Roche Pharma Research - A smart path for novel biologics

Optimizing fermentation takes time and people

The production of large biological molecules for therapeutic use is complex, requiring expression of the target peptide, protein or antibody in suitable host systems, followed by extraction and purification to yield the final drug. Efficient expression requires not just the right host organism and clone, but also the right physical conditions and chemical environment to promote production.

Exploring these numerous parameters to optimize biotherapeutic production is a very time-consuming complex process, requiring cell expansions in the seed train to subsequently run numerous fermentations in parallel to identify the best candidate and its conditions for expression. With more data points being obtained for each variable it’s more likely to establish a highly productive final process. Fermentation development has historically relied on performing parallel experiments using a number of shake flasks or 2 l bioreactors, with continuous monitoring via an array of samples from each of these bioreactors to enable analytics. Unfortunately, this approach is both time consuming and labor intensive, with one researcher able to handle only a few 2 l bioreactors simultaneously.

Streamlined data collection with custom lab automation

“We have a huge number of laboratory automation systems here in Penzberg and, based on this experience, we decided that a Tecan liquid handling platform would be the best fit for our needs. A key requirement for our workflow was the ability to integrate a large centrifuge to spin down the samples before analytics, and the Fluent^® Automation Workstation’s ability to mount a robotic centrifuge below the worktable was a real benefit. We simply place the samples from the bioreactors on the workdeck, and the system is able to automatically load them into the centrifuge using its Robotic Gripper Arm™ (RGA). Once spun down, the Fluent platform splits the supernatant into several aliquots in different labware formats, depending on the downstream application.”

“We now have two different sized Fluent systems with slightly different configurations, giving us more than enough capacity to process samples for every microbioreactor every day, although we have this many experiments running in parallel at present. The smaller system is equipped with an RGA for lab ware movements and an 8-channel Liquid Handling Arm™ (LiHa) for pipetting, while the larger system has a third arm equipped with a Multiple Channel Arm™, allowing entire 96-well microplates to be duplicated or transferred simultaneously. Each platform also has on deck integrated Tecan microplate readers for some onboard analytics. Although both have cooling modules, we have now developed for mass spectrometry analytics a workflow based on sealed, pre-pierced plates that can be accessed by the LiHa. This avoids evaporation without the need for cooling, further simplifying the workflow.”