Application Of Disposable Bioreactor And Filtration System In Recombinant Antibody Production By CHO-GS Cell Line

With the development of genetic and cell engineering, recombinant antibody drug by mamalian cell culture shows promising market interest. More attention has been drawn and big progress has been made on single-use bioproduct development due to time-consuming cell culture process, high standard of aseptic operation and requirement of short antibody drug developemnt phase. In this thesis, single-use bioreactor and disposable clarification system are evaluted on mamalian cell culture process.Two disposbile bioreactors including single-use stir bioreactor and wave bag bioreactor were evaluated with the comparison of traditional stir tank bioreactor. Comparable antibody expression level, product quality, cell growth and metabolites are obtained between single-use stir bioreactor and classic bioreactor since both bioreactors have similar construction and control design. However, wave bag bioreacor shows lower expression level and cell density, and different metabolite profile. In the beginning of cell culture, similar results are obtained from all three bioreactors. However, in the late phase of cell culture, lower cell density and expression level are obtained in wave bag due to high concentration of byproduct metabolites, while antibody quality is not affected on wave bag process. Process optimization could be required to reach similar results as the other tow bioreactors in the future.New disposable filtration device Clarisolve MS20 shows good performance on sample clarification step with 262 L/m2 loading capacity and low turbidity(10 NTU) of clarified sample using acidification sample from cell supernatant. This promising new one step filtration process can reach the similar results on turbidity, yield and quality, compared to current two step filtration process using filter Milistak+ D0 HC and X0 HC.