|
|||||
|
|
Generation of reference cell lines,media, and a process platform for CHO cell biomanufacturing |
|
| Authors: | Lauren T. Cordova Hussain Dahodwala Kathryn S. 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 S. Morris Seongkyu Yoon Michael Betenbaugh Jon Coffman Frank Swartzwelder Michael P. Gillmeister Sarah W. Harcum Kelvin H. Lee |
| Affiliation: | 1. Department of Chemical and Biomolecular Engineering, University of Delaware, Newark, Delaware, USA;2. Department of Chemical and Biomolecular Engineering, University of Delaware, Newark, Delaware, USA National Institute for Innovation in Manufacturing Biopharmaceuticals, Newark, Delaware, USA;3. Department of Bioengineering, Clemson University, Clemson, South Carolina, USA;4. Department of Chemical and Biomolecular Engineering, University of Delaware, Newark, Delaware, USA Department of Biological Sciences and Bioengineering, Inha University, Incheon, South Korea;5. Department of Chemical and Biomolecular Engineering, Clemson University, Clemson, South Carolina, USA;6. Department of Chemical and Biomolecular Engineering, Johns Hopkins University, Baltimore, Maryland, USA;7. Department of Chemical Engineering, University of Massachusetts Lowell, Lowell, Massachusetts, USA;8. AstraZeneca, Gaithersburg, Maryland, USA;9. MilliporeSigma, St. Louis, Missouri, USA;10. Regenxbio, Rockville, Maryland, USA |
| 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. |
| Keywords: | biopharmaceuticals chemically defined media monoclonal antibodies platform process reference CHO cell |