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In Vitro Diagnostic Devices for Detection and Differentiation of Influenza Viruses - Performance Testing and Validation Requirements

This guidance provides recommendations for studies to establish the analytical and clinical performance of in vitro diagnostic devices (IVDs) intended for the detection or detection and differentiation of influenza viruses. It covers devices that detect influenza viral antigens or viral gene segments (protein or nucleic acid) in human specimens or culture isolates. The guidance does not address serological tests or non-influenza components of multi-analyte devices.

  1. Develop comprehensive validation protocol including analytical and clinical studies
  2. Establish and validate LoD for each specimen type and analyte
  3. Conduct multi-site reproducibility studies
  4. Perform analytical reactivity testing against recommended strain panels
  5. Complete interference studies with recommended substances
  6. Validate specimen stability and transport conditions
  7. Implement appropriate controls and quality measures
  8. Develop post-market monitoring plan for viral mutations
  9. Prepare comprehensive labeling with required elements
  10. Document software validation and risk analysis
  11. Establish procedures for handling unsubtypeable results
  12. Validate all recommended extraction methods (for molecular assays)
  13. Implement contamination control measures for automated systems

Key Considerations

Clinical testing

  • Conduct prospective clinical studies comparing device to established reference methods
  • Include specimens from individuals with influenza-like illness
  • Collect samples within 3 days of symptom onset
  • Include minimum number of positive samples per specimen type:
    • Rapid antigen tests: 50 for Flu A, 30 for Flu B
    • Molecular tests: Show 90% sensitivity with lower bound of 95% CI >80%
  • Include multiple geographically diverse study sites
  • Include appropriate age stratification

Non-clinical testing

  • Determine Limit of Detection (LoD) for each specimen type and analyte
  • Test analytical reactivity against multiple strains (minimum 5 for Flu B, 10 for each Flu A subtype)
  • Evaluate precision/reproducibility across multiple sites, operators, and days
  • Assess specimen storage/shipping stability
  • Validate viral transport media compatibility

Human Factors

  • For point-of-care devices, include testing at non-laboratory sites with intended users
  • Evaluate impact of operator training/experience on performance
  • Validate instructions for use with intended operators

Software

  • Moderate level of concern documentation required
  • Include software development lifecycle documentation
  • Validate algorithms for result interpretation
  • Document data flow from raw signals to results

Labelling

  • Include limitations, warnings, precautions
  • Specify specimen types, collection methods
  • Define interpretation criteria and cutoffs
  • Describe quality control requirements
  • List interfering substances

Safety

  • Include risk analysis for specimen handling
  • Address biosafety requirements for novel influenza strains
  • Define procedures for unsubtypeable results

Other considerations

  • CLSI EP5-A2: Evaluation of Precision Performance of Quantitative Measurement Methods
  • CLSI EP7-A2: Interference Testing in Clinical Chemistry
  • CLSI EP12-A2: User Protocol for Evaluation of Qualitative Test Performance
  • CLSI EP15-A2: User Verification of Performance for Precision and Trueness
  • CLSI EP17-A: Protocol for Determination of Limits of Detection and Limits of Quantitation
  • CLSI M41-A: Viral Culture
  • ISO 14971-1: Medical devices - Risk management
  • AAMI 62304:2006: Medical device software - Software life cycle processes

Original guidance

  • In Vitro Diagnostic Devices for Detection and Differentiation of Influenza Viruses - Performance Testing and Validation Requirements
  • HTML / PDF
  • Issue date: 2011-07-14
  • Last changed date: 2024-04-11
  • Status: FINAL
  • Official FDA topics: Medical Devices, Pediatric Product Development
  • ReguVirta summary file ID: 3029271d866158e613e3488348421dda
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