Generation of reference cell lines, media, and a process platform for CHO cell biomanufacturing
Lauren T. Cordova, Hussain Dahodwala, Kathryn Elliott, Jongyoun Baik, Daniel C. Odenewelder, Douglas Nmagu, Bradley A. Skelton, Lisa Uy, Stephanie R. Klaubert, Benjamin F. Synoground, Dylan G. Chitwood, Venkata Gayatri Dhara, Harnish Mukesh Naik, Caitlin Morris, Seongkyu Yoon, Michael J. Betenbaugh, Jon Coffman, Frank Swartzwelder, Michael P. Gillmeister, Sarah W. Harcum, Kelvin H. Lee
Abstract
Due to the favorable attributes of Chinese hamster ovary (CHO) cells for therapeutic proteins and antibodies biomanufacturing, companies generate proprietary cells with desirable phenotypes. One key attribute is the ability to stably express multi-gram per liter titers in chemically defined media. Cell, media, and feed diversity has limited community efforts to translate knowledge. Moreover, academic, and nonprofit researchers generally cannot study "industrially relevant" CHO cells due to limited public availability, and the time and knowledge required to generate such cells. To address these issues, a university-industrial consortium (Advanced Mammalian Biomanufacturing Innovation Center, AMBIC) has acquired two CHO "reference cell lines" from different lineages that express monoclonal antibodies. These reference cell lines have relevant production titers, key performance outcomes confirmed by multiple laboratories, and a detailed technology transfer protocol. In commercial media, titers over 2 g/L are reached. Fed-batch cultivation data from shake flask and scaled-down bioreactors is presented. Using productivity as the primary attribute, two academic sites aligned with tight reproducibility at each site. Further, a chemically defined media formulation was developed and evaluated in parallel to the commercial media. The goal of this work is to provide a universal, industrially relevant CHO culture platform to accelerate biomanufacturing innovation.