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Cervical Cytology Device Development and Validation Requirements

This guidance provides comprehensive information for manufacturers developing cervical cytology devices, including collection devices, cell suspension devices, staining devices, computer-assisted cell locators, and automated image analyzers. It addresses the specific challenges in validating these devices given the critical nature of Pap testing and the lack of reliable controls.

  1. Develop comprehensive protocol before starting any studies
  2. Consult with FDA early in development process
  3. Establish statistical analysis plan with biostatistician input
  4. Implement proper masking procedures for all evaluations
  5. Document all manufacturing processes according to GMP
  6. Validate software systems thoroughly if automated components involved
  7. Establish clear training requirements and procedures
  8. Define workload limits through specific studies
  9. Create detailed record keeping procedures
  10. Plan for appropriate patient follow-up procedures for abnormal findings
  11. Validate device performance across multiple sites
  12. Establish clear procedures for handling equivocal results

Key Considerations

Clinical testing

  • Must include prospective patient sampling for new methods
  • Multiple testing sites (3-5) required with geographic diversity
  • Need to include both low and high disease prevalence populations
  • Must follow Bethesda System (TBS) diagnostic criteria
  • Requires masked readings and comparisons
  • Need to establish clinical endpoints (outcomes, biopsy, colposcopy)
  • Must validate workload limits and fatigue factors

Non-clinical testing

  • Accuracy and precision validation required
  • Reproducibility testing (inter/intra observer, laboratory, instrument)
  • Stability testing of reagents and buffers
  • Morphological structure preservation validation
  • Validation of endocervical component capture
  • Demonstration of ability to detect inflammation and infectious agents

Human Factors

  • Training requirements must be defined for all users
  • Impact on cytotechnologists and pathologists workflow
  • Procedures for laboratory conversion from conventional methods
  • Workload limits evaluation required

Software

  • Software validation required for automated systems
  • Documentation per FDA computer control guidance
  • Data integrity and permanent recording requirements
  • Masking protocols for data analysis

Labelling

  • Must clearly state intended use and any exclusions
  • Need to specify training requirements
  • Documentation of any limitations

Safety

  • Risk-benefit analysis required
  • Protocol for handling abnormal findings
  • Patient follow-up procedures

Other considerations

  • 21CFR 884.4530: Collection devices classification
  • 21CFR 864.3800: Staining devices classification
  • 21CFR 864.5260: Computer-assisted cell locator devices classification

Original guidance

  • Cervical Cytology Device Development and Validation Requirements
  • HTML / PDF
  • Issue date: 1994-07-25
  • Last changed date: 2020-03-17
  • Status: FINAL
  • Official FDA topics: Medical Devices
  • ReguVirta summary file ID: c1fdeaec6b6142c4dab346df16767c01
This post is licensed under CC BY 4.0 by the author.