Fermentation

The BPF fermentation pilot module processes sugars into bio-based intermediates using fermentation processes.

Our fermenters range from 10 L up to 4000 L, including a dedicated food fermentation section. We have ample experience with a broad range of micro organisms, like bacteria, fungal, yeast, GMO and non-GMO.  

Our recommendation on scaling-up is to always keep the scale-down approach in mind. A process optimized on lab scale for maximum productivity without keeping the end-goal in mind is likely to run into some kind of limitation during scale-up trials. It's important to understand the limiting transport phenomena and the robustness of the fermentation process.  

This is where experience comes in. BPF brings industrial scale experience and translates this into the right set of piloting conditions. 

Best practices

Choice of raw materials

Use the final product target as starting point. Should the product be used in Pharma (non-clinical)/Feed/Food/Bulk Chemical? Choose the right raw material grade from the start.

Furthermore, take into account the raw material costs:

Assume production scale is 200 m3. Kanamycin is needed to maintain plasmid stability of the production organism. Its concentration is 50 mg/l and the cost price is 3 USD/g. The process has been developed on lab scale by the customer. The total cost of kanamycin is 1.50 USD at 10 L scale.

However, customer targets to produce at 200 m3 scale. This makes the total cost of Kanamycin at this scale 30.000 USD. A great technical choice at lab scale is not always economically viable at commercial scale depending on the targeted end-product selling price.

Seed train optimization

The seed train is the starting point for a fermentation process. A typical example: 1 culture cryo-tube is added to a flask containing 500 mL of medium.

After 48 hours of incubation the complete flask is transferred to a lab scale fermenter containing 9500 mL medium (5% inoculum ratio). This means on 200 m3 factory scale you will need 20.000 flasks to inoculate your fermenter in order to obtain a similar amount of generations of growth. As you can imagine this is not practical.

If more generations are needed on planned scale of production, make sure to study the effect of more generations and the inoculum strategy on the process on lab scale or pilot scale. Are productivities maintained? Is the plasmid stable? Do viscosities change?

Anti-foam agents

Foaming behaviour is complex to model and in some cases unpredictable. Finding the right balance between aeration and agitation while the fermentation is proceeding without interruption is a challenge.

Extensive foaming interrupts the process and leads to yield loss or loss of the complete fermenter. Dosing anti-foam to the fermenter can keep foaming under control.

Anti-foaming agents are however known to potentially inhibit growth and can affect DSP by, for example, blocking membrane filters or negatively influencing product crystallization. Depending on the final application, the choice of antifoam can give rise to issues with final product registration.

Careful selection of a suitable antifoam type and determination of the maximum amount of antifoam that can be added without hampering DSP needs to be determined on lab or pilot scale.