new device is not an easy feat.

IVDs in the UK

Early diagnosis is a topical thread 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 £21m fund. This move resonates with government plans to make the UK the global home of medical technology and breeding ground for innovation as set out in the Medical Technology Strategy but also with a recent road map by Cambridge Design Partnership, in partnership with CPI, the Association of British HealthTech Industries (ABHI).

From a regulatory standpoint, following Brexit, the UK now has the freedom to look at innovative and new ways to increase IVD products on market and reduce the regulatory burden, whilst maintaining high patient safety standards. For the time being, while the MHRA is increasing its engagement with industry and industry bodies (BIVDA, ABHI etc), the use of CE marking for IVDs in the UK market has been extended up to June 2030 (date to be confirmed). In addition to this the UK is working towards dual country approvals and supporting the UK's intention to be a hotbed for innovative technology and IVDs, and the MHRA announced in September 2023 the introduction of the Innovative Devices Access Pathway (IDAP) to ‘bring new technologies and solutions to the National Health Service (NHS) to help with medical needs that are not currently being met’. As healthcare moves towards a more proactive form of prescribing which 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.

In this complex international scenario, with constant changes and pushback, IVD manufacturers are struggling to keep up with the latest news and the role of the regulatory consultancy takes on critical importance in informing, advising and supporting them so that their devices can be safely commercialised in the shortest time possible. Cutting down time-to-market grants national health services speedy access to a range of IVDs to help catch disease at the early stages, that can be treated with drugs or minor procedures that are not particularly expensive and are minimally invasive for patients.

References

1. Test and Trace England – Progress Update, UK National Audit Office, June 25, 2021
2. Christian Wienberg, Denmark spent 0.5% of its GDP on Covid testing last year, Bloomber, 16 June 2022
3. Visit: health.ec.europa.eu/system/files/2024-01/mdr_in-vitroproposal.PDF
4. Visit: www.gov.uk/government/news/21-million-to-roll-outartificial-intelligence-across-the-nhs
5. Gov.uk website, Guidance: The Innovative Devices Access Pathway( IDAP) , visit: www.gov.uk/government/publications/the-innovative-devices-access-pathway-idap