AEGiS-FDA: Draft Guidance - assessing signals for potential drug induced severe liver injury during drug development

Important note: Information in this article was accurate in 2007. The state of the art may have changed since the publication date.

Draft Guidance - assessing signals for potential drug induced severe liver injury during drug development

Food and Drug Administration - October 25, 2007
Richard Klein & Kimberly Struble

On October 25, 2007, FDA published draft guidance intended to assist the pharmaceutical industry and other investigators who are conducting new drug development in assessing the potential for a drug to cause severe liver injury (i.e., fatal, or requiring liver transplantation). The document may be of interest to those involved in drug development related to HIV/AIDS, although the guidance is broader in scope.

In particular, the guidance addresses how laboratory measurements that signal the potential for such drug-induced liver injury (DILI) can be obtained and evaluated during drug development. This evaluation is important because most drugs that cause severe DILI do so infrequently; typical drug development databases with up to a few thousand subjects exposed to a new drug may not show any cases. Databases do, however, often show evidence of a drug's potential for severe DILI if the clinical and laboratory data are properly evaluated for evidence of lesser injury that may not be severe, but may predict the ability to cause more severe injuries.

The guidance describes an approach that can be used to distinguish signals of DILI that identify drugs likely to cause significant hepatotoxicity from signals that do not suggest such a potential. The guidance does not address issues of preclinical evaluation for potential DILI, nor the detection and assessment of DILI after drug approval and marketing.

FDA is soliciting comments on the proposed guidance during the next 60 days. Comments and suggestions regarding this draft document should be submitted before December 24, 2007 to the Division of Dockets Management (HFA-305), Food and Drug Administration, 5630 Fishers Lane, room 1061, Rockville, MD 20852. Comments should be identified with docket number 2007D-0396.

You can view the draft guidance on the FDA web site at http://www.fda.gov/cder/guidance/7507dft.htm. The Federal Register Notice can be found at http://www.fda.gov/OHRMS/DOCKETS/98fr/E7-21060.htm.

Richard Klein
Office of Special Health Issues
Food and Drug Administration

Kimberly Struble
Division of Antiviral Drug Products
Food and Drug Administration

071025
FD071004

SOURCE: Food and Drug Administration (FDA).

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