Investigational new drug applications, investigational device exceptions, FDA, IND, IDE

4.1.16 Investigational New Drug Applications/Investigational Device Exceptions

To be eligible for NIH funding, all clinical research involving investigational drugs and devices, or other products regulated by the FDA, must comply with all applicable FDA requirements, including those for INDs, IDEs, and human subjects protections. Among other provisions, FDA regulations for human subjects protections are published in 21 CFR Parts 50 and 56 with additional standards found in Parts 312 and 812.

When applicable, the sponsor of the IND/IDE, whether NIH, a recipient, or a third party, is legally responsible for meeting the FDA requirements for sponsors. If the sponsor is also the PI, then the sponsor will need to satisfy FDA's requirements for sponsor-investigators. If the IND/IDE sponsor is a third party, such as a pharmaceutical company or research organization under contract to a recipient or to a pharmaceutical company, the legal responsibility for monitoring the clinical trial and reporting to FDA rests with the sponsor rather than the recipient. This generally will be the case for larger, multi-site clinical trials. If the recipient is the IND/IDE holder, commonly referred to as an "investigator-initiated IND/IDE," the recipient or the investigator serves as the sponsor and assumes the legal responsibility. In any case, the recipient is ultimately responsible to NIH for ensuring compliance with the applicable requirements for protection of human subjects, including compliance with FDA's requirements.

Following the filing of an IND, FDA has a 30-day period in which to review it. FDA may allow the IND to proceed or may defer approval of the IND until changes it deems acceptable are made. FDA also may order a clinical trial to be suspended or terminated, at any time, based on information it receives about that clinical trial.

When NIH funds any part of a clinical study involving an IND or an IDE, NIH must be knowledgeable about any significant communications with FDA concerning the study. The recipient organization must report certain types of FDA communications to the NIH awarding IC The NIH organizational component responsible for a particular grant program or set of activities. The terms "NIH IC," or "awarding IC" are used throughout this document to designate a point of contact for advice and interpretation of grant requirements and to establish the focal point for requesting necessary prior approvals or changes in the terms and conditions of award. within 72 hours of receiving a copy of, or upon being informed of, the FDA communication (through the PD/PI or another person acting on behalf of the recipient), whichever occurs first. This notification requirement applies to any of the following communications from FDA with the sponsor of the IND or IDE:

  • Warning letters (whether sent to the recipient or to the for-profit sponsor)
  • Notices of Initiation of Disqualification Proceedings and Opportunity to Explain
  • Notice of Opportunity for Hearing
  • Notice of Disqualification
  • Consent Agreements
  • Clinical hold letters that pertain to breaches of good manufacturing practices, good clinical practices, or other major issue requiring significant changes in the protocol.

The notification should be made in writing, but also may be done by telephone if a written notice would delay the notification. It should include a statement of the action taken or contemplated and the assistance needed to resolve the situation. These requirements apply to the recipient even if the recipient or the NIH-funded PD/PI is the sponsor. Failure to comply with this requirement may result in NIH imposing a corrective and/or enforcement action (see Administrative Requirements-Enforcement Actions). FDA communications are considered grant-related records for purposes of retention and access (see Administrative Requirements-Monitoring-Record Retention and Access).