Presented by Andrew Sinclair
Andrew Sinclair is president and founder of Biopharm Services, UK.
Biopharm Services has compared the process economics of four monoclonal antibody (MAb) production processes, each at three different scales to understand the benefits of switching to continuous bioprocessing. The company made these comparisons using its BioSolve Process software.
The processes compared were standard fed-batch with three-step purification, a perfusion process with batch purification, a fed-batch upstream with continuous downstream purification, and an integrated continuous upstream and downstream process. The modelers performed this analysis on facilities able to produce 100 kg/year, 500 kg/year, and 2,000 kg/year of antibody drug product. They assumed fed-batch culture durations of 18 days (final product titers of 5 g/L) and continuous culture durations of 30 days (giving titers of 1.2 g/L) at a perfusion rate of one vessel volume per day.
Biopharm Services believes that no formal cost analysis that compares perfusion with fed-batch cultures has previously been published, despite the industry having operated perfusion bioreactors for over 20 years.
Although continuous chromatography is an established technique for purifying small-molecule drugs, and the technology is maturing in the bioprocessing sector, some continuous biopharmaceutical downstream steps have yet to be developed. Biopharm Services addressed this problem by creating continuous models with multiple units of what are currently discontinuous steps. This allows the temporary diversion of process fluid flow to other units while operators replace exhausted consumables.
Preliminary studies allowed cost optimization of the four process configurations before their comparison. The studies showed that to optimize costs, biomanufacturers must consider aspects such as their approach to pooling and processing the harvested material from multiple batch bioreactors as well as the optimum batch volume from a continuous process.
Results of our comparison analysis showed that at the 100 kg/year scale of operation, the configuration with the lowest capital cost was a perfusion bioreactor purified by a batch downstream process. However, at 500 kg/ year and 2,000 kg/year scales, moving to a process with an integrated continuous upstream and downstream process resulted in the lowest capital cost.
The fed-batch upstream process with a continuous downstream process gave the lowest cost of goods (CoG), irrespective of scale. Continuous cell cultures allow the use of smaller bioreactors (which helps to reduce capital outlays). However, it is important to recognize that these cultures require larger volumes of media to produce an equivalent quantity of product, which can make a significant contribution to the overall process CoG. Processes using fed-batch cultures have lower media costs.
Large infrastructure is required to feed continuous processes with the media and buffer they require. For this reason, continuous process facility footprints are unlikely to be much smaller than batch process facilities, despite reductions in process equipment size.