The intensification of cell culture production and continuous downstream processing are two important features of many new biomanufacturing schemes. Perfusion of cell culture bioreactors using an alternating tangential flow (ATF) device can increase viable cell density 5-10 fold and can be used to continuously harvest product suitable for immediate downstream processing. Perfusion can also be applied to high density cell banking and preparation of N-l cell inoculum to greatly accelerate production turnover in fed batch processes. The capture of continuous upstream production can be made practical by prepacked columns of uniform performance and rapid load using low aspect ratio columns. To maintain an aseptic environment we are developing gamma irradiated proteinA capture media that can operate for long periods with low bioburden. Together these tools of perfusion and aseptic capture can facilitate the engineering of a more cost and time efficient manufacturing process.
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