How to Handle FDA Feedback on Your IND

This is the third part of our series on What to Expect After You File Your IND.

Click here for Part I: Filing an IND
Click here for Part II: What is the FDA Looking For in Your IND?
Click here for Part IV: What Are the Grounds for Clinical Holds?

If there are concerns about the data in the IND or the Sponsor’s clinical plan that can be addressed within the review period (e.g., by amending the protocol), the reviewing FDA Division will typically either send an email communication and/or request a video or teleconference. The purpose of those last-minute meetings is to ensure that there is sufficient time for the sponsor to address the questions and submit the requested information before the 30-day deadline. Typically, the Clinical, Clinical Pharmacology, CMC, and Pharm/Tox reviewers and their leadership are present to articulate the issues that were identified during the review and discuss a plan to address them. Here are a few examples of the types of last-minute issues that commonly arise:

1. The Division disagrees with the NOAELs defined in the toxicology report(s), and the Division requires the Sponsor to lower the FIH starting dose. The purpose of the meeting is to communicate the new dose level, discuss the impact on the clinical plan and dose escalation. The Division may also require the sponsor to revise the Investigator’s Brochure (IB) to reflect their interpretation.
2. The Division has safety concerns about the proposed patient population, such as use in healthy volunteers. For some drug classes or mechanisms of action, the Division may require the Sponsor to conduct their Phase 1 trial in patients. They may request that the Sponsor amend the protocol to exclude healthy volunteers.
3. The Division has concerns about a specific toxicity and would like to discuss the monitoring plan. The Division may impose a dose-limit and request additional monitoring. The purpose of the meeting is to aid in modifying the protocol.

If the Division and Center for Drug Evaluation and Research (CDER) or Center for Biologics Evaluation and Research (CBER) Leadership feel that the study is unable to proceed under the conditions outlined in the IND, they will inform the Sponsor of the need for a clinical hold. The Sponsor may be able to discuss the concerns with the review team at that time.

Akkeri’s experts have handled hundreds of Agency interactions during their careers and can help you address reviewers’ concerns appropriately while minimizing the impacts on your program. Reach out to us at hello@akkeri.com.