Perfusion Cell Culture Decreases Process and Product Heterogeneity in a Head-to-Head Comparison With Fed-Batch

Biotechnology Journal
Jason WaltherKevin Brower

Abstract

In this study, the authors compared the impacts of fed-batch and perfusion platforms on process and product attributes for IgG1- and IgG4-producing cell lines. A "plug-and-play" approach is applied to both platforms at bench scale, using commercially available basal and feed media, a standard feed strategy for fed-batch and ATF filtration for perfusion. Product concentration in fed-batch is 2.5 times greater than perfusion, while average productivity in perfusion is 7.5 times greater than fed-batch. PCA reveals more variability in the cell environment and metabolism during the fed-batch run. LDH measurements show that exposure of product to cell lysate is 7-10 times greater in fed-batch. Product analysis shows larger abundances of neutral species in perfusion, likely due to decreased bioreactor residence times and extracellular exposure. The IgG1 perfusion product also has higher purity and lower half-antibody. Glycosylation is similar across both culture modes. The first perfusion harvest slice for both product types shows different glycosylation than subsequent harvests, suggesting that product quality lags behind metabolism. In conclusion, process and product data indicate that intra-lot heterogeneity is decreased in perfusi...Continue Reading

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Citations

Jan 24, 2019·Bioprocess and Biosystems Engineering·Kahina MellahiOlivier Henry
Apr 6, 2019·Biotechnology and Bioengineering·Matthew GagnonGregory W Hiller
Feb 6, 2020·Biotechnology and Bioengineering·Duarte L MartinsAlois Jungbauer
Feb 8, 2019·Biotechnology Journal·Suzanne S Farid
Jan 11, 2020·Frontiers in Bioengineering and Biotechnology·Nagesh K Tripathi, Ambuj Shrivastava
Jan 8, 2021·Biotechnology and Bioengineering·Michael J CoolbaughKevin Brower
Jan 26, 2021·Biotechnology and Bioengineering·Matthias BrunnerJochen Schaub
Apr 13, 2021·MAbs·Ohnmar Khanal, Abraham M Lenhoff
Dec 1, 2021·Critical Reviews in Biotechnology·Michael A MacDonaldTrent Munro

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