兽用治疗用蛋白药物免疫原性评估

Immunogenicity Assessment of Veterinary Therapeutic Protein Drugs

关键词:  兽用治疗用蛋白药物  免疫原性  抗药抗体  安全性相关性分析  有效性相关性分析

Key words:  veterinary therapeutic protein drugs  immunogenicity  anti-drug antibody  safety-related analysis  efficacy-related analysis

摘要:

近年来，兽用治疗用蛋白药物已经逐渐成为药物研发热点。免疫原性是治疗用蛋白药物的固有属性，可能导致药物体内暴露量改变、药物疗效下降、甚至引发严重不良反应。兽用治疗用蛋白药物免疫原性评估和研究贯穿于该类药物非临床评价、临床评价、上市后评价的整个研发过程，是该类药物研发评价的重点，更是药物评价的难点。本文参考人用治疗用蛋白药物免疫原性相关技术规范要求以及上市药物分析评价方法，对免疫原性检测分析方法的建立和评价要求进行分析。同时，对临床免疫原性设计评价方法和对药代动力学、药效学以及不良反应相关性统计分析方法等进行简要分析。旨在为兽用治疗用蛋白药物的免疫原性评价和临床研究提供参考。

Abstract:

In recent years, therapeutic protein drugs for veterinary have gradually gained increasing attention in drug development. Immunogenicity, which is inherent to these drugs, has emerged as a significant concern due to its potential to alter drug exposure, reduce efficacy, and elicit severe adverse reactions. Consequently, addressing immunogenicity has become a primary focus and challenge in drug development and evaluation. It is essential to comprehensively assess the immunogenicity of veterinary therapeutic protein drugs throughout all stages of drug development, including preclinical studies, clinical trials, and post-market surveillance. This article analyzes the establishment and evaluation requirements of immunogenicity detection methods by referring to technical guidelines on the immunogenicity of therapeutic protein drugs and drawing insights from experiences with evaluation methods used for marketed drugs. Additionally, it explores techniques for conducting clinical immunogenicity research and scrutinizes statistical analysis methods commonly employed to investigate the impact of immunogenicity on pharmacokinetics, pharmacodynamics, and adverse effects. Ultimately, the aim of this article is to provide a valuable reference for the assessment of immunogenicity and clinical research pertaining to therapeutic protein drugs for veterinary.