Continuous Fermentation: Unlocking the Future of Biomanufacturing

Our recent webinar on continuous fermentation highlighted the potential and challenges of this innovative approach for industrial biotechnology and biomanufacturing. We first asked the over 200 participants to generate a word cloud of their opinions on continuous fermentation. Most expected that it could increase productivity (space/time yield, increased automation, more efficient processes), but many expressed concerns about the risk of contamination and increased process complexity. Experts from academia and industry then shared their insights on optimising space-time yield, managing costs, and overcoming technical hurdles.

Continuous fermentation offers the potential for improved space-time yield compared to traditional batch processes. However, our speakers noted that in practice, batch and fed-batch processes often still have higher space-time yield, process stability, and reproducibility. One challenge in continuous fermentation is the potential for GMOs to develop subpopulations during long fermentation periods, often leading to accumulation of non-productive mutants over time. This can be exacerbated by strong selective pressure, for example by the accumulation of residues in the fermentation broth.

Managing risks in continuous fermentation includes considerations for yield and quality control. Strategies to cope with these challenges includes using ultra-sterile conditions, operating at very selective conditions (low pH, high temperature, high salinity), and accepting and managing genetic drift.

One viewpoint echoed by several speakers was that “continuous” is a continuum, rather than actually infinite. They argued that increasing the batch time and managing “feed and draw” phases could be a more pragmatic way to achieve the benefits of continuous biomanufacturing without establishing an infinitely run bioprocess.

While continuous fermentation shows promise for improving biomanufacturing efficiency, it presents unique challenges that require careful consideration and innovative solutions. As the field evolves, a combination of process engineering, strain optimization, and creative approaches to process design will likely drive the adoption of continuous fermentation in industrial biotechnology.