title: The ICH S8 immunotoxicity guidance. Immune function assessment and toxicological pathology: autonomous or synergistic methods to predict immunotoxicity?
abstract: 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.
authors.affiliation: Johnson & Johnson Pharmaceutical Research & Development, Division of Janssen Pharmaceuticals, Turnhoutseweg 30, B-2340 Beerse, Belgium. sspanhaa@prdbe.jnj.com
authors.forename: Steven
authors.initials: S
authors.lastname: Spanhaak
mesh_terms: D000818:Animals; D004357:Drug Synergism; D017408:Guidelines as Topic; D006801:Humans; D007107:Immune System / Q000187:drug effects* / Q000473:pathology; D007166:Immunosuppressive Agents / Q000633:toxicity*; D007391:International Cooperation; D018675:Toxicity Tests / Q000379:methods / Q000592:standards*; D015262:Xenobiotics / Q000633:toxicity*
chemical_list: D007166:Immunosuppressive Agents; D015262:Xenobiotics