Abstract
Disk-stack and tubular centrifuges have been used to separate soluble and insoluble proteins for biopharmaceutical processing. There are three common host-cell technology platforms, namely yeast, mammalian cells, and bacteria. The first two use the host cells to express extracellular protein, while the latter uses the host cell to express intracellular protein in form of submicron-sized inclusion bodies. For the yeast host-cell process, the first step is to separate yeast cells using centrifugation from dissolved protein, followed by clarification of protein solution product using centrifugation to meet the minimal turbidity requirement. The flow sheet of separating mammalian cells such as Chinese Hamster Ovaries (CHO) cells using centrifuge from the protein product is presented. The key concern is to reduce shear on the cells in the suspension (maintain high cell viability) through gentle feed acceleration to high-speed rotation to effect separation in a centrifuge. The subsequent step is to use a depth filter or microfiltration to clarify the separated liquid product removing any submicron fine solids. It is critical to ensure the centrifuge-filter work together as a system. The flow sheet of processing bacteria bearing protein is to concentrate using centrifugation the bacteria solution followed by lysing the bacteria to release the inclusion bodies. The resultant suspension is reslurried and washed, with the protein-bearing inclusion bodies separated from any impurities by centrifugation until the desired purity is reached suitable for downstream processing. Separation by centrifugation is used extensively in these three host-cell platforms, which is a major application in production of antibotics and intermediate drug substances for the biopharmaceutical market. Other important large-scale centrifugal separation in biotech processes has also been discussed. Finally, throughput and sizing of centrifuge and simulation tools are presented.
Original language | English |
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Title of host publication | 21st American Filtration and Separations Society Annual Conference 2008 |
Pages | 1053-1062 |
Number of pages | 10 |
Volume | 2 |
Publication status | Published - 1 Dec 2008 |
Event | 21st American Filtration and Separations Society Annual Conference 2008 - Valley Forge, PA, United States Duration: 19 May 2008 → 22 May 2008 |
Conference
Conference | 21st American Filtration and Separations Society Annual Conference 2008 |
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Country/Territory | United States |
City | Valley Forge, PA |
Period | 19/05/08 → 22/05/08 |
Keywords
- Biopharmaceutical
- Biotechnology
- Centrifugation
- Centrifuge
- Disk-stack
- Tubular
ASJC Scopus subject areas
- Filtration and Separation
- Industrial and Manufacturing Engineering
- General Environmental Science