(27d) Pilot Scale Manufacturing in Single Use Bioreactors: Case Study and Engineering Considerations

The utilization of single-use bioreactors (SUB's) has rapidly expanded throughout the bioprocessing industry, while the design and type of SUB technology has proliferated as well. SUB's have been primarily employed for mammalian cell, insect cell and vaccine production processes, and, in context with these applications, have demonstrated performance analogous to stirred tank reactors (STR's). In this study, a pilot scale evaluation of two SUB technologies was conducted using a Chinese Hamster Ovary (CHO) cell culture process for monoclonal (mAb) production. Pilot scale STR, wave-mixing (Wave®) and stirred-bag (Hyclone S.U.B.) bioreactor designs were compared, with the STR used as a control. Final working volumes for each bioreactor type were 100L, 90L and 230L, respectively. The bioreactors were evaluated in regards to their impact on CHO cell growth, cell metabolism, mAb production and mAb product quality. Scale dependent parameters were assessed for each SUB and design modifications were employed as required, in particular, for the stirred-bag variety. With these modifications, CHO cell culture performance and mAb production comparability and reproducibility were achieved for both the Wave® and Hyclone S.U.B. bioreactors as compared to the STR production process. Additionally, an economic analysis of pilot scale SUB systems will be briefly discussed.