End-to-end approach for the characterization and control of product-related impurities in T cell bispecific antibody preparations

• Main Authors: Laurent Larivière (Author), Julia Eva Krüger (Author), Thomas von Hirschheydt (Author), Tilman Schlothauer (Author), Katharine Bray-French (Author), Martin Bader (Author), Valeria Runza (Author)
• Format: Book
• Published: Elsevier, 2023-12-01T00:00:00Z.
• Subjects: article
• Online Access: Connect to this object online.
• Notes: 2590-1567; 10.1016/j.ijpx.2023.100157
• Keywords: Antibody manufacturing process; Product-related impurities control; Functional characterization; End-to-end approach; Pharmacy and materia medica; RS1-441
• Source: International Journal of Pharmaceutics: X, Vol 5, Iss , Pp 100157- (2023)

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.