Maintaining Your IND

Sponsor-Investigators are expected to submit protocol amendments for new protocols or changes to existing protocols before implementing changes. 

Protocol amendments include new protocols, changes in an existing protocol, and new investigators. Information amendments include any amendment that contains information essential to the IND and does not fall within the scope of a protocol amendment, an IND safety report, or an annual report.

IND Sponsor-Investigators are required to notify FDA in a written safety report of:

1) any adverse experience associated with the use of the drug that is both serious and unexpected; or

2) any findings from other studies or tests in laboratory animals that suggest a significant risk for human subjects, including reports of mutagenicity, teratogenicity, and carcinogenicity.

IND Sponsor-Investigators are expected to submit brief annual reports of the progress of the investigations conducted under their IND application within 60 days of the anniversary date that the application went into effect.

IND Withdrawal (21 CFR 312.38 ) initiated by the sponsor

• An IND application may be withdrawn by the applicant if a study is complete and the follow-up period has ended, or if development of the investigational product has been abandoned for any reason
• The FDA must be notified through the IND annual report or as a separate submission, and all clinical investigations conducted under the IND must be halted.
• If the IND is withdrawn for safety reasons, the sponsor shall promptly notify the FDA, all participating investigators, and all reviewing IRBs.

Inactive Status (21 CFR 312.45 ) initiated by the sponsor or the FDA

• The FDA may inactivate an IND if no subjects are entered into clinical studies for a period of 2 years or more or an investigation remains on clinical hold for ≥1 year.
• A sponsor is not required to submit an annual report while an IND is in inactive status.
• An inactive IND can be reactivated via a protocol amendment.
• INDs inactive for over 5 years may be terminated by the FDA.

IND Termination (21 CFR 312.44 ) initiated by the FDA

• If an IND is terminated, the sponsor must end all clinical investigations under the IND and recall or otherwise provide for the disposition of all unused supplies of the drug.
• Termination is typically based on safety issues or deficiencies in the IND or in the conduct of the investigation.
• Sponsors usually have a chance to respond within 30 days.
• Immediate termination of an IND may occur if the FDA concludes that continuation of the investigation presents an immediate and substantial danger to the health of individuals.