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Bioprocessing Scale Up

Bioprocessing scale up requires the careful implementation of parameter control strategies to ensure the maintenance of high yields and product quality.
Bioprocessing scale up involves the increase in working volumes from small scale through to production scale. During scale up it is desirable to reproduce the process performance, which has been optimized at small scale, at larger scale, ideally without much need for process optimization at large working volumes. This requires reproducing the cells’ or organisms’ growth environment across scales. Several factors play a role in a reliable bioprocess scale up. Kinetics and thermodynamics are virtually unaffected by the reaction volume. However, the mass transfer within a process is highly dependent on the scale. On this page you can learn more about the parameters to control during bioprocessing scale up, as well as several strategies to ensure maximum efficiency and product quality is maintained.

Moving to a bioreactor

On this page we focus on bioprocessing scale up from small to large bioreactors. If you are currently cultivating your cells or organisms in shake flasks or dishes, this first requires a process transfer from shakers or incubators to bioreactors. Interested in how to move from shaker to bioreactor?

Bioprocess scale up strategies

An established strategy when transitioning to larger working volumes is to monitor and control a single parameter. However, keeping one process parameter constant will change others; therefore, the cells’ growth environment can only be partly reproduced at different scales. Bioengineers must identify the parameters which influence cell growth and productivity most, to decide, which scale up strategy is the most suitable. Although bioprocessing scale up strategies that control several criteria are the most powerful, those that control singular parameters can still be effective, and are historically the most widely used due to their simplicity. Common singular parameters to control include:

Constant power input per liquid volume‌

Constant tip speed‌

Constant kLa‌

Constant mixing time‌

Scale-up strategies: recommended resources

  • Watch our webinar to find out more about bioprocess scale up strategies and how we scaled-up a cell culture bioprocess from 3 L to 40 L.
  • Read in our application note , how we investigated scale up-relevant engineering parameters for differently sized fermentors, including power numbers, tip speed range, and oxygen transfer capabilities.

Which factors are relevant during bioprocessing scale up?

As depicted above, a tailored scale up strategy is needed to reproduce product yield and quality in an upstream bioprocess across scales. Various other factors need to be considered as well while scaling-up, including space requirements in the lab, staff training, equipment choice, and scaling-up the downstream process. In this panel discussion, industry experts from Eppendorf and other companies share their thoughts on scale up challenges from an economical, operational, and application-related point of view.

Eppendorf products for powerful bioprocessing scale up

With a portfolio of bioreactor systems, Eppendorf products can help you transition cell culture and microbial bioprocesses from small to pilot production scale, using single-use or reusable bioreactors. The Eppendorf range of bioreactor systems:

Cell culture scale up

For cell culture scale up Eppendorf offers scalable solutions from 100 mL to 2000 L.
  • Single-use bioreactors: The BioBLU® c Single-Use Bioreactor portfolio covers working volumes from 100 mL to 40 L. To make the progression from bench-scale to production-scale, the BioFlo® 720 is a bioreactor control system which is compatible with Thermo Scientific™ HyPerforma™ 5:1 Single-Use Bioreactors with working volumes up to 2000 L.
  • Glass bioreactors: Eppendorf glass bioreactors for cell culture applications cover working volumes from 60 mL to 10.5 L and are compatible with the small and bench scale Eppendorf bioprocess systems .
  • Sterilize in place systems: The CelliGen 510 bioreactor control system covers working volumes from 10.5 L to 32 L.

Fermentation scale up

For fermentation scale up Eppendorf offers scalable solutions from 60 mL to 2400 L.

Scalable portfolio

The Eppendorf applications team has determined scale up-relevant parameters, like OTR and kLa, impeller power numbers, tip speed range, and vessel geometries for many of its bioreactors and makes them available to smoothen bioprocess scale up. The BioFlo® 320 and BioFlo® 720 bioreactor control systems include a Scale up Assist feature that automatically calculates the parameter changes needed for various vessel sizes.

How our customers use our products

Find some application examples of how the Eppendorf bioprocess products were used for bioprocessing scale up and scale down.