Larivière Laurent, Krüger Julia Eva, von Hirschheydt Thomas, Schlothauer Tilman, Bray-French Katharine, Bader Martin, Runza Valeria
Roche Pharmaceutical Research and Early Development, Roche Innovation Center Munich, Penzberg 82377, Germany.
Roche Pharmaceutical Research and Early Development, Roche Innovation Center Basel, Basel 4058, Switzerland.
Int J Pharm X. 2023 Jan 2;5:100157. doi: 10.1016/j.ijpx.2023.100157. eCollection 2023 Dec.
Antibody-based T cell-activating biologics are promising therapeutic medicines being developed for a number of indications, mainly in the oncology field. Among those, T cell bispecific antibodies are designed to bind one tumor-specific antigen and the T cell receptor at the same time, leading to a robust T cell response against the tumor. Although their unique format and the versatility of the CrossMab technology allows for the generation of safer molecules in an efficient manner, product-related variants cannot be completely avoided. Therefore, it is of extreme importance that both a manufacturing process that limits or depletes product-related impurities, as well as a thorough analytical characterization are in place, starting from the development of the manufacturing cell line until the assessment of potential toxicities. Here, we describe such an end-to-end approach to minimize, quantify and control impurities and -upon their functional characterization- derive specifications that allow for the release of clinical material.
基于抗体的T细胞激活生物制剂是正在为多种适应症开发的有前景的治疗药物，主要用于肿瘤学领域。其中，T细胞双特异性抗体被设计为同时结合一种肿瘤特异性抗原和T细胞受体，从而引发针对肿瘤的强烈T细胞反应。尽管其独特的形式和CrossMab技术的多功能性允许以高效的方式生成更安全的分子，但与产品相关的变体仍无法完全避免。因此，至关重要的是，从制造细胞系的开发到潜在毒性的评估，都要有一个限制或去除与产品相关杂质的制造工艺以及全面的分析表征。在此，我们描述了这样一种端到端的方法，以最小化、量化和控制杂质，并在对其进行功能表征后得出允许放行临床材料的规格。
