In mammalian cell culture, single-use bioreactors are widely used. Different hardware designs are available, ranging from stirred tank reactors to wave mixed and cubical shaken systems. Unlike in stainless steel systems, where standards exist, in singleuse bioreactors aeration devices are often predefined by the supplier. While ring sparger systems are the gold standard in stainless steel bioreactors, not all singleuse bioreactors are available with ring spargers. In this study, a comprehensive characterization of two stirred tank single-use bioreactor systems (XDR TM from Xcellerex and S.U.B. from Thermo Scientific Hyclone) was performed under GMP conditions with 200/250 L and 1000 L bioreactors. Engineering facts like mass transfer rates for oxygen k L a o2 and carbon dioxide k L a CO2 as well as mixing number were evaluated. To achieve improved similarity in key engineering parameters and in consequence cell culture performance, the submerse aeration device of the S.U.B.(to date only open tube and frit) was remodeled resulting in a drilled hole sparger design. Results of the characterization showed that k L a o2 in the S.U.B. was enhanced from 8.5 h −1 to 11.5 h −1 at the maximum, and the k L a CO2 was very similar between both bioreactor types. Knowledge of the characterization data as well as improved oxygen transfer rate in the S.U.B. allows for an interchangeable usage of the two different single-use bioreactors.
A systematic and integrated use of single‐use technologies was combined with a robust monoclonal antibody platform, which led to a substantial reduction of manufacturing costs, reduced timelines and increased flexibility in clinical manufacturing. A direct scale‐up of a high titer monoclonal antibody‐expressing CHO DG44‐based cell culture platform was performed from shake flasks to a 1000 L production scale in a completely single‐use manufacturing facility. The scale‐up was done on the basis of calculating the specific volumetric power input which allowed a direct transfer from small culture volumes to the production scale. The timelines for process development were reduced to 3 months from the Research Cell Bank to the drug substance with highly optimized cells and appropriate culture conditions.
Process transfer is associated with a considerable risk potential. The most critical equipment aspects in upstream operations are the type and scale of bioreactors. Single‐use systems have the advantage of a relatively fixed bioreactor design where only few adaptations can be made, e.g. in stirrer geometry or type of submerse aeration. Here, we describe the transfer of a Chinese hamster ovary fed‐batch process in the 1000 L scale from a XDR™ to a Thermo Scientific Hyclone Single‐Use Bioreactor (S.U.B.) used for GMP compliant manufacturing of biologics. The transfer method, which was based on a preceding intensive characterization of both bioreactors, aimed either to keep the oxygen mass transfer or the power input constant. The transfer strategies were evaluated theoretically based on derived empirical correlations for the mass transfer coefficients, kLaO2 and kLaCO2. An operation boundary of 10–31 W m−3 for the S.U.B. bioreactor was defined, which is an approximately 35 % higher power input compared to that in the XDR™. The transfer strategy succeeded in maintaining essential biological parameters such as cell concentration (±5%), viability (±2%), and product formation (±3%) very similar. This is, to the authors’ knowledge, the first time that distinct process performance comparison in different 1000 L SUBs is published.
scite is a Brooklyn-based organization that helps researchers better discover and understand research articles through Smart Citations–citations that display the context of the citation and describe whether the article provides supporting or contrasting evidence. scite is used by students and researchers from around the world and is funded in part by the National Science Foundation and the National Institute on Drug Abuse of the National Institutes of Health.
hi@scite.ai
10624 S. Eastern Ave., Ste. A-614
Henderson, NV 89052, USA
Copyright © 2024 scite LLC. All rights reserved.
Made with 💙 for researchers
Part of the Research Solutions Family.