Top IVDR Notified Body concern: Lack of E.U. reference laboratories for high-risk diagnostics

Quick regulatory background on the MDCG

• The Medical Device Coordination Group (MDCG) is an expert group addressing “key issues from the medical devices sector” (including IVDs). Article 103 of the Medical Device Regulation (“MDR”, Regulation (EU) 2017/745) established the MDCG to “deal with key issues from the medical devices sector.” Article 105 of the MDR outlines the tasks of the MDCG, including “to contribute to the development of guidance aimed at ensuring effective and harmonized implementation of this Regulation.” The MDCG also addresses issues related to in vitro diagnostic devices and the In Vitro Diagnostic Regulation (IVDR; Regulation (EU) 2017/746).
• Thirteen subgroups address different aspects of the regulations by providing “advice and draft guidance on their expertise field;” each subgroup has one expert representative (with designated alternates) from each Member State. Subgroups address Notified Body oversight, standards, clinical investigation/evaluation, post-market surveillance and vigilance, market surveillance, borderline and classification, new technologies, unique device identification (UDI), IVDs, nomenclature, Annex XVI products, EUDAMED, and international matters. These groups “meet regularly with the EU Commission as Chair.”
• There is a yearly calendar of meetings for the group that sets out when the MDCG plans to meet, when it will meet with stakeholders, and the subgroup meeting schedule. Stakeholders are largely industry groups (e.g., APPLiA, AESGP, BioMed Alliance, MedTech Europe), but also include associations representing Notified Bodies, authorized representatives, healthcare professionals (e.g., ECOO, HOPE, ESC) and patients (e.g., EPF). Additional information about the meetings can be found here; this includes meeting attachments, general agendas, minutes and presentations. These resources provide a look into what each group is working on before the policy, regulation or guidance document being developed is ultimately published.

AgencyIQ walked through the newly available May meeting notes to highlight key developments for the device and diagnostic industries

• The MDCG met privately and with stakeholders in May 2024 to discuss implementation of the MDR and IVDR; these minutes have just been made public. This analysis focuses on a handful of the projects with the biggest impact for device and diagnostic manufacturers, including the E.U. Reference Laboratories, a recent poll of Notified Bodies on their views of MDR/IVDR implementation challenges, the Medical Device Single Audit Program (MDSAP) and overlap with other E.U. regulations, specifically the Substances of Human Origin (SoHo) regulation and the AI Act.
• Some news on E.U. Reference Laboratories: E.U. Reference Laboratories, or EURLs, are a key component of both assessing high-risk diagnostic devices and ensuring they maintain performance, by testing them against common specifications or other validated tests. [ Read more about what EURLs are and what they do here.] The Commission designated the first five EURLs in December 2023, but these covered just four of the eight categories of high-risk diagnostic tests – hepatitis or retrovirus, herpesvirus, bacterial infection, and respiratory virus infection. The other four categories do not yet have designated EURLs (arboviruses, hemorrhagic fever and other biosafety level 4 viruses, parasites and blood grouping).
• In February 2024, the Commission launched a new expression of interest to find more EURLs, asking for labs that could cover the four remaining diagnostic categories. If enough interest was generated, the Commission would launch a formal second call. Labs had until April 30, 2024 to contact the Commission. As of May 6, 15 Member States responded that they found 14 laboratories from eight countries that were interested in applying to be EURLs. Based on that information, the Commission proposed launching a second call for parasites and blood grouping testing labs; however, it didn’t find enough expertise or coverage for arboviruses and biosafety level 4 virus testing. As of this week, the Commission hadn’t yet launched the formal second call.
• NBCG-Med poll of Notified Bodies: NBCG-Med is a Commission expert group composed of Notified Bodies with observer status for the MDCG. In April 2024, the group held a plenary meeting at which it took the opportunity to poll its members on their greatest MDR and IVDR concerns. NBCG-Med presented the results of the poll at the MDCG/stakeholders meeting in May.
• MDR poll concerns: The top concern from Notified Bodies was the amount of effort it was taking Notified Bodies to implement Regulation (EU) 2023/607 (the mid-2023 extention and transitional provisions for IVDR/MDR implementation). Notified Bodies complained about receiving MDR applications from manufacturers with no real intention to transfer to MDR, as well as the burden of handling change requests for legacy devices and surveillance of devices with expired certificates. The next biggest concern was manufacturers’ overall lack of preparedness – including those not submitting technical documentation, not responding to Notified Body requests, threats of legal procedures, and not submitting clinical data. Next on the list of concerns was harmonization among Notified Bodies on questions of substantial change, depth of manufacturer and product assessment, clinical requirements and interpreting MDCG documents. The last concern was MDR implementation, wherein some parts of the regulation were difficult to implement and there had been an unrealistic expectation that all Notified Bodies would be designated and would have reviewed and certified all devices within four years.
• IVDR poll responses: By far the top concern for IVDR-designated Notified Bodies was the EURLs; in particular, the first batch of designations took a long time, and even then the first group designated covered only half of the high-risk diagnostics. The first group isn’t yet operational, but is expected to start testing activities by October 1, 2024. The second major concern was the amount of effort Notified Bodies are having to put toward implementing Regulation (EU) 2024/1860, which further lengthened the transition period for IVDs and allowed for a gradual rollout of the EUDAMED database, rather than focusing on IVDR implementation. The next concern was the IVD designation codes outlined in Regulation (EU) 2017/2185, with Notified Bodies complaining that five-factor coding was too granular, IVT codes (which are intended to describe technologies) were not all relevant to IVD manufacturing processes, and there was a lack of clarity in how to apply codes. The fourth area of concern was the Notified Body designation process, the lack of pathways for innovation and the lack of manufacturer preparedness.
• Update on Europe and the Medical Device Single Audit Program (MDSAP): MDSAP participation means that a single regulatory audit can cover multiple jurisdictions; Europe is not currently a participant in the program, but is an observer has been an observer but not a participant. [ Read more about the MDSAP program and who participates here.] The Commission has been evaluating participating fully in the program for some time, and the NBCG-Med took the opportunity at the May 2024 MDCG meeting to tout its benefits. The group suggested that adding the E.U. to the MDSAP certificate might increase acceptance of MDR/IVDR and lower trade barriers, as the Global Harmonization Task Force did in previous years. NBCG-Med also pointed to its predictable and uniform audit process and reduction of inspectors. For Notified Bodies also certified for MDSAP, it would allow for uniform audit checklists, planning, and reports, thereby reducing administrative burden. The group did acknowledge more groundwork would be needed, to include guidance on performing MDR/IVDR audits under MDSAP and an assessment as to whether an extra MDR/IVDR QMS assessment would be needed on top of MDSAP audit.
• The interaction of the Substances of Human Origin (SoHo) Regulation on MDR and IVDR: The SoHo sector relies on diagnostics to have safe products for use in humans. The use of human tissues and tissue derivatives in devices now need to take into account the SoHo regulation. Blood bags and the chemical classification of bisphenol A, di(2-ethylhexyl)phthalate (DEHP) can impact SoHo and their collection and use. Critical devices for the SoHo space are those diagnostics used for testing the blood supply and devices that separate blood components for use in stem cell transplants, CAR-T cell therapy and other applications. At the May 2024 meeting, MDCG members and stakeholders received updates on the “state of play of the new EU legal framework” under the SoHo regulations. These regulations enter into force during 2024 but have a three-year implementation period. As reflected in the meeting minutes, “stakeholders highlighted the importance of involving all the necessary stakeholders for the proper implementation of the new legislation.”
• And finally: The AI Act. The long-awaited AI Act was formally published in the Official Journal earlier this month. As of the May 2024 MDCG meeting minutes, the Commission had “provided an update on the AI Act and the interplay with MDR and IVDR.” While the Commission has committed to prioritizing guidance on this topic – specifically a Q&A document – there are other things that needed to happen first: “The Commission explained that the prioritisation of these activities depended on the appointment of the AI board, which would adopt their Terms of Reference during their first meeting in June 2024.” While industry is still awaiting a formal Q&A guidance, AgencyIQ has a two-part analysis of the implications of the AI Act for device and diagnostics companies available here: Part One, Part Two.

Summary and analysis

• Once again, a dive into MDCG meetings uncovers information that isn’t easily available elsewhere. Summing up the details:
• The next call for EURLs won’t cover all eight categories of high-risk diagnostics. At best, it will cover two of those four, parasites and blood grouping. But in the EURL meeting presentation, the Commission noted that there will likely be a drop-off in the number of labs that meet all the EURL requirements, similar to what happened with the first call. This leaves arboviruses and biosafety level 4 viruses with no designated laboratories, though the Commission is quick to note that EURLs aren’t required for conformity assessment where laboratories aren’t yet available.
• Not all manufacturers that submitted MDR notifications really meant it. Notified Bodies are concerned about manufacturer readiness for the MDR and IVDR, but they also struggle with implementing the regulations themselves. A new issue that hasn’t been discussed much is Notified Bodies receiving MDR applications from manufacturers that don’t plan to actually complete the MDR transition. This may be related to the complaint that manufacturers aren’t submitting documentation or responding to Notified Body inquiries. There wasn’t much other information besides the poll responses at the NBCG-Med plenary meeting, but if this is a real concern, we should start to see it raised more publicly soon.
• Europe keeps saying it wants to join MDSAP, but when? The MDCG has had many discussions on the viability of adopting the MDSAP audit model and participating in the certification program. The NBCG-Med pointed out benefits to doing so at the May 2024 MDCG meeting, including the possibility of increasing the overall acceptance of MDR and IVDR. But we have yet to see discussions on how to operationalize MDSAP within the MDR/IVDR or any firm plans for Europe to become a full member of MDSAP.
• The policy landscape continues to increase in complexity. With regulations like SoHo and the AI Act impacting the device and diagnostics industries, and intersecting with the ongoing MDR/IVDR challenges, industry is facing a complicated landscape ahead.

To contact the author of this item, please email Corey Jaseph ( cjaseph@agencyiq.com).
To contact the editor of this item, please Laura DiAngelo ( ldiangelo@agencyiq.com).

Key Documents and Dates

• Medical Device Coordination Group (MDCG) meeting, May 13, 2024
• Meeting between the Medical Device Coordination Group (MDCG) and Stakeholders, May 13, 2024