IVD Manufacturers & EU IVD Regulation Changes (May 2022)

Due diligence now ensures regulatory compliance and streamlines global marketing for in vitro diagnostics manufacturers

In May 2017, the EU published the In Vitro Diagnostic Regulation (IVDR).¹ This regulation replaces the In Vitro Diagnostic Directive (IVDD)² and will be implemented on May 26,2022. In vitro diagnostic (IVD) manufacturers must understand the full scope of changes to ensure regulatory compliance and smooth placement and maintenance of safe, effective products on the EU market. IVDR’s better harmonisation with broadly used regulations such as those of the US Food and Drug Administration (FDA) will benefit manufacturers by streamlining access to the global market.

Updates to the IVDR are designed to enable transparency, quality, and safety in the manufacture of medical devices

• New clinical evidence requirements are expected to affect existing quality systems, including the structure and content of technical files
• Evolving lifecycle information for all EU products must be submitted to the new European Databank on Medical Devices
• Manufacturers must collect more real-world data about device usage for post-market surveillance and vigilance
• Premarket review is required for new and most existing IVDs; there will be no grandfathering of devices
• Manufacturers must designate a representative responsible for regulatory compliance
• A new medical device traceability system utilises unique device identifiers (UDI)
• EU-wide coordinated procedure to authorise multicentre IVD clinical studies
• Product labelling is to be enhanced

While a more harmonised regulatory framework – simplified procedures within the EU and streamlined access to the global market – offers advantages, timely compliance with these significant changes to the EU IVD CE marking process may be challenging.

New IVD classifications complicate requirements and ratchet up demand for notified bodies

Under the new IVDR, a four-class, risk-based system replaces the old two-class approach. (See table below.) Risk is defined as the probability of occurrence of harm resulting from the IVD’s use (for example, incorrect diagnosis) and the severity of that harm. Note that certain products not previously identified under the IVDD, such as laboratory-developed tests, companion diagnostics, and standalone software products, are now included.

Risk Class	Manufacturer's Responsibility
A) Laboratory devices, instruments, and specimen receptacles	Declare conformity with the regulation, but sterile aspects must be assessed by an NB
B) All IVDs not covered specifically in other classification rules. Also covers self-testing IVDs for pregnancy and fertility, detection of cholesterol levels, and detection of glucose, erythrocytes, leukocytes and bacteria in urine	Provide a full quality-management system, audit with an NB, and review of at least one technical file per generic device group, unless the devices are classified as self-testing or near-patient testing, in which case the technical files of all devices must be assessed (IVDR Annex IX, chapters I and III)
C) A diverse mix of high-risk IVDs that present a lesser risk to the wider population. Also covers most self-testing IVDs and testing for infectious diseases and cancer, companion diagnostics and genetic screening	Provide either a full quality-management system, audit with an NB, and review of at least one technical file per generic device group (IVDR Annex IX, chapters I and III) or an EU type-examination (IVDR annexes X; XI [except for Section 5])
D) Covers general life-threatening conditions and, more specifically, transmissible agents in blood or other biological materials intended to be transplanted or re-administered to the body	Same as for Class C, along with batch verification and reference laboratory involvement (IVDR annexes X; XI)

Assessing gaps and prioritising products

Resultant attrition and increased workload for NBs has created a bottleneck. In response, the European Commission approved an updated, gradual rollout of the new IVDR for current IVDD CE Marked devices in late 2021.³ Even so, plan thoughtfully when preparing for the new mandates, especially where you’ll need NB approval. As the IVDR deadline approaches, focus on a limited number of products to ensure timely compliance.

Meet complex clinical evidence requirements

The IVDR requires far more clinical evidence than the IVDD, in proportion to each device’s risk class.

• Perform a gap analysis of the quality of existing evidence and gauge the effort needed to generate additional supporting data. If the IVD has already cleared the FDA, the necessary technical documentation data may already exist but may need restructuring. For products evaluated only for EU commercialisation, addressing and interpreting these new demands poses a challenge.

Prioritise currently marketed IVDs for submission, especially those with robust post-market surveillance programs.

• Surveillance data can support the clinical evidence report and help create the template for future submissions. IVD clinical evidence reports may include scientific validity, analytical performance, and clinical performance data, based on the product’s intended purpose. The intended purpose must include details on functionality and target for detection (e.g., biomarker, disorder, condition, or risk factor). As this is a living document, assay formulation and/or performance refinements, new publications about the utility of the type of device, and post-market surveillance activities must be updated throughout the product’s lifecycle to support marketing and IVD labeling.

Update your supply chain control

The IVDR’s new requirements on supply-chain control encompass compliance verification, vigilance, unannounced inspections, and traceability.

• Each “actor” in the supply chain — manufacturers, authorised representatives, system and procedure pack producers, and importers — must independently verify compliance of the previous actor and implement vigilance procedures, notifying authorities of noncompliant devices, and taking corrective action. Traceability information needs to be retained for at least 5 years after the last device was placed on the market.

Amend IVD post-market surveillance and vigilance programs

Implement new, continuous evaluation and improvement loops to manage risk, update the public on safety and performance, and review and update the clinical evidence report continuously.

• New processes, such as post-market performance follow-up, periodic safety update reporting, and post-market surveillance planning and reporting will require you to review relevant data on product quality and performance safety throughout the device lifecycle. Furthermore, the reporting window for serious adverse events will be 15 days, not 30.

Get help if required

Significant IVDR preparations are required for compliance with the new regulations.

• However, as an IVD manufacturer, reinvented product development strategies can globalise your approach to product launches, to seek EU and US marketing approval simultaneously. Access Precision’s unmatched experience in diagnostic development to get help with the latest regulatory changes and expedite your product from bench to bedside.

Learn more about Precision’s end-to-end diagnostics development services >

Key takeaways

• The IVDR mandates sweeping changes in performance evaluation and post-market activities. Preparation requires strong quality management systems for ongoing risk monitoring and safety reporting.
• Given the shortage of NBs, increased documentation requirements, and cost associated with the IVDR, a more gradual rollout has been approved for existing IVDD CE Marked devices.
• Although the IVDR presents challenges in the short term, its expanded clinical evidence requirements may streamline global commercialisation.
• In good news for IVD manufacturers, IVDR helps harmonise the development processes across submissions.
• IVDR also benefits manufacturers by mandating operational and commercial improvements that could enhance safety, quality, and innovation.

Explore Precision's Regulatory Expertise >

References: 

1. Official Journal of the European Union. Regulation (EU) 2017/745 of the European Parliament and of the Council of 5 April 2017 on medical devices, amending Directive 2001/83/EC, Regulation (EC) No 178/2002 and Regulation (EC) No 1223/2009 and repealing Council Directive 90/385/EEC and 93/42/EEC. http://eur-lex.europa.eu/legal-content/EN/TXT/PDF/?uri=CELEX:32017R0745&from=DE Published 5 May 2017. Accessed 13 February 2022.

2. Official Journal of the European Union. 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. http://eur-lex.europa.eu/legal-content/EN/TXT/PDF/?uri=CELEX:32017R0746&from=DE Published 5 May 2017. Accessed 13 February 2022.

3. European Commission. Public health: Commission proposes a progressive roll-out of the new In Vitro Diagnostic Medical Devices Regulation. Brussels, 14 October 2021. https://ec.europa.eu/commission/presscorner/detail/en/IP_21_5209 Published 14 October 2021. Accessed 13 February 2022.