Progressive roll-out of the In Vitro Diagnostic Medical Device Regulation for "legacy" IVDD-CE-marked devices.

An extension of the transition periods should certainly reduce the pressure on IVD manufacturers and the Notified Bodies involved.

The substantial technological and scientific progress in the IVD sector over the last 20 years triggered the repeal of Directive 98/79/EC.1 The upcoming IVDR 2017/7462 significantly reinforces key elements of the existing approach in Directive 98/79/EC of the European Parliament and of the Council, such as the supervision of notified bodies, risk classification, conformity assessment procedures, performance evaluation and performance studies, vigilance and post market surveillance, will be significantly strengthened, whilst introducing provisions ensuring transparency (EUDAMED and economic operators) and traceability (UDI) regarding in vitro diagnostic medical devices in IVDR 2017/746.

Risk of disruption to the supply of in vitro diagnostics devices.

However, due to the severe lack of capacity of designated bodies, manufacturers were unable to carry out the legally required conformity assessment procedures in a timely manner. Without legislative action, there was a risk of significant disruption in the supply of several key in vitro diagnostics on the market, affecting diagnosis for patients and their access to appropriate healthcare.

The European Commission wants to ensure the uninterrupted supply of in vitro diagnostic (IVD) devices to the market to meet the challenges faced by manufacturers in pandemic coronavirus conditions by taking into account the new IVDR 2017/746.

Thus, progressive roll out of new provisions to IVDs according to IVDR 2017/7463 with date of application 26 May 2022 and prolongation of transitional periods (“grace period”) for specific IVD risk class devices already marketed shall contribute to assure uninterrupted market supply by amended Article 110-112 of the IVDR 2017/746. 4

No change is proposed for CE-marked devices that do not require Notified Body involvement under the IVD Regulation or for "new" devices, i.e. devices for which neither a Notified Body certificate nor a Declaration of Conformity under the current Directive 98/79/EC is available. For these types of devices, the IVD Regulation will therefore apply as planned from 26 May 2022.

Deferral of the deadlines for certain devices.

In addition, application conditions according to IVDR 2017/746 for health institutions fighting against COVID-19 pandemic by using in-house devices (specific regime for devices manufactured and used in the same health institution, which are not marketed or transferred to other legal entities and do not bear the CE marking) will be deferred.

The health institutions need a complete overview of CE-marked in vitro diagnostic medical devices available on the market. As laid down in the IVDR 2017/746, as now amended, the condition obliging the health institution to justify that the target patient group’s specific needs cannot be met, or cannot be met at the appropriate level of performance, by an equivalent device available on the market should not become applicable until the now extended transitional periods (otherwise until 26 May 2024). With a justification that target patient group's specific needs cannot appropriately be met by an equivalent in vitro diagnostic medical device available on the market the transitional period can be extended until 26 May 2028.

Regulation (EU) 2017/746 is amended according to Article 1 (of the amendment4), while the adoption of the amendment to the Regulation takes place under exceptional circumstances arising from the COVID-19 pandemic and the associated public health crisis.4

Devices for which the conformity assessment procedure pursuant to Directive 98/79/EC did not require the involvement of a notified body, for which a declaration of conformity was drawn up prior to 26 May 2022 in accordance with that Directive, and for which the conformity assessment procedure pursuant to this Regulation requires the involvement of a notified body, may be placed on the market, or put into service until the following dates:4

(a) 26 May 2025 for class D devices;
(b) 26 May 2026 for class C devices;
(c) 26 May 2027 for class B devices;
(d) 26 May 2027 for class A devices placed on the market in sterile condition.

IVD Regulation will continue to apply from 26 May 2022.

Overall, the IVD Regulation will apply as planned from 26 May 2022. No change is proposed for CE-marked devices that do not require the involvement of a notified body under the IVD Regulation or for "new" devices, i.e. devices that do not have a certificate from a notified body or a declaration of conformity under the current Directive 98/79/EC. For these types of devices, the IVD Regulation will therefore apply as planned from 26 May 2022.4

In addition, from the date of application May 26, 2022, all IVDs lawfully placed on the market, are available on the market or put into service shall comply with requirements for Vigilance and PMS (Annex III, IVDR 2017/746), irrespective of the transition periods! Also, the provisions for registration of economic operators and of devices and data entry in EUDAMED are NOT affected by the transitional provisions.

The IVDR 2017/746 undoubtedly sets higher standards for safety, quality and performance for IVDs and fundamentally improves transparency (the European databank already announced in DIR 98/79/EC, Art. 12), and new, the requirements on economic operators (manufacturer and importers) and on the traceability system based on unique device identifier (UDI). Also, the IVDR dramatically reinforces the criteria and designation and the oversight of the Notified Bodies (which – not unexpectedly5 - might be the root cause of the currently low number of IVDR-accredited Notified Bodies (NB)6 while there are currently only 1 NB in France, 3 NBs in Germany and 2 NBs in the Netherlands) building the bottleneck.

In addition, the IVDR 2017/746 improves coordination mechanisms between EU countries on vigilance and post-market surveillance, tightens rules for clinical evidence and performance evaluation, including an EU-wide coordinated procedure for the approval of multicentre performance characteristic studies, and strengthens post-market surveillance requirements for manufacturers.7 As an example, the PSUR (Periodic Safety Update Reports) can be mentioned. The PSUR is intended to provide an assessment of the risk-benefit balance of a medical device at specific points in time after it has been approved.8 and has been known for years from the pharmacovigilance requirements for medicinal products. PSURs have now become mandatory for certain higher risk classes of IVDs.

Following the revision of the IVD classification for more than 30 years, most notably the revision of the IVD classification that ultimately (and for good reason) moved from Annex II/A, II/B, self-test and "other" or "general" medical device classes in the IVDD to classes A, B, C, D in the IVDR as presented many years ago by the Global Harmonization Task Force (GHTF), the risk-based IVD medical device classification9 is now more than adopted with the IVDR 2017/746. As a result, approximately 80% of IVDs CE marked under the IVDD (Directive 98/79/EC, IVD self-certification declaration) are now subject to NB oversight and involvement for CE marking.8

The prolongation of the transitional periods surely releases the pressure on IVD manufacturers and involved notified bodies. Still, achieving compliance to the new regulations remains a challenging task and bears tremendous effort for everybody involved.

Literature.

  1. DIRECTIVE 98/79/EC OF THE EUROPEAN PARLIAMENT AND OF THE COUNCIL of 27 October 1998 on in vitro diagnostic medical devices
  2. REGULATION (EU) 2017/746 OF THE EUROPEAN PARLIAMENT AND OF THE COUNCIL of 5 April 2017 on in vitro diagnostic medical devices and repealing Directive 98/79/EC and Commission Decision 2010/227/EU
  3. Progressive roll-out of the In Vitro Diagnostic Medical Devices Regulation Brussels, 20 December 2021, https://ec.europa.eu/commission/presscorner/detail/en/ip_21_6965, accessed 13 Jan 2022.
  4. P9_TC-COD(2021)0323 Transitional provisions for certain in vitro diagnostic medical devices and deferred application of requirements for in-house devices https://www.europarl.europa.eu/doceo/document/TA-9-2021-0498_EN.html#title2 - accessed 24 JAN 2022
  5. Hess R D, Aumer D M and Schulz S D. "Implementation of IVDR and MDR Into National Legislation: a mission impossible?" Regulatory Focus. September 2019. Regulatory Affairs Professionals Society
  6. NANDO (New Approach Notified and Designated Organisations) Information Systems: https://ec.europa.eu/growth/tools-databases/nando/index.cfm?fuseaction=directive.notifiedbody&dir_id=35, accessed 24 JAN 2022.
  7. Q&A: New In Vitro Diagnostic Medical Devices Regulation (europa.eu), accessed 24 JAN 2022.
  8. Evaluation of cell substrates for the production of biologics. Revision of WHO recommendations. Report of the WHO Study Group on cell substrates for the production of biologicals. Bethesda, USA: WHO; 22-23 April 2009.
  9. Periodic safety update reports (PSURs) | European Medicines Agency (europa.eu), accessed 24 JAN 2022
  10. GHTF/SG1/N045:2008: Principles of In Vitro Diagnostic (IVD) Medical Device Classification. , 19 FEB 2008.

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Persons to the article.

Dr Ralf Hess

Principal Consultant IVD

Dr. Ralf Hess studied biology at the Albert-Ludwigs-University of Freiburg, where he also completed his doctorate at the Institute of Virology. Dr. Hess has many years of experience in the development of medical devices and medicinal products and their combination, in laboratory analysis and quality assurance. The quality expert has set up, implemented and maintained QM systems in accordance with ISO and GxP for various areas of application. The customer service portfolio ranges from manufacturers of classical and biological drugs, medical device companies and vaccine manufacturers to immunohistochemical, immunological, molecular biological and serological diagnostic laboratories. Dr. Hess works worldwide as an auditor in the GxP/ISO area and has many years of experience in FDA remediation projects and the regulatory development of combination products (drug device products).
Dr. Ralf Hess supports Entourage as Principal Consultant IVD.

Assoc. Prof. Dr Simon Schulz

Senior Management Consultant

Assoc. Prof. Dr. Simon Schulz received his diploma in chemistry from the Ruprecht Karls University of Heidelberg. He received his doctorate from the Institute of Physical and Biophysical Chemistry; Heidelberg, and the Max-Planck Institute for Intelligent Systems, Stuttgart. In 2016, he was appointed Associate Professor in Experimental Medicine by the University Medical Centre Freiburg.
Dr. Schulz has many years of experience in GLP compliance and computer validation as well as the development and testing of medical devices and combination products. He has extensive expertise in the compliance of medical devices with ISO 13485 and FDA 483 according to 21 CFR 820 and the development of compliant SOPs for their design and manufacturing process. Furthermore, he has distinct competence in CAPA management, complaint handling and process validation. He is lecturer for quality of medical devices and medicinal products at the University Freiburg, Faculty for Chemistry & Pharmacy.
Dr. Simon Schulz supports Entourage as Senior Management Consultant.

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