scholarly journals A high cell density perfusion process for Modified Vaccinia virus Ankara production: Process integration with inline DNA digestion and cost analysis

2021 ◽  
Author(s):  
Gwendal Gränicher ◽  
Masoud Babakhani ◽  
Sven Göbel ◽  
Ingo Jordan ◽  
Pavel Marichal‐Gallardo ◽  
...  
Keyword(s):  
Cost Analysis ◽  
Vaccinia Virus ◽  
Production Process ◽  
Cell Density ◽  
Process Integration ◽  
High Cell Density ◽  
High Cell ◽  
Perfusion Process ◽  
Modified Vaccinia Virus Ankara

The utility and performance of near-infra red spectroscopy in simultaneous monitoring of multiple components in a high cell density recombinant Escherichiacoli production process

1997 ◽  
Vol 17 (3) ◽  
pp. 157-167 ◽  
Author(s):  
G. Macaloney ◽  
J. W. Hall ◽  
M. J. Rollins ◽  
I. Draper ◽  
K. B. Anderson ◽  
...  
Keyword(s):  
Production Process ◽  
Cell Density ◽  
High Cell Density ◽  
High Cell ◽  
Multiple Components ◽  
Infra Red ◽  
And Performance

scholarly journals A high cell density perfusion process for MVA virus production: process integration with inline DNA digestion and cost analysis

2021 ◽  
Author(s):  
Gwendal Gränicher ◽  
Masoud Babakhani ◽  
Sven Göbel ◽  
Ingo Jordan ◽  
Pavel Marichal-Gallardo ◽  
...  
Keyword(s):  
Cost Analysis ◽  
Viral Vectors ◽  
Process Integration ◽  
Virus Production ◽  
Batch Process ◽  
Small Scale ◽  
Perfusion Process ◽  
Modified Vaccinia Virus Ankara ◽  
Exclusion Chromatography ◽  
Space Time Yield

By integrating continuous cell cultures with continuous purification methods, process yields and product quality attributes were improved over the last 10 years for recombinant protein production. However, for the production of viral vectors such as Modified Vaccinia virus Ankara (MVA), no such studies have been reported although there is an increasing need to meet the requirements for a rising number of clinical trials against infectious or neoplastic diseases. Here, we present for the first time a scalable suspension cell (AGE1.CR.pIX cells) culture-based perfusion process in bioreactors integrating continuous virus harvesting through an acoustic settler with semi-continuous chromatographic purification. This allowed to obtain purified MVA particles with a space-time yield >600% higher for the integrated perfusion process (1.05 x 1011 TCID50/Lbioreactor/day) compared to the integrated batch process. Without further optimization, purification by membrane-based steric exclusion chromatography resulted in an overall product recovery of 50.5%. To decrease the level of host cell DNA prior to chromatography, a novel inline continuous DNA digestion step was integrated into the process train. A detailed cost analysis comparing integrated production in batch versus production in perfusion mode showed that the cost per dose for MVA was reduced by nearly one third using this intensified small-scale process.

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