"We use TideCell to produce rabies viruses for pet protection market. We are able to produce 1 log magnitude higher titer than from roller bottles. Operate 15 L glass roller bottles are a heavy and tedious work. Thanks for TideCell that it reduces our burden on vaccine production not only on the cost saving."
Rabies Virus Production
Rabies is a viral disease that causes acute inflammation of the brain in humans and other warm-bloodedanimals. Early symptoms can include fever and tingling at the site of exposure. These symptoms are followed by one or more of the following symptoms: violent movements, uncontrolled excitement, fear of water, an inability to move parts of the body, confusion, and loss of consciousness. Once symptoms appear, death nearly always results. The time period between contracting the disease and the start of symptoms is usually one to three months; however, this time period can vary from less than one week to more than one year. The time is dependent on the distance the virus must travel to reach the central nervous system. (cited from wikipedia)
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No.
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Process Character
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How TideCell supports the process requirement?
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Can other systems do the same?
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1.
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High cell density is required to achieve high titer, and reduce medium consumption.
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High surface area provided in TideCell increase cell density. Cell density reach around 4 x106 cells/ml.
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Roller bottle
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No. low cell density due to limitation of surface area
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Microcarrier stir tank
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No. the bead density is limited
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Fixed bed bioreactor,
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Yes, but the scale is limited.
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hollow fiber bioreactor
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Yes, but the scale is limited.
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2.
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Infection time and MOI is crucial.
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Capability of carrier sampling from the matrix vessel. Each carrier is with similar surface area and total number of carriers in a matrix vessel is fixed. The total cell count is easy.
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Roller bottle
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Yes/No. Cell density and morphology could be observed under microscope. However, MOI is difficult to estimate.
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Microcarrier stir tank
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Yes. Carrier sampling is available.
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Fixed bed bioreactor
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No. carrier sampling is not available.
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3.
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CPE occurs slowly. A long term harvest is required.
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Cells are immobilizd in a fixed-bed containing porous carriers. Medium exchange is straight-forward and won’t damage or lost cells.
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Roller bottle
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Yes. Medium could be exchange directly.
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Microcarrier stir tank
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Yes/No, additional tool such as filter is required to stop microcarriers inside stir tank. Long term perfusion is difficult.
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Fixed bed bioreactor
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Yes, cells are immobilized. Medium could be exchange directly.
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4.
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Require to reduce impurities to increase the recovery rate, reduce the host cell protein and DNA residues.
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Cells, even lysis after virus infection, will be trapped inside the matrixes without flushing into the harvest medium. The host cell protein and DNA/RNA nucleic acid residues is several folds lower than conventional system.
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Roller bottle
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Yes, cells will retain on the bottle walls.
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Microcarrier stir tank
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No. Cells will be detached and milled by the microcarrier beads during agitation after infection and release high host cell protein and nucleic acids
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Fixed bed bioreactor
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No. Cells will be detached and milled by the microcarrier beads during agitation after infection and release high host cell protein and nucleic acids
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5.
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Final Achievement
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TCID50: Log 9.0
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Roller bottle
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Log 8.0
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Microcarrier stir tank
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Not available
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Packed-bed bioreactor
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Not available
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Type
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Roller bottle
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TideCell Bioreactor
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Performance Analysis
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Scale
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15 L, 3000 cm2
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10 L
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Carrier
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None
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550 g
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Max. cell density
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4~6×108
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1×1011
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Culture days
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3
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4
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Culture medium (cell culture)
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1.5 L
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290 L
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Virus production days
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4
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6
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Culture medium (virus production)
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1.5 L
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65 L
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Equivalency
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1/226
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1
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Space
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100 m2
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3~6 m2
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Labor
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10~20
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3
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Carriers
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None
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550 g
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Culture medium
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678 L
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355 L
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Virus concentration
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Low
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High
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Produce multivalent vaccine
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Difficult
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Easy
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