Kawabata Thomas T, Evans Ellen W
Drug Safety R&D, Pfizer, Inc., Groton, Connecticut 06340, USA.
Toxicol Pathol. 2012;40(2):288-93. doi: 10.1177/0192623311430238. Epub 2012 Jan 6.
The ICH S8 immunotoxicity testing guideline for human pharmaceuticals was published in 2006 and was intended to provide guidance for assessing the immunotoxicity potential of low-molecular-weight drugs that are not intended to alter the immune system. For drugs intended to modulate the immune system, immunotoxicity testing strategies are generally developed on a case-by-case approach since the targets, intended patient population, and mechanisms of action of the test compound will determine the type of testing needed. Some of the general principles of ICH S8, however, may be applied to immunotoxicity testing strategies for immunomodulatory drugs. A weight-of-evidence approach using factors discussed in ICH S8 in concert with an assessment of the potential value of additional immunotoxicity testing should be considered. For most situations, immunotoxicity studies with immunomodulatory compounds evaluate off-target effects on the immune system and exaggerated pharmacology. The potential use of data from these studies and considerations such as translatability to humans are discussed.
人用药品的国际协调会议（ICH）S8免疫毒性测试指南于2006年发布，旨在为评估无意改变免疫系统的低分子量药物的免疫毒性潜力提供指导。对于旨在调节免疫系统的药物，免疫毒性测试策略通常根据具体情况制定，因为受试化合物的靶点、目标患者群体和作用机制将决定所需的测试类型。然而，ICH S8的一些一般原则可应用于免疫调节药物的免疫毒性测试策略。应考虑采用证据权重法，结合ICH S8中讨论的因素，并评估额外免疫毒性测试的潜在价值。在大多数情况下，免疫调节化合物的免疫毒性研究评估对免疫系统的脱靶效应和过度药理学作用。讨论了这些研究数据的潜在用途以及可转化性等因素。
