Abstract:
:It is a common practice in biotherapeutic manufacturing to define a fixed-volume feed strategy for nutrient feeds, based on historical cell demand. However, once the feed volumes are defined, they are inflexible to batch-to-batch variations in cell growth and physiology and can lead to inconsistent productivity and product quality. In an effort to control critical quality attributes and to apply process analytical technology (PAT), a fully automated cell culture feedback control system has been explored in three different applications. The first study illustrates that frequent monitoring and automatically controlling the complex feed based on a surrogate (glutamate) level improved protein production. More importantly, the resulting feed strategy was translated into a manufacturing-friendly manual feed strategy without impact on product quality. The second study demonstrates the improved process robustness of an automated feed strategy based on online bio-capacitance measurements for cell growth. In the third study, glucose and lactate concentrations were measured online and were used to automatically control the glucose feed, which in turn changed lactate metabolism. These studies suggest that the auto-feedback control system has the potential to significantly increase productivity and improve robustness in manufacturing, with the goal of ensuring process performance and product quality consistency.
journal_name
Biotechnol Bioengjournal_title
Biotechnology and bioengineeringauthors
Zhang A,Tsang VL,Moore B,Shen V,Huang YM,Kshirsagar R,Ryll Tdoi
10.1002/bit.25684subject
Has Abstractpub_date
2015-12-01 00:00:00pages
2495-504issue
12eissn
0006-3592issn
1097-0290journal_volume
112pub_type
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