Stirred Tank Bioreactors

Manufacture, supply, and validation of biocontainers with cubical geometry

Pall’s high performance single-use, stirred tank bioreactors bring superior mixing and mass transfer, and support higher cell densities

The design and development of single-use equipment that fully satisfies the performance, functionality, and validation requirements for user process systems can be particularly difficult for complex, automated equipment such as bioreactors. However, it also opens up opportunities for innovation, which then lead to enhanced performance over traditional systems, and offer practical benefits; such as faster system set-up, shorter turnover time and equipment downtime, and safer product handling. 


This article from BioProcess International discusses the design process considerations leading to a next generation of single-use stirred tank bioreactors. With the requirement to steam-in-place and clean-in-place no longer present, a novel design being cubical, instead of cylindrical, was possible. This brings a series of performance advantages and advancements around product usability and process assurance. 


Key considerations when choosing a single-use stirred tank bioreactor platform 


A single-use bioreactor must perform at least equal to or better than its traditional stainless-steel counterpart and has to be able to reproducibly and reliably yield high cell densities, high cell viability and high expression levels. The entire design needs to contribute to optimal mixing and mass transfer properties, both being the key performance indicators of a successful bioreactor batch. Effective cell culture performance relies on a homogenous growth environment to sustain adequate gas enrichment and nutrient delivery over a shorter time period. 


A well-designed bioreactor platform needs to ensure there is minimal operator interaction required with the single-use biocontainer during initial bioreactor installation, cell culture processing steps, and final biocontainer removal, in order to avoid operator errors. With leaking biocontainers having been the challenge with many single-use bioreactors - especially at larger scale - considerations must be given to safeguard biocontainer manufacturing, packaging and shipment, to make sure it is automated as much as possible.  


Single-use components facilitate some parts of the end user qualification process and eliminate cleaning validation. However, they do bring new challenges linked to regulatory requirements around material contact in pharmaceutical drug manufacturing. To facilitate its implementation, single-use bioreactors must be well-documented. As an example, single-use components used are tested in alignment with the standardized BPOG guidelines for extractable and leachable profiles. Apart from material characterization data, single-use bioreactors need to come with extensive validation, qualification and application packages.  


To maximize on the manufacturing flexibility offered by a move to single-use equipment, a well scalable family of stirred tank reactors, that each have a high turndown ratio, is of benefit. For CMOs and process development laboratories in particular, it is also of interest that the bioreactors support a wide variety of cell line requirements through robust software capabilities, to cater to dynamic process demands.


Single-use bioreactors have to be controlled and automated, similarly to the traditional stainless-steel equipment, with on demand cascading communication from one controller to another, at any time in a process. In addition to the standard offering of pH, dissolved oxygen and temperature control, having the flexibility to insert other probes into the bioreactor offers another desired feature. Ideally, the single-use biocontainer has several single-use sensors, already integrated. This eliminates yet another set of user manipulation and potential sources of error and contaminations.


What Are Our Customers Saying?

Divya Goel, MBS

Technology and Business Development

Celltheon Corporation

"The Allegro platform is an integrated, highly scalable manufacturing solution making process development and subsequent production more streamlined. By addressing previous limitations of key scalability parameters such as P/V, the time and resources spent on scale-up is reduced. Thus, the impact of this platform is reduction in timeline and COGS which directly benefits patients.


"Many biosimilar developers are successful in developing a "bench-scale" biosimilar but when they scale up, they lose productivity and/or quality preventing these programs from being commercially viable. The first generation of Single Use Bioreactors had certain limitations; the Allegro platform has addressed many of these concerns making it unique in replicating bench scale processes. It is truly a scalable platform."



"The large-volume production of viral vectors is typically achieved in bioreactors. However, the design of the bioreactor can have a significant impact on process performance. Brammer bio therefore invested time and resources to evaluate different potential bioreactor technologies, both on paper and in the process development lab.


"After careful deliberation, Pall upstream and downstream platforms have been selected, including the Allegro™  STR Single-Use stirred-tank bioreactor line and for adherent processes, the iCellis®  bioreactor system. the advantages of this reactor technology for viral vector production include ease of use, compatibility with the production of cells used in vector manufacturing, cell growth and vector yield, reliable supply chain for consumables, and scalability to 2,000L. The bioreactors are being installed in Brammer’s Cambridge and Alachua facilities."

Richard Snyder, PHD

Chief Scientific Officer, Founder

Brammer Bio

Square is the new round:

advantages of a cubical single-use bioreactor design

When clean-in-place and steam-in-place cleaning processes are no longer required, considering a cubical bioreactor design could provide many benefits for its users, such as:


  • Superior mixing, excellent mass transfer, with integrated baffles
  • Ergonomic bag loading and unloading 
  • Reduced footprint, 1:1 aspect ratio, with height < 3 m 
  • Simplified biocontainer manufacturing with lower chances of leaks


The Pall Allegro™ STR family of single-use bioreactors complements this design with a direct bottom-driven impeller allowing high power inputs, resulting in high oxygen transfer rates and short mixing times. Extensive characterization and engineering performance work has been done to demonstrate this.




For scale-up and process transfer between cylindrical and cubical bioreactor designs, normal scaling strategies should be used. In the following application note, a strategy was applied where kLa (the volumetric mass-transfer coefficient that describes the efficiency with which oxygen can be delivered to a bioreactor for a given set of operating conditions) was maintained constant during scale-up from a 10 L cylindrical benchtop vessel to the Allegro STR 200L, and subsequently 1000L bioreactor. However, due to their effect on the fluid dynamics, and hence the potential to impact on process performance, power input per volume, tip speed, superficial gas velocity and aeration were also taken into consideration during scale-up. 


Allegro™ STR Bioreactors

Allegro™ STR Bioreactors

Single-use Bioreactors

Single-use Bioreactors

Allegro™ XRS 25 Bioreactors

Allegro™ XRS 25 Bioreactors