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Assay Development and Validation Requirements for Lamotrigine and Zonisamide Testing in Clinical Laboratories

This guidance addresses lamotrigine and zonisamide assays that: - Employ immunoassay technologies - Are for use in central clinical laboratories - Are for use with serum or plasma samples - Are regulated under 21 CFR 862.3350 as Class II devices

  1. Design comprehensive validation protocol covering all performance characteristics
  2. Conduct precision studies over 20 days with multiple concentrations
  3. Perform recovery/bias studies using reference materials
  4. Evaluate linearity across entire measuring range
  5. Validate lower limits of quantitation
  6. Complete interference testing for endogenous and exogenous substances
  7. Test cross-reactivity with key metabolites
  8. Conduct method comparison with minimum 100 patient samples
  9. Validate stability of calibrators and controls
  10. Prepare detailed labeling addressing all required elements
  11. Document traceability of calibrators to reference materials
  12. Consider need for external site studies based on assay complexity

Key Considerations

Clinical testing

  • Method comparison study with minimum 100 patient samples across measuring range
  • Samples should be from intended use population with unaltered patient samples
  • Multiple specimens from individual patients should be appropriately analyzed statistically

Non-clinical testing

  • Precision evaluation over 20 day period for 3+ drug concentrations spanning reportable range
  • Recovery/bias studies using reference materials spiked into drug-free clinical samples
  • Linearity evaluation across entire reportable range with 7-9 concentration levels
  • Lower limits evaluation including precision and bias relative to reference materials

Software

  • Follow FDA guidance for software contained in medical devices if device includes software

Labelling

  • Must satisfy requirements in 21 CFR 809.10
  • Include specimen collection/storage instructions
  • Detail quality control and calibration procedures
  • List warnings and precautions
  • State limitations of procedure
  • Provide reference ranges with appropriate context
  • Summarize performance characteristics

Safety

  • Test blood products for communicable disease agents per 21 CFR 610.40
  • Include appropriate warnings for hazardous materials

Other considerations

  • CLSI EP5-A2: Evaluation of Precision Performance of Quantitative Measurement Methods
  • CLSI EP7-A2: Interference Testing in Clinical Chemistry
  • CLSI EP9-A2: Method Comparison and Bias Estimation Using Patient Samples
  • CLSI EP17-A2: Evaluation of Detection Capability for Clinical Laboratory Measurement Procedures
  • ISO 17511: Metrological Traceability of Values Assigned to Calibrator and Control Materials

Original guidance

  • Assay Development and Validation Requirements for Lamotrigine and Zonisamide Testing in Clinical Laboratories
  • HTML / PDF
  • Issue date: 2016-02-09
  • Last changed date: 2019-03-14
  • Status: FINAL
  • Official FDA topics: Medical Devices, 510(k), Premarket
  • ReguVirta summary file ID: c20af0d3645b7260873af2c74d8df291
This post is licensed under CC BY 4.0 by the author.