The changing workflows of cell line development – Quality, not Quantity
Damp weather did little to suppress the energy in the rooms at last week’s 10th Annual BioProcessing Summit in Boston. There were over 1,000 delegates, including many from the US West Coast and Europe, all there to listen, learn, and participate in what promised to be a valuable week.
With seven parallel sessions running through the event there was a lot to choose from, however, in tracking the cell line development presentations over the five days, certain significant themes emerged.
Improved Vector Design dramatically improves the workflow
Traditional techniques based on creating stable, highly productive cell lines have previously relied on a high throughput approach, with random integration followed by time-consuming screening and analysis of huge numbers of plates of clones. Many companies have created products to facilitate these techniques, including robotics for handling more plates, proprietary chips or pens for thousands of samples, or fluorescence enrichment techniques to try and find the highest producers. However, as we heard in numerous presentations at the summit, approaches are changing, and new technology is coming to market focused on streamlining and optimising the workflow.
For example, Leap-in Transposase (from ATUM) for genomic integration of DNA constructs, enabling multiple copies (40-50 copies) of a transposon to be independently integrated into the genome of a single cell. This sort of technique means that all the cells in which transfection is successful are highly producers, reducing the need for mass screening, and speeding up the workflow. As we heard in a presentation by Thomas Kelly of Janssen (see photo of him presenting), our own Solentim VIPS™ can be used in concert with these technologies, creating a streamlined and efficient production line with only 5-10 microtitre plates now needed per cell line project. This approach is also attractive as it avoids the minefield of CRISPR patents which are clearly still a deterrent for companies developing biotherapeutics.
This transition in cell line development was earlier touched upon in the keynote presentation by Dr Zhimei Du, Merck Research Labs, in her talk ‘Product Quality Control Strategies during Cell Line Development’. In highlighting the importance of better cells and good vectors to reduce the quantity of clone screening, she opened the floor to discussions around how we can change our approach to cell line production by starting right at the beginning of the process. Both Dr Neal Schilling, Abbvie Bioresearch Centre, and from Janssen R&D echoed this message.
Starting analytics earlier
There was a presentation on ‘Novel analytic solutions for cell line development’, explaining the importance of establishing key information and critical quality attributes at the plate stage, and not later in process development – these could include IgG secretion, titre, earlier determination of cell line stability. This also touched on the importance of outgrowth factors.
Analytics were also discussed in relation to the need for improved Trypan blue cell counting methods. This was emphasized during talks by NIST (National Institute of Standards and Technology), highlighting the need for improved tools and strategies to increase confidence during the cell counting process. Related to this, it was interesting that a presenter from Nexelcomm put up a slide highlighting that “65% of error in cell counting comes from sample preparation – this needs to change”.
If you’d like to hear more about what happened at the BioProcessing Summit or find out more specifics on the Janssen presentation using VIPS in their process for optimizing cell line development, then please contact me.
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