Dataset Information

High throughput screening data for a case study of CHO cell culture process development.

ABSTRACT: In this article, we present four sets of data from high-throughput screening (HTS) studies of different chemically defined media using an industrially relevant Chinese hamster ovary (CHO) cell line. While complex hydrolysate media was used in the early phase process development and manufacturing of a monoclonal antibody (mAb), here we seek to determine an appropriate chemically defined media for late phase process development. Over 150 combinations of chemically defined basal media, feed media, and basal and feed media supplements, such as polyphenolic flavonoid antioxidants (including rosmarinic acid (RA)), were evaluated in four HTS studies to replace the complex hydrolysate media. Specifically, these four screening studies incorporated custom design of experiment (DOE), one-factor-at-a-time (OFAT), and definitive screening design methodologies for titer improvement. Titer was improved two fold compared to the early phase process using the addition of RA to chemically defined media. This dataset exemplifies how HTS can be used as an effective approach to systematically and statistically determine media composition and supplementation to increase mAb titer. These data were presented in connection with a published paper [1].

SUBMITTER: He Q

PROVIDER: S-EPMC8531557 | biostudies-literature | 2021 Dec

REPOSITORIES: biostudies-literature

ACCESS DATA

Publications

High throughput screening data for a case study of CHO cell culture process development.

He Qin Q Xu Jianlin J Vandermark Erik E Tian Jun J Qian Yueming Y Chelius Cynthia C Lee Jongchan J Borys Michael C MC Li Zheng Jian ZJ Pendse Girish G

Data in brief 20211017

In this article, we present four sets of data from high-throughput screening (HTS) studies of different chemically defined media using an industrially relevant Chinese hamster ovary (CHO) cell line. While complex hydrolysate media was used in the early phase process development and manufacturing of a monoclonal antibody (mAb), here we seek to determine an appropriate chemically defined media for late phase process development. Over 150 combinations of chemically defined basal media, feed media, ...[more]

PMID: 34712760

Similar Datasets

Project description:Microbioreactors play a critical role in process development as they reduce reagent requirements and can facilitate high-throughput screening of process parameters and culture conditions. Here, we have demonstrated and explained in detail, for the first time, the amenability of the automated ambr15 cell culture microbioreactor system for the development of scalable adherent human mesenchymal multipotent stromal/stem cell (hMSC) microcarrier culture processes. This was achieved by first improving suspension and mixing of the microcarriers and then improving cell attachment thereby reducing the initial growth lag phase. The latter was achieved by using only 50% of the final working volume of medium for the first 24 h and using an intermittent agitation strategy. These changes resulted in >150% increase in viable cell density after 24 h compared to the original process (no agitation for 24 h and 100% working volume). Using the same methodology as in the ambr15, similar improvements were obtained with larger scale spinner flask studies. Finally, this improved bioprocess methodology based on a serum-based medium was applied to a serum-free process in the ambr15, resulting in >250% increase in yield compared to the serum-based process. At both scales, the agitation used during culture was the minimum required for microcarrier suspension, NJS . The use of the ambr15, with its improved control compared to the spinner flask, reduced the coefficient of variation on viable cell density in the serum containing medium from 7.65% to 4.08%, and the switch to serum free further reduced these to 1.06-0.54%, respectively. The combination of both serum-free and automated processing improved the reproducibility more than 10-fold compared to the serum-based, manual spinner flask process. The findings of this study demonstrate that the ambr15 microbioreactor is an effective tool for bioprocess development of hMSC microcarrier cultures and that a combination of serum-free medium, control, and automation improves both process yield and consistency. Biotechnol. Bioeng. 2017;114: 2253-2266. © 2017 Wiley Periodicals, Inc.

Project description:Over the past decade, global interest in the development of therapeutic monoclonal antibodies (mAbs) has risen rapidly. As therapeutic agents, antibodies have shown marked efficacy in combatting a range of cancers and immune diseases with high target specificity and low toxicity (Carla Lucia et al. in PLoS ONE 6:e24071, 2011; Donaghy in MAbs 8:659-671, 2016; Nasiri et al. in J Cell Physiol 9:6441-6457, 2018; Teo et al. in Cancer Immunol Immunother 61:2295-2309, 2012). Recent advances in cell culture technology, such as high-throughput clone screening, have facilitated antibody production at concentrations exceeding 10 g/L (Chen et al. in BMC Immunol 19:35, 2018; Huang et al. in Biotechnol Prog 26:1400-1410, 2010; Lu et al. in Biotechnol Bioeng 110:191-205, 2013; Singh et al. in Biotechnol Bioeng 113:698-716, 2016). As titers have improved, the industry has begun to focus on the adjustment of target antibody quality profiles to improve efficacy. Cell lines, culture media, and culture conditions impact protein quality (Van Beers and Bardor in Biotechnol J 7:1473-1484, 2012). Optimization of critical quality attributes (CQAs), such as charge variants, can be achieved through bioprocess development and is the preferred approach as changes to the cell line or growth media used is considered unfavorable by regulatory bodies (Gawlitzek et al. in Biotechnol Bioeng 103:1164-1175, 2009; Jordan et al. in Cytotechnology 65:31-40, 2013; Pan et al. in Cytotechnology 69:39-56, 2016). In this study, the effect of process control and ion supplementation on charge variants of mAbs produced by Chinese hamster ovary (CHO) cells was investigated. Results of this study demonstrated that the concentration of Zn2+, duration of culturing, and temperature affect charge variants of a given mAb. Under the optimum conditions of 3L bioreactors, the most significant was that Zn2 + and temperature shift could further improve the quality of antibody. The main peak increased by 12%, and the acid peak decreased by 16%. At the same time, there was no significant loss of titer. This study provided supporting evidence for methods to improve charge variants arising during mAb production.

Dataset Information

High throughput screening data for a case study of CHO cell culture process development.

Publications

High throughput screening data for a case study of CHO cell culture process development.

Similar Datasets

OmicsDI is part of the ELIXIR infrastructure

Tweets