C-Reactive Protein (CRP) Assays - Premarket Notification 510k Submissions
This guidance provides recommendations for manufacturers and FDA staff concerning 510(k) submissions for various types of C-Reactive Protein (CRP) assays, including conventional CRP, high sensitivity CRP (hsCRP), and cardiac CRP (cCRP). It addresses performance validation requirements and labeling considerations for these assays, with particular focus on supporting claims for cardiovascular risk assessment.
Recommended Actions
- Determine the appropriate CRP assay type based on intended use (conventional, hsCRP, or cCRP)
- Validate analytical performance:
- Precision at clinical decision points
- Interference studies
- Method comparison with predicate device
- Sensitivity/LOQ for high sensitivity assays
- Linearity assessment
- For cCRP assays:
- Ensure standardization to IFCC/BCR/CAP CRM 470
- Conduct bridging studies if using literature support
- Include AHA/CDC recommendations in labeling
- Prepare comprehensive labeling including:
- Clear intended use statement
- Limitations and warnings
- Performance characteristics
- Result interpretation guidelines
- Consider need for clinical studies based on:
- Similarity to predicate devices
- Ability to transfer reference intervals
- Supporting literature availability
- Document risk analysis and mitigation measures
- Prepare 510(k) submission with complete performance data and labeling
Key Considerations
Clinical testing
- Clinical studies may be required if:
- Indications for use are dissimilar from CRP assays of the same type
- Performance does not allow for reference interval transfer from previous clinical studies
- Data can be based on clinical studies or literature with adequate bridging studies
Non-clinical testing
- Method comparison studies against predicate devices
- Sample testing across the reportable range
- Minimum of 3 sites for point-of-care testing
- At least 40 samples per site with 25% near cutoff
Labeling
- Clear instructions for use and technological features
- Explanation of CRP as acute phase protein
- Limitations and interpretation of results
- Performance characteristics summary
- Standardization information
- Warning about non-specific nature of CRP elevation
Safety
- Risk of improper patient management due to:
- Device failure to perform as indicated
- Misdiagnosis based on incorrect use
- Need for complete clinical evaluation with elevated results
Other considerations
- Precision studies at relevant concentrations
- Interference testing
- Sensitivity/LOQ determination for high sensitivity assays
- Linearity assessment
- Specimen handling validation
- Calibration traceability
Relevant Guidances
- In Vitro Diagnostic Devices for Detection of Antibodies to Borrelia burgdorferi - Performance Characteristics and Testing Requirements
- In Vitro Diagnostic Devices for Detection and Differentiation of Influenza Viruses - Performance Testing and Validation Requirements
- In Vitro Diagnostic Device Studies Exempt from Investigational Device Exemption Requirements
- Applying Previously Cleared IVD Assays to Additional Automated Laboratory Instruments
Related references and norms
- CLSI EP5-A2: Evaluation of Precision Performance of Quantitative Measurement Methods
- CLSI EP7-A: Interference Testing in Clinical Chemistry
- CLSI EP12-A: User Protocol for Evaluation of Qualitative Test Performance
- CLSI EP17-A: Protocols for Determination of Limits of Detection and Limits of Quantitation
- CLSI EP6-A: Evaluation of the Linearity of Quantitative Measurement Procedures
- CLSI EP9-A2: Method Comparison and Bias Estimation Using Patient Samples
- CLSI C28-A2: How to Define and Determine Reference Intervals in the Clinical Laboratory
Original guidance
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