The effect of hyperosmolality application time on production, quality, and biopotency of monoclonal antibodies produced in CHO cell fed-batch and perfusion cultures

Qin, Jinyan; Wu, Xiang; Xia, Zhigang; Huang, Zheng; Zhang, Ying; Wang, Yanchao; Fu, Qiang; Zheng, Chen

doi:10.1007/s00253-018-9555-7

Cited by 20 publications

(21 citation statements)

References 43 publications

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“…Alternatively, process control strategies were used to keep cells in a physiological state using lactate consumption and the resulting rise in culture pH to regulate perfusion media addition or minimizing growth and maximize productivity by reduced culture temperatures or limiting CSPR . Culture pH, pCO 2 levels, and osmolality were also shown to profoundly impact cell growth and productivity and may be used for future perfusion control strategies. Indeed, valid regression models confirm the general observation that supplementation with CB1, 3, 7a, or 7b suppresses VCD exp by 1.0–3.0 × 10 6 c/ml and daily viable cell days (∆IVCD exp ) by 0.8–2.3 × 10 6 c × d/ml during exponential phase in CDM4NS0 (Table A).…”

Section: Resultsmentioning

confidence: 99%

“…Despite the two markers are often used for describing best cell performance, the focus of critical parameters is shifted toward increased product quality . Thereby, critical quality attributes have to be defined for each molecule of interest individually and quality characteristics are predominantly defined by the process operation mode/conditions and harvest time …”

Section: Resultsmentioning

confidence: 99%

“…[24][25][26] Thereby, critical quality attributes have to be defined for each molecule of interest individually and quality characteristics are predominantly defined by the process operation mode/conditions and harvest time. 22,[27][28][29][30][31][32][33] In semicontinuous small-scale models, N-glycosylation and charge profiles changed distinctly along different culture harvest times, but not by the addition of the CB1 and CB3 feed supplements (Figure 5d, e). The variation of product quality attributes was higher between different harvest times than between different media.…”

Section: Verification Of Performance By Semicontinuous Small-scale mentioning

confidence: 99%

“…17 Alternatively, process control strategies were used to keep cells in a physiological state using lactate consumption and the resulting rise in culture pH to regulate perfusion media addition 18 or minimizing growth and maximize productivity by reduced culture temperatures 19,20 or limiting CSPR. 21 Culture pH, pCO 2 levels, and osmolality were also shown to profoundly impact cell growth and productivity 22,23 and may be used for future perfusion control strategies.…”

Section: Suppression Of Cell Growth At High Viabilities and Productivmentioning

confidence: 99%

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Rapid development of clone‐specific, high‐performing perfusion media from established feed supplements

Mayrhofer

Reinhart

Castan³

et al. 2019

Biotechnology Progress

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Perfusion cultivation of recombinant CHO cells is of substantial interest to the biopharmaceutical industry. This is due to increased space–time‐yields (STYs) and a short residence time of the recombinant protein in the bioreactor. Economic processes rely on cultivation media supporting rapid growth in the exponential phase and high protein production in the stationary phase at minimal media consumption rates. To develop clone‐specific, high‐performing perfusion media we present a straightforward and rapid two‐step approach combining commercially available basal media and feed supplements using design‐of‐experiment. First, the best performing feed supplements are selected in batch cultures. Then, the mixing ratio of selected feed supplements is optimized in small‐scale semicontinuous perfusion cultures. The final media formulation is supported by statistical response surface modeling of a set of cultivation experiments with blended media formulations. Two best performing novel media blends were finally applied to perfusion bioreactor verification runs to reach 200 × 106 c/ml within 2 weeks at minimum cell‐specific perfusion rates as low as 10–30 pL/c/d. Obtained STYs of 0.4–1.2 g/L/d represent a 10‐fold increase compared to batch cultures. This general workflow is universally applicable to any perfusion platform combining a specific cell line, basal medium, and established feed solutions.

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Section: Resultsmentioning

confidence: 99%

Section: Resultsmentioning

confidence: 99%

Section: Verification Of Performance By Semicontinuous Small-scale mentioning

confidence: 99%

Section: Suppression Of Cell Growth At High Viabilities and Productivmentioning

confidence: 99%

See 2 more Smart Citations

Rapid development of clone‐specific, high‐performing perfusion media from established feed supplements

Mayrhofer

Reinhart

Castan³

et al. 2019

Biotechnology Progress

View full text Add to dashboard Cite

show abstract

“…Inorganic salt components in the medium mainly include sodium, potassium, magnesium, calcium, and phosphorus. Their main function is to help maintain a stable osmotic pressure during the cell culture process because each cell line has its tolerable osmotic pressure range (Qin et al, 2019). In addition, inorganic salt ions are involved in many cellular metabolic regulations.…”

Section: Inorganic Saltionmentioning

confidence: 99%

Serum-Free Medium for Recombinant Protein Expression in Chinese Hamster Ovary Cells

Liu

Fan

Lin

et al. 2021

Front. Bioeng. Biotechnol.

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At present, nearly 70% of recombinant therapeutic proteins (RTPs) are produced by Chinese hamster ovary (CHO) cells, and serum-free medium (SFM) is necessary for their culture to produce RTPs. In this review, the history and key components of SFM are first summarized, and its preparation and experimental design are described. Some small molecule compound additives can improve the yield and quality of RTP. The function and possible mechanisms of these additives are also reviewed here. Finally, the future perspectives of SFM use with CHO cells for RTP production are discussed.

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Strategies for controlling afucosylation in monoclonal antibodies during upstream manufacturing

Rish

Siddiquee

Huang

et al. 2023

Biotechnology Journal

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Core fucosylation is a highly prevalent and significant feature of N-glycosylation in therapeutic monoclonal antibodies produced by mammalian cells where its absence (afucosylation) plays a key role in treatment safety and efficacy. Notably, even slight changes in the level of afucosylation can have a considerable impact on the antibody-dependent cell-mediated cytotoxicity. Therefore, implementing control over afucosylation levels is important in upstream manufacturing to maintain consistent quality across batches of product, since standard downstream processing does not change afucosylation. In this review, the influences and strategies to control afucosylation are presented. In particular, there is emphasis on upstream manufacturing culture parameters and media supplementation, as these offer particular advantages as control strategies over alternative approaches such as cell line engineering and chemical inhibitors. The review discusses the relationship between the afucosylation influences and the underlying cellular metabolism to promote increased process understanding. Also, briefly highlighted is the value of empirical and mechanistic models in evaluating and designing control methods for core fucosylation.

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The effect of hyperosmolality application time on production, quality, and biopotency of monoclonal antibodies produced in CHO cell fed-batch and perfusion cultures

Cited by 20 publications

References 43 publications

Rapid development of clone‐specific, high‐performing perfusion media from established feed supplements

Rapid development of clone‐specific, high‐performing perfusion media from established feed supplements

Serum-Free Medium for Recombinant Protein Expression in Chinese Hamster Ovary Cells

Strategies for controlling afucosylation in monoclonal antibodies during upstream manufacturing

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