IND review process
Once the IND has been successfully transmitted to the FDA, your organization’s regulatory point of contact will receive via email an acknowledgment letter from the FDA’s Regulatory Project Manager (RPM) assigned to your IND. At this point, the FDA’s pre-clinical, CMC and clinical subject matter experts will begin their review and the 30-day review clock starts. The FDA has adopted an interactive review process which allows reviewers to request clarification and additional information throughout the review process. Once the 30 days have passed, you will receive one of three letters through email:
Study May Proceed
Study May Proceed with Follow Up Comments, or a
Letter
A phone call from the FDA Regulatory Project Manager will accompany a Clinical Hold letter and is intended to notify you of the major concerns identified during review. For additional information on Clinical Holds, please refer to IND Application Procedures: Clinical Hold (fda.gov).
IND maintenance
Annual reports
Once your IND is active, you will be required to notify the FDA of any critical updates on your drug product, on an annual basis. This update is referred to as an Annual Report (AR). The AR is due within 60 days of your IND anniversary date. For example, if you received your Study May Proceed letter on January 15, 2023, you must submit the AR every year thereafter between January 16 and March 16. The data collection (reporting period) for the first AR would be January 15, 2023 – January 14, 2024, and you would have until March 15 to submit the AR. For additional information on IND Annual Reporting, please refer to: IND Application Reporting: Annual Reports (fda.gov).
Safety reporting
Throughout the year, additional information is required to maintain the IND. The most important and time sensitive notifications are those involving clinical trial safety. These are known as safety reports and are to be documented and submitted to the FDA on Form 3500A (https://www.fda.gov/safety/medical-product-safety-information/medwatch-forms-fda-safety-reporting).
Safety reporting involves two steps: an Initial Report and a Follow Up report. You are required to report any adverse reaction confirmed or suspected due to the investigational treatment (as identified in both animal and human studies), that is determined to be both serious and unexpected. You must submit the reports as soon as possible but no later than within 15 calendar days following initial receipt of the information. Unexpected fatal or life-threatening suspected adverse reactions are especially important and must be reported to the FDA as soon as possible but no later than 7 calendar days following receipt of the information. The Follow-up report will include details of the investigation of the adverse experience and should be submitted no later than 15 calendar days after you receive the information. For additional information on safety reporting, please refer to: MedWatch Forms for FDA Safety Reporting (fda.gov).
IND amendments
Throughout the year, any critical changes or updates to your IND’s CMC, Non-Clinical, and Clinical information must be submitted as an IND amendment. Amendments will either be referred to as Information Amendments (pertaining to Non-Clinical and CMC changes) or Protocol Amendments (pertaining to your protocol(s) and study activities or information). The degree of risk the change may have on trial subjects will determine whether you need to obtain approval from the FDA prior to implementation. For example, if you plan to widen a lot release specification, such a change may pose a risk to purity and potency of the drug product. This type of change will require clearance from the FDA prior to implementation of the change.
Similarly, any changes affecting the safety, design or scientific quality of an existing protocol must be submitted to the FDA prior to implementation. Any new protocols are also to be cleared by the FDA in advance. All protocols open under your IND, such as a long-term follow-up study, fall within the scope of IND maintenance requirements. For additional information on IND amendments, please refer to: IND Application Reporting: Protocol Amendments (fda.gov) and IND Application Reporting: Information Amendments (fda.gov).