For clinical research studies directed at evaluating the safety and/or effectiveness of an unapproved device, the prior submission of an Investigational Device Exemption (IDE) is required if the reviewing institutional review board (IRB) determines that the device, or its proposed use in the research study, constitutes a "significant risk" to the research subjects.

• A significant risk device is an investigational device that: (1) is intended as an implant and presents a potential for serious risk to the health, safety, or welfare of a subject; (2) is for use in supporting or sustaining human life and represents a potential for serious risk to the health, safety, or welfare of a subject; (3) is for a use of substantial importance in diagnosing, curing, mitigating, or treating disease or otherwise preventing impairment of human health and presents a potential for serious risk to the health, safety, or welfare of a subject; or (4) otherwise presents a potential for serious risk to a subject.

• A "non-significant risk device study" is a study of a device that does not meet the FDA's definition for a "significant risk device study."

• If a device is found to be a Non-Significant Risk device (NSR), an IDE application to the FDA for their approval is NOT required. A nonsignificant risk device study requires only IRB approval prior to initiation of a clinical study. Federal regulations still apply to a non-significant risk investigation [812.2(b)], but the IRB assumes responsibility for oversight of the study. This is called an "abbreviated IDE". Submissions for nonsignificant device investigations are made directly to the IRB of each participating institution. Sponsors should present an explanation to the IRB where the study will occur of why the device does not pose a significant risk. If the IRB disagrees and determines that the device poses a significant risk, the sponsor must report this finding to FDA within five working days [812.150(b)(9)]. FDA considers an investigation of a nonsignificant risk device to have an approved IDE when IRB concurs with the nonsignificant risk determination and approves the study.

  For Devices NOT Currently Approved for General Marketing by the U.S. Food and Drug Administration (FDA):

For Devices NOT Currently Approved for General Marketing by the U.S. Food and Drug Administration (FDA):

Exceptions to the general requirements for an IDE submission

• Clinical research studies involving the use of an unapproved device may be exempt from the requirement for an IDE submission if the research is not being conducted for the purpose of determining the safety and effectiveness of the device and the research use of the unapproved device does not put the subjects at significant risk.
• Clinical research studies of diagnostic devices are exempt from the IDE regulations if the testing:

1. is non-invasive*;
2. does not require an invasive sampling procedure that presents significant risk;
3. does not by design or intention introduce energy into a subject; and
4. is not used as a diagnostic procedure without confirmation by another medically established diagnostic product or procedure.

• If the use of the unapproved device in the research study involves greater than a minimal risk, the investigator is advised to seek clarification of the IDE submission from the FDA's Center for Devices and Radiological Health.

For Devices Currently Approved for General Marketing by the U.S. Food and Drug Administration (FDA): For clinical research studies directed at evaluating the safety and/or effectiveness of an approved device for an indication that does not appear currently in the FDA-approved product labeling (i.e., an "off-label" indication), the prior submission of an IDE is required if the reviewing IRB determines that the device, or its proposed use in the research study, constitutes a "significant risk" to the research subjects.

Devices Currently Approved for General Marketing by the U.S. Food and Drug Administration (FDA) Exception to the general requirements for an IDE submission.

• Clinical research studies involving the use of an approved device for an "off-label" indication may be exempt from the requirement for an IDE submission if the research is not being conducted for the purpose of determining the safety and effectiveness of the device for this "off-label" indication and the research use of the device does not place the subject at a significant increase in risk (i.e., compared to the FDA-approved use of the device).
• The prior submission of an IDE is not required for clinical research studies (e.g., product comparison studies) directed at evaluating the safety and/or effectiveness of an approved device for an indication that appears currently in the FDA-approved product labeling.
• If the "off-label" use of the approved device in the research study involves greater than a minimal risk, the investigator is advised to seek clarification of the IDE submission requirements from the IRB or the FDA's Center for Devices and Radiological Health.

If you would like to receive guidance in determining if an IDE is needed for your research study or to determine if your study is exempt from the requirement for an IDE submission, please contact Amanda Wood to discuss your research project and the potential need for an IDE.

For additional help, download a detailed IDE submission template with instructions. The NC TraCS Regulatory Service is available to assist Sponsor-Investigators with preparing IDE submissions, annual reports, supplements, and other FDA correspondence. Through our partnership with RTI International, we can also provide pre-clinical guidance for Investigational Device studies, to facilitate thorough pre-clinical testing and trouble-free regulatory submissions.

The Investigational Device "life cycle" can be complicated. It's a good idea to plan pre-clinical and clinical studies well in advance of actual FDA submission to avoid unnecessary roadblocks.

CDRH Learn

The FDA's Center for Device and Radiological Health (CDRH) has developed several learning modules with regard to medical device regulations. These modules are intended as an interactive and accessible tool for those involved in medical device manufacturing and research.

Additional guidance on submitting an IDE application

• ReGARDD.org: Regulatory Guidance for Academic Research of Drugs and Devices — prepared by a consortium of regulatory specialists from UNC, RTI, Duke, and Wake Forest to assist investigators with regulatory submissions
• FDA.gov: information for sponsor-investigators submitting IDEs
• ClinicalTrials.gov: all applicable clinical trials must be registered on clinicaltrials.gov