THE DILI CHALLENGE
Drug-induced liver injury (DILI) is the leading cause of acute liver failure and the primary reason for drug withdrawals from market. Traditional preclinical models fail to predict approximately 50% of clinical hepatotoxicity, representing a critical gap in drug safety assessment that organ-chips and liver organoids are now addressing.
FDA ISTAND ACCEPTANCE
In September 2024, the FDA accepted Emulate's Liver-Chip into the Innovative Science and Technology Approaches for New Drugs (ISTAND) Pilot Program. Validation studies demonstrated 87% sensitivity for detecting compounds that cause DILI in humans, with 100% specificity (no false positives). This represents a significant advancement over traditional hepatocyte cultures and animal models.
Source: FDA ISTAND Pilot Program, Emulate press release September 2024
TECHNOLOGY COMPARISON
Liver-chips incorporate primary human hepatocytes with liver sinusoidal endothelial cells, Kupffer cells, and stellate cells under physiological flow conditions. This enables assessment of bile transport, immune-mediated hepatotoxicity, and metabolic drug interactions.
Liver organoids derived from hepatic progenitors or iPSCs provide patient-specific models for hepatotoxicity screening. They express key drug-metabolizing enzymes (CYP450) and can be maintained for extended culture periods for chronic toxicity studies.
ADME-TOX APPLICATIONS
Beyond DILI prediction, liver models support comprehensive ADME-Tox assessment:
KEY TECHNOLOGY PROVIDERS
Emulate
FDA ISTAND validated Liver-Chip platform
CN Bio
PhysioMimix liver models for DILI
InSphero
3D liver microtissues for toxicity
PRIMARY SOURCES
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FDA: ISTAND Pilot Program - Liver-Chip acceptance
View on FDA.gov → -
Toxicological Sciences: In vitro liver models for toxicity testing
View on Oxford Academic → -
PMC: Drug metabolism in hepatocyte-like organoids
View on PubMed Central →