Improved Clone Evaluation and Selection of CHO Cell Lines using Ambr® 15
The global market for biopharmaceutical products continues to expand, making it a highly attractive market for biopharmaceutical companies. Due to the rising number of projects with variant protein drug candidate molecules, increasing productivity of cell culture process development to support material production for early phase clinical trials has been an important task in recent years.
In the past, Sartorius Stedim Cellca performed clone screening and evaluation using shake flasks, which has some limitations e.g. limited control of pH and dissolved oxygen (DO) and it is difficult to replicate the environments of stirred-tank bioreactors. The Ambr 15® is an automated micro bioreactor system, that mimics the cell culture conditions of large 5L and 10L bioreactor systems, providing comparable results rapidly and cost effectively. As part of the on-going continuous improvement of our cell line development platform we implemented Ambr 15® to perform the clone evaluation and selection of CHO cell lines.
This article is posted on our Sartorius Blog.
Shake Flask vs Ambr® 15
In this study, clone evaluation using the Ambr® 15 system was compared to clone assessment in benchtop bioreactor systems and conventional shake flasks for a CHO production system. The methodology was applied to a range of clones producing different mAb products, all of which were based on the same Sartorius Stedim Cellca DG44 host cell line. Clone evaluation outcome in shake flasks and Ambr® 15 system was benchmarked against clone performance in a 5L benchtop reactor as reference, all of which were operated in fed-batch mode. Product titer, cell growth, and product quality were investigated as key performance properties in the comparison.
CHO Production System
The applied CHO fed-batch process in this study comprised 13 CHO DG44 cell lines that were transfected to produce 3 different recombinant proteins using a chemically defined media system. The process including CHO cell line, medium and feeding strategy was designed and developed by our Technology Development department at Sartorius Stedim Cellca.
Standard CHO Production System and part of Sartorius Stedim Biotech bioreactor family: Ambr® 15 and UniVessel® 5L Glass.
Sartorius Stedim Cellca established a process and clone evaluation strategy to identify the top clones, which resulted in improved product quality compared to the shake flask. The study also identified that Ambr® 15 parameter settings improved comparability to 5L bioreactor.