Characterizing Mixing Performances in Bioprocesses

Effective mixing is essential to establishing a robust and reproducible bioprocess. How can we ensure single-use mixers are performing as expected?

^{This article is posted on our Science Snippets Blog}

Evaluating Today’s Mixing Challenges

Mixing is a fundamental yet often overlooked part of all bioprocesses. Compared to the many advanced and complex operations that take place during biopharmaceutical manufacturing, it could appear to be a relatively ordinary activity requiring limited optimization. However, the importance of effective mixing cannot be understated: inadequate mixing can result in poor homogenization of the sample and degradation of products, limiting batch-to-batch consistency.  Therefore, evaluating the performance of your mixing operations is essential.

Modern Biopharmaceutical Processes Bring New Mixing Challenges

Traditional mixing vessels are increasingly being replaced with single-use technologies, which have their own features and challenges. As a result, proper characterization of mixing performance has never been more important.

Manufacturers require reliable strategies to evaluate mixing across new equipment and consumables to ensure performance matches expectations. In this blog post, we discuss the importance of evaluating mixing performance and point you in the direction of some tools to simplify your characterizations.

What Factors Influence Mixing Performance?

Mixing quality in a stirred tank is influenced by many parameters:

• Raw material features - particle size, solubility, and shear sensitivity
• Process parameters - mixing time, volume, and speed.  
• Equipment characteristics - tank diameter and features of the impeller.
• Human | environmental factors - temperature, operator, and relative humidity.

Mixing in Traditional vs. Single-Use Containers – What’s Changed?

Single-use, cubical, bottom-mounted mixers are becoming increasingly common in modern bioprocesses because they offer reduced contamination risk, low shear stress, and ease of use ^[1].

Limited Knowledge
Since single-use containers are relatively new in the industry (at least compared to their single-use counterparts), our collective understanding of mixing behavior within them is limited. As such, more research is required to evaluate their performance in each application.  

The single-use bioprocessing containers and media bags segments accounted for over 28% of the market in 2021. These segments are projected to reach over $ 2 million by 2026^[2].

Shaping Up
While traditional containers (such as bioreactors) are often cylindrical, single-use mixing containers are usually cubical. Since they do not conform to the well-defined standard, additional experimentation is required to characterize their mixing performance.  
 

^{Figure 2. Mixing in a cubical, single-use container}

Confounding these challenges is that - despite the seemingly simple concept of mixing, fluid dynamics in mixers is a highly complex; fluid flow becomes turbulent and multiphase systems are created ^[3].

Solutions for Characterizing Mixing Performance  

Computational fluid dynamics (CFD) is a powerful engineering tool that simulates fluid motion. Powerful computers and applied mathematics are used to model fluid flow situations to provide valuable information about various mixing properties. These numerical insights allow bioprocess engineers to optimize mixing operations without extensive experiments^[4].  
 

^{Figure 3. An example of CFD data showing the flow pattern inside a cubical mixer (side view)}  

Because CFD is in high agreement with empirical data, the number of experimental runs are greatly reduced, significantly speeding up process development and scaling activities.

The information generated by CFD can be used to develop optimal conditions for mixing in a bioprocess to ensure high performance, consistency, and product quality.

    +      Download “Uses of Computational Fluid Dynamics for Evaluating the Performance of Cubical Mixers in Bioprocessing”
 

Learn More About Flexsafe^® Pro Mixer 

 
^References

^{1.     Gikanga, B., Chen, Y., Stauch, O. B., & Maa, Y. F. (2015). Mixing monoclonal antibody formulations using bottom-mounted mixers: impact of mechanism and design on drug product quality. PDA journal of pharmaceutical science and technology, 69(2), 284–296. https://doi.org/10.5731/pdajpst.2015.01031}

^{2.     Single use Technologies for Biopharmaceuticals: Global Markets. (2022).}

^{3.     Niño, L., Peñuela, M., & Gelves, G. (2018). CFD: A New Challenge in Bioprocess Engineering. International Journal of Applied Engineering Research (Vol. 13). International Journal of Applied Engineering Research. Retrieved from http://www.ripublication.com}

^{4.     Xia, B., & Sun, D. W. (2002). Applications of computational fluid dynamics (CFD) in the food industry: A review. Computers and Electronics in Agriculture. https://doi.org/10.1016/S0168-1699(01)00177-6}