The Evolving Role of Investigative Toxicology in Drug Safety: Insights from a 2025 Industry-Wide Survey

To assess evolving practices in Investigative Toxicology (I-Tox) across the pharmaceutical industry, a 30-question survey was conducted in 2025, following earlier editions in 2015 and 2020. Seventeen mid- to large-sized pharmaceutical companies participated, all active in both traditional (NCEs, NBEs) and emerging modalities. Respondents included in vitro toxicologists from the Investigative Toxicology Leadership Forum, providing company-level input on team structure, objectives, assay capabilities, and future outlook. Most companies reported a dedicated I-Tox function embedded within nonclinical safety organizations. While I-Tox teams remain lean—around 1% of R&D staff—their focus has shifted toward high-impact project support, with greater reliance on CROs and GLP-compliant outsourcing. Internal laboratory activities have become more streamlined, but scientific scope remains broad, with growing emphasis on general toxicology and in silico approaches. I-Tox involvement now occurs earlier in discovery to enable proactive safety de-risking. Core I-Tox contributions span the R&D continuum, from target selection to clinical support. Compared to 2015, greater emphasis is placed on early-phase activities, including SAR guidance, off-target risk assessment, and chemistry support. In later phases, I-Tox focuses on elucidating mechanisms of toxicity, translational relevance, and signal interpretation in both nonclinical and clinical settings. The growing proportion of GLP work managed by I-Tox prompted further exploration of adjacent disciplines. Safety Pharmacology (SP) and Genetic Toxicology (GT) are now integrated into I-Tox functions in 50% and 75% of companies, respectively. These functions are supported by GLP-compliant assays conducted internally (25%), at CROs (58%), or through a combination of both (17%). Notably, one-third of respondents reported incorporating SP into I-Tox within the past five years. Assay availability has improved over the past decade, particularly for in vitro and in silico platforms targeting key organ systems. However, translational confidence remains a limiting factor. Technologies such as iPSC models and high-content imaging are now routinely applied, while others—like organ-on-chip and metabolomics—are still maturing. Respondents also highlighted emerging tools with near-term disruptive potential. Overall, I-Tox continues to evolve as a strategic enabler of drug safety, increasingly contributing to early de-risking, mechanistic insight, and the integration of innovative, non-animal technologies across pharmaceutical R&D.