抗体类药物非临床研究相关种属选择的一般考虑

General considerations on selection of relevant species in non-clinical studies of antibody products

生物制品的生物活性往往具有种属和/或组织特异性,采用相关种属进行非临床研究有助于阐明其药理学和毒理学特征。ICH S6(R1)建议采用多种技术(如免疫化学或功能学检测)确定相关种属。抗体类药物是一类既能与靶点(抗原)特异性结合又能与相关受体(如FcRn和FcγR等)结合的生物制品,往往涉及较为复杂的体内功能。因此,抗体类药物的相关种属选择应考虑更多的因素,能涵盖生物制品种属选择时的一般考虑。本文基于多个抗体类药物的非临床研究案例,对相关种属选择的关注点和思路进行了总结,供申请人和监管机构关注或参考。

Bioactivities of biological products are often species-specific and/or tissue-specific,thus using relevant animal species in non-clinical studies are helpful to elucidate their potential pharmacological and toxicological characteristics for human use. ICHS6 (R1) recommends that a variety of techniques (such as immunochemical or functional tests) should be used to identify the relevant species. Antibody products belong to biological products that can not only specifically bind to their targets (antigens) but also bind to related receptors (such as FcRn and FcγR),which often involve in complicated functions in vivo. Therefore,more factors should be considered in the selection of relevant species for antibody products,which can cover the general consideration of biological products. This paper summarizes the concerns and thoughts on the selection of species based on the non-clinical practices of several antibody products,so as to draw attention or provide reference for researchers and regulators.