Integrated and continuous processing of biopharmaceuticals

Alois Jungbauer

Austrian Centre of Industrial Biotechnology, Vienna, Austria, and Department of Biotechnology, University of Natural Resources and Life Science, Vienna, Vienna, Austria

Continuous integrated manufacturing is one of the grand challenges in biopharmaceutical industry to reduced costs, to tackle the increasing demand of products ,and to improve manufacturing flexibility. The transition from a batch wise to a continuous  production can be managed by several strategies. The simplest and most obvious one is to produce in parallel in a staggered fashion, then the product can be already harvested in a pseudo-continuous manner. The individual steps in up and downstream processing are still operated in a batch wise fashion. The next step towards continuous manufacturing is the seamless processing. This is  important for downstream processing, where the eluate of one step is directly loaded on the next column. The ultimate goal is the fully  integrated continuous manufacturing, where all unit-operations are interconnected in a functionally closed space, continuously operated and controlled.  An overview will be given of the concepts  for integration of precipitation, flocculation with chromatography or how precipitation and flocculation can replace echotomography separation. The reactor designs, the problem of residence time distribution, effect of startup, shut down and steady state will be discussed. Examples will be provided from own laboratory and discussed in context of literature.