FDA's ISTAND Pilot Program accepts a submission of first organ-on-a-chip technology designed to predict human drug-induced liver injury (DILI)
[9/24/2024] FDA's Center for Drug Evaluation and Research (CDER) has accepted the first letter of intent (LOI) into the Innovative Science and Technology Approaches for New Drugs (ISTAND) Pilot Program for an organ-on-a-chip technology, a type of micro-physiological system (MPS), to study drug-induced liver injury (DILI) for certain drug candidates.
This accepted LOI is for a human Liver-Chip drug development tool (DDT) used to assess the risk of DILI in adults to create relevant data for a drug’s investigational new drug (IND) submission. The Liver-Chip model works by growing four human liver cell types in a micro-engineered environment that recreates the natural physiology and mechanical forces that cells experience within the human body. This allows real time monitoring of signs of drug induced damages compared to control conditions.
The Liver-Chip is used to evaluate drug’s relative DILI risk compared to the risk of a drug from the same class. This data will be used to assess whether the candidate drug has lower, similar, or greater risk of causing liver injury (hepatotoxicity) relative to another drug.
“DILI is a leading reason drugs do not progress through the IND process, and emerging technologies like MPS show promise in assessing risks of hepatotoxicity in preclinical phases of drug development.” said Jeffrey Siegel, M,D. director of the Office of Drug Evaluation Science in CDER’s Office of New Drugs, “We support ISTAND’s efforts to advance novel approaches to drug development and its contribution to bringing safe and effective therapies to patients faster and more efficiently.”
The LOI acceptance is the first step of a three-step qualification process in the DDT qualification programs. For the next step, FDA will work with the applicant to provide feedback on a qualification plan. The final step is a full qualification package, after which developers may use the qualified DDT in any drug development programs for that specific context of use.
Launched in 2020 by CDER and the Center for Biologics Evaluation and Research (CBER), ISTAND aims to support the development of DDTs to be used in regulatory applications for new medical products. ISTAND opens opportunities for drug development tools that do not fit into established pathways for evaluation and application such as for biomarkers and clinical outcome assessments.