Radiation Biodosimetry Devices: Performance Testing and Documentation Requirements

What You Need to Know? 👇

What are the key regulatory requirements for radiation biodosimetry medical countermeasure devices?

Biodosimetry devices must obtain FDA premarket clearance or approval, conform to general controls under the FD&C Act, and include comprehensive analytical validation, animal studies, and clinical validation with human samples when available.

How should manufacturers address the challenge of limited human clinical samples for biodosimetry device validation?

Manufacturers can use contrived samples (ex vivo irradiated specimens, spiked analytes, or animal-derived specimens) as supplements to clinical samples, but must provide scientific justification and demonstrate how results translate to clinical settings.

What animal models are recommended for biodosimetry device effectiveness studies?

Large-animal models (non-human primate, canine, or porcine) are preferred over rodent models as their radiation responses more closely resemble humans. The chosen model must demonstrate high analyte homology and similar biological pathway responses.

What statistical considerations are critical for biodosimetry device study design?

Studies require pre-specified Statistical Analysis Plans with defined performance measures, success criteria, appropriate sample sizes, and methods for handling missing data. Cross-validation may be needed for algorithm-based devices with multiple analytes.

How do CLIA categorization requirements apply to radiation biodosimetry devices?

Biodosimeters intended for field triage and cleared for home use are CLIA waived. Other devices may qualify for CLIA waiver if they demonstrate simple, accurate methodologies with negligible error likelihood.

What specific labeling requirements must biodosimetry devices meet beyond standard IVD requirements?

Labeling must specify radiation exposure timeframes, testing limitations, clinical decision cut-points, performance characteristics from all studies (bench, animal, clinical), and clear interpretation guidance emphasizing use with other clinical signs and radiation monitoring data.

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What You Need to Do 👇

Recommended Actions

1. Develop comprehensive validation plan including analytical, pre-clinical, and clinical performance testing
2. Submit pre-submission to FDA to discuss:
   • Clinical study design
   • Statistical analysis plan
   • Animal study protocols
   • Sample acquisition strategies
3. Establish analytical performance through:
   • Accuracy studies
   • Precision studies
   • Interference testing
   • Stability testing
4. Conduct animal studies to:
   • Bridge to human data
   • Evaluate confounding factors
   • Assess performance at doses/scenarios not possible in humans
5. Perform clinical validation using:
   • Prospective studies when possible
   • Banked samples if analytes are stable
   • Appropriate controls and documentation
6. Develop comprehensive labeling including:
   • Clear instructions for use
   • Limitations and warnings
   • Performance characteristics
   • Result interpretation guidance
7. Prepare post-market testing plan for real-world emergency scenarios
8. Submit complete electronic data package in appropriate format

Key Considerations

Clinical testing

• Clinical validation studies should be performed using human samples when possible
• Both prospective studies and banked samples can be used if analytes are stable
• Basic demographic information and radiation exposure profiles must be documented
• Studies should assess performance beyond claimed timeframes post-exposure
• Limitations of clinical studies must be acknowledged and addressed

Non-clinical testing

• Animal models can supplement human clinical data
• Must justify animal model selection based on biological pathway similarities
• Multiple animal models may be needed if single model is insufficient
• Animal studies must comply with welfare regulations and GLP requirements
• Animal studies should standardize husbandry conditions and timing of radiation exposure

Human Factors

• Instructions must be appropriate for intended user (lay person vs healthcare provider)
• Step-by-step procedures must be clearly outlined
• Quality control procedures must be described
• Training requirements must be specified for intended users

Software

• Software documentation requirements based on “level of concern”
• Must follow FDA software guidance for medical devices
• Statistical analysis plans must be pre-specified
• Electronic data should be provided in appropriate format

Labeling

• Must include limitations, contraindications, and warnings
• Must describe specimen collection and handling requirements
• Must provide interpretation guidance for results
• Must include performance characteristics summary
• Must specify appropriate timeframes for testing post-exposure

Safety

• Must assess risks of false positive and false negative results
• Must evaluate impact on patient management decisions
• Must consider risks in emergency/disaster scenarios

Other considerations

• Device description must specify all components
• Intended use statement must be clearly defined
• Quality control and calibration requirements must be specified
• CLIA categorization must be determined
• Post-market testing plan should be included

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Relevant Guidances 🔗

• Human Factors Information Needed in Medical Device Marketing Submissions (Draft)
• Content of Premarket Submissions for Device Software Functions
• Recommended Format and Content for Non-Clinical Bench Performance Testing in Medical Device Premarket Submissions
• Animal Testing for Medical Device Safety and Performance Evaluation

Related references and norms 📂

• CLSI EP6-A: Evaluation of the Linearity of Quantitative Measurement Procedures
• CLSI EP17-A2: Evaluation of Detection Capability for Clinical Laboratory Measurement Procedures
• CLSI EP07-A2: Interference Testing in Clinical Chemistry
• CLSI EP05-A3: Evaluation of Precision of Quantitative Measurement Procedures
• CLSI EP09-A3: Measurement Procedure Comparison and Bias Estimation Using Patient Samples
• CLSI EP24-A2: Assessment of the Diagnostic Accuracy of Laboratory Tests Using ROC Curves
• CLSI GP-14: Labeling of Home-Use In Vitro Testing Products

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Original guidance

• Radiation Biodosimetry Devices: Performance Testing and Documentation Requirements
• HTML / PDF
• Issue date: 2016-04-18
• Last changed date: 2019-03-14
• Status: FINAL
• Official FDA topics: Radiation-Emitting Products, Medical Devices, Laboratory Tests, Emergencies, Premarket, IVDs (In Vitro Diagnostic Devices), Radiological Health
• ReguVirta ID: 57bcf94b87e2cdd72d928cd235ac5b46