If you were going to transition vaccine production from roller bottles to bioreactors using microcarriers, what steps would be necessary to both determine the appropriate bioreactor configuration? How would you begin to explore this process?


This would begin with an understanding of the cells and the microcarriers you choose to examine. Preliminary studies in spinner flasks are most often a prelude to a bioreactor application. Keep in mind that the choice of microcarrier bead is critical. The specific gravity and diameter of the bead is an important aspect to scaling-up an attached process in any reactor, Much of the work I have performed in the XDR has been with Cytodex I microcarriers. Choose a bioreactor with the ability to maintain your critical process parameters, even during the different phases of the process i.e growth, infection, post infection etc. Then you want to operate the single-use bioreactor with an agitation rate (rpm) and sparge that will not disrupt the health or attachment. You want an agitation rate such that the beads are uniformly suspended without generating excess shear due to high rpm or excessive sparging. There is a special consideration with attached cultures in that you need to prevent the cells from being stripped off of the beads during normal cultivation (potential result of a small kolmorgorov eddy due too high rpm) in addition to preventing the beads themselves from being damaged.