Evaluation of a Single-Use Bioreactor for the Fed-Batch Production of a Monoclonal Antibody - Despite different material, agitation, and aeration, the performance of the disposable bioreactor is simil

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Evaluation of a Single-Use Bioreactor for the Fed-Batch Production of a Monoclonal Antibody
Despite different material, agitation, and aeration, the performance of the disposable bioreactor is similar to that of stainless steel bioreactors.


BioPharm International Supplements


Abstract

In this study, we tested the combination of a disposable bioreactor and a disposable dissolved oxygen sensor as a replacement for our standard bioreactors. The possibility to run a fed-batch cell culture process developed for the production of a monoclonal antibody in a 50-L single-use bioreactor was investigated. The single-use bioreactor was assessed both as a seed train and as a production bioreactor. Therefore, three configurations corresponding to different combinations of the 50-L disposable bioreactor and the reference 5-L glass bioreactor (fully scalable up to 300 L) were compared.


(MERCK SERONO SA)
In the past decade, biopharmaceutical manufacturing processes have undergone multiple changes resulting in significant improvements in efficiency. In parallel with the development of high producing cell lines and robust chemically defined media for cell culture, the constant evolution of disposables has led to simpler operations. The use of disposables eliminates cleaning and sterilization steps, as well as cleaning validation, thus reducing costs and the time of operation per batch. Traditional disposable devices such as filters, tubing, bags, bottles, and syringes have commonly been used in biopharmaceutical manufacturing since the 1990s. The breakthrough in disposable bioreactor technology development in terms of larger capacities was the use of bag systems for cell culture. The 20-L rocker system was commercially available in 1998 and the technology became a success, especially in cell expansion operations. It allowed working with complete sterility, thereby securing the industrial cell culture processes. Further development of this system led to higher volumes and to the equipment available today on the market.

The next step was the development of stirred-tank bioreactors with a configuration similar to conventional stainless steel bioreactors. Compared to traditional wave bioreactors, stirred-tank bioreactors offer the benefits of sparging, stirring of the suspension, and a higher utilization rate of the bag size as cultivation space. Such bioreactors are considered for use in the industry in cell amplification processes, to reach higher cell densities, or as production bioreactors. The single-use disposable bioreactor (SUB) from HyClone (Thermo Fisher Scientific) entered the market in 2006. Currently, disposable bioreactors up to 2,000 L (SUB, Hyclone and XDR, Xcellerex) culture volume are commercially available and plans are to develop 3,000 L bioreactor systems over the next few years.1

In addition to disposable bioreactors, innovative single-use sensors are currently being developed, which will allow a cell culture process to run long-term in a fully disposable system. Single-use sensors also will solve technical problems sometimes raised by using plastic bags in single-use bioreactors, which can interfere with the functioning of stainless steel sensors because of static electricity problems, and therefore create drifts especially for pH measurement.2

In this study, we tested the combination of a disposable bioreactor and a disposable dissolved oxygen (DO) sensor as a replacement of a standard bioreactors to run a fed-batch cell culture process developed for the production of a monoclonal antibody (MAb). The disposable equipment selected was the 50-L stirred-tank SUB by HyClone coupled to the TruLogic RDPD controller based on DeltaV technology and the disposable TruFluor DO probe by Finesse Solutions.

The SUB was assessed both as a seed train and as a production bioreactor. Therefore, three configurations corresponding to different combinations of the 50-L disposable bioreactor and the reference 5-L glass bioreactor (fully scalable up to 300 L) were compared (Figure 1): seed train and production in a 5-L glass bioreactor (named 5L/5L); seed train in the 50-L SUB; production in 5-L glass bioreactor (named SUB/5L); and seed train and production in the 50-L SUB (named SUB/SUB).


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