Document Detail

The ICH S8 immunotoxicity guidance. Immune function assessment and toxicological pathology: autonomous or synergistic methods to predict immunotoxicity?
MedLine Citation:
PMID:  16723215     Owner:  NLM     Status:  MEDLINE    
The new ICH S8 guideline on Immunotoxicology Studies for Human Pharmaceuticals indicates that additional, functional testing of pharmaceuticals is not mandatory to screen for unintended immunotoxicity. The usefulness of conventional parameters like clinical pathology, organ weights and histopathology as measured in Standard Toxicity Studies (STS) to screen for potential unintended immunotoxicity was investigated in an ICH survey. Data of this survey appear to support the notion that properly evaluated STS endpoints would be sufficient for the detection of the majority of unintended immunosuppression by investigational pharmaceutical compounds. Thus the ICH S8 guideline was based on a cause for concern approach using a weight of evidence review of various factors like: findings from STS, pharmacological properties of the drug, intended patient population, structural similarities to known immunomodulators, drug disposition and/or clinical information. Overall the S8 guideline allows for more flexible approaches, and requires a weight of evidence review for which there is no given set of rules. For a proper use this asks for a sensible, realistic and above all a responsible approach both from Industry and Regulators. Some examples regarding the use of clinical pathology parameters like immunoglobulin levels and lymphocyte phenotyping have been included to illustrate this. In conclusion, to detect and evaluate potential immunotoxic effects of human pharmaceuticals the ICH S8 guideline allows for a more flexible, scientifically sound approach. For a proper evaluation of potential immunotoxic effects integration of data from standard toxicological parameters like clinical pathology, histopathology and functional assays are important.
Steven Spanhaak
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Publication Detail:
Type:  Journal Article     Date:  2006-05-24
Journal Detail:
Title:  Experimental and toxicologic pathology : official journal of the Gesellschaft für Toxikologische Pathologie     Volume:  57     ISSN:  0940-2993     ISO Abbreviation:  Exp. Toxicol. Pathol.     Publication Date:  2006 Jul 
Date Detail:
Created Date:  2006-06-21     Completed Date:  2006-08-24     Revised Date:  2007-11-15    
Medline Journal Info:
Nlm Unique ID:  9208920     Medline TA:  Exp Toxicol Pathol     Country:  Germany    
Other Details:
Languages:  eng     Pagination:  373-6     Citation Subset:  IM    
Johnson & Johnson Pharmaceutical Research & Development, Division of Janssen Pharmaceuticals, Turnhoutseweg 30, B-2340 Beerse, Belgium.
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MeSH Terms
Drug Synergism
Guidelines as Topic*
Immune System / drug effects*,  pathology
Immunosuppressive Agents / toxicity*
International Cooperation
Toxicity Tests / methods,  standards*
Xenobiotics / toxicity*
Reg. No./Substance:
0/Immunosuppressive Agents; 0/Xenobiotics

From MEDLINE®/PubMed®, a database of the U.S. National Library of Medicine

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