The purpose of a seed train is the generation of an adequate number of cells for the inoculation of a production bioreactor. The cells are usually run through many cultivation systems which become larger with each passage (e.g. T-flasks, roller bottles or shake flasks, small scale bioreactor systems and subsequently larger bioreactors). The production bioreactor (N stage) is inoculated out of the largest seed train scale.
Challenges
8 steps
42 days to product
28 days to N
14 days in N stage
Intensified seed trains perform process intensification, using a cell retention device such as the XCell ATF® Device, at optimal points during cell expansion to attain the highest cell density inoculum for the production (N) bioreactor. Seed train intensification promotes flexibility and scalability, allowing small labs and global players alike to grow the exact amount of cell culture required, irrespective of whether they are needed for a clinical study, a new therapy or a personalized treatment.
Benefits
Intensify cell growth in the step (N-1) prior to the production bioreactor (N). This process intensification is done by attaching a cell retention device to the N-1 bioreactor to attain high cell density and viability. This seeds the production bioreactor at a higher starting cell density and shortens the production bioreactor run time. This can dramatically increase the facility output without direct change to the core production process.
Variations are possible on this theme, depending on existing facility layouts, one common one being that one N-1 bioreactor might inoculate two production vessels.
8 steps
37 days to product
30 days to N
7 days in N stage
Perform process intensification earlier in the workflow by attaching the XCell ATF® Device to the N-2 or earlier bioreactors. This can save as much as 1 week in the seed train and reduce or eliminate several bioreactors later in the workflow. This means less bioreactors to purchase, operate, clean, and validate - saving clean room floor space while mitigating risk.
6 steps
31 days to product
24 days to N
7 days in N stage
De-couple cell bank and variable early cell culture expansion from manufacturing by producing and freezing intermediate cells. This ensures cells of high cell concentration and viability, and known volume, are provided to manufacturing every time. This process intensification option can be performed in a central facility and distributed globally, making scheduling vastly easier with inoculation occurring “on demand”.
5 steps and time not relevant
(performed outside production timeline)
Combine Frozen Process Intermediaries and N-1 or earlier intensification. This enables Manufacturing on Demand, and a truly flexible facility ready for batch or continuous operation.
3 steps
13 days to product
6 days to N
7 days in N stage
Alternating Tangential Flow (ATF) Filtration
An award-winning technology, ATF allows the removal of spent media while keeping cells in culture. Applied using an XCell ATF® Device attached to a bioreactor, ATF minimizes cell shear and keeps cells in constant equilibrium with bioreactor contents. This results in faster cell growth at higher densities with higher productivity. Today, the XCell ATF® Device is the leading perfusion device for mAb and rProtein production.
Potent cell culture supplements
Repligen developed and manufactures cell culture supplements that provide the benefits of serum supplementation while maintaining an animal-free process.
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September 2022
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by Maribel Rios
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A Brief History of Perfusion Biomanufacturing: How High-Concentration Cultures Will Characterize the Factory of the Future
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