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Clinical Trials Resource Group

Clinical Trials Resource Group

Number2IDE Process: Determination of Significant Risk

Devices used on human subjects to conduct investigations of safety and effectiveness are considered “Investigational Devices” (Section 520(g) of FDCA). See helpful FDA Guidance for determination of Significant vs Non-Significant Risk.

Significant Risk (SR) device presents a potential for serious risk of health, safety and welfare of a subject, and:

 Intended to be used as an implant
• Purported to support or sustain human life
• Is for a use of substantial importance in diagnosing, curing, mitigating or treating disease

Examples of SR devices include:  sutures, cardiac pacemakers, hydrocephalus shunts, and orthopedic implants.

Conversely, non-significant risk (NSR) device study does not pose a significant risk to patients. Non-significant risk should not be confused with “minimal risk”, a term used by the FDA to classify studies. Examples of NSR devices include most daily-wear contact lenses and lens solutions, ultrasonic dental scalers, and foley catheters.

NSR device studies may commence without the FDA approval, based solely on the IRB approval. IRB has to make SR/NSR determination for every device study. The IRB acts as a surrogate overseer for the FDA. If NSR determination is made, the sponsor-investigator must follow abbreviated IDE requirements, which are, in essence, the same requirements as regular IDE only without FDA submission (21 CFR 812.2 (b)).

SR devices must meet all regulatory requirements set in 21 CFR 812, including the requirement for approval by both IRB and the FDA before commencing the study. This include submission of an investigational device exemption (IDE) is to the CDRH (Center for Devices and Radiological Health). If approved, IDE allows the investigational device to be used in a clinical study in order to collect safety and effectiveness data.

If NSR go to Step 3 

If SR go to Step 4 


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