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Establishing Performance Characteristics for Human Papillomavirus (HPV) Detection In Vitro Diagnostic Devices

This guidance provides recommendations for establishing performance characteristics of in vitro diagnostic devices (IVDs) for HPV detection or detection and differentiation. It specifically covers: - Devices used with cervical cytology for cervical cancer screening or as first-line primary screening - Qualitative detection of HPV nucleic acid from cervical specimens - Class III devices requiring premarket approval (PMA) The guidance does not cover: - HPV testing from non-cervical specimens - Testing for HPV infection susceptibility - Quantitative/semi-quantitative HPV assays - HPV-associated biomarkers

  1. Determine intended use(s) and design validation studies accordingly
  2. Conduct comprehensive analytical validation:
    • Establish LoD for each HPV genotype
    • Validate precision and reproducibility
    • Evaluate cross-reactivity and interference
    • Determine specimen/reagent stability
  3. Perform clinical validation studies:
    • Design prospective studies for each intended use
    • Include appropriate controls and blinding
    • Follow recommended statistical analyses
    • Document all procedures thoroughly
  4. Prepare PMA submission:
    • Include detailed device description
    • Provide complete analytical and clinical data
    • Submit comprehensive statistical analyses
    • Include proposed labeling
  5. Consider post-market studies if needed for certain claims
  6. Implement appropriate quality control measures:
    • External positive/negative controls
    • Internal controls as needed
    • Proper documentation systems

Key Considerations

Clinical testing

  • Prospective clinical studies needed for ASC-US triage, adjunct screening, and primary screening intended uses
  • Studies must be conducted at minimum 3 US representative sites
  • All subjects with ASC-US cytology should proceed to colposcopy regardless of HPV status
  • Blinding required for investigators, patients and clinicians
  • Detailed documentation needed for specimen collection dates and processing
  • Longitudinal follow-up recommended for certain intended uses

Non-clinical testing

  • Analytical validation studies required for:
    • Limit of detection
    • Precision/reproducibility
    • Cross-reactivity
    • Interference
    • Carryover/contamination
    • Specimen stability
    • Reagent stability

Labelling

  • Must specify specimen types and collection devices
  • Must include warnings about control limitations
  • Must provide interpretation guidance for results
  • Must specify storage conditions and stability claims

Safety

  • False negative results could delay cancer diagnosis
  • False positive results could lead to unnecessary procedures
  • Risk mitigation through proper validation and controls required

Other considerations

  • EP17-A2: Evaluation of Detection Capability for Clinical Laboratory Measurement Procedures
  • EP05-A3: Evaluation of Precision of Quantitative Measurement Procedures
  • EP12-A2: User Protocol for Evaluation of Qualitative Test Performance
  • EP07-A2: Interference Testing in Clinical Chemistry
  • EP25-A: Evaluation of Stability in In Vitro Diagnostic Reagents
  • MM17-A: Verification and Validation of Multiplex Nucleic Acid Assays
  • MM03-Ed3: Molecular Diagnostic Methods for Infectious Disease

Original guidance

  • Establishing Performance Characteristics for Human Papillomavirus (HPV) Detection In Vitro Diagnostic Devices
  • HTML / PDF
  • Issue date: 2017-09-15
  • Last changed date: 2019-04-11
  • Status: FINAL
  • Official FDA topics: Medical Devices, Laboratory Tests, Premarket Approval (PMA), Premarket, IVDs (In Vitro Diagnostic Devices), Microbiology
  • ReguVirta summary file ID: 8dd70ba85f1baf2ab8e24d816066c59e
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