Optimizing drug discovery by Investigative Toxicology: Current and future trends

Area of Science:

• Pharmaceutical Toxicology
• Drug Safety
• Mechanistic Toxicology

Background:

• Investigative Toxicology supports early safety decisions in pharmaceuticals, driving a shift from descriptive to mechanistic approaches.
• High costs, low throughput of in vivo studies, and animal welfare (3R principles) necessitate new toxicological methods.
• The field embraces new technologies for in silico, in vitro, and in vivo mechanistic understanding to predict human response.

Purpose of the Study:

• To highlight the current position, challenges, and perspectives of Investigative Toxicology.
• To foster interaction between industry, academia, and regulatory bodies in toxicology.
• To advance animal-free safety testing and improve preclinical decision-making.

Main Methods:

• A Think-Tank workshop organized by the Investigative Toxicology Leaders Forum (ITLF) and CAAT-Europe.
• Discussions involving 14 European pharmaceutical industry leaders, academic experts, and regulatory bodies.
• Synthesis of key topics and discussions from the workshop.

Main Results:

• Investigative Toxicology is crucial for de-risking and elucidating toxicities, supporting early safety decisions.
• Progress enables the development of humanized in vitro test systems and medicines less reliant on animal testing.
• The field aims to improve preclinical decisions and aligns with animal-free safety testing goals.

Conclusions:

• Investigative Toxicology is evolving into an evidence-based, mechanistic discipline, driven by technological advancements and ethical considerations.
• Collaboration through forums like ITLF and workshops is essential for advancing the field.
• The future of pharmaceutical safety testing lies in integrated, mechanistic approaches that minimize animal use.