Delay, delay, delay, mixed with more uncertainty. This is the nature of the European regulatory landscape in 2022. Although the European Parliament decided at the beginning of the year to extend the grace period for various in vitro diagnostic products that require CE-IVD marking

Delay, delay, delay, mixed with more uncertainty. This is the nature of the European regulatory landscape in 2022.

Although the European Parliament decided at the beginning of the year to extend the grace period for various in vitro diagnostic products that require CE-IVD marking under the new in vitro diagnostic regulations, the issues that forced these extensions persisted throughout the year. Shortages in regulatory capacity continue to delay the implementation of new regulations, while some of the resources needed to fulfill regulatory requirements are not ready.

While IVDR does not directly apply to every country in Europe, its effects are likely to be widespread across the continent, with at least one country, Switzerland, , concerned about the shift to IVDR and its deadlines, as well as the availability of healthcare products holding the certificate, voting last month to recognize diagnostics approved by the U.S. Food and Drug Administration (FDA).

At the same time, the UK has also decided to postpone the end of the transition period of its own regulatory system by one year.

Furthermore, given the ongoing challenges faced in implementing IVDR's sister regulation, the Medical Devices Regulation (MDR) at the height of the COVID-19 pandemic, the regulation's application was delayed by one year from May 2020 to May 2021 and faces new potential delays and amendments to its transition regime, while the end of the transition period for some IVDs covered by IVDR is also likely to be brought forward.

Life sciences and IP lawyer based in AmsterdamErik, one of the founding partners of , Axon Law Firm "The capacity of notified bodies for IVDR will be insufficient in the long term, which will lead to a similar situation to MDR, where many IVDs will not receive IVDR certification before the end of their grace period," Vollebregt said in an email this week.

Vollebregt added that while IVDR applications have slowed down as manufacturers may want to see if the grace period will indeed be extended, MDR appears to be happening soon.

"Notified bodies are actually advertising places for IVDRs as the application stream for IVDRs has dried up. IVD companies have adopted a waiting game when they really should be applying now as there is capacity at the moment."

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MDR and IVDR were enacted in 2017, replacing older directives that had been in force since the 1990s, including the 1990 Active Implantable Medical Devices Directive (AIMDD) and the 1993 Medical Devices Directive (MDD). The 1998 IVD Directive (IVDD) had allowed many IVD to obtain the CE mark through a self-certification process, but the new regulations require that most IVDs must be evaluated by a Notified Body (NB) before being marketed.

Initially, manufacturers of medical devices and IVDs have until May 26, 2020 and May 26, 2022, respectively, to obtain new certificates for their products from designated NBs. By these dates, both regulations will begin to apply. However, given the large administrative burden of the new regulations and the insufficient capacity to process these applications, EU decided to postpone the MDR application date by one year to May 2021. The ongoing COVID-19 pandemic influenced this decision in part, as travel restrictions make in-person audits of state agencies difficult.

The EU has not changed the final date for products holding AIMDD and MDD certificates to require new MDR certificates, which is May 26, 2024. However, earlier this month, the European Commission proposed that this deadline may be extended again, citing ongoing shortages in regulatory capacity and the threat that Europe will face a shortage of compliant medical devices.

As a result, the Commission said it is considering publishing a legislative proposal in January 2023 that would postpone the deadline for obtaining a new certificate under the MDR to May 2027 for certain categories of high-risk devices, and to May 2028 for low-risk device categories.

The reason for the postponement of the deadline is that although 36 NBs have been designated to evaluate medical devices under the MDR so far, industry stakeholders believe that these NBs still do not have sufficient capacity to evaluate all devices holding certificates by May 26, 2024. The committee is likely to recommend revisions to the MDR in January.

While the proposal to extend the MDR transition period does not directly affect IVDs, the fact that the committee made the revision does not bode well for the implementation of IVDR, as so far only seven NBs have been designated to evaluate IVDs under the new regulations.

These designated bodies include 3EC International for Slovakia , the German and Dutch branches of Dekra Certification Company, BSI in the Netherlands, GMED SAD in France, and TÜV Rheinland LGA and TÜV SÜD in Germany.

Earlier this year, the EU decided not to extend the application dates for IVDR like the MDR, but instead to extend the application dates for traditional tests in a staggered manner based on device risk level, with all IVDs expected to be compliant by 2028.

Since most molecular devices fall into category C under the IVDR, those holding a CE-IVD mark obtained under the IVDD, or a mark obtained before May 26, 2022, currently need to obtain a license by May 2026.

It is worth noting that this situation has not changed at present, although this small number of designated NBs are responsible for reviewing all molecular tests in the EU within four years (while 21 NBs are already designated under IVDD). In October, the EU's Medical Device Coordination Group (MDCG), which oversees issues related to the medical sector, announced an investigation into NBs with industry stakeholders.

Among them, they report that 40% of IVDR-specified IVD customers are in the EU, while 60% are outside the EU. According to the survey, for most submissions, it takes an average of one year to 18 months to get your quality management system and products certified by IVDR.

Despite these ongoing bottlenecks, the EU has been developing guidance to support its transition to the new regulatory regime, and some resources have come online, albeit behind schedule. For example, in May, the MDCG published a guidance on the validation of Class D devices (the highest risk category) under IVDR.

In October, a draft guidance emerged on the role of authorized representatives. According to the MDR and IVDR, non-EU companies need an authorized representative in the EU to support the launch of their products on the EU market. This month, the EU published an information package to support the development of European Reference Laboratories (EURLs), which will play a role under the terms of the IVDR by validating reagent manufacturers' claims by assessing the performance of their diagnostics.

According to the information package, candidate laboratories should prepare evaluation documents in early 2023 and are scheduled to be designated by the committee in the summer of 2023. Parts of the

Eudamed database, which is also central to the IVDR implementation, are also up and running, although it has yet to be reviewed as a full feature or made mandatory for use. However, some EU member states have begun requiring the use of Eudamed's modules, which can be used on a voluntary basis. Under the IVDR, reagent manufacturers should upload data about their products to Eudamed, including notified body conformity assessments, performance study data and post-marketing surveillance information.

EirMed, a company that helps others manage Eudamed submissions, has already submitted data from thousands of devices for clients this year, said CEO Richard Houlihan, although entering your own data into the database will remain voluntary until the end of 2024, when it will become mandatory.

Houlihan added in an email that the proposed changes to the MDR transition date have had a "surprising effect" as more companies have recently been looking to upload data from devices holding certificates obtained under the MDD. "We are waiting to see if there are more changes to the IVDR deadline," Houlihan said. Some

features remain offline for the time being, including those related to vigilance, market surveillance and clinical investigations.

"Overall, Eudamed is stable.", Houlihan said. "While Eudamed will not be fully functional until the fourth quarter of 2024, our advice is still to enter your data now to avoid the headache of a stressful project later."

Meanwhile, in a sign of the impact of IVDR across Europe, and not just in the EU, Switzerland recently updated its own diagnostic regulations, at least in part due to the changing IVDR landscape.

Switzerland has other issues to deal with, such as the expiration of Switzerland’s mutual recognition agreement with the EU on IVDD and the Swiss government’s refusal to ratify a broad internal market access instrument known as the Institutional Framework Agreement, or IFA. The latter was a negotiation between Switzerland and the EU from 2014 to 2019, including IVDR, which resulted in IVDR not being applicable in Switzerland.

In late November, The Swiss Federal Parliament, the Alpine country's federal legislative body, voted to accept FDA-authorized medical devices onto its market, in part to avoid potential shortages caused by regulatory bottlenecks in the European Union. The decision still needs to be incorporated into Swiss law.

Prior to this, Switzerland only accepted devices holding CE-IVD to enter the market. In a statement, the Swiss Medical Technology Association made it clear that the decision was related to continued delays in the implementation of MDR and IVDR.

Swiss Medical Technology Association general manager Peter Biedermann said in a statement on November 28 that the move was "a response to a situation that can no longer be ignored," citing "implementation issues with Europe's new [MDR] and the negative impact on the supply, product range and quality of medical devices across Europe."

Biedermann noted that because more and more innovative products are launched first in the U.S. market, the arrival of new products in Europe is "delayed at best."

Switzerland is neither a member of the EU nor a signatory to the European Economic Area (EEA) agreement, unlike other non-EU members Iceland, Liechtenstein and Norway. It does have a mutual recognition agreement with the EU. However, in May 2021, when the MDR came into effect, the EU decided that the MRA no longer applied to Swiss medical technology products because Switzerland had not signed an institutional agreement. In response, Switzerland passed a decree requiring registration of non-Swiss medical technology products sold in the country.

Since then, there have been mutual trade barriers between the EU and Switzerland, Anita Holler, a spokesperson for Swiss Medical Technologies, said in an email.

Switzerland is now considered a third country in the EU and local manufacturers require an authorized representative in the EU and CE-IVD marking to sell their products outside of Switzerland. EU manufacturers now require the same conditions to sell their products within Switzerland. According to Holler, opportunities to resolve the issue receded into the distance when the Swiss Federal Council broke off negotiations with the EU on an MDR-related institutional agreement.

Regarding the federal parliament's vote to accept FDA-certified products into the Swiss market, Holler said that the Swiss Federal Council must now implement the parliamentary order within two years.

UK still on hold

While the transition to the MDR and IVDR within the EU continues to be plagued by delays, the UK is facing its own delays this year. When the island nation left the EU in February 2020, it did not have an agreement with the bloc on the mutual recognition of medical devices and IVDs.

A year later, The UK Parliament passed the Medicines and Medical Devices Act 2021, which enables the UK to establish a new regulatory framework. Later in 2021, the UK Medicines and Healthcare products Regulatory Agency launched a public consultation on a new regulatory system that broadly reflects IVDR. Under the proposed regulations, UK companies and foreign companies seeking to sell molecular tests into the UK will need to obtain a certification mark, known as the UK Conformity Assessment or UKCA mark, from a recognized standards organization (called an accreditation body) designated to assess IVDs.

Following its original advice, MHRA said companies could continue to sell IVD products holding a CE-IVD mark obtained under the IVDD or IVDR until July 2023, when they will obtain the UKCA mark. The condition only applies to products placed in the UK island and its countries of England, Scotland and Wales, while Northern Ireland continues to operate under a mixed regime, with both the CE-IVD and UKCA marks being recognized.

But on October 21, the MHRA decided to postpone its so-called 'standstill period' by a year to July 2024. The delay still requires legislative approval, which could come in early 2023, according to Stephen Lee, director of diagnostic regulation at the UK Health Technology Industry Association.

Lee noted that ABHI is working with the MHRA and the UK Life Sciences Office on international recognition, innovation routes and system capabilities for UK-approved IVDs. Li said preliminary proposals for these priority areas will be announced in February 2023. The

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