Investigational In Vitro Diagnostic Devices Used in Therapeutic Product Clinical Trials (DRAFT)
This guidance addresses the use of investigational In Vitro Diagnostic (IVD) devices in clinical investigations of therapeutic products. It aims to inform stakeholders, including institutional review boards (IRBs) and sponsors, about IDE regulation requirements and risk assessment for investigational IVDs used in therapeutic product trials.
This is a draft guidance. Not for implementation.
Recommended Actions
- Determine if IVD is investigational by assessing if it’s a novel IVD, used for different intended use, or significantly modified
- Assess risk level (Significant Risk, Non-Significant Risk, or Exempt) based on:
- Clinical consequences of erroneous results
- Impact on subject treatment decisions
- Risks of specimen collection
- Therapeutic product risks
- For Significant Risk devices:
- Submit IDE application to FDA
- Obtain FDA approval before starting investigation
- Ensure IRB approval
- For Non-Significant Risk devices:
- Obtain IRB approval
- Comply with abbreviated IDE requirements
- Monitor for changes that could affect risk level
- For IDE applications:
- Include complete device description
- Provide analytical validation data
- Document software validation
- Include risk analysis and benefit/risk assessment
- Define cut-off values and intended use
- Ensure proper labeling and informed consent documentation
- Consider Q-submission meetings with FDA for guidance on study design and requirements
- Maintain ongoing surveillance of risk level throughout the investigation
- Ensure compliance with CLIA requirements if applicable
- Consider cross-referencing between IDE and IND through letters of authorization or master files when appropriate
Key Considerations
Clinical testing
- Clinical protocols must contain description of laboratory tests used to monitor drug effects and minimize risk
- Clinical investigation design must be well-designed and sufficiently powered
- Ongoing surveillance during clinical investigation is recommended to monitor IVD risk
Non-clinical testing
- Preclinical information must justify subject exposure to investigational IVD
- Complete report of prior investigations including clinical, animal and lab testing required for IDE application
Software
- Software validation level information critical for evaluating appropriate IVD use
- Complex multivariate algorithmic software may require extensive data submission
- All necessary instruments and software must be listed and described
Labelling
- Must be labeled according to 21 CFR 809.10(c)
- For investigational use, must bear statement “For Investigational Use Only. The performance characteristics of this product have not been established”
- Informed consent documents must clearly explain investigational nature and risks
Safety
- Risk analysis including investigation justification required
- Benefit/risk assessment must demonstrate benefits outweigh risks
- Analytical performance around cut-off values critical for subject safety
- Risks of invasive sampling procedures must be considered
Other considerations
- Sample type, acquisition and processing descriptions required
- Intended use must be clearly defined including analyte detection, specimen type, conditions
- Cut-off values must be established and justified
- Analytical validity including precision, reproducibility, sensitivity, specificity must be demonstrated
Relevant Guidances
- Vocal Fold Medialization Devices - Testing and Documentation Requirements
- Early Feasibility Medical Device Clinical Studies Including First in Human (FIH) Studies
- Changes to Investigational Device Exemption (IDE) Protocols and When FDA Approval is Required
- Clinical Study Design for Surgical Ablation Devices Used in Treatment of Atrial Fibrillation Under Direct Visualization
- Clinical Study Design for Medical Devices Treating Urinary Incontinence
- Format for Clinical Data Presentations in Orthopedic Implant Device Submissions
- Clinical Trial Considerations for Neurological Devices Intended to Slow, Stop, or Reverse Disease Progression
- Clinical Study Design Recommendations for Devices to Treat Opioid Use Disorder
- Clinical Decision Support Software Functions: Criteria for Non-Device Classification and Implementation Requirements
- Clinical Investigation Requirements for Prostate Tissue Ablation Systems
Related references and norms
- 21 CFR Part 50: Protection of Human Subjects
- 21 CFR Part 56: Institutional Review Boards
- 21 CFR Part 812: Investigational Device Exemptions
- 21 CFR 809.10: Labeling for in vitro diagnostic products
- 42 CFR Part 493: Laboratory Requirements
Original guidance
- Investigational In Vitro Diagnostic Devices Used in Therapeutic Product Clinical Trials
- HTML / PDF
- Issue date: 2017-12-18
- Last changed date: 2020-03-02
- Status: DRAFT
- Official FDA topics: Medical Devices, Good Clinical Practice (GCP), Investigational New Drug Application (INDA), Laboratory Tests, Drugs, Labeling, IVDs (In Vitro Diagnostic Devices), Biologics, Investigational Device Exemption (IDE)
- ReguVirta summary file ID: 2e5180856cffbe65582befab97106f84
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