Process Intensification of Spodoptera frugiperda (Sf) Cell Growth via Multi-Parallel Bioreactor System

Thesis: M.B.A., Massachusetts Institute of Technology, Sloan School of Management, in conjunction with the Leaders for Global Operations Program at MIT, May, 2020Thesis: S.M., Massachusetts Institute of Technology, Department of Chemical Engineering, in conjunction with the Leaders for Global Operations Program at MIT, May, 2020Cataloged from PDF version of thesis.Includes bibliographical references (pages 101-106).The objective of this project is to improve the yield of the fed-batch manufacturing process for the production of Flublok influenza vaccine, which was approved by the FDA in 2018. In short, Spodoptera frugiperda (SF+) insect cells are grown to a specific target cell density and then infected with baculovirus containing the gene of interest (GOI). For this particular process, the recombinant hemagglutinin (rHA) is extracted from the cell and used to produce the influenza vaccine. Protein Sciences developed a fed-batch process which improved on the traditional batch process by feeding supplementary nutrients to boost cell growth. The Fed-Batch process doubled the target cell density at the time of infection which resulted in a two-fold increase in the final yield of rHA and a 30% reduction in cost of goods. This Fed-Batch process can be further optimized to increase rHA yield and reduce the cost of goods. It is important to note that simply increasing cell biomass is not enough; the cells must also be able to produce rHA at a similar specific productivity in order to increase the yield. Exploratory process improvement experiments were performed on the ambr250 ® multi-parallel bioreactor system, with the goal of identifying the growth conditions for maximizing SF+ cell density. The conditions yielding the best results from these experiments were replicated in 3L glass bioreactors. Using data from these experiments, an optimized Fed-batch process can be developed. In addition, a statistical model was developed to relate key process parameters to SF+ cell density. This model can be used to quantitively ascertain how cell density is impacted by changing process parameters.by Randy Stein.M.B.A.S.M.M.B.A. Massachusetts Institute of Technology, Sloan School of ManagementS.M. Massachusetts Institute of Technology, Department of Chemical Engineerin