Integrated Continuous Manufacturing of Biopharmaceuticals

Jungbauer, Alois; Hammerschmidt, Nikolaus

doi:10.1002/9781119001348.ch7

Cited by 7 publications

(8 citation statements)

References 78 publications

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“…In this review, we summarize how continuous cultures have been used to understand basics of recombinant cell physiology, for process development and industrial production of recombinant proteins. As semi-continuous perfusion processes have been used for mammalian cell-based recombinant processes for a long time and reviewed elsewhere [ 10 , 11 , 12 ], our review focuses on microorganisms.…”

Section: Introductionmentioning

confidence: 99%

Application of Continuous Culture Methods to Recombinant Protein Production in Microorganisms

Peebo

Neubauer

2018

Microorganisms

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Depending on the environmental conditions, cells adapt their metabolism and specific growth rate. Rearrangements occur on many different levels such as macromolecular composition, gene and protein expression, morphology and metabolic flux patterns. As the interplay of these processes also determines the output of a recombinant protein producing system, having control over specific growth rate of the culture is advantageous. Continuous culture methods were developed to grow cells in a constant environment and have been used for decades to study basic microbial physiology in a controlled and reproducible manner. Our review summarizes the uses of continuous cultures in cell physiology studies and process development, with a focus on recombinant protein-producing microorganisms.

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Section: Introductionmentioning

confidence: 99%

Application of Continuous Culture Methods to Recombinant Protein Production in Microorganisms

Peebo

Neubauer

2018

Microorganisms

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“…The large number of doses of mRNA vaccines that can be made from small volumes ( Box 2 ) is suited to small, distributed operations. If a bioprocess is still required, then the size and footprint of that process can be decreased through cell culture process intensification, such as fed batch [ 14 ] and, in the future, continuous manufacturing [ 25 ]. Smaller footprint processes would benefit from the use of single-use disposable culture systems that reduce fixed costs dramatically and can be established more quickly than hard-pipe facilities [ 26 ].…”

Section: Downstream Of Synthetic Biologymentioning

confidence: 99%

Build a Sustainable Vaccines Industry with Synthetic Biology

Kitney

Bell²,

Philp

2021

Trends in Biotechnology

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The vaccines industry has not changed appreciably in decades regarding technology, and has struggled to remain viable, with large companies withdrawing from production. Meanwhile, there has been no let-up in outbreaks of viral disease, at a time when the biopharmaceuticals industry is discussing downsizing. The distributed manufacturing model aligns well with this, and the advent of synthetic biology promises much in terms of vaccine design. Biofoundries separate design from manufacturing, a hallmark of modern engineering. Once designed in a biofoundry, digital code can be transferred to a small-scale manufacturing facility close to the point of care, rather than physically transferring cold-chain-dependent vaccine. Thus, biofoundries and distributed manufacturing have the potential to open up a new era of biomanufacturing, one based on digital biology and information systems. This seems a better model for tackling future outbreaks and pandemics. The Vaccine Production Model Needs to ChangeThe COVID-19 crisis has cast the vaccines industry into scrutiny [1]; an industry that has been silently beleaguered for decades (https://www.who.int/immunization/programmes_systems/ procurement/mi4a/platform/module2/2019_Global_Vaccine_Market_Report.pdf?ua=1). A United States National Academy of Sciences study from 2003 [2] concluded that the amount that the nation spent on vaccines 'appears to be insignificant compared with that spent on other medical and social interventions that may have lesser social benefits.' Large company numbers that supply vaccines have steadily reduced [3]: some 80% of vaccines arise from five multinationals (https://www.who.int/immunization/programmes_systems/procurement/market/ global_supply/en/). At the heart of the problem is a tension between relatively poor financial returns to the vaccine industry and the high costs in production and R&D [4].Compared to small molecule pharmaceuticals, centralised vaccine production facilities are capital intensive [5]. Fixed costs are high [6], especially for new vaccines. For example, the need for eggs for production is at least 70 years old, is expensive and time-consuming, but difficult to replace [7]. In past high-income countries have paid a higher price until the fixed costs are amortised. Then lower-income countries have adopted vaccines as the price has dropped after paying the fixed costs. However, there is now tremendous pressure for a COVID-19 vaccine to be available for all who need it, effectively everyone. Distributed Manufacturing, a More-Sustainable Vaccine ModelThe long distribution chains of centralised vaccine production are patchy, resulting in incomplete geographical coverage [8] (Box 1). Even if there is no overall shortage, there may be where they are needed most. Centralisation of labour and production has been the norm in many industries, but in 2015 the World Economic Forum (WEF, see Glossary) put distributed manufacturing in its top ten emerging technologies for the year (https://www.weforum.org/agenda/2015/03/top- HighlightsBiofoun...

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“…In case of manufacturing with mammalian host cells, such as Chinese Hamster Ovarian (CHO) cells, two virus clearance steps based on orthogonal principles are mandatory. [3,4] Currently, manufacturing of antibodies is a combination of chromatography, filtration, and virus inactivation/clearance steps. The cell culture broth generated usually by fed batch culture is harvested by filtration or centrifugation or a combination of both and then captured by affinity chromatography.…”

Section: Alois Jungbauermentioning

confidence: 99%

“…In case of manufacturing with mammalian host cells, such as Chinese Hamster Ovarian (CHO) cells, two virus clearance steps based on orthogonal principles are mandatory . Currently, manufacturing of antibodies is a combination of chromatography, filtration, and virus inactivation/clearance steps.…”

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confidence: 99%