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Upstream Processing
Jun 16, 2022
| 4 min read

Rocking the Boat in the Culture of Shear-Stress-Sensitive Cells

Cultivating shear-stress-sensitive cell lines is tricky and could require a significant amount of parameter optimization. Rocking motion bioreactors might be the answer for maximizing productivity and cell viability.

This article is posted on our Science Snippets Blog

Biostat® RM 200 Rocking Motion Bioreactor


Stirred-tank single-use bioreactor systems are typically used to culture cells at commercial scale, owing to their scalability, flexibility, and productivity. However, stirred bioreactors generate significant shear forces by impeller energy dissipation, which the cells would not normally be exposed to in their ‘natural’ environment. While this is acceptable for some cells, others cannot withstand these forces, reducing cell viability and significantly compromising product yields.

Typical bioprocesses use relatively robust host cell lines; 70% of biopharmaceuticals manufactured between 2014 and 2018 were produced in CHO cells (1). However, newer modalities, such as vaccines and cell and gene therapies, require the use of much more sensitive cell lines. This is particularly true for cultures in regenerative medicine applications, such as stem cells and CAR-T cells, and viral-vaccine applications, such as HEK293 and sensitive carrier cultures. Some biologics, including bioconjugates, are also sensitive to shear stress.

Here, we acknowledge the challenges of working with shear-stress-sensitive cell lines before shedding light on some solutions.


Challenges of Working with Shear-Sensitive Cells

Culturing such cells requires special considerations and likely numerous parameter optimization steps, such as:

  1. Bioreactor type and mode (for example, stirred-tank or rocking motion technology; fed-batch or perfusion culture)
  2. Agitation speed
  3. Gassing rates
  4. pH
  5. Dissolved oxygen
  6. Viable biomass

On top of these factors, choosing the right culture set-up during process development does not guarantee that conditions will be ideal during production; it may be challenging to find an appropriate bioreactor size to cultivate the required cell densities for commercial manufacturing.


What Solutions are Available?

Rocking bioreactors rely on wave-induced motion for mixing. This movement is much more gentle than typical stirred-tank bioreactors, providing a low-shear environment for sensitive cells. Sartorius offers rocking motion bioreactors and corresponding consumables starting from 1L and up to 200L, facilitating flexible scale-up from process development to commercial production.


       White Paper - Flexibility in Next-Generation Facilities Through Rocking Motion Bioreactors


Biostat® RM Rocking Motion Bioreactors Powered by Biobrain®

Biostat® RM Bioreactor

Biostat® RM bioreactors do not use submersed gassing or stirrer elements. Instead, oxygen transfer and mixing are accomplished by wave-induced motion. These features provide a gentle environment for all cell types.

The modular concept of the Biostat® RM portfolio allows the set-up of multiple configurations within the same rocking platform, providing flexibility to manage multiple molecules in the pipeline, including shear-stress-sensitive cell lines, bioconjugates and inocula preparation. They also deliver adaptability, as they are compatible with both fed-batch and perfusion culture scenarios.
Additionally, the Biostat® RM can save space, reduce costs, and achieve high cell densities for increased yields as a part of an intensified seed train. Our unique Biostat® RM 200 bioreactor is appropriate for commercial manufacturing – when used in intensified mode with the corresponding Flexsafe® RM bags, biomanufacturers can reduce culture days by up to 20%.

Single-Use Compatibility

Biostat® RM bioreactors are compatible with single-use Flexsafe® RM bags,  which have been validated for various cell lines. These sterile culture vessels promote consistency and safety across the process steps and scales, as the same Flexsafe® film can be implemented throughout the production process. Flexsafe® film is at the heart of our single-use bioreactors, which produce reproducible cell cultures, maximize flexibility, and simplify validation.

Driven by Automation

Our Biostat® RM portfolio is powered by Biobrain®, an automation platform that supports seamless scale-up and process control. The Biobrain® platform is integrated with both Biostat® RM and Biostat STR®, simplifying the transition between process development and manufacturing. Compatible with sensors and software in the BioPAT® toolbox, such as BioPAT® Viamass for measuring viable biomass, and BioPAT® Trace for monitoring glucose and lactate levels.

Rocking Motion Technology Supports Process Intensification

In a recent white paper, Sartorius discuss the value of rocking motion technology in process intensification. Specifically, they discuss how the flexible features of single-use rocking motion bioreactors, such as the Biostat® RM, allow drug developers to intensify their seed train. Discover how rocking motion technology could promote versatility and improve productivity in your upstream bioprocess.


       White Paper - Flexibility in Next-Generation Facilities Through Rocking Motion Bioreactors


References

(1) Walsh, G. (2018). Biopharmaceutical benchmarks 2018. Nature Biotechnology, 36(12), 1136–1145.

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