Jonathan Ripley, IVD and MD consulting services director at IMed Consultancy discusses the role of IVDs, regulatory perspectives for their adoption and increased market access.
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The EU has recently 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 Invitro Diagnostic Medical Devices Regulation (EU) 2017/746 (‘IVDR’).
The transitional provisions would be amended as follows:
- Legacy IVDs Class D (IVDR) must comply by December 31, 2027
- Legacy IVDs Class C (IVDR) must comply by December 31, 2028
- Legacy IVDs Class B and Class A sterile (IVDR) must comply by December 31, 2029
However, it’s also important to note that manufacturers need to meet certain conditions 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). Therefore, this extension doesn’t mean manufacturers should pause their compliance activity, especially with current limited NBs availability.
This article will analyse the key role of IVDs in supporting healthcare systems with early diagnosis to tackle common and rising diseases and comes at a critical time for manufacturers that still have not started the process of registering legacy devices under the EU IVDR.
The early screening imperative
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. Early diagnosis and treatment of often asymptomatic conditions such as type 2 diabetes, hypertension, and hyperlipidaemia could have a huge impact on patients as well as health system budgets. With oncology patients specifically, early diagnosis is closely linked to survival rates: prostate cancer, for example, has extremely high one year survival rates (around 100%) whether it is detected in stages 1, 2, or 3, falling to 87.6% if detected in stage 4. Research by McKinsey suggests that the health improvement opportunity in Europe lies mainly in the area of disease prevention and earlier intervention.
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 £10.4 billion on IVD testing in 2020 and 2021, up from £850 million 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.
Challenges to IVD introduction in Europe
The regulatory landscape in Europe is experiencing 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, 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 risk classification system has been established following seven classification rules described in ANNEX VIII of the EU-IVDR. 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).
It is the manufacturer that is responsible for applying the right risk class to its IVD, and to provide a justification for this decision. Higher risk devices will of course be subject to more regulatory scrutiny, however wrong classifications that result in a deviated conformity assessment route are likely to end up causing delays to market entry, stopping patients and healthcare providers from accessing the tools they need for speedy diagnosis.
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. 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.
Despite this, frequent pushing back of deadlines and lack of access to EUDAMED have lulled manufacturers into a state of inactivity with many failing to make contact with an NB in good time for an 18 months regulatory approval pathway. As a result, the much-needed instruments to help national health systems make early diagnoses, improving patient outcomes and system efficiency may not be on the market when they are needed.
The UK landscape for IVDs
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 £21 million 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 roadmap 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. The development of a new UK-only regulatory system therefore represents a key opportunity to ensure that more IVDs are able to make their way onto the market. For the time being, while the MHRA is increasing its engagement with industry and industry bodies (BIVDA, ABHI etc.), extended the use of CE marking for IVDs in the UK market has been taken up to June 2030 (Date to be confirmed). In addition to this, the UK is working towards dual country approvals and supporting the UKs intention to be a hotbed for innovative technology and IVDs 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.”
It is not possible, however, to increase use of IVDs in healthcare unless these are making their way through regulatory pathways steadily and successfully. In this complex international scenario, the role of the regulatory consultancy takes on critical importance in informing, advising and supporting IVD manufacturers 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.
As healthcare moves away from a “pill for all ills approach” and 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.