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Human Liver Microphysiological System for Assessing Drug-Induced Liver Toxicity In Vitro
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DILI and drug development: a regulatory perspective

Mark I Avigan1

  • 1Center for Drug Evaluation and Research, Food and Drug Administration, Silver Spring, Maryland.

Seminars in Liver Disease
|June 1, 2014
PubMed

Insights

Predicting rare, serious drug-induced liver injury (DILI) requires analyzing pre- and postmarket data. Rigorous monitoring and analysis are key to identifying hepatotoxic drugs and susceptible individuals.

Area of Science:

  • Pharmacovigilance
  • Hepatotoxicity
  • Drug Safety

Background:

  • Serious drug-induced liver injury (DILI) is rare but life-threatening.
  • Predicting DILI risk from clinical trials is challenging due to data limitations.
  • Identifying drugs causing idiosyncratic DILI is crucial for public health.

Purpose of the Study:

  • To outline strategies for assessing DILI risk using pre- and postmarket data.
  • To emphasize the importance of rigorous data collection and causality analysis for DILI cases.
  • To highlight the need for improved predictive tools in drug development.

Main Methods:

  • Iterative analysis of pre- and postmarket datastreams.
  • Identification of cases consistent with Hy's law.
  • Rigorous standards in subject monitoring and liver injury case analysis.

Main Results:

  • Current methods rely on analyzing available data streams.
  • Hy's law criteria aid in identifying potential hepatotoxic drugs.
  • Adherence to rigorous standards is essential for accurate DILI assessment.

Conclusions:

  • Accurate DILI risk assessment depends on robust data analysis and monitoring.
  • Future predictive tools will enhance the identification of hepatotoxic agents.
  • Identifying susceptible individuals is key to preventing serious DILI.

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