Top 5 Reasons for FDA Clinical Holds on IND Submissions in 2025

An FDA clinical hold is a sponsor’s worst nightmare, immediately halting all study activities. Our review of 2025 enforcement actions reveals that insufficient toxicology data remains the number one cause of full clinical holds. Specifically, the FDA is increasingly scrutinizing the relevance of animal models in relation to human dose selection, particularly for biologics.

Secondly, Investigator Brochures (IB) that fail to clearly communicate risk mitigation strategies are a frequent sticking point. The agency expects a transparent summary of all safety signals, not just a data dump of preclinical results. Quality of the drug substance is the third major factor; impurities that are not adequately characterized or qualified according to ICH Q3 guidelines will trigger an immediate red flag.

It is worth noting that "partial holds" are becoming a more common regulatory tool, allowing some arms of a trial to proceed while others are paused. While less devastating than a full hold, they still signal a lack of confidence from the review division. To mitigate this risk, Mevoq recommends a rigorous mock-audit of the entire IND package prior to submission, simulating the FDA review process to catch these gaps early.