Current status and burning issues in immunotoxicity testing of drugs.
Besides pathology endpoints, additional immune function endpoints have been included in the Note for Guidance on Repeated Dose Toxicity by the European Union (July 2001), which concern the analysis of antibody responses to a T-cell-dependent antigen. Guidance papers of other regulatory authorities are published as well. The main issue is the need for functional immunotoxicity testing to detect unintended immunosuppression. The International Conference on Harmonization (ICH) has surveyed studies from the files of the pharmaceutical industry to find the proportion of compounds that can be detected by additional immunotoxicity testing. Preliminary analysis shows that 10-15% of the compounds in the survey only react positively to the additional tests. More data are requested from the pharmaceutical industry. The Expert Working Group of the ICH has decided to choose a cause-for-concern approach to immunotoxicity rather than a routine-screening approach. The causes for concern are to be defined during ICH negotiations.
Centre for Biological Medicines and Medical Technology, National Institute of Public Health and the Environment, P.O. Box 1, NL-3720 BA Bilthoven, The Netherlands. jan-willem.van.der.laan@rivm.nl
Jan Willem
JW
van der Laan
Henk
H
van Loveren
D004345:Drug Industry; D005062:European Union; D006801:Humans; D007107:Immune System / Q000187:drug effects*; D018675:Toxicity Tests