Comment from Trames Bio

Docket No. FDA-2026-N-4699 for Expedited IND Pilot Program; Request for Information C.1. What additional or alternative approaches could achieve similar goals of accelerating Phase 1 FIH IND study initiation in the U.S.? [Comment] The proposed rolling IND submission and review process has the potential to improve the quality of IND submissions by enabling earlier identification and resolution of issues before the formal 30-day IND review period begins. However, several operational considerations should be addressed to ensure that the proposed process delivers meaningful reductions in time to FIH studies. First, FDA should clearly define expected timelines for review and feedback on each rolling submission component. The value of rolling review depends upon sponsors receiving timely, actionable feedback that enables deficiencies to be resolved before submission of the final IND component. If substantive CMC or nonclinical issues remain unresolved when the final IND component is submitted and the statutory review period begins, the anticipated benefit of rolling review may be substantially reduced. Second, individual IND components should be reviewed within the context of the proposed clinical investigation. Although CMC and nonclinical information may be submitted before the clinical protocol, review should consider the intended patient population, starting dose, dose-escalation strategy, treatment duration, and other key study design considerations. Review of isolated components without sufficient clinical context may generate comments that are ultimately not relevant to the proposed clinical investigation, resulting in unnecessary review cycles for both sponsors and FDA. FDA should therefore provide guidance regarding the minimum clinical context that should accompany early component submissions. More fundamentally, the value of rolling IND review is likely to vary across development programs. For many first-in-human studies, completion of GLP toxicology studies, together with the associated SEND datasets, usually represents the critical path to IND submission. Sponsors frequently complete CMC documentation and much of the remaining IND package while awaiting these final nonclinical deliverables needed to support the proposed clinical dosing. Consequently, opportunities for meaningful schedule compression through rolling submission may be limited for many development programs. Similarly, although some CMC information could potentially be reviewed before completion of nonclinical studies, interpretation of proposed specifications, impurity limits, and the safety of proposed clinical doses often requires supporting nonclinical data and cross-functional context. In addition to the proposed rolling IND submission process, FDA should consider shortening the timeline for pre-IND meetings to accelerate completion of the pre-IND process. FDA should consider shortening the current 60-day Type B pre-IND meeting timeline to 45 days, while maintaining the existing 15-day meeting-grant decision and 30-day briefing package submission requirements. FDA should also consider targeted regulatory process improvements that directly address common bottlenecks to IND submission. Where scientifically justified, reducing requirements for submission of complete Module 4 study reports or providing greater flexibility regarding the timing of SEND dataset submission may meaningfully shorten IND preparation timelines without compromising participant safety. Because SEND datasets often become available several weeks after audited GLP toxicology reports, such flexibility could reduce the time to IND submission by several weeks. Finally, FDA may wish to evaluate regulatory approaches used in jurisdictions such as Australia and New Zealand, where Phase 1 clinical studies can often be initiated more rapidly under different regulatory frameworks. While these systems differ from the U.S. IND process, selected aspects may provide useful insights into opportunities for improving efficiency while maintaining appropriate scientific and ethical standards.