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In Vitro Diagnostic Devices for Detection of Parvovirus B19 Antibodies in Human Serum and Plasma

This guidance provides criteria for premarket approval of in vitro diagnostic devices intended for qualitative or semi-quantitative measurement of antibodies to Parvovirus B19 in human serum or plasma using immunochemical and other methodologies.

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By ReguVirta
3 min read

What You Need to Know? 👇

What are the key regulatory requirements for Parvovirus B19 antibody detection devices?

Parvovirus B19 antibody detection devices require Premarket Approval (PMA) as Class III medical devices. Submissions must demonstrate clinical utility, safety, and efficacy through comprehensive analytical and clinical studies, including cross-reactivity testing, reproducibility studies, and validation with diverse patient populations.

How should cut-off values be established for Parvovirus B19 antibody assays?

Cut-off values must be validated using statistically significant populations from diverse geographical areas, with samples categorized by gender, age groups, and collection timing. ROC analysis should support cut-off selection, and equivocal zones must be defined with appropriate clinical correlation studies.

What cross-reactivity testing is required for B19 antibody detection devices?

Cross-reactivity studies must include sera with high titers against rubella, measles, mumps, influenza A/B, parainfluenza, HSV1/2, CMV, EBV, VZV, and Mycoplasma pneumoniae. Five patients per condition should be tested, with antibody titers documented using validated methods.

What clinical populations should be included in B19 antibody device validation studies?

Clinical studies should include patients with suspected B19 infection presenting with rash or related symptoms, documented community outbreak contacts, and patients with similar symptomatology from other diseases like Kawasaki disease, aplastic anemia, rheumatoid arthritis, and various rash-producing conditions.

How many testing sites are required for clinical validation of B19 devices?

Clinical testing must be performed by at least three independent investigators at separate locations not affiliated with the manufacturer. Reproducibility studies require testing at three laboratory sites using different instruments when applicable, with triplicate testing over three days.

What specimen types and storage conditions must be validated for B19 testing?

All claimed specimen types (serum, plasma with different anticoagulants) must be validated through concurrent testing studies. Storage stability must be documented under recommended conditions, and interference from hemolysis, lipemia, freeze-thawing, and heating must be evaluated with appropriate controls.

What You Need to Do 👇

  1. Develop comprehensive clinical testing protocol across 3 independent sites
  2. Conduct complete analytical validation studies
  3. Perform cross-reactivity testing with specified viral antibodies
  4. Document stability data from 3 different manufactured lots
  5. Prepare detailed labeling including all required sections
  6. Establish quality control procedures compliant with CLIA ‘88
  7. Generate performance data for different patient populations
  8. Validate all specimen types claimed for use
  9. Document software validation if applicable
  10. Prepare comprehensive documentation of reproducibility studies

Key Considerations

Clinical testing

  • Testing must be performed at 3 independent sites not affiliated with manufacturer
  • Must test samples from patients with symptoms of B19 infection
  • Clinical confirmation through:
    • Clinical diagnosis based on specific criteria
    • Immune electron microscopy
    • Other standard methods
  • Testing required for sera from diseases with similar symptoms (Kawasaki, aplastic anemia, etc.)
  • Optional testing of well-documented panels (e.g. CDC panel)

Non-clinical testing

  • Analytical laboratory studies required for:
    • Cut-off validation
    • Prevalence studies in asymptomatic populations
    • Assay specificity
    • Interference studies
    • Reproducibility testing
    • Stability studies

Software

  • Requirements for Minor Level of concern per FDA Reviewer Guidance for computer-controlled devices
  • Must provide algorithms for result calculations
  • Documentation needed for dedicated instrumentation

Labelling

  • Must include:
    • Intended use statement
    • Test methodology
    • Specimen collection/handling instructions
    • Quality control procedures
    • Expected results
    • Test limitations
    • Performance characteristics

Other considerations

  • Cross-reactivity studies required with other viral antibodies
  • Stability testing under various storage and shipping conditions
  • Documentation of reproducibility across different lots

Relevant Guidances 🔗

Related references and norms 📂

  • NCCLS I/LA 18-P: Specifications for immunological testing for infectious diseases
  • NCCLS EP5-T2: Evaluation of precision performance of clinical chemistry devices

Original guidance

  • In Vitro Diagnostic Devices for Detection of Parvovirus B19 Antibodies in Human Serum and Plasma
  • HTML / PDF
  • Issue date: 1992-05-15
  • Last changed date: 2020-03-17
  • Status: FINAL
  • Official FDA topics: Medical Devices, Laboratory Tests, Premarket, IVDs (In Vitro Diagnostic Devices)
  • ReguVirta ID: ab25b264d7d51969ea28da2010c195b7
FDA guidance, Final
Medical Devices Laboratory Tests Premarket IVDs (In Vitro Diagnostic Devices)
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