Changes to Investigational Device Exemption (IDE) Protocols and When FDA Approval is Required
This guidance provides information on implementing changes or modifications during clinical investigations under IDE (Investigational Device Exemption). It explains when prior FDA approval is required versus when changes can be implemented with a 5-day notice or reported in annual reports.
Recommended Actions
- Establish process to assess if changes require prior approval, 5-day notice, or annual reporting
- Document risk analysis and credible information supporting changes
- Complete all testing before implementing changes under 5-day notice
- Submit changes within required timeframes (5 days or annual)
- Maintain documentation of changes and supporting rationale
- Notify/obtain IRB approval as needed
- Consider impact on data poolability and validity
- Consult FDA if uncertain about change category
- Review agreements/determinations before implementing changes
- Keep participating IRBs informed of all changes
Key Considerations
Clinical testing
- Protocol changes affecting data validity, risk/benefit relationship, scientific soundness, or subject safety require prior FDA approval
- Minor protocol changes not affecting these aspects can be implemented with 5-day notice
- Changes to sample size or number of investigational sites require prior approval
Non-clinical testing
- Preclinical/animal testing data can serve as credible information to support device changes
- Testing must be completed before implementing changes under 5-day notice
Labelling
- Minor labeling changes clarifying instructions or increasing safety can be reported in annual reports
- Adding contraindications, warnings, precautions may require protocol changes and prior approval
Safety
- Changes enhancing safety without significant design changes can be implemented with 5-day notice
- Changes affecting subject safety require prior approval
Other considerations
- Manufacturing changes not constituting significant design changes can use 5-day notice
- Changes to basic principles of operation require prior approval
- Minor changes to study purpose, risk analysis, monitoring procedures can be reported annually
Relevant Guidances
- Design Controls for Medical Device Manufacturers
- Early Feasibility Medical Device Clinical Studies Including First in Human (FIH) Studies
- IDE Clinical Investigation Decision Process and Requirements
- Continuing Review of Clinical Investigations by Institutional Review Boards (IRBs)
Related references and norms
- 21 CFR 812: Investigational Device Exemptions
- 21 CFR 820.30: Design Controls
Original guidance
- Changes to Investigational Device Exemption (IDE) Protocols and When FDA Approval is Required
- HTML / PDF
- Issue date: 2001-05-28
- Last changed date: 2023-08-10
- Status: FINAL
- Official FDA topics: Medical Devices, Investigational Device Exemption (IDE), Premarket
- ReguVirta summary file ID: d449cfdc001b39cf85d4d1a5db61980f
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