Single versus multiple bioreactor scale-up: economy for high-value products

Area of Science:

• Biotechnology
• Chemical Engineering
• Process Economics

Background:

• Scaling up biopharmaceutical production presents economic challenges, particularly concerning downstream processing costs.
• Tissue plasminogen activator (t-PA) is a high-value biopharmaceutical produced using animal cell culture.
• Traditional scale-up often relies on increasing bioreactor size, impacting overall process economics.

Purpose of the Study:

• To evaluate the economic feasibility of scaling up bioreactor production by increasing the number of units versus using a single large unit.
• To compare the return on investment (ROI) for a multiple bioreactor approach versus a single large bioreactor for t-PA production.
• To analyze the impact of scale-up strategy on downstream processing costs and equipment contributions.

Main Methods:

• Integrated flowsheet simulations were developed for both single large bioreactor and multiple smaller bioreactor scenarios.
• Economic analysis focused on return on investment (ROI) and breakdown of equipment purchase costs.
• Downstream unit scheduling was optimized to allow equipment sharing in the multiple bioreactor case.

Main Results:

• A multiple bioreactor scale-up strategy increased the ROI of the base process by 122%.
• This significant ROI increase is attributed to the reduced size and cost of downstream processing units.
• Downstream processing costs, which account for approximately 80% of total costs for products like t-PA, were substantially lowered.
• The proportion of cell culture equipment cost increased from 14% to 37%, while chromatography column costs decreased from 52% to 33% of total equipment purchase cost.

Conclusions:

• Scaling up bioreactor production through a multiple-unit approach offers substantial economic advantages over the single large-unit method.
• Optimized scheduling and equipment sharing in downstream processing are key drivers for improved ROI in multi-bioreactor systems.
• This strategy effectively mitigates the high cost associated with downstream processing for valuable biopharmaceuticals like t-PA.