Regulatory Case Studies Encountered by Project Toxicologists in Drug Development

Area of Science:

• Regulatory Toxicology
• Pharmaceutical Drug Development
• Toxicological Risk Assessment

Background:

• Toxicologists are integral members of multidisciplinary drug development teams.
• A continuing education course at the 2024 American College of Toxicology (ACT) meeting focused on regulatory toxicology case studies.

Purpose of the Study:

• To summarize case studies on regulatory toxicology in pharmaceutical drug development.
• To illustrate key nonclinical challenges and regulatory considerations across various therapeutic modalities.

Main Methods:

• Review of six case studies from a continuing education course.
• Discussion of challenges including formulation changes, impurities, route-specific toxicology, and risk assessment.
• Examination of residual solvent evaluation and weight-of-evidence approaches.

Main Results:

• Case studies covered small molecules, biologics, and gene therapy, highlighting diverse nonclinical challenges.
• Integration of chemistry, manufacturing, and controls (CMC), nonclinical, and clinical pharmacology data is essential.
• Emerging themes include exposure-based assessments, integrated weight-of-evidence, novel therapeutic adaptations, and proactive regulatory engagement.

Conclusions:

• Toxicologists must manage uncertainty and interpret complex datasets for regulatory strategies.
• The evolving role of toxicologists involves translating multidisciplinary data for safe and efficient drug development.
• Early and proactive regulatory engagement is critical for navigating drug development timelines.