IDE Clinical Investigation Decision Process and Requirements
This guidance clarifies FDA's decision-making process for Investigational Device Exemption (IDE) clinical investigations. It explains the different types of FDA decisions (approval, approval with conditions, staged approval, disapproval) and their regulatory implications. The guidance aims to facilitate timely initiation of device clinical studies while maintaining appropriate subject protections.
What You Need to Know? 👇
What are the different types of FDA decisions for IDE applications?
FDA can render three types of decisions: Approval (without conditions), Approval with Conditions, and Disapproval. Additionally, FDA may grant Staged Approval or Staged Approval with Conditions for a portion of the intended study cohort while outstanding questions are addressed concurrently.
When can a sponsor begin subject enrollment after receiving IDE approval?
Sponsors may begin subject enrollment immediately upon receiving IDE approval or approval with conditions, provided they have IRB approval and comply with the limits specified in FDA’s decision letter, including maximum numbers of subjects and investigational sites.
What is the difference between “Study Design Considerations” and “Future Considerations” in FDA communications?
Study Design Considerations are concerns FDA believes should be addressed to enable the study to support stated goals (like marketing applications). Future Considerations are recommendations for preparing future submissions but aren’t necessary for the current study’s success.
How long does a sponsor have to respond to an IDE approval with conditions?
Sponsors must submit information addressing the conditions within 45 days from the date of FDA’s decision letter. Extensions may be requested with proper justification that won’t impact study integrity or subject protection.
What circumstances might lead to a staged approval instead of full study approval?
Staged approval may be appropriate when additional clinical confirmation of safety is needed from early subjects, or when additional non-clinical testing is required to characterize device performance before exposing the full subject cohort to study risks.
Can FDA disapprove an IDE because the study may not support a future marketing application?
No. Under FDASIA Section 601, FDA cannot disapprove an IDE because the investigation may not support substantial equivalence, de novo classification, or approval determinations, or because additional investigations may be necessary for device clearance or approval.
What You Need to Do 👇
Recommended Actions
- Submit comprehensive IDE application addressing all regulatory requirements
- Consider staged approval approach if additional safety data needed during study
- Address informed consent requirements before initiating enrollment
- Implement appropriate monitoring and safety reporting procedures
- Submit required supplements for changes and periodic reports
- Consider FDA’s study design recommendations if marketing application is planned
- Maintain compliance with manufacturing controls and facilities requirements
- Track enrollment limits and site restrictions per FDA approval
- Respond to FDA conditions within 45 days when applicable
- Consider Pre-Submission interaction for complex study design issues
Key Considerations
Clinical testing
- Clinical investigations must be scientifically sound and pose reasonable scientific questions
- Study design must adequately protect study subjects through monitoring and review
- For pivotal studies, data from full planned cohort expected at time of marketing application
- Staged enrollment may be appropriate to gather initial safety data before full enrollment
Non-clinical testing
- Adequate device characterization and safety data required before human studies
- Additional non-clinical testing may be needed concurrent with early enrollment
- Long-term durability testing may be required for permanently implanted devices
- Basic device evaluation needed (biocompatibility, mechanical, electrical safety, etc.)
Labelling
- Informed consent document must meet 21 CFR Part 50 requirements
- Major informed consent issues require FDA review before implementation
- Minor informed consent issues can be addressed as conditions of approval
Safety
- Risk-benefit profile must be favorable to justify enrollment
- Adequate monitoring and protection of study subjects required
- Safety concerns may limit initial enrollment (staged approval)
- Unanticipated adverse device effects must be reported
Other considerations
- Manufacturing controls and facilities must be adequate
- Changes to device or study require FDA approval via supplements
- Annual reports and other periodic reporting required
- Study design should support marketing application goals if intended
- Statistical considerations for pivotal studies (endpoints, sample size, etc.)
Relevant Guidances 🔗
- Design Considerations for Medical Device Pivotal Clinical Studies
- Early Feasibility Medical Device Clinical Studies Including First in Human (FIH) Studies
- Benefit-Risk Factors in IDE Applications for Medical Device Clinical Investigations
- Format and Content of IDE Progress Reports
Related references and norms 📂
- 21 CFR Part 812: Investigational Device Exemptions
- 21 CFR Part 50: Protection of Human Subjects