Blog 5

Guidance
Drug Induced Liver Injury: Premarketing Clinical Evaluation

Status: Final

Link to Guidance
http://www.fda.gov/downloads/Drugs/GuidanceComplianceRegulatoryInformation/Guidances/UCM174090.pdf

Release date: July 2009

Target Audience
Pharmaceutical industry; investigators conduction research in new drug development; Healthcare providers, nurses, physicians, pharmacist, clinical researchers, medical writers, and anyone dealing with the care and safety and welfare of patients

Laws & Regulations
Center for Drug Evaluation and Research (CDER)
Center for Biologics Evaluation and Research (CBER)
U.S. Department of Health and Human Services
FDA

Summary
The guidance provides an approach for the pharmaceutical industry and research study doctors that can be used to identify signals of drug induced liver injury (DILI). This guidance does not address issues of preclinical evaluation for signals of DILI, nor the detection and assessment of DILI after drug approval and marketing. Evaluations for DILI are infrequent. Evidence or signals of a drug’s potential for severe DILI are identified and logged into a new drug development database. DILI has been the single most frequent cause of safety-related drug marketing withdrawals over the past 50 years. In some cases liver toxicity or liver failure has been discovered after the approval of some marketed drug. Use of these drugs, are limited and approval in other countries have been banned due to reported liver toxic side effects. The type of liver injury that leads to severe DILI is a mainly liver cells injury. Liver cell injury is indicated by the significant rise in the liver enzymes in the blood.

Rationale
This guidance intended for people involved in new drug development compounds in assessing the potential for drug induced liver injury. The guidance explains how lab measurements that signal the potential for drug induces liver injury can be obtained and evaluated during the drug development.


Resulting Recommendations
This guidance is an important reference in early phase drug development. Appropriate testing and analysis in premarketing clinical trials can detect drugs that can provide signals for severe liver cell injury.


Impact
This guidance has a major impact on whether the compound will be terminated based on findings with liver cell injury in early development and a major impact on or patient safety.