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Exploring the linkage between cell culture process parameters and downstream processing utilizing a plackett‐burman design for a model monoclonal antibody
Author(s) -
Agarabi Cyrus D.,
Chavez Brittany K.,
Lute Scott C.,
Read Erik K.,
Rogstad Sarah,
AwotweOtoo David,
Brown Matthew R.,
Boyne Michael T.,
Brorson Kurt A.
Publication year - 2016
Publication title -
biotechnology progress
Language(s) - English
Resource type - Journals
SCImago Journal Rank - 0.572
H-Index - 129
eISSN - 1520-6033
pISSN - 8756-7938
DOI - 10.1002/btpr.2402
Subject(s) - downstream processing , plackett–burman design , biopharmaceutical , downstream (manufacturing) , quality by design , upstream (networking) , critical quality attributes , upstream and downstream (dna) , chromatography , monoclonal antibody , chemistry , bioreactor , process (computing) , process engineering , antibody , biology , microbiology and biotechnology , computer science , response surface methodology , immunology , computer network , operations management , organic chemistry , engineering , economics , operating system
Linkage of upstream cell culture with downstream processing and purification is an aspect of Quality by Design crucial for efficient and consistent production of high quality biopharmaceutical proteins. In a previous Plackett‐Burman screening study of parallel bioreactor cultures we evaluated main effects of 11 process variables, such as agitation, sparge rate, feeding regimens, dissolved oxygen set point, inoculation density, supplement addition, temperature, and pH shifts. In this follow‐up study, we observed linkages between cell culture process parameters and downstream capture chromatography performance and subsequent antibody attributes. In depth analysis of the capture chromatography purification of harvested cell culture fluid yielded significant effects of upstream process parameters on host cell protein abundance and behavior. A variety of methods were used to characterize the antibody both after purification and buffer formulation. This analysis provided insight in to the significant impacts of upstream process parameters on aggregate formation, impurities, and protein structure. This report highlights the utility of linkage studies in identifying how changes in upstream parameters can impact downstream critical quality attributes. © 2016 American Institute of Chemical Engineers Biotechnol. Prog., 33:163–170, 2017