Assess your IND submission against 20 evidence-based rules derived from published regulatory hold data. Identify gaps before they become clinical holds.
| Risk Factor | Impact | Evidence |
|---|---|---|
| First-in-human + first-time sponsor | Highest hold rate profile | Manning et al. 2020 (PubMed 31678263) |
| No Pre-IND meeting | ~30% higher hold risk | Manning et al. 2020 |
| Long gap after Pre-IND meeting | Higher hold rate vs. timely submission | Manning et al. 2020 |
| Limited sponsor experience | Less benefit from Pre-IND meetings | Manning et al. 2020 |
| CGT product type | 20% hold rate vs. 8.9% average | Liao et al. 2023 (PMC10597781) |
| Offshore CRO without recent audit | GLP data integrity risk | FDA Warning Letters 2024-2026 |
| Rank | Cross-Therapeutic | Oncology | Cell & Gene Therapy |
|---|---|---|---|
| #1 | CMC (20-25%) | Clinical (protocol/safety) | Clinical (70%) |
| #2 | Clinical (15-20%) | CMC (quality) | CMC (21%) |
| #3 | Nonclinical (35-40%) | Nonclinical (tox) | Preclinical (9%) |
| #4 | Statistical (5-10%) | Statistical (rare) | Statistical (rare) |
The cross-therapeutic nonclinical figure (35-40%) from Getz 2016 is notably higher than the oncology-specific figure from Manning 2020, where clinical issues rank first. This difference likely reflects oncology's more established regulatory pathways — sponsors in oncology tend to have better CMC preparation, making clinical protocol issues the primary gap.
For CGT, the 20% hold rate is driven overwhelmingly by clinical safety reporting (70% of hold deficiencies), not preclinical or manufacturing — though CMC holds take the longest to resolve (average 8.4 months).
| Strategy | Risk Reduction | Details |
|---|---|---|
| Pre-IND Meeting | High (~30% fewer holds) | Request 60+ days before planned IND. Include focused questions with supporting data. |
| Complete Nonclinical Package | High | Addresses #1 hold reason cross-therapeutically. All pivotal studies GLP with final reports. |
| Robust CMC Section | High | Stability data, specs, batch records, analytical validation. #2 most common hold trigger. |
| Conservative Starting Dose | Moderate | NOAEL-based HED with appropriate safety factor. Show math transparently. |
| Internal Mock Review | Moderate | Simulate regulatory review before submission to catch known gaps. |
Statistics derived from: Getz et al. 2016 (PubMed 26911627, n=1,410 CDER INDs); Manning et al. 2020 (PubMed 31678263, oncology INDs 2014-2017); Liao et al. 2023 (PMC10597781, CGT INDs 2021-2023); FDA IND Activity Reports 2024; Regfo GLP Warning Letter analysis (17 letters, 2019-2026).
Walk through 20 checklist items across 4 categories. For each item, mark whether your IND submission meets the requirement (✓), does not meet it (✗), or is not applicable (—). The tool will calculate a risk score and provide specific remediation guidance for any gaps identified.
Explore each deficiency category in detail — subcategories, severity, prevention checklists, and data from regulatory enforcement.
Ask questions about regulatory deficiency patterns. Answers are grounded in real Complete Response Letter data and published clinical hold statistics.