CRITICAL CHALLENGE
Toxicity accounts for ~30% of drug failures in clinical development, with drug-induced liver injury (DILI) being the leading cause of post-market withdrawals. Traditional animal models poorly predict human toxicity due to species differences in drug metabolism, transporter expression, and cellular sensitivity. Human simulation technologies address this gap with physiologically relevant models.
ORGAN-SPECIFIC APPLICATIONS
- Hepatotoxicity (DILI): InSphero 3D liver microtissues predict idiosyncratic and intrinsic liver toxicity with 80%+ sensitivity
- Cardiotoxicity: Emulate Heart-Chip and Hesperos cardiac modules detect QT prolongation and contractility effects
- Nephrotoxicity: Mimetas kidney tubule models identify proximal tubule damage biomarkers
- Neurotoxicity: AxoSim NerveSim detects chemotherapy-induced peripheral neuropathy (CIPN)
- Pulmonary Toxicity: Lung-on-chip models assess inhaled drug and environmental toxicant effects
REGULATORY ACCEPTANCE
- FDA ISTAND: Qualification pathway for novel toxicology methods
- OECD Test Guidelines: TG 442C/D/E for skin sensitization, TG 439 for skin irritation
- ICH S7B: CiPA initiative accepts human iPSC-cardiomyocyte assays
- EPA NAMs: ToxCast/Tox21 high-throughput screening replacing animal tests
PERFORMANCE METRICS
Human liver organoids and organ-chips demonstrate 80-90% sensitivity and 90%+ specificity for DILI prediction, compared to 50-60% for animal models. Multi-organ systems capture systemic toxicity from metabolite formation, while long-term culture (28+ days) enables repeat-dose toxicity assessment matching regulatory requirements.