Novel therapeutic molecules of biological origin, or biotherapeutics, are addressing an increasing number of medical needs. The development of biotherapeutics, such as monoclonal antibodies (MAbs) and novel modalities, encompasses the discovery of a clinically relevant target and the identification of a therapeutic compound, via progressive phases: target selection and validation, screening preparation, drug candidate (DC) identification and optimization. The selection of Chinese Hamster Ovary (CHO) cell clones that express the desired DC protein is the mission of cell line development (CLD). These activities stand out because they command a relatively large portion of the cumulative development time required. Recent opportunities to streamline CLD include the precise screening of clones, the implementation of high-throughput techniques, and the consistent scale-up to process development (PD). The characterization and control of cell growth can improve the productivity of biotherapeutic molecules, and leverage the biomanufacturing process, but it's typically performed during late PD and disregarded during the early CLD. The absence of this control at the early stage influences the ability to properly screen candidate cell lines, and can cause suboptimal process efficiencies. Those issues delay the bench-to-bed progression of the biotherapeutic molecule, and the dosing of drugs to patients in need. The objective of this thesis project is to characterize and control the markers of cellular growth influencing the productivities of CHO cell lines, during a biotherapeutic manufacturing process. Through the development and incorporation of this characterization work, we demonstrated a novel means to increase the efficiency and productivity of a typical biotherapeutic manufacturing process.

Our results showed: I. More efficient biological processing of the therapeutic molecule II. Accelerated DNA-to-product manufacturing time III. Increased biological understanding of the particular CHO expression system Three relevant case studies are provided by way of example.