It’s Not Just About Size: Talking about Shake Flasks and Bioreactors

Easy, fast, and inexpensive

Shake flasks have been used for decades to cultivate bacteria and fungi, as well as plant and animal cells in suspension. Protocols have been established for all common organisms, even the more unusual ones. It is hard to imagine a biotechnology lab in industry or research that doesn't use shake flask cultures. They are an easy-to-use and inexpensive choice for basic applications, such as organism screening, media design, and early process development. All that is needed is a flask and a shaker to move it. The user doesn't need technical knowledge, advanced equipment or sensing and control technologies.

This very simplicity, however, is the biggest disadvantage. Shake flasks do not provide detailed insight into culture performance or the opportunity to monitor and control the process parameters.

Shaken not stirred

Further technical options that support running different cultivation modes include the ability to feed the bioreactor culture, to change medium while the cells are retained, to measure the biomass online or simply to pump in and out the bioreactor. While batch and fed-batch cultivation are commonly used to optimize growth in microbial applications, continuous culture and perfusion modes work out well in animal and human cell culture, for example.

Going great—scaling up with bioreactors

Industrial-scale bioprocesses require the use of bioreactors. The challenge is to scale up the production process from small-scale development to bench scale, and then to pilot and production scales. Being able to optimize the process for product formation, quality, and yield at a small scale and then scale it up with minimal adjustments to production scale can save a great deal of time and money.

Fully functional, stirred-tank bioreactors are even available for working volumes of less than 100 mL, perfect for early bioprocess development. Bioreactors of increasing volume provide reliable scalability if the vessels have similar geometries, heat and mass transfer capabilities, monitoring and control possibilities, and documentation tools. This streamlines the process development laboratory work, and eases the production of regulatory conformance documentation throughout the whole process.

Comprehensive software

The advantages of bioreactor processes over shake flask cultivations for complex bioprocesses are all the more convincing when bioprocess management software is applied. Special software solutions can interconnect multiple laboratory devices and help to automate the process. They can apply Design of Experiment (DoE) and process modeling, can support comprehensive data analysis, and can connect to historians and central data storage tools. Process Analytical Technology (PAT) approaches and Quality by Design (QbD) are facilitated.

Shake flasks vs bioreactors?

No, there is no competition. It’s a question of objectives—each system has its own applications and advantages.

Bioreactors provide users with almost unlimited flexibility, functionality, and freedom of action, but cost much more and need well-educated operators. Shake flasks, however, also have a place for simple screening and media development.

Literature:
Büchs J: Introduction to advantages and problems of shaken cultures. Biochemical Engineering Journal 7:2 (2001) 91-98
Büchs J and Klockner W: Advances in shaking technologies.
Trends in Biotechnology 30:6 (2012) 307-314
Meier K, Regestein L, Büchs J: Correlation for the maximum oxygen transfer capacity in shake flasks for a wide range of operating conditions and for different culture media. Biochemical Engineering Journal 109 (2016) 228-235

References:

[1] DECHEMA Arbeitskreis Single-Use-Technologie: Empfehlung für Leachable-Studien Standardisierter Zellkulturtest zur Identifizierung kritischer Filme. Januar 2014
[2] U.S. Pharmacopeial Convention: In-Process Revision: <661.3> Plastic Components and Systems Used in Pharmaceutical Manufacturing. In: PF 42(3), May-June 2016
[3] Denise Bestwick and Raymond Colton: Extractables and Leachables from Single-Use Disposables. Supplement to BioProcess International, February 2009
[4] Angelo DePalma: Extractables and Leachables: Standardizing Approaches to Manage the Risk. BioProcess eBook Series 2017, 15(3)E, March 2017
[5] Kevin A. Lannon et al.: Quantitative Risk Assessment of Bioaccumulation Attributes to Extractables and Leachables in Cellular Immunotherapy Biomanufacturing. BioProcess International, 13(10), November 2015