Augmentation therapy is a treatment option available in the market that has been approved by the U.S. Food and Drug Administration (FDA) for alpha-1-antitrypsin (A1AT) deficient patients. The treatment requires weekly injections of purified A1AT for the patients and relies on plasma donor. The demand for A1AT is also high due to its functional role in various diseases. However, scaling up production of purified human plasma A1AT remained costly and challenging. It is therefore of great interest to generate A1AT at larger scale in ensuring a consistent supply to the market. In this paper, we evaluated the stability and productivity of ten Chinese Hamster Ovary (CHO) single cell clones over 12 weeks. This was followed by scaling up the fed-batch production of A1AT with the selected cell clone in a 10L single-use surface aerated orbital shaken bioreactor SB10-X. The cell specific productivity of the two bioreactor runs were at 9.6 and 12 pg/cell/day (pcd) respectively, which were comparable to shake flasks. While the paper focuses on the possibility to scale up A1AT production, process conditions such as feeding regime could be investigated to further prolong the culture longevity and increase productivity.
Tang et al. (Sun,) studied this question.