ArticleBiotechnology progress2022
Rapid intensification of an established CHO cell fed-batch process.
Article in Biotechnology progress, 2022. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 16 papers.
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Who cites it
16 citing papers in PubMed, 26 citations in OpenAlex.
- Multivariate analysis of the effects of high seeding density on therapeutic protein production and sialylation in an intensified CHO cell culture process.Bioprocess and biosystems engineering · 2026Article
- Impact of N-1 phase media optimization as a bioprocess intensification strategy on fed-batch production.Bioprocess and biosystems engineering · 2026Article
- Cultivation strategy optimisation for NK-92 cell line expansion in static conditions.BMC biotechnology · 2026Article
- Impact of keto leucine and isoleucine on CHO cell central carbon metabolism and performance in fed-batch and steady-state perfusion.Frontiers in bioengineering and biotechnology · 2026Article
- 3D-bioprinted microenvironments shape the growth and IgG1 monoclonal antibody production of CHO DG44 cells.Frontiers in bioengineering and biotechnology · 2026Article
- Bioprocess Engineering for Cultivated Meat.Advances in biochemical engineering/biotechnology · 2026Review
- Establishment of a high-throughput scale-down clone screening platform for intensified fed-batch culture of CHO cells.Biotechnology letters · 2025Article
- Investigating the impact of synonymous gene recoding on a recombinantly expressed monoclonal antibody under different process parameters.Bioengineering & translational medicine · 2025Article
- Impact of fed-batch process intensification on the productivity and product quality of two CHO cell lines expressing unique novel molecular format proteins.Bioprocess and biosystems engineering · 2024Article
- Progress in fed-batch culture for recombinant protein production in CHO cells.Applied microbiology and biotechnology · 2023Review
- A novel hybrid bioprocess strategy addressing key challenges of advanced biomanufacturing.Frontiers in bioengineering and biotechnology · 2023Article
- Transcriptomic analysis reveals mode of action of butyric acid supplementation in an intensified CHO cell fed-batch process.Biotechnology and bioengineering · 2022Article
- Increase recombinant antibody yields through optimizing vector design and production process in CHO cells.Applied microbiology and biotechnology · 2022Article
- Rapid intensification of an established CHO cell fed-batch process.Biotechnology progress · 2022Article
- Machine learning-assisted clone selection for intensified cell culture processes.Biotechnology progressArticle
- N-1 semi-continuous transient perfusion in shake flask for ultra-high density seeding of CHO cell cultures in benchtop bioreactors.Biotechnology progressArticle
Corrections and comments
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Authors and funding
5 authors at 3 institutions in 3 countries.
Funding
No grant is acknowledged in the PubMed record.
Abstract
Currently, the mammalian biomanufacturing industry explores process intensification (PI) to meet upcoming demands of biotherapeutics while keeping production flexible but, more importantly, as economic as possible. However, intensified processes often require more development time compared with conventional fed-batches (FBs) preventing their implementation. Hence, rapid and efficient, yet straightforward strategies for PI are needed. In this study we demonstrate such a strategy for the intensification of an N-stage FB by implementing N-1 perfusion cell culture and high inoculum cell densities resulting in a robust intensified FB (iFB). Furthermore, we show successful combination of such an iFB with the addition of productivity enhancers, which has not been reported so far. The conventional CHO cell FB process was step-wise improved and intensified rapidly in multi-parallel small-scale bioreactors using N-1 perfusion. The iFBs were performed in 15 and 250 ml bioreactors and allowed to evaluate the impact on key process indicators (KPI): the space-time yield (STY) was successfully doubled from 0.28 to 0.55 g/L d, while product quality was maintained. This gain was generated by initially increasing the inoculation density, thus shrinking process time, and second supplementation with butyric acid (BA), which reduced cell growth and enhanced cell-specific productivity from ~25 to 37 pg/(cell d). Potential impacts of PI on cell metabolism were evaluated using flux balance analysis. Initial metabolic differences between the standard and intensified process were observed but disappeared quickly. This shows that PI can be achieved rapidly for new as well as existing processes without introducing sustained changes in cellular and metabolic behavior.
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Registered trials
Read under generation 80e0d062 · epoch 390. Bibliography from PubMed, PubMed Central and OpenAlex; grants from NIH RePORTER; trial links from ClinicalTrials.gov; estimates, votes and beliefs from the OpenQuestion graph.