-In 1997, two drugs, bromfenac and troglitazone, prompted the Food and Drug Administration (FDA) to begin a cycle of yearly conferences to review issues of drug – induced liver injury (DILI). This was after the two drugs had shown serious fatal liver toxicity. Drug application reviewers were the first invitees to the conference in 1999. Academic consultants and pharmaceutical industry were later involved in 2001. As a result, FDA released a guidance entitled: “Guidance for Industry Drug-Induced Liver Injury: Premarketing Clinical Evaluation” (Senior 2014). This presentation was a rational approach was meant to assist in assessment of liver safety in clinical trials.
FDA identified DILI as a key area of focus in a joint effort to broaden the industry’s knowledge in liver toxicity. Since the guideline in 2009, DILI has been the main cause of most drug marketing withdrawals. FDA proposes standard non-clinical toxicity as the cornerstone for preventing hepatotoxicity in humans despite their predictive power being unsatisfactory (Senior 2014). As such, new tests with improved sensitivity and specificity are needed are required to predict hepatotoxicity in clinics.
The guidance describes observations needed to evaluate indicators of hepatotoxic potential. According to Senior (2014), these observations include detection, reaffirmation and examining of liver test abnormalities. The industry then does close evaluation excluding other possible caused of liver toxicity. Lastly, the FDA guidance requires the industry to those affected. This largely involves supportive care till return to baseline status or normality. FDA also makes specific recommendations in the presentation on why some people are more susceptible to DILI. It proposes the use and evaluation of Hy’s Law cases that are discovered through clinical examination.
Senior, J. R. (2014). Evolution of the Food and Drug Administration approach to liver safety assessment for new drugs: current status and challenges. Drug safety, 37(1), 9-17.