General Requirements for the Submission of IDE
Applications for Clinical Research Studies
I. General Applicability of the FDA Regulations Governing the Submission
of IDE Applications
Clinical investigations involving the use of a FDA-approved or unapproved
device are generally exempt from the requirement for submission of an IDE
application if the research is not being conducted for the purpose of
evaluating the safety and effectiveness of the device for a specific clinical
indication1
II. Clinical Investigations to Evaluate the Safety and/or Effectiveness of
Devices Not Currently Approved for Commercial Marketing by the U.S.
Food and Drug Administration (FDA)2
A. Significant risk device studies.
The submission of an IDE application is required if the reviewing
institutional review board (IRB) determines that the non-approved device,
or its proposed use in the research study, constitutes a “significant risk” to
the research subjects.
1. A “significant risk device study” is defined by FDA regulations3 as “a
study of a device that presents a potential for serious risk to the health,
safety, or welfare of a subject and (1) is an implant4; or (2) is used in
supporting or sustaining human life; or (3) is of substantial importance
in diagnosing, curing, mitigating or treating disease, or otherwise
prevents impairment of human health; or (4) otherwise presents a
potential for serious risk to the health, safety, or welfare of a subject.”
2. 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.”
B. Studies of diagnostic devices.
21 CFR 812.2 Applicability – “General. The IDE regulations apply to all clinical investigations of
devices to determine safety and effectiveness.”
2 I.e., devices for which the FDA has not previously granted Pre-Market Approval (PMA) or 510k
approval.
3 21 CFR 812.3(m)
4 An “implant” is defined by the FDA as “a device that is placed into a surgically or naturally
formed cavity of the human body and is intended to remain there for a period of 30 days or more”.
The FDA may determine that devices placed into human subjects for shorter periods of time are
also implants.
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Clinical investigations of diagnostic devices are exempt from the
requirement for the submission of an IDE application if the testing:
1. Is non-invasive5;
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.
III. Clinical Investigations to Evaluate the Safety and/or Effectiveness of
Devices Currently Approved for General Marketing by the U.S. Food and
Drug Administration (FDA)
A. Clinical investigations to evaluate (compare) the safety and/or
effectiveness of a FDA-approved device for the clinical indication(s)
currently specified in the FDA-approved product labeling
The submission of an IDE application is not required for clinical
investigations (e.g., product comparison studies) directed at evaluating the
safety and/or effectiveness of an approved device for a clinical indication
that appears currently in the FDA-approved product labeling for that
device.
B. Clinical investigations to evaluate the safety and/or effectiveness of
a FDA-approved device for a clinical indication that is not currently
specified in the FDA-approved product labeling (i.e., an “off-label”
indication)
The submission of an IDE application 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.
1. A “significant risk device study” is defined by FDA regulations6 as “a
study of a device that presents a potential for serious risk to the health,
21 CFR 812.3 (k) “Noninvasive” means a device or procedure “that does not by design or
intention: (1) penetrate or pierce the skin or mucous membranes of the body, the ocular cavity, or
the urethra; or (2) enter the ear beyond the external auditory canal, the nose beyond the nares,
the mouth beyond the pharynx, the anal canal beyond the rectum, or the vagina beyond the
cervical os.” Blood sampling that involves simple venipuncture is considered noninvasive, and
the use of surplus samples of body fluids or tissues that are left over from samples taken for noninvestigational purposes are also considered noninvasive.
6 21 CFR 812.3(m)
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safety, or welfare of a subject and (1) is an implant7; or (2) is used in
supporting or sustaining human life; or (3) is of substantial importance
in diagnosing, curing, mitigating or treating disease, or otherwise
prevents impairment of human health; or (4) otherwise presents a
potential for serious risk to the health, safety, or welfare of a subject.”
2. 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.”
An “implant” is defined by the FDA as “a device that is placed into a surgically or naturally
formed cavity of the human body and is intended to remain there for a period of 30 days or more”.
The FDA may determine that devices placed into human subjects for shorter periods of time are
also implants.
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