FDA Accepts First In Silico Drug Development Tool Under ISTAND Program to Predict Drug-Induced Liver Injury (DILI)

On 3 June 2026, FDA's Center for Drug Evaluation and Research (CDER) announced the acceptance of the first in silico drug development tool under the Innovative Science and Technology Approaches for New Drugs (ISTAND) pilot program. The accepted tool is designed to predict drug-induced liver injury (DILI) — one of the leading causes of clinical drug failure and post-market safety withdrawals. Regulatory significance: (1) ISTAND is FDA's programme to qualify novel drug development tools (DDTs) that do not fit existing qualification pathways. Acceptance marks the tool as suitable for submission in support of IND/NDA applications within the defined context of use (CoU). (2) This is the first computational/in silico model formally accepted through ISTAND — setting a precedent for future AI/ML and quantitative systems pharmacology (QSP) tools. (3) DILI prediction is one of the highest-priority challenges in preclinical safety — a validated in silico tool could reduce reliance on animal hepatotoxicity studies and enable earlier identification of at-risk compounds. Sponsors developing hepatotoxic compound classes (e.g., kinase inhibitors, antibiotics, metabolically active compounds) should consider whether this tool's CoU is applicable to their development programs and engage FDA early.