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A High-throughput Automated Platform for the Development of Manufacturing Cell Lines for Protein Therapeutics
Published on: September 22, 2011
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A deep-well plate enabled automated high-throughput cell line development platform.
Xiaoyan Tang1, Jorge Quiroz2, Yixiao Zhang1
1Process Cell Sciences, MRL, Merck & Co., Inc., Rahway, New Jersey, USA.
Biotechnology Progress
|February 20, 2024
Summary
Developing a deep-well plate enabled high throughput (DEHT) platform streamlines cell line development for biologics manufacturing. This automated system significantly reduces the resources needed to identify ideal production cell lines by enabling five times more cultures to be screened.
Area of Science:
- Biotechnology
- Bioprocessing
- Cell Line Development
Background:
- Cell line development (CLD) is critical for therapeutic biologic manufacturing, primarily using Chinese hamster ovary (CHO) cells.
- CHO cell characteristics like random integration and plasticity lead to significant diversity in productivity, growth, and quality, necessitating extensive screening.
- Conventional CLD is laborious and resource-intensive due to the need to screen numerous cell pools and clones.
Purpose of the Study:
- To develop and validate a novel deep-well plate (DWP) enabled high throughput (DEHT) platform for accelerated cell line development.
- To assess the suitability of 24-well DWPs for key CLD steps, including cell passaging, imaging, expansion, and fed-batch production.
- To demonstrate the DEHT platform's efficiency in screening more cultures compared to traditional methods.
Main Methods:
- Implementation of a DEHT CLD platform utilizing 24-well DWPs, liquid handlers, and automation.
- Validation of 24DWP suitability by assessing well-to-well and plate-to-plate variability and cross-contamination.
- Comparison of growth, production, and product quality in 24DWP cultures versus conventional shake flask cultures.
Main Results:
- The DEHT platform successfully integrated key CLD steps within a 24DWP format.
- Minimal variability and absence of cross-contamination were confirmed in 24DWP cultures.
- 24DWP cultures demonstrated comparable growth, production, and product quality to shake flask cultures.
- The DEHT platform enables screening of five times more cultures than conventional CLD.
Conclusions:
- The DEHT platform offers a robust and efficient solution for cell line development in biologics manufacturing.
- This automated approach significantly reduces the time and resources required for identifying high-producing cell lines.
- The DEHT platform represents a substantial advancement in optimizing the early stages of biopharmaceutical production.
