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With the continuous improvement of cell culture technology, the combination of high-density fed-batch culture and perfusion culture can achieve higher cell density and product expression concentration, so now only a smaller culture volume and bioreactor size can be used. Production of therapeutic proteins or antibodies. The development of this technology has made the production equipment smaller, which in turn reduces some of the unpredictable problems from the scale of clinical research to the scale of commercial production. At present, the cell culture process is becoming more and more intensive, and the use of disposable reactors will become more advantageous, because the disposable bioreactor BIOSTAT® SRT can provide a production scale of up to 2000L, and the past ten to two can be obtained. A production scale of ten times or more bioreactors can be achieved. In addition, the goal of modern state-of-the-art cell culture processes is to maintain cells in a good metabolic state to control protein folding and glycosylation, ensuring stable quality products, so the main purpose is not to achieve very high cell densities. It is necessary to ensure a stable supply of nutrients and metabolites in the bioreactor. 
How to carry out high-density fed-batch culture or perfusion culture
After bioreactor inoculation and the initial 1-2 day batch growth phase, start using appropriate equipment (eg, RefineATF system, etc.) to remove cell-free supernatant at a constant harvest flow rate while replenishing fresh in the culture medium Medium...
Full-text view of disposable bioreactor for large-scale perfusion culture and high-density fed-batch culture details: Download Fulltext
Perfusion culture is a well-known drug production method that has been widely used in many biotechnological drug production processes for many years, such as coagulation factors (coagulation factor VIII: Bayer's Kogenate and Pfizer's Refacto; coagulation factor VII: Novoseven of Novo Nordisk, Protein C (Xigris of Lilly) and other enzymes, of course, also include monoclonal antibodies (ReoPro and Remicade of Janssen Biotech; Simulect of Novartis, etc.). Recently, perfusion culture has also been used for seed culture at high cell densities to reduce the seed culture steps required to reach the final production scale.