June 13, 2025

When companies file an Investigational New Drug (IND) application, the FDA reviews it before trials in humans. Sometimes, the FDA puts a clinical hold, which means the trial must stop until safety questions are answered. This protects patients but can delay progress and increase costs. Most holds happen because of missing or weak nonclinical (animal or lab) data.

What is a Clinical Hold?

  • Complete Hold: All trial activities stop.
  • Partial Hold: Only part of the trial (a study group or protocol) is paused.

Common Nonclinical Triggers

  • Missing Toxicology Studies: No GLP-compliant repeat-dose, Geno toxicity, or safety pharmacology studies.
  • Animal Study Problems: Severe toxic effects or signs of cancer without solutions.
  • Weak Dose Justification: Poor explanation of how the human dose was chosen from animal data.
  • Bad Study Design: Non-GLP studies, missing key safety endpoints, or weak data quality.
  • Product Safety Gaps: Impurities not tested or no stability data.

How to Prevent a Clinical Hold

  • Make a nonclinical plan specific to your drug.
  • Follow ICH guidelines (M3(R2), S6, S9, S11).
  • Use the right animal models and run GLP-compliant studies.
  • Give a strong, science-based reason for your first human dose.
  • Add lab-based or computer-based studies to support safety.
  • Keep documents clear, complete, and well organized (use expert writers if needed).

How to Respond if You Get a Hold

  • Read FDA feedback carefully.
  • Do a gap check against FDA expectations.
  • Run focused GLP studies to fix missing data.
  • Re-check and clarify existing results.
  • Stay in direct contact with FDA (e.g., Type A meetings).
  • Send a clear, complete, and well-structured response.

Final Thoughts

Most clinical holds can be avoided with good planning and complete data. If a hold happens, act quickly: fix gaps, explain results clearly, and work closely with the FDA. This helps restart your trial faster and keeps development on track.