Definition and dynamic control of a continuous chromatography process independent of cell culture titer and impurities

Journal of Chromatography. a
Rebecca A ChmielowskiDavid Roush

Abstract

Advances in cell culture technology have enabled the production of antibody titers upwards of 30g/L. These highly productive cell culture systems can potentially lead to productivity bottlenecks in downstream purification due to lower column loadings, especially in the primary capture chromatography step. Alternative chromatography solutions to help remedy this bottleneck include the utilization of continuous processing systems such as periodic counter-current chromatography (PCC). Recent studies have provided methods to optimize and improve the design of PCC for cell culture titers up to about 3g/L. This paper defines a continuous loading strategy for PCC that is independent of cell culture background and encompasses cell culture titers up to about 31g/L. Initial experimentation showed a challenge with determining a difference in change in UV280nm signal (ie. ΔUV) between cell culture feed and monoclonal antibody (mAb) concentration. Further investigation revealed UV280nm absorbance of the cell culture feedstock without antibody was outside of the linear range of detection for a given cell pathlength. Additional experimentation showed the difference in ΔUV for various cell culture feeds can be either theoretically predicted by...Continue Reading

References

Jun 16, 2015·Journal of Biotechnology·Rahul GodawatVeena Warikoo
Jul 15, 2015·Biotechnology and Bioengineering·Andrew L Zydney
Jul 31, 2016·Biotechnology and Bioengineering·Sarah A JohnsonKurt A Brorson

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Citations

Mar 27, 2018·Journal of Separation Science·Jingbo ZhuYonghua Wang
Feb 28, 2019·Journal of Separation Science·Ana Mayela Ramos-de-la-PeñaOscar Aguilar
Sep 24, 2019·Biotechnology Journal·Karol M Łącki, Frank Riske
Jan 15, 2021·Journal of Chromatography. a·Dong-Qiang LinShan-Jing Yao
Jul 31, 2020·Biosensors & Bioelectronics·Ujwal PatilRichard C Willson
Apr 13, 2021·MAbs·Ohnmar Khanal, Abraham M Lenhoff
Feb 7, 2021·Biotechnology and Bioengineering·Garima ThakurAnurag S Rathore
Apr 6, 2021·Biotechnology and Bioengineering·João P MendesManuel J T Carrondo

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