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In Vitro Diagnostic Devices for Detection of Antibodies to Borrelia burgdorferi - Performance Characteristics and Testing Requirements

This guidance provides recommendations for establishing analytical and clinical performance characteristics of in vitro diagnostic devices (IVDs) for detecting antibodies to Borrelia burgdorferi in human serum, plasma, and blood, used to aid in Lyme disease diagnosis. It specifically applies to EIA and Western blot devices but not to nucleic acid amplification assays.

  1. Develop detailed study protocol with patient inclusion/exclusion criteria
  2. Contact Division of Microbiology Devices for review of proposed studies
  3. Conduct cross-reactivity and interference studies
  4. Perform precision and reproducibility studies
  5. Execute clinical performance studies at minimum 3 US sites
  6. Test CDC reference panel
  7. Validate specimen storage and handling conditions
  8. Document assay cut-off point selection process
  9. Prepare comprehensive labeling documentation
  10. Consider CLIA waiver requirements if applicable
  11. Ensure use of correct B. burgdorferi strain for antigenic reagents
  12. Prepare complete documentation for FDA submission

Key Considerations

Clinical testing

  • Two-step testing procedure required: EIA/IFA first, followed by Western blot for positive/equivocal results
  • Minimum 100 well-characterized clinically/culture confirmed Lyme disease specimens needed
  • Specimens should cover early, early disseminated, and late disease phases
  • Prospective study with non-selected specimens from 3 distinct US locations required
  • Testing at minimum 3 sites, including endemic and non-endemic regions
  • CDC reference panel testing required

Non-clinical testing

  • Cross-reactivity testing with minimum 10 specimens for each potentially cross-reactive condition
  • Interference testing for common blood components (triglycerides, hemoglobin, bilirubin, etc.)
  • Precision/repeatability studies over 12 days minimum
  • Reproducibility studies at 3 testing sites over 5 days

Labelling

  • Must comply with 21 CFR 809.10
  • Include quality control recommendations
  • Clear explanation of controls and calibrators usage

Other considerations

  • CLSI EP7-A2: Interference Testing in Clinical Chemistry
  • CLSI EP5-A2: Evaluation of Precision Performance of Quantitative Measurement Methods
  • CLSI EP12-A: User Protocol for Evaluation of Qualitative Test Performance
  • CLSI EP15-A2: User Verification of Performance for Precision and Trueness
  • CLSI H18-A: Procedures for Handling and Processing of Blood Specimens

Original guidance

  • In Vitro Diagnostic Devices for Detection of Antibodies to Borrelia burgdorferi - Performance Characteristics and Testing Requirements
  • HTML / PDF
  • Issue date: 2013-03-27
  • Last changed date: 2020-02-28
  • Status: FINAL
  • Official FDA topics: Medical Devices, Laboratory Tests, Premarket
  • ReguVirta summary file ID: 259ac244b75e98b1de3132a68de35e88
This post is licensed under CC BY 4.0 by the author.