In Vitro Diagnostic Medical Devices Regulation (IVDR)

The EU IVDR (In Vitro Diagnostic Medical Devices Regulation), officially known as EU Regulation 2017/746, is the regulatory framework governing in vitro diagnostic (IVD) medical devices within the European Union (EU).

1. Purpose and Historical Context

• Governing Scope: The EU IVDR (EU Regulation 2017/746) specifically governs in vitro diagnostic (IVD) medical devices.
• Replacement: The EU IVDR replaced the previous In Vitro Diagnostic Directive (IVDD) 98/79/EC.
• Enhanced Requirements: The IVDR imposes stricter and enhanced requirements on IVD manufacturers compared to the previous directive, particularly concerning device classification, clinical evidence, risk management, and Post-Market Surveillance (PMS) to ensure device safety and performance.

2. Key Compliance Requirements for Manufacturers

Manufacturers of IVD devices subject to the EU IVDR have several mandatory obligations, often integrating them into their Quality Management System (QMS):

• Quality Management System (QMS): Manufacturers are mandated to implement a QMS that includes Corrective and Preventive Action (CAPA) procedures.
• CAPA System Integration: IVDR requires manufacturers to document corrective and preventive actions, assess their effectiveness, and integrate them into their overall QMS. CAPA management, therefore, relies on EU IVDR (Regulation 2017/746).
• Post-Market Surveillance (PMS): The regulation requires manufacturers to enhance PMS by systematically monitoring product performance, analyzing post-market data, and taking corrective and preventive actions to mitigate risks. This is specifically addressed in Annex IX (Conformity Assessment Based on a Quality Management System and Post-Market Surveillance).
• Conformity Assessment: Like the EU Medical Device Regulation (EU MDR), the IVDR requires manufacturers to demonstrate compliance to achieve market approval. The conformity assessment based on a QMS and PMS requires manufacturers to monitor product performance, analyze post-market data, identify trends, investigate nonconformities, and implement and verify corrective actions.
• Risk Management: IVDR enhances requirements related to risk management.
• QMS Standard Alignment: Medical device companies must comply with CAPA requirements outlined in the EU IVDR and standards such as ISO 13485:2016. ISO 14971 (Risk Management) is specifically noted as being intended to apply to in vitro diagnostic devices (IVD).

3. Context of In Vitro Diagnostic Products (U.S. FDA Perspective)

While the EU IVDR is a European regulation, the concept of IVD products is closely managed under U.S. FDA regulations (21 CFR Part 809), which provide context on what these products entail:

• Definition of IVD Products: In vitro diagnostic products are reagents, instruments, and systems intended for use in the diagnosis of disease or other conditions, including a determination of the state of health, in order to cure, mitigate, treat, or prevent disease. These products are intended for use in the collection, preparation, and examination of specimens taken from the human body.
• FDA Compliance: Under FDA regulations, IVD products must be manufactured in accordance with the good manufacturing practices requirements found in part 820 of the CFR (Quality System Regulation).
• Labeling: The label for an in vitro diagnostic product must state information such as warnings or precautions for users and the limiting statement "For In Vitro Diagnostic Use".
• Examples: The CFR lists numerous examples of IVD test systems, reagents, and equipment, including:
  • Creatinine test systems
  • High-throughput genomic sequence analyzers
  • Instrumentation for clinical multiplex test systems
  • Specific disease assays like Hepatitis C Virus antibody tests and HIV viral load monitoring tests.

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