Regulatory aspects of immunotoxicology.

Since years, differences among the regulatory requirements on preclinical immunotoxicity testing for pharmaceuticals in the EU, Japan and US indicated a need for an internationally accepted approach. Requests for immunotoxicity investigations are also addressed by guidelines in non-drug areas. While some contain more detailed information in their requirements, other regulations comprise only vague descriptions for consideration of (non-intended) effects on the immune effects. Since 2002, the International Conference on Harmonisation (ICH) of Technical Requirements for Registration of Pharmaceuticals for Human Use put effort in the development of a harmonised approach for testing of immunosuppression and immunoenhancement. Consensus on the ICH S8 guideline on immunotoxicity testing for pharmaceuticals was achieved which now can be implemented into national regulations. The new concept contains in-depth testing, e.g., by functional tests in a concern/weight of evidence approach if the standard toxicity studies or other causes of concern give evidence of an immunotoxic potential or when the target populations are specifically vulnerable. It is expected that the progress on immunotoxicity testing reached by the ICH process will also have an impact on other regulatory areas. Additionally, the regulatory differences in testing requirements on immunotoxicity in other pharmaceutical areas including biotechnology-derived drugs, medicinal products and vaccines and in non-drug areas consisting of chemicals, agrochemicals or food additives are briefly highlighted.