Points to consider in establishment of cell substrate used for manufacture of biotechnological products

Abstract

In the production of biotechnological products, cell substrates established by introducing the expression construct into animal or microbial cells are used. Since the properties of cell substrates affect resultant product quality and safety, establishing an appropriate cell substrate for use in manufacturing is of quite importance for ensuring the quality of the final product. ICH Q5B and Q5D guidelines provide the basic concepts for the analysis of gene expression constructs and the establishment and characterization of cell banks. Since both guidelines were developed more than 20 years ago, there have been various technological innovation and accumulation of relevant knowledge. In this review, in order to contribute to the efficient development and manufacture of biotechnological products such as next-generation therapeutic antibodies, an overview of existing ICH guidelines for establishment, characterization, and control of cell substrates used in the production of biotechnological products is provided. In addition, methods for the evaluation and basic concepts for control of cell substrate clonality and product sequence variants are introduced based on the international trends and the discussion in AMED research group.