Identification, Characterization and Removal of Host-Cell Proteins (HCP) in Chinese Hamster Ovary (CHO) Monoclonal Antibody Biomanufacturing Processes

Performance Period: 3/1/2019 to 2/28/2022

We propose to develop a consistent, comprehensive approach to identify and clear problematic HCPs in mAb biomanufacturing. Our starting point will be to determine the identities and levels of HCPs in representative mAb bioprocesses based on CHO cells, which will serve as the foundation for a CHO HCP knowledge base that will include biophysical properties and downstream process characteristics for individual HCPs. This knowledge base can support a wide variety of related activities, among which we will pursue two avenues. First, our analysis of clearance of individual HCPs will allow identification of a set of HCPs that are not easily cleared, and these problematic HCPs will be identified as such in the database. Second, we will develop a novel approach to bioprocessing by using a tailored mixture of peptide ligands (PepMix) designed to capture the broad spectrum of HCPs secreted by CHO cells. The approaches to be used will be primarily at MRL 4 or above; the database to be developed will be applicable to both process development and analytics (e.g., general HCP reagent for conserved HCPs) and processes currently in manufacturing, while the new bioprocessing component is expected to reach MRL 5–‐6 by the end of the project.