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Fed-Batch Culture Processes
Published in Wei-Shou Hu, Cell Culture Bioprocess Engineering, 2020
The operation of a bioreactor is generally classified as batch or continuous mode. In a continuous process, the feed is continuously being introduced to the reactor and the product stream is continuously being withdrawn. In a batch process, the medium, including all the nutrients (except oxygen), is added at the beginning to support cell growth and production until the end of cultivation. A variant of batch process is the fed-batch process, in which additional nutrients are added during the cultivation period to sustain the growth and production longer than that of a batch culture. The vast majority of cell culture manufacturing processes employ batch culture for cell expansion and fed-batch culture in the production-scale reactor (Figure 9.3). The series of batch cultures for cell expansion is often referred to as a seed train. At the termination of a fed-batch reactor, the cell viability may be low and the product is recovered in downstream operations. Continuous culture is not commonly practiced in the cultivation of mammalian cells unless it is in conjunction with cell recycling. This process allows for continuous discharge of metabolites and product, thus alleviating the growth inhibition caused by metabolite accumulation and prolonging the culture (Figure 9.2b). The different types of continuous cultures will be discussed in the next chapter.
Cell Culture Process Validation Including Cell Bank Qualification
Published in James Agalloco, Phil DeSantis, Anthony Grilli, Anthony Pavell, Handbook of Validation in Pharmaceutical Processes, 2021
Anne B. Tolstrup, Steven I. Max, Denis Drapeau, Timothy S. Charlebois
Currently, the most prevalent manufacturing mode by far for large biopharmaceuticals including monoclonal antibodies is fed-batch culture, although perfusion and continuous processing are becoming more popular, too, these years. In fed-batch, production cells are expanded through several seed train stages in vessels of increasing size prior to inoculation of the production bioreactor. The cells are further expanded here while the culture is supplied with nutrient feeds at specified time points. A temperature reduction to <37°C is often done after 4–6 days of exponential growth, after which the main recombinant protein production phase starts. The entire content of the production bioreactor is harvested as cell viability drops or productivity levels out, typically after about two weeks. Fed-batch processes are most often associated with a single thaw from a MCB or WCB according to a one-vial-one-run concept, although some companies do maintain prolonged seed bioreactor cultures for staggered inoculation of the production bioreactors. Perfusion cultures are also initiated by a cell expansion after cell bank vial thaw, but the production stage involves maintenance of a constant working volume in the bioreactor by continuous introduction of fresh culture medium and removal of spent medium through the use of a scalable cell retention system. Perfusion systems allow for extended culture durations (several weeks or months) and continuous harvest and purification operations. Variations to the perfusion mode, such as N-1 perfusion culture systems in which the cell culture inoculum is grown to high cell density in a seed bioreactor prior to inoculation of the production tank at high VCD, are also employed.
Bioethanol production from sugarcane molasses with supplemented nutrients by industrial yeast
Published in Biofuels, 2023
Hasan Shahriar Raby, Md Anowar Saadat, Ahmed Nazmus Sakib, Fatema Moni Chowdhury, Abu Yousuf
In order to achieve high productivity and high cell density in fed-batch culture, an exponential feeding strategy has been recognized as a potential pathway [38]. This strategy involves continuously feeding the culture with nutrients at an exponentially increasing rate, which can help to sustain rapid cell growth and maintain favorable conditions for optimal productivity. By providing nutrients in a controlled manner based on the growth rate of the cells, an exponential feeding strategy can enhance the efficiency of nutrient utilization, minimize nutrient limitations, and promote higher cell densities, ultimately leading to improved productivity in fed-batch cultures. Nutrients can be fed in an exponential method either at the beginning of the cell culture or can be distributed in a time interval. The current study applied the exponential feeding method by doubling and quadrupling the intake of nutrients. Growth supplements were fed during the initial stage of the batch culture.
Control algorithms and strategies of feeding for fed-batch fermentation of Escherichia coli: a review of 40 years of experience
Published in Preparative Biochemistry & Biotechnology, 2021
Mohammad Mahmoodi, Ehsan Nassireslami
Differ from batch culture, in fed-batch culture fresh medium is added to a well-mixed fermenter according to a predetermined feed flow rate when the nutrients are about to run out. Thus the resulting cell concentration by this method of fermentation is usually higher than in a batch culture.[3] In this method of fermentation, growth curve maybe either exponential or other growth profiles, depending on the feeding strategy. In addition to higher biomass concentration, fed-batch culture superiority can be seen in a higher ultimate concentration of product as well as higher yield of product.[4]