Clarity in cell line development

Customer case study in brief: Celonic AG

Enrichment by FACS combined with Solentim’s VIPS & Cell Metric cut CLD workflow timelines at a major European CDMO by nearly 50% and reduced plate numbers by up to 96%

Celonic Solentim

Celonic AG, a premium biologics contract development and manufacturing organisation (CDMO) specialising in mammalian cell line production, came to Solentim looking for new technologies to shorten its timelines and lighten its workload. The Company also required a gentler fluidics system for single cell cloning as the shear stress from fluorescence activated cell sorting (FACS) was restricting cell recovery and outgrowth for certain cell lines.

Unsuitable methods and slow timelines

The Cell Line Development (CLD) department at Celonic is routinely commissioned by customers to generate stable cell lines. Until recently, this process was slow, taking around 29 weeks from receipt of the DNA sequence to ambr screening for lead clone selection, and involving up to 500 96-well plates, which was logistically challenging to manage.

Established methods used at Celonic until mid-2018 involved using minipools for enrichment followed by limiting dilution steps and required the screening of more than 1000 clones to find the best producers. In an attempt to speed up the enrichment step for top producer clones, the department had previously acquired a BD FACS instrument. Although effective at sorting and enriching for the highest producing cells in bulk, the shear stress applied to cells by the FACS for single cell seeding resulted in low cell survival and outgrowth.

Boosting workflow efficiency

Celonic purchased and rapidly implemented Solentim’s VIPSTM and Cell Metric® instruments in mid-2018. The gentle, low pressure fluidics of the VIPS matched the seeding efficiency of the FACS (~80%) without the need for any optimisation, however the VIPS enabled much higher cell survival, and resulted in an immediate two to three-fold improvement in outgrowth using basal media compared to the FACS. Media optimisation further improved outgrowth for the VIPS significantly.

The use of the FACS for the enrichment step, the VIPS for cell seeding and the Cell Metric for daily whole-well imaging increased workflow efficiency significantly, decreasing the number of seeded plates needed to generate the same target number of colonies, enabling the team to image the plates more frequently for documenting clonality. Moreover, Solentim’s instruments can synchronise  data between instruments, producing the most complete history and documentation of each clone from the initial cell in a droplet, in the form of an Enhanced Clonality Report.

Powering new business
Implementation of the VIPS and Cell Metric has allowed Celonic to shorten CLD workflow timeline by nearly 50% and to reduce the number of plates required by up to 96%. The new technology has enabled Celonic to quickly and consistently deliver high producing cell lines to its clients with the most complete documentation for a clonally-derived MCB (Master Cell Bank) population, as required by the medicines’ agencies. Logistically, the new instruments have a much shorter and less onerous workflow, saving time and enabling Celonic to scale out and do more projects without any FTE increase, increasing output without compromising quality.

The full case study can be downloaded here.