SHI Ce, YU Ji, GAO Dong, et al. Process simulation and economic evaluation of monoclonal antibody production[J]. CIESC Journal, 2018, (7): 3198-3207.DOI: 10.11949/j.issn.0438-1157.20171645.
Monoclonal antibody (mAb) is the most important biopharmaceuticals. With the continuous expansion of industrial-scale production and competition
the process rationality and economy have attracted more and more attention. In this paper
four scales of mAb manufacturing processes of 500
2000
5000 and 15000 L were established by using SuperPro Designer software
a bioprocess simulation software. Through the process analysis and cost evaluation
the economic 'hotspots' were determined and the optimization strategies were then proposed. The results showed that the scale effect on the production cost was obvious. With the increase of production scale
the cost would be significantly reduced
and the economic hotspots were transferred from equipment-dependent costs to raw materials and consumables
including serum-free medium and Protein A affinity resin. The key for upstream optimization was to increase the titer of mAb expression during cell culture. But when the titer was higher than 5 g/L
the effect of titer increasing on the cost was weakened and the cost was then mainly controlled by downstream process. The downstream optimization should focus on Protein A affinity resins
including capacity
price and the reuse cycles. The optimization of overall process would be the stagger mode with three main bioreactors corresponding one downstream line
for which the production scale and equipment cost were two key factors. The results demonstrated that with the aid of reasonable process simulation and economic evaluation
some hotspots of manufacture process could be identified and the appropriate optimization strategies would be proposed to improve the process efficiency and reduce the production cost.