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A Comparison of Different Clonal Phenotypes in Perfusion CHO Cell Culture
A Single Cycle Cell Line Approach
Continuous Manufacturing: Cell Line and Clone Selection Strategies
This presentation will describe a case study which highlights the challenges with the screening and selection of cell lines destined for a perfusion process of a complex non antibody molecule.
These challenges include the lack of a representative small scale perfusion system for clone screening and the inability of standard shake flask stability studies to identify stability issues.
Merck KGaA is following the global trend of continuous manufacturing. To support perfusion cell culture development, small-scale semi-continuous screening methods were developed. These methods were applied on a set of different clones and compared to real continuous conditions (lab-scale bioreactors). Growth and productivity performance were compared and helped to define a ranking strategy for screening application, specific to perfusion.
Product Quality Control and Cell Line Development
New product-related impurities have been found to accompany non-mAb complex modalities, which usually don’t exist in standard mAb production. Many of these PQAs are related to protein folding and assembly efficiency inside the cell, which impact post-translational modifications directly or indirectly. Our presentation will illustrate the importance of selecting appropriate cell/upstream conditions through screening and/or engineering, as part of quality control strategy to obtain the desired recombinant protein PQA profile.
Automation and High Throughput Cell Line Screening and Clone Selection Platforms for Faster, More Predictive Identification of High Quality Producers
CHO cells are the most frequently applied host-cell system for the industrial manufacturing of recombinant protein therapeutics. The rapid generation and identification of high-producing clones that do not lose their expression capability over time is a major focus of the industry. The use of cytogenetic analysis with next-generation sequencing (NGS) combined to the proprietary bioinformatic tool SUREscan™, allows us to analyze the whole genome of any generated cell line, improving monoclonality assessment and traceability of RCBs. We will show that our CHO-M cell line is chromosomally stable indicating that the SUREtechnology Platform™ generates RCBs with chromosomally stable lineages.
The concept of high stringency selection of cells producing high amounts of a desired protein of interest is well known in the art and different solutions exist. However, many existing solutions exhibit different drawbacks e.g. need to engineer a host cell line or use of an antibiotic. The presentation will introduce a high stringency selection system using an endogenous metabolic selection marker without the need for cell line engineering.
Cell Line Manufacturability Assessment and Integration at the Interfaces
The ability to generate cell lines capable of supporting both early and late stage clinical as well as commercial programs requires a holistic cross-functional approach to assessing cell line suitability. By leveraging an integrated manufacturability assessment and cell line and process development platforms we have proposed such an approach. This presentation will focus on the strategies required to enable single cycle cell line development.