Protocol Amendments: Change in Protocol
An IND Sponsor-Investigator is expected to submit a protocol amendment for new protocols, new investigators, or when there are changes in an existing protocol that significantly affect the safety of subjects, scope of the investigation, or scientific quality of the study.
Documentation: In addition to a copy of the revised/updated protocol, a submission of this type should include a brief summary of the differences between the revised protocol and previous protocol(s), and the rationale for the proposed change. For new investigators, the FDA must be notified of the new Principal Investigator within 30 days of the investigator being added and the sponsor must collect and submit the FDA Form 1572 and CV of the Investigator from each research site to the FDA.
Timing: Per regulation, there is no required 30-day clock wait for protocol amendments. Protocol changes may be implemented following submission to FDA and IRB approval. FDA and IRB submissions of this nature may occur in any order. Best practice is to include IRB approval letters with the FDA submission.
Examples of IND Protocol Amendments include:
- Any increase in drug dosage or duration of exposure of individual subjects to the drug beyond that described in the current protocol, or any significant increase in the number of subjects under study.
- Any significant change in the design of a protocol (such as the addition or elimination of a control group).
- Addition of a new test or procedure intended to improve monitoring for, or reduce the risk of, a side effect or adverse event; or elimination of a test intended to monitor safety.
Exception for immediate hazards: a protocol change intended to eliminate an apparent immediate hazard to human subjects may be implemented immediately, provided the FDA is subsequently notified by protocol amendment and the reviewing IRB is also notified.
Information Amendments
Any amendment for information essential to the IND which does not fit within the scope of a protocol amendment, IND safety report, or annual report should be submitted as an information amendment. Information amendments to INDs may include new toxicology, chemistry, or other technical information or a report regarding discontinuance of a clinical or non-clinical investigation.
- Submitted as necessary but not more than every 30 days, if feasible.
- The amendment should clearly:
- Identify its contents:
- Chemistry, Manufacturing, and Control
- Pharmacology/Toxicology
- Clinical
- Statistics
- Clinical Pharmacology
- State the purpose of amendment
- Summarize/present data
- Request for FDA comment, if applicable
- Identify its contents:
Submitting Protocol and Information Amendments to the FDA
It is recommended that Sponsor-Investigators of IND applications submit Protocol and Information Amendments through the method used for submitting the initial IND. This will typically be electronically through the CDER NextGen Portal or the FDA Electronic Submissions Gateway (ESG), or as a hard-copy submission directly to the FDA.
Depending on the submission type, include:
- Form 1571 (PDF - 830KB) should accompany all amendments or reports.
- Form 3674 (PDF - 3MB) should be submitted for all new clinical trials.
- Form 1572 (PDF - 718KB) should be included if the amendment concerns change in application sponsor, addition of a new investigator, or transfer of IND obligations.