Microbial Cultivation in Biopharmaceutical Manufacturing - Are Single-Use Bioreactors Up to the Challenge?
The flexibility and easy installation of single-use bioreactors speeds up facility setups and drives quick batch-to-batch turnover. These features, coupled with the suitability of SU equipment for commercial manufacturing, increase productivity and accelerate the development of new drugs.
There is rising interest in reaping the benefits of these SU bioreactors in microbial cultivation. While the largest number of commercially available single-use bioreactors support mammalian cell cultures (40%), only 14% are designed to support microbial cultures [ref]. Here, we discuss why that might be the case and introduce a high-performing single-use fermenter capable of handling demanding microbial cultures.
Evolving Interest in Microbial Cultures
On top of emerging microbial drug modalities - such as therapeutic plasmid DNA (pDNA) which is crucial for the development of gene therapies and vaccines – there is a trend towards replacing traditional mammalian-manufactured monoclonal antibodies for antibody fragments and other often microbially-manufactured antibody-like agents.
Microbial cultures are typically performed in stainless steel in situ fermenters, setting the benchmark for cultivation performance across the industry. While they have long been the standard, there is an increasing push to adopt more single-use solutions across the production pipeline. Single-use solutions help solve many production challenges associated with stainless-steel microbial processes, outlined below.
Challenges of Stainless-Steel Fermenters for Microbial Applications
Cost-Intensive
Building a stainless-steel facility comes with expenditures beyond the high installation cost: They also require piping and steam-in-place, and steam-in-place capabilities, which are expensive to maintain.
Limited Productivity
The cleaning and validation required for stainless steel fermenters mean low batch-to-batch turnover, slowing production. For instance, a typical stainless-steel facility might be able to produce around 50 batches a year vs. 100 batches a year in single-use facilities.
Long Timelines
Process development timelines are longer due to scalability studies, time-consuming installation, and low batch-to-batch turnover.
Risk
Contamination and operator safety risks are increased due to the need for cleaning, which may be insufficient, and exposure to potentially harmful products.
While single-use solutions have been widely adopted in mammalian culture applications, the same uptake has not been seen in microbial processes. This is partly because of the differences between the cell cultures: the single-use equipment used for mammalian cultivations cannot simply be used in microbial processes.
Why Do We Need Different Single-Use Cultivation Equipment for Microbial Cultures?
Compared to mammalian cell cultures, microbial cell cultures require higher stirring and gassing rates as well as heat transfer required to cope with the cells' oxygen consumption and metabolic heat generation.
This means single-use components must withstand these increased pressures – a challenge they don't have to cope with in mammalian cultures.
To establish single-use fermenters as a real alternative to in situ bioreactor technology, we must be able to demonstrate that they meet critical parameters and achieve comparable performance.
Biostat STR® Microbial – A Viable Single-Use Alternative
The Biostat STR® Microbial has a conventional stirred-tank design with an 11 to 40 L working volume.
We tested its limits (with respect to oxygen transfer and cooling power) to demonstrate its performance and test the robustness of the single-use Flexsafe® Microbial bag during the culture of Escherichia coli (E. coli) to ensure it is compatible with challenging microbial processes.
Our results showed that the Biostat® STR Microbial supporting excellent growth performance of E. coli cultures (Figure 1) and successfully controlled and maintained process parameters - DO, pH, and temperature (Figure 2).
Figure 1 Growth profiles of E. coli cultivated in the Biostat STR® Microbial represented by wet and dry cell weight (WCW and DCW)
Figure 2 Temperature control in the Biostat STR® Microbial [from ID 202627]
This control is maintained thanks to advanced sensors and automation powered by Biobrain® and supported by BioPAT ® MFCS for monitoring and storing data.
To learn more about the performance of the Biosat STR® Microbial, download the application note.
Grow Your Microbial Cells in the Best-Performing Single-Use Fermenter
The production of next-generation modalities requires tools that can handle demanding microbial applications while still providing the repeatability and convenience of single-use solutions.
The Biosat STR® Microbial is a high-performance fermenter that has the capacity to cope with high-density E. coli cultures. Its single-use design (with qualified Flexsafe STR® Microbial bags) accelerates time to market through increased productivity. Moreover, batch failure risks are limited with enhanced control of key process parameters.
