Использование приматов в доклинических исследованиях препаратов моноклональных антител

Abstract

Listen

Translate article

The emergence of new biopharmaceuticals, including therapeutic monoclonal antibodies (MABs), required a revision of the preclinical development strategy. To provide human risk assessment data, preclinical in vivo efficacy and safety studies of biotechnology-derived pharmaceuticals should be conducted in pharmacologically relevant species. A relevant species is one in which the test material is pharmacologically active due to the expression of the epitope and is one which demonstrate a similar tissue cross-reactivity profile as for human tissues. Often, the only relevant species for preclinical safety assessment of therapeutic MABs are non-human primates (NHPs). If there are no other alternatives (homologous proteins, genetically modified animals), all measures should be taken to reduce the number of animals involved in preclinical studies in accordance with the 3Rs principle. There is not a single solution for therapeutic MABs preclinical development program. When planning research, a scientifically-based approach should always be applied, taking into account all available data. While NHPs are currently necessary to provide risk assessment data for many therapeutic MABs, the very characteristics of MABs biology such as high target specificity, predictable metabolic pathways, and low toxicity, also provide opportunities to minimize the use of NHPs in safety testing and to increase the efficiency of MABs development. The opportunities to adapt development program for MAB at low risk of toxicity include reducing the number of chronic studies, dose groups and recovery group animals. If rodents are also a pharmacologically relevant species, the use of NSPs may be reduced. The paper discusses examples of preclinical programs for therapeutic MABs and possible strategies aimed to minimize the number of NHPs during preclinical safety studies without compromising human safety.