Beyond preclinical research: production of CHO-derived biotherapeutics for toxicology and early-phase trials by transient gene expression or stable pools

Abstract

Chinese Hamster Ovary (CHO) cells are a workhorse expression host for production of protein-based biotherapeutics. Expression from stably transfected CHO clones is just one means of recombinant protein production in CHO cells, but lower productivity and longstanding regulatory guidelines have restricted the use of alternative approaches, such as non-clonal stable pools and transient gene expression (TGE), for drug manufacturing. Recently, the performance of stable pool and TGE methods has improved dramatically, making them viable options for producing drug substance for GLP-toxicology, early-phase clinical trials, and other scenarios that demand rapid production timelines. Based on these results and our evolving understanding of the genetic heterogeneity of CHO cells, we propose that regulatory guidelines be updated to permit alternative expression modes, enabling more rapid and cost-effective clinical evaluation of potentially life-saving drugs