Cell line development is a critical component of cell-based biomanufacturing. Companies must be able to identify clones with good manufacturing characteristics and they must do this as quickly and efficiently as possible. If cell line development takes too much time it can be a constraint on the overall drug development timeline because in most cases the cell line must be selected prior to final molecule selection. A common goal for the biomanufacturing industry is to shorten drug development timelines and ideally cell line development occurs prior to final molecule selection so that it doesn’t become a roadblock.
As expected, cell line development improvement often focuses on decreasing the time and resources required for cell line generation. At the same time, the likelihood of finding high producing clones is greatly increased by screening higher numbers of clones, so increasing the number of quality clones produced is also an important component.
Implementing automation is a very successful method for decreasing resources while still increasing throughput. Several aspects of the cell line development workflow can be automated, including incubation, plate imaging and clone evaluation. Liquid handling systems permit companies to generate and evaluate more clones faster with fewer manual steps and personnel resources.
While automating a manual cell line development workflow is an attractive solution, it does require adaptation of the manual workflow.
This week we are excited to have Rob Ballinger, Development Associate IV, Biological Process Development at Alexion Pharmaceuticals, Inc. join us as our expert. Rob and his team recently adapted their manual cell line development workflow to automation and his recent first hand experience makes him an excellent expert for this topic.
If you have considered moving to automation for cell line development, please submit your questions using the form below.
Questions could include topic areas such as:
- Designing an automated system
- Adapting your current manual process
- Lessons learned and things to watch out for
- What kind of improvements can be gained with automation
- And many others!
0 0 0 Total: 0 The switch from 96-well to 384-well increased our clone density 4-fold. Concurrent improvements in cloning processes increased our clone outgrowth. This increased the number of clones reaching screening. With automation we can screen hundreds to thousands of clones. This is approximately 4-fold higher than what was practical with a single … Continued
I realize that the liquid handler provides much of the automation, but what other equipment have you incorporated? I am wondering how much of the process can be automated.
0 0 0 Total: 0 We have a plate hotel (for ambient storage of source labware including plates and pipette tips), incubator and plate imager integrated. Other equipment that can be integrated includes analytical devices such as plate readers or the Octet HTX. Even an automation-friendly centrifuge can be integrated. Lab space and budget are … Continued
Are you running your process over the weekend/holidays? How long have you run the process continuously?
0 0 0 Total: 0 We have not had the need to perform any plate manipulations/liquid handling outside of working hours. We have run plate manipulations/liquid handling through much of a working day. Cultures are processed by the automation system from plating through scale up, a process that takes up to 8 weeks.
0 0 0 Total: 0 We have not evaluated cell lines transfected with the same plasmid using the manual and automated workflows side by side.
This might be a little off topic but how are you proving monoclonality? Is it part of your automated process?
0 0 0 Total: 0 Monoclonality is established using probability based on limited dilution. We also have the ability to image plates for assurance of monoclonality using a plate imager that is integrated into the automated platform.
0 0 0 Total: 0 Initial dilution for limited dilution cloning and culture scales larger than 6 well plates (such as T flasks and shake flasks) as well as banking are still manual operations.