Alternative Models of Developmental and Reproductive Toxicity in Pharmaceutical Risk Assessment and the 3Rs

Area of Science:

• Pharmacology
• Toxicology
• Drug Development

Background:

• Preclinical developmental and reproductive toxicity studies are crucial for drug safety but are animal-intensive and occur late in development.
• Current methods necessitate significant animal use and delay crucial decision-making in the drug development pipeline.

Purpose of the Study:

• To review the current state and future needs of alternative models for developmental and reproductive toxicity (DART) testing.
• To explore the potential of early, simple, and inexpensive screening assays to enhance drug safety evaluations and reduce animal usage.

Main Methods:

• Review of established and emerging alternative models for DART assessment.
• Focus on embryonic stem cell tests, rodent whole embryo culture, and zebrafish assays for developmental toxicity.
• Exploration of in vitro/ex vivo assays for male and female reproductive toxicity.

Main Results:

• Embryonic stem cell assays, rodent whole embryo culture, and zebrafish models are popular and effective for predictive developmental toxicity screening.
• Alternative methods for reproductive toxicity are less established but show promise for mechanism elucidation and backup compound screening.
• Significant progress has been made in developing alternative DART models, with strong industry enthusiasm for their advancement.

Conclusions:

• Alternative DART models offer a viable path towards smarter drug development decisions and reduced animal use.
• These alternative approaches are poised for wider adoption in the pharmaceutical industry in the near future.
• Continued development and validation of these models are essential for enhancing drug safety and efficiency.