Ask the Expert – Addressing Shear Stress in Bioreactors

Sponsored by: MilliporeSigma
Session ends: October 27th, 2017, 3:00pm MST
Answers by: Jochen Sieck, Head of Perfusion Systems Lab, Life Science, BioProcessing R&D, Merck


Introduction of oxygen to cell culture media via sparging is critical for efficient bioreactor operation. Since oxygen is sparingly soluble in culture media, efficient sparging methods are important to ensure cells have enough oxygen for growth and productivity. However, hydrodynamic stress in bioreactors and specifically shear caused by sparging, can present a challenging issue in commercial biopharmaceutical manufacturing.

A solution was found in the use of Poloxamer 188, a surface-active, non-ionic polymer that when added to cell culture media acted as a shear protectant. Poloxamer 188 became a standard ingredient in cell culture media for commercial production. However, as cell culture technology improved including process intensification, which increased cell densities and productivities in fed-batch and perfusion modes, issues with poloxamer were reported. Issues included unexpected loss of cell density and viability in biopharmaceutical manufacturing. This loss could be traced back to lot-to-lot variation in the Poloxamer 188. This variation was a major problem and was the subject of several investigations to understand the source of the variation.

MilliporeSigma, a life science leader, is a business of Merck KGaA, Darmstadt, Germany.

This session is sponsored by

We recently published a Cool Tool, “Improved, High Quality Poloxamer 188 Produces Consistent Performance in Cell Culture, “ that discusses how MilliporeSigma addressed this issue by developing proprietary analytical and biological methods to identify the critical properties of Poloxamer 188. These methods were based on a reference library of over 100 blinded customer and supplier samples.

We asked, Jochen Sieck, Head of Perfusion Systems Lab, Life Science, BioProcessing R&D, Merck, if he would host an Ask the Expert session on the topic. Jochen was kind enough to agree to answer questions from readers this week on the topic of addressing shear stress in bioreactors and the use of cell culture optimized, Poloxamer 188 EMPROVE® EXPERT as a shear protectant

This Ask the Expert session is sponsored by MilliporeSigma and is hosted by Jochen Sieck. Jochen has more than 10 years of experience in mammalian cell culture, upstream process development, bioreactor characterization and scale-up. He studied Biotechnology and received his PhD in bioprocess engineering from ETH Zurich, working on Scale-Down Models of CHO fed-batch processes at Novartis. He stayed at Novartis for 2 years of Postdoc, working on perfusion process and medium development, before joining Merck in 2014. Since then, his team’s focus is perfusion medium development for customer as well as catalog products. Furthermore, his team investigates specific critical cell culture ingredients for their quality and impact on mammalian cells, targeting increase of reproducibility, reduced variability and improved quality. He has authored several journal articles and a textbook chapter on medium development for perfusion processes. Also, he is in the final stages of his MBA focusing on Innovation and Technology Management.

Please take advantage of the opportunity to ask our expert a question and participate in a lively discussion on shear stress in bioreactors.


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Questions & Answers

Do you have a recommendation for concentration level of poloxamer in the media, is it different for different cell lines and is there any reason to optimize?

The typical concentration in chemically defined cell culture media is usually 1-2g/L but this is always dependent on the cell line, the media composition, the process, etc. We also had some applications where we could reduce the concentration to 0,5g/L thanks to our improved Poloxamer 188 and still had full shear protection in our model […]» Read More

Can you tell me what are the advantages of using a protectant over managing mixing speed, impeller choice etc. to control shear?

Poloxamer 188 is commonly used in the biopharmaceutical industry as a cell culture media additive to protect cells from the turbulent environment of sparged bioreactors. It has been demonstrated that Poloxamer 188 can function as highly effective shear protectant as it decreases physical damage to suspensions of animal cell cultures by physical and biochemical means. […]» Read More

Have you used the new poloxamer to protect against shear when using microcarriers in vaccine production?

We have developed our new Poloxamer 188 EMPROVE® EXPERT to achieve reliable quality and consistency providing shear stress protection for large scale cell culture processes in biopharmaceutical productions. We have mainly worked together with mAb manufacturers and performed several tests to identify correlations between physical and chemical properties and cell culture performance. It has been […]» Read More