Immune function testing of human pharmaceuticals: regulatory overshoot?

Suppression of the activity of the immune system can result in decreased resistance to (opportunistic) infection and cancer. Experimental animal studies have identified many immunotoxic agents, but data on unintended immuno-toxicity of human pharmaceuticals are limited. To enhance the sensitivity of the non-clinical screening of human pharmaceuticals, immunotoxicity endpoints in standard toxicity studies, as well as an immune function study, are requested by the EU, incorporating a T-cell-dependent antigen response in the first screening phase. Authorities from other areas in the world follow similar lines for immunotoxicity testing, but differ in whether or not the functional assay is seen as a primary requisite or can be secondary to other factors or observations. Based on a limited survey in the framework of the International Conference on Harmonization, the European position has been reconsidered to negotiate a broad cause-for-concern approach. The relevance of functional testing of the immune system to show effects of human pharmaceuticals is shown in this review. There is certainly a need for more in-depth testing of the integrity of the immune system and a cause-for-concern approach is, therefore, needed. A broad category is the number of compounds that might interact via binding to receptor sites at the broadly taken population of leukocytes (e.g., lymphocytes, macrophages). Criteria to differentiate among compounds in this category have yet to be ascertained.