What puts an IND on clinical hold
FDA reviews every new IND within 30 days and can place it on clinical hold if subjects would face unreasonable risk or the application lacks information to assess that risk. Published FDA and peer-reviewed analyses show most initial INDs proceed; when holds occur, product quality (CMC), clinical and nonclinical deficiencies are the recurring causes.
Initial INDs submitted to CDER in fiscal year 2013 placed on hold within 30 days (125 of 1410)
Lapteva L et al. 2016: Investigational New Drug applications: a 1-year pilot study on… (abstract), p. 1
CDER FY 2013 initial INDs placed on hold that became active within one year of the hold
Lapteva L et al. 2016: Investigational New Drug applications: a 1-year pilot study on… (abstract), p. 1
New commercial oncology INDs (FDA OHOP) placed on hold or withdrawn within the 30-day safety review
Manning ML et al. 2020: An FDA analysis of clinical hold deficiencies affecting… (abstract), p. 1
Publicly announced cell and gene therapy holds (2020–2022) imposed after IND submission, before any patient was dosed
Wills CA et al. 2023: Clinical holds for cell and gene therapy trials: Risks, impact, and…, p. 2
Publicly announced cell and gene therapy holds (2020–2022) caused by CMC concerns (7 of 33)
Wills CA et al. 2023: Clinical holds for cell and gene therapy trials: Risks, impact, and…, p. 2
Publicly announced cell and gene therapy holds (2020–2022) where FDA requested additional preclinical data (3 of 33)
Wills CA et al. 2023: Clinical holds for cell and gene therapy trials: Risks, impact, and…, p. 2
Average time to resolve lifted cell and gene therapy holds where FDA requested CMC amendments or data (6 of 26)
Wills CA et al. 2023: Clinical holds for cell and gene therapy trials: Risks, impact, and…, p. 2
Average duration of publicly announced cell and gene therapy clinical holds, January 2020 to December 2022
Wills CA et al. 2023: Clinical holds for cell and gene therapy trials: Risks, impact, and…, p. 2
Common reasons and patterns
Across all initial CDER INDs in fiscal year 2013, chemistry, manufacturing and controls (CMC) was the most cited hold reason, ahead of clinical and then toxicology.
“CMC reasons were most commonly cited, followed by clinical, then toxicology reasons.”✓ VerifiedLapteva L et al. 2016: Investigational New Drug applications: a 1-year pilot study on… (abstract), p. 1Source ↗In oncology INDs reviewed by FDA's OHOP, hold deficiencies were mainly clinical, followed by pharmaceutical quality and then nonclinical development.
“Of INDs that were placed on hold, deficiencies were mainly clinical, followed by concerns related to pharmaceutical quality and nonclinical development.”✓ VerifiedManning ML et al. 2020: An FDA analysis of clinical hold deficiencies affecting… (abstract), p. 1Source ↗In the FDA oncology analysis, held INDs were mostly first-in-human trials or came from sponsors with limited regulatory experience.
“INDs that were placed on hold were mostly for first-in-human trials or submitted by sponsors with limited regulatory experience.”✓ VerifiedManning ML et al. 2020: An FDA analysis of clinical hold deficiencies affecting… (abstract), p. 1Source ↗FDA lists nonclinical data that cannot support the proposed clinical dosing regimen as an example reason for clinical hold.
“Data from nonclinical studies are insufficient to support the dosing regimen in the proposed clinical trial”✓ VerifiedU.S. Food and Drug Administration 2026: IND Application Procedures: Clinical Hold, p. 1Source ↗FDA also cites poor-quality non-GLP toxicology studies, with hard-to-interpret results and an unexplored safety signal, offered as pivotal studies.
“Poor quality non-GLP toxicology studies with difficult to interpret results and a safety signal that has not been sufficiently studied are proposed as pivotal toxicology studies to support use of the product in humans”✓ VerifiedU.S. Food and Drug Administration 2026: IND Application Procedures: Clinical Hold, p. 1Source ↗For cell and gene therapies, failing to show that preclinical test material represents the clinical material can trigger a hold.
“lack of demonstration that the material used in the preclinical studies is representative of the material to be used in the clinical trial can also lead to a clinical hold.”✓ VerifiedWills CA et al. 2023: Clinical holds for cell and gene therapy trials: Risks, impact, and…, p. 8Source ↗
What these numbers can't tell you
The CDER rate and reason ranking come from a single fiscal-year cohort (FY 2013); only the abstract is openly available.
“A retrospective study of rates and reasons for clinical hold for all initial INDs submitted to CDER in fiscal year (FY) 2013 was performed.”✓ VerifiedLapteva L et al. 2016: Investigational New Drug applications: a 1-year pilot study on… (abstract), p. 1Source ↗The oncology analysis covers only new commercial INDs at one FDA office (OHOP); only the abstract is openly available.
“A systematic analysis of new commercial investigational new drug applications (IND) submitted to the FDA's Office of Hematology and Oncology Products (OHOP) in the Center for Drug Evaluation and Research was conducted”✓ VerifiedManning ML et al. 2020: An FDA analysis of clinical hold deficiencies affecting… (abstract), p. 1Source ↗The cell and gene therapy data cover only 33 holds that sponsors chose to disclose publicly; academic and private-company holds are missing.
“our analysis of clinical hold data is limited primarily to press releases and other publicly available documents released by sponsors and does not include academic-sponsored, private company-sponsored, or any other trials in which a clinical hold may be deemed not material information.”✓ VerifiedWills CA et al. 2023: Clinical holds for cell and gene therapy trials: Risks, impact, and…, p. 1Source ↗
Score your species, study length and first-dose approach against the precedent in your modality. Or work through the pre-IND readiness checklist.