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

Laurent Larivière; Julia Eva Krüger; Thomas von Hirschheydt; Tilman Schlothauer; Katharine Bray-French; Martin Bader; Valeria Runza

doi:10.1016/j.ijpx.2023.100157

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

Int J Pharm X. 2023 Jan 2:5:100157. doi: 10.1016/j.ijpx.2023.100157. eCollection 2023 Dec.

Authors

Laurent Larivière¹, Julia Eva Krüger¹, Thomas von Hirschheydt¹, Tilman Schlothauer¹, Katharine Bray-French², Martin Bader¹, Valeria Runza¹

Affiliations

¹ Roche Pharmaceutical Research and Early Development, Roche Innovation Center Munich, Penzberg 82377, Germany.
² Roche Pharmaceutical Research and Early Development, Roche Innovation Center Basel, Basel 4058, Switzerland.

Abstract

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.

Keywords: Antibody manufacturing process; CE-SDS, capillary electrophoresis‑sodium dodecyl sulfate; CRS, cytokine release syndrome; ELISA, enzyme-linked immunosorbent assay; End-to-end approach; Fc, fragment crystallizable; Functional characterization; GMP, good manufacturing process; HIC, hydrophobic interaction chromatography; HMW, high molecular weight (species); IEX, ion exchange chromatography; PBS, phosphate buffer saline; Product-related impurities control; SEC, size-exclusion chromatography; SPR, surface plasmon resonance; TAA, tumor-associated antigen; TCB, T cell bispecific; TCR, T cell receptor.