Conference Dates

November 1-5, 2015


We have developed an integrated continuous processing framework for end-to-end production of complex fragile proteins based on perfusion cultivation and automated multi-step purification [1,2,3]. Upstream, the integrated system consists of a stirred tank bioreactor with an ATF cell retention system. The clarified harvest directly enters an off-the-shelf ÄKTA chromatography system converted into a continuous purification unit. Two alternating capture columns precede an automated multi-step purification train with full flexibility and control of individual columns.

The integrated set-up enables compact automated bench-top factories converting cell culture media to purified protein in an efficient manner without intermediate storage. It provides monitoring of the production progress, allowing for “just-enough” production and better use of resources, and it also supports monitoring of product quality attributes. The latter aspect is obviously relevant in a manufacturing setting but perhaps even more so for process development. Importantly, the integrated approach facilitates assessment of how final product quality will be affected of changes in one or several individual process steps thereby enabling holistic process development.

Benefits for process intensification as well as process development will be demonstrated by case studies from production of fragile proteins for pre-clinical supply. Furthermore, challenges encountered when integrating upstream and downstream processes in the continuous framework will be discussed and shared.