The In Vitro Diagnostic Regulation (IVDR) has fundamentally changed how in vitro diagnostics (IVD) are regulated in the EU. As a result, scrutiny for review and documentation has increased substantially, including a dramatic increase in required reviews by notified bodies (NB).
For IVD companies, the challenge of adapting to a significant set of regulatory updates is compounded by a NB bottleneck. In this blog, we discuss these added challenges and how to plan for them.
Dramatic increase in demand for notified bodies (NB)
In the past, under in vitro diagnostic medical devices directive (IVDD), the vast majority of IVDs could be self-certified by their manufacturers, who could obtain a CE Mark without a notified body’s review. Now, under the IVDR, Conformity assessment procedures have tightened.
Most IVDs — other than Class A, non-sterile — will need their quality management system and their technical file or design dossier audited by a notified body to ensure compliance with IVDR classification and other requirements.
The new regulations categorize IVDs based on main characteristics and intended purpose. The majority will be classified as Class B, C or D. It’s estimated that, under the new system, the proportion of products requiring NB oversight will increase from 7 percent to 84 percent.
Scrutiny has increased overall — but what does this mean in practice?
The tradeoff for improved patient safety is greater oversight from all directions and more time to achieve the CE mark. The IVDR demands more complex, detailed, and time-consuming data gathering and document preparation.
If a device has multiple intended purposes that fall under different classes, the device falls under the highest risk category. Current data can be repurposed, but often, it’s insufficient, and more clinical evidence is needed.
As previously noted, one of the most significant changes created by the IVDR is the level of third-party oversight. This will increase the regulatory burden for IVD manufacturers and their notified bodies, since most products will now require NB review.
Additional reporting responsibilities will change sponsor relationships with stakeholders in the supply chain, including manufacturers, authorized representatives, importers, and distributors. Post-market activities must increase as well.
There is a significant summit of work required to transition from the IVDD to the IVDR. This means manufacturers will need more time to prepare and can expect a longer review and approval process with a change in their relationship with sponsors and economic operators.
Combined pressures have produced a NB bottleneck
With the increased oversight expected under IVDR, demand for NBs is at an all-time high. Meanwhile, the number of NBs has decreased such that many in the industry wonder how all the necessary evaluations will possibly get done. What’s going on?
The number of NBs has decreased for several reasons. The increased training requirements under the Consolidated NB Initiative, increased expectations, and reluctance to operate during a pandemic caused some NBs to withdraw. It now takes two years to fully train an NB expert, and during this time, they have limited utilization. Furthermore, the number of in-house experts required to achieve NB designation has increased. The result for the entire EU is: 22 IVD NBs -> 7 IVDR NBs.1
It is expected that there will be a significant bottleneck not only for NBs, but also for European reference labs, especially for class D devices.
European Commission amends Article 110 to address the shortage of notified body capacity
In October 2021 the European Commission issued COM(2021) 627,2 amending the transitional provisions for certain IVDs in Regulation (EU) 2017/746. This update extends the transitional periods for devices requiring a conformity assessment by a notified body.
Higher-risk (Class D) devices must be IVDR-certified sooner in the amendment’s progressive rollout of transition times. Class D and class C devices already existing under the IVDD may be placed on the market or put into service until May 2025 and May 2026, respectively. For existing Class B and Class A sterile devices, the transition is now May 2027.
Most devices with certificates issued under the IVDD may continue to be sold for one year after the transition date. The exception is class A non-sterile devices, which are expected to be fully compliant as of May 26th this year. This sensible extension aims to balance NB capacity when regulatory resources are limited while keeping the focus on patient safety.
Adapt by planning for extended certification timelines
A look at the steps to IVDD certification and their expected timelines reveals that there’s no time to waste even with the rollout amendment.
Consider a Class D device journey, for which the level of scrutiny is highest.
Typically, manufacturers will start with a gap assessment. This will lead to the preparation of the IVDR technical file. If new clinical evidence is missing, further analysis may be required. Then the manufacturer must secure a NB contract, but has to be IVDR ready first.
The next step is the application review, which involves significant sharing of information between manufacturers and NBs. For this step, document quality is key and will impact the start of the conformity assessment. Also, experts in European reference labs may need to be consulted to check the common specifications — another potential delay.
All in all, this could be a 30-month journey for a single class D device, 26 months for Class C, or 23 months for Class B or Class A sterile devices. A Class D IVDR application process started in May 2022 will finish around May 2025, assuming each step goes to plan. Any last-minute surprise could prevent the product from getting to market on time.
Be proactive in meeting IVDR requirements
The transition from IVDD to IVDR is a significant undertaking. IVDR is more detailed and complex with far more oversight than IVDD and will require more resources to implement and maintain. This includes a vast increase in NB involvement when the number of NBs is at a low point. The key is to anticipate change and be proactive in meeting the requirements.
At Premier, our regulatory team tracks the latest global policy shifts. We will ensure you stay on top of new guidance and requirements as well as shifting timelines as we help you optimize your diagnostic’s development pathway.
1 European Commission. Internal Market, Industry, Entrepreneurship and SMEs. Available at: https://ec.europa.eu/growth/tools-databases/nando/index.cfm?fuseaction=directive.notifiedbody&dir_id=35
2European Commission. COM(2021)627 – Regulation of the European Parliament and of the Council amending Regulation (EU) 2017/746 as regards transitional provisions for certain in vitro diagnost. Available at: https://ec.europa.eu/health/latest-updates/com2021627-regulation-european-parliament-and-council-amending-regulation-eu-2017746-regards-2021-10-14_en