FDA Responses

Once the initial IDE submission has been sent to the FDA, a team of staff reviews the IDE and provides one of several standard responses within 30 days of receipt. Click over the flowchart below to see what to expect from the FDA. For additional information, see FDA's Guidance document entitled FDA Decisions for Investigational Device Exemption Clinical Investigations .

Video explanation

If FDA approves an IDE application, the sponsor may begin subject enrollment upon receipt of IRB approval and in accordance with the limits described in FDA's decision letter, including the maximum numbers of U.S. subjects and investigational sites. An IDE application is approved if FDA has determined that: the sponsor has provided sufficient data to support initiation of a human clinical study; no subject protection concerns preclude initiation of the investigation; and no additional conditions must be met.

In some cases, FDA may determine that an outstanding issue remains that can be addressed with data that will be gathered concurrently with the enrollment of a portion of study subjects (i.e., staged approval). FDA may also inform the sponsor of recommended modifications to the study design that FDA believes will improve the study and may be necessary to enable the study to support a future marketing application (i.e., study design considerations) as well as other issues that FDA believes should be considered in preparing for a marketing application or a future clinical investigation (i.e., future considerations).

If FDA approves an IDE application with conditions, the sponsor may begin subject enrollment upon,

Receipt of IRB approval with start date.
May have limits described in FDA's decision letter, including the maximum numbers of U.S. subjects and investigational sites.
Within 45 DAYS = Sponsor must submit information addressing the issues identified as conditions of approval in FDA's letter as an amendment.

Outstanding issues that may lead to approval with conditions include:

Requests for additional information or data involving non-clinical testing issues that do not need to be resolved prior to initiation of subject enrollment;
Late-stage follow-up procedures and assessments that relate to the care of study subjects but, because they occur late in the study, can likely be addressed in response to FDA's letter prior to subjects' reaching that point in the study;
Minor issues related to the informed consent document that must be corrected before initiation of subject enrollment but FDA can review after implementation;
Other minor clarifications, corrections, or modifications (not related to study design) that do not need to be resolved prior to initiation of subject enrollment.

30 DAYS AFTER FDA'S RECEIPT OF AMENDMENT = Sponsor will be informed of FDA's decision. During this time, the sponsor may continue to conduct the study. If FDA determines that the issues have been adequately resolved, it will grant approval.

If any issues remain, FDA may again grant approval with conditions and will communicate those remaining outstanding issues to the sponsor by letter. In this case, the sponsor may continue to enroll subjects in the study provided that, within 45 days, the sponsor responds to the remaining issues identified in FDA's letter. If the sponsor's response to FDA's questions raises concerns regarding subject safety, or the sponsor does not respond, FDA may take appropriate regulatory actions to protect study subjects, including placing a clinical hold on the study. If the study is placed on hold, no additional subjects may be enrolled, and previously enrolled study subjects should receive appropriate monitoring and treatment for their safety.

"Staged approval" or "staged approval with conditions" (which are subsets of approval and approval with conditions decisions) means that FDA grants approval or approval with conditions for a portion of the intended study cohort (i.e., the first stage). These decisions enable certain outstanding questions to be answered concurrently with enrollment in this cohort, and thereby mitigate risk by limiting exposure of the investigational device to a smaller subject population.

The IDE sponsor will be permitted to expand enrollment once an IDE supplement containing the necessary additional information is submitted to FDA and found to be acceptable. In some cases, a partial expansion of enrollment may be granted (i.e., an additional stage of enrollment rather than expansion to full enrollment) while additional data are gathered to answer FDA’s outstanding questions. In such cases, as with the first stage, the sponsor will be permitted to expand enrollment once a second IDE supplement is submitted to FDA and found to be acceptable.

If an IDE application is disapproved, the sponsor may not initiate enrollment in the clinical investigation until the sponsor submits an amendment to the IDE to respond to the deficiencies identified in FDA’s letter and subsequently receives a new letter from FDA granting approval or approval with conditions.

Consistent with 21 CFR 812.30(b) and section 520(g) of the FD&C Act, FDA may disapprove an IDE for any of the following reasons:

Failure to comply with any requirement in 21 CFR Part 812 or section 520(g) of the FD&C Act, any other applicable regulation or statute, or any condition of approval imposed by an IRB or FDA. (21 CFR 812.30(b)(1)).
The application or a report contains an untrue statement of material fact, or omits material information required by 21 CFR Part 812. (21 CFR 812.30(b)(2)).
The sponsor fails to respond to a request for additional information within the time FDA prescribes. (21 CFR 812.30(b)(3)).
There is reason to believe that risks to the subjects are not outweighed by the anticipated benefits to the subjects and the importance of the knowledge to be gained (21 CFR 812.30(b)(4)).
The informed consent is inadequate. (21 CFR 812.30(b)(4)).
The investigation, as proposed, is scientifically unsound. (21 CFR 812.30(b)(4)).
There is reason to believe that the device as used is ineffective. (21 CFR 812.30(b)(4)).
It is otherwise unreasonable to begin or to continue the investigation owing to the way in which the device is used or the inadequacy of (i) the report of prior investigations or the investigational plan; (ii) the methods, facilities, and controls used for the manufacturing, processing, packaging, storage, and where appropriate, installation of the device; or (iii) monitoring and review of the investigation. (21 CFR 812.30(b)(5)).