Highly Multiplexed Microbiological/Medical Countermeasure In Vitro Nucleic Acid Based Diagnostic Devices
This guidance addresses highly multiplexed microbiological/medical countermeasure in vitro nucleic acid based diagnostic devices (HMMDs) capable of detecting ≥20 different organisms/targets in a single reaction. It covers devices using technologies like PCR, RT-PCR, bead-based arrays, microarrays, and re-sequencing approaches to aid in diagnosis of infections from viruses, bacteria, parasites, or fungi and determine drug resistance markers. The guidance does not apply to non-nucleic acid based approaches or devices intended for blood donor screening.
Recommended Actions
- Develop comprehensive validation plan covering analytical and clinical performance requirements
- Establish proper controls and quality measures for:
- Specimen handling
- Cross-contamination prevention
- Test performance monitoring
- Design and execute clinical studies:
- Prospective study for specificity
- Retrospective study for sensitivity
- Multi-site testing
- Proper documentation
- Implement software validation procedures according to moderate level of concern
- Create detailed labeling with all required elements
- Establish post-market surveillance system to monitor device performance
- Document procedures for device modifications and updates
- Implement quality system meeting 21 CFR Part 820 requirements
- Maintain proper control of ancillary reagents
- Develop comprehensive risk management system
Key Considerations
Clinical testing
- Clinical validation through a two-part study:
- Prospective study with minimum 1500 patients for specificity evaluation
- Retrospective study using archived specimens for sensitivity evaluation
- Minimum 50 positive specimens per claimed organism
- Testing at minimum 3 sites (2 in US)
- Collection of relevant clinical information
- Proper monitoring and quality control of clinical studies
Non-clinical testing
- Analytical validation studies required for:
- Limit of Detection (LoD)
- Analytical reactivity (inclusivity)
- Analytical specificity
- Cross-reactivity
- Interference studies
- Precision/reproducibility
Software
- Software validation required according to moderate level of concern
- Documentation of software development life cycle
- Risk analysis and hazard mitigation
- Validation of proprietary databases if used
- Software verification and validation testing
Labelling
- Clear intended use statement specifying:
- Pathogens detected
- Specimen types
- Clinical indications
- Target populations
- Qualitative/quantitative nature
- Limitations
Safety
- Controls to prevent cross-contamination
- Quality control measures
- Proper specimen handling procedures
- Biosafety considerations
Other considerations
- Post-market monitoring for performance erosion
- Device modification procedures
- Stability testing
- Ancillary reagents control
- Quality system requirements
Relevant Guidances
- Content of Premarket Submissions for Device Software Functions
- Off-The-Shelf Software in Medical Devices: Documentation Requirements for Premarket Submissions
- Software Validation for Medical Device Production, Quality Systems, and Device Components
- Use of ISO 10993-1 for Biological Evaluation and Testing of Medical Devices
- Recommended Format and Content for Non-Clinical Bench Performance Testing in Medical Device Premarket Submissions
Related references and norms
- CLSI EP05-A2: Evaluation of Precision Performance of Quantitative Measurement Methods
- CLSI EP07-A2: Interference Testing in Clinical Chemistry
- CLSI EP12-A2: User Protocol for Evaluation of Qualitative Test Performance
- CLSI EP24-A2: Assessment of the Diagnostic Accuracy of Laboratory Tests Using ROC Plots
- ISO 14971-1: Medical devices - Risk management
- AAMI SW68:2001: Medical device software - Software lifecycle processes
- ANSI/AAMI/IEC 62304:2006: Medical device software - Software life cycle processes
Original guidance
- Highly Multiplexed Microbiological/Medical Countermeasure In Vitro Nucleic Acid Based Diagnostic Devices
- HTML / PDF
- Issue date: 2014-08-27
- Last changed date: 2020-03-02
- Status: FINAL
- Official FDA topics: Medical Devices, Laboratory Tests, IVDs (In Vitro Diagnostic Devices)
- ReguVirta summary file ID: a843e865300db92c84541ed2ca254987
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