Process design of a fully integrated continuous biopharmaceutical process using economic and ecological impact assessment

Continuous biomanufacturing is a promising alternative to current batch operation as it offers benefits in terms of improved productivity, product quality, and reduced footprint. This study aims to build a fully integrated continuous platform for monoclonal antibody (mAb) production incorporating novel technologies (like intensified seed expansion and continuous high cell density perfusion operations, single-pass tangential flow filtration, and single-use technologies) as well as media and buffer preparation steps. Economic assessment is performed on the basis of the total cost of goods (COGs), which is $102.2/g in the base-case scenario with a bioreactor scale of 500 L. E-factor is used as an environmental indicator and the result shows that 4865.6kg of process water and 11.1 kg of consumables are required to produce 1 kg mAbs. After the development and analysis of the benchmark process, scenario analysis is performed to assess the impacts of the bioreactor scale (60-2000 L) and upstream titers (1.12-2.08 g/L) on the process economics as well as on the environmental footprint. With the increase of bioreactor scale and mAb titer, the operating COGs per unit product decrease. Moreover, increasing the mAb titer is more favorable in terms of the ecological impacts. To investigate the production capacity, the upstream production is increased and the downstream bottlenecks are determined. It is found that only the multicolumn chromatographic (MCC) operations become the process bottleneck and the order of the MCC unit operation that becomes the process bottleneck depends on capacity utilization for that step. Finally, a new platform is built with the integration of membrane chromatography and the two designed processes are compared in terms of economic and ecological impacts.

Automated summary

This study aims to build a fully integrated continuous platform for monoclonal antibody (mAb) production and assesses the economic and ecological impacts of the process. The results show that increasing the bioreactor scale and mAb titer can decrease the operating cost per unit product, and increasing the mAb titer is more favorable in terms of ecological impacts.