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Exploring Greater Flexibility for Chronic Toxicity Study Designs to Support Human Safety Assessment While Balancing
Helen Prior1, Paul Baldrick2, David O Clarke3
1National Centre for the Replacement, Refinement and Reduction of Animals in Research (NC3Rs), London, UK.
International Journal of Toxicology
|June 1, 2024
Summary
Optimizing chronic toxicity studies can reduce drug development time, costs, and animal use. A workshop explored flexible approaches, including shorter study durations and single-species designs, to enhance efficiency and safety assessments.
Area of Science:
- Pharmacology and Toxicology
- Drug Development
- Regulatory Science
Background:
- Chronic toxicity studies are essential for long-term clinical trial support and human safety assessment.
- Current regulatory guidances offer some flexibility, but broader application could improve efficiency.
- Reducing time, cost, compound usage, and animal numbers in drug development is a key objective.
Purpose of the Study:
- To summarize discussions on optimizing chronic toxicity study designs from the 43rd Annual Meeting of the American College of Toxicology.
- To explore flexible approaches for chronic toxicity studies across different drug modalities.
- To identify opportunities for reducing animal use and resource requirements in drug development.
Main Methods:
- Review of presentations from a workshop on chronic toxicity studies.
- Discussion of an industry collaboration evaluating weight of evidence (WOE) models for monoclonal antibodies (mAbs).
- Exploration of single-species study designs and alternative study durations (e.g., 3-month vs. 6-month, 6-month vs. 9-month).
Main Results:
- A weight of evidence (WOE) model suggests a 3-month study may suffice for some monoclonal antibodies, instead of the traditional 6-month study.
- Opportunities exist for single-species chronic toxicity studies for small molecules, peptides, and oligonucleotides.
- Consideration of using 6-month non-rodent studies more routinely and optimizing recovery animal usage.
Conclusions:
- Flexible application of regulatory guidances for chronic toxicity studies can significantly reduce drug development timelines and costs.
- Alternative study designs, including shorter durations and single-species approaches, show promise for various drug types.
- Further exploration and broader adoption of these optimized approaches are warranted to enhance efficiency and reduce animal use in drug safety evaluations.
