Confidently scaling-up microbial fermentation: Overcoming common challenges

Challenge 1: Ensuring process consistency

Consistency is essential for successful bacterial, fungal, or yeast fermentation scale-up. Small variations in temperature, dissolved oxygen, pH, and agitation can significantly impact results at larger scales. INFORS HT bioreactors feature vessel geometry designed for a range of cell types and a set of standard and customizable agitation designs, ensuring uniform conditions. Many of INFORS HT’s small-scale vessels also come equipped with multiple ports, allowing the use of the same number and types of sensors as in large-scale systems, streamlining the scale-up process and reducing variability. Coupled with INFORS HT’s eve® software, these systems manage parameters effectively through automated feedback loops. Labs like Universiti Sains Malaysia and Daisy Lab have successfully maintained consistent microbial growth by leveraging these bioreactor features.

Dr. Maria Ester LuccaMicrobial Biotechnology, Proimi, Argentina

Challenge 3: Simplifying regulatory compliance

Meeting regulatory standards, such as GMP and FDA guidelines, becomes increasingly demanding at commercial scales, especially for bacterial and fungal-based biopharmaceutical production. Techfors and Techfors-S bioreactors incorporate GMP-compliant materials and designs, making validation processes simpler. Additionally, bioprocess control software aids compliance through automated documentation and batch record tracking. Rapid COVID-19 antibody test production streamlined regulatory adherence by leveraging these bioreactor systems.

Challenge 4: Managing technical complexity

As processes move from the lab to production, the technical complexity of microbial fermentation increases. Factors such as oxygen transfer, nutrient delivery, and integration of multiple sensors become more difficult to manage. INFORS HT bioreactors help address these issues with advanced aeration strategies and seamless sensor integration for real-time monitoring. These capabilities offer researchers better control over challenging scale-up conditions and are widely used across academic and industrial settings to simplify the path from development to production.

Challenge 6: Optimizing yield and productivity

Improving productivity and yield in microbial fermentation often requires overcoming physical limitations related to oxygen transfer, pH stability, foam formation, and nutrient delivery. These factors can vary considerably depending on whether you're culturing bacterial, mammalian cells, plant cells, and yeast.

Techfors bioreactors address these challenges with a range of customizable configurations. High-efficiency Rushton or pitched-blade impellers optimize mixing for both high-density and shear-sensitive organisms. The system’s sparger design supports enhanced gas transfer rates, which is especially important for aerobic fermentations. Real-time parameter control allows for adaptive feeding strategies, such as exponential fed-batch modes, which can maximize biomass accumulation and product formation. These capabilities support higher yields while reducing batch variability and operational downtime.

Challenge 7: Minimizing contamination risks

At pilot and production scales, the consequences of contamination can mean the loss of entire batches, costly investigations, and compliance setbacks. Risks increase with manual sampling, frequent system openings, or inadequate sterilization protocols. Techfors-S bioreactors mitigate these risks with multiple layers of built-in protection. The system supports steam-in-place (SIP)  sterilization and integrates aseptic connectors, reducing human intervention during culture handling. The use of magnetically coupled agitators eliminates the need for dynamic seals, one of the most common contamination points. Sterile sampling systems allow for in-process checks without compromising the vessel’s closed system integrity. These features are particularly critical for facilities operating under GMP or ISO-certified workflows.

Challenge 8: Efficient scale-down modeling

When a problem occurs in production, being able to reproduce those conditions at lab scale is essential for root cause analysis. However, differences in geometry, mixing, and gas flow between small and large systems often make this difficult.

INFORS HT’s Techfors-S and Techfors bioreactors address this challenge by maintaining geometric similarity across vessel sizes from 15 – 1,000 L, and offering identical software, sensors, and control systems at all scales. This design enables researchers to mirror full-scale processes in smaller fermentors, ensuring data relevance. Combined with comprehensive data logging and export capabilities through eve®, this makes it easier to compare runs, simulate stress scenarios, and fine-tune protocols before reimplementation at scale. Scale-down modeling thus becomes a reliable tool for reducing troubleshooting time and improving process robustness.

"The seamless transition from Multifors to Labfors to Techfors-S through the unified use of eve accelerates the scale-up of our processes and helps us avoid errors." 

- Dr. Tobias Thiele, Science Manager, Novonesis, Berlin

Confidently scaling up your microbial fermentation

Scaling bacterial, fungal, and yeast fermentations does not have to be daunting. INFORS HT’s Techfors-S and Techfors bioreactor systems are specifically designed to address microbial fermentation scale-up challenges. Their advanced agitation and aeration systems ensure optimized yield and productivity. Features such as sterile sampling ports, integrated sterilization, and GMP-compliant materials minimize contamination risks and simplify compliance. Standardized bioreactor designs provide precise scale-up and scale-down modeling capabilities, enabling seamless process optimization. Combined with powerful eve® bioprocess control software and expert technical support, Techfors bioreactors equip you to confidently navigate scale-up challenges and achieve consistent, high-quality production outcomes.