Figure 2: Typical approaches how to conduct a biopharmaceutical process shown for a chromatographic step exemplarily. It can be either (A) Based on Fixed time / volume for loading and elution; (B) Threshold based e.g. stop loading or start collecting the eluate at a certain UV absorbance; (C) Model based online monitoring with sensors implemented before and / or after the column to predict product quality and quantity in feed and / or eluate; (D) Model predictive control. While (A) and (B) rely on time and material offline analysis and do not allow in process control, (C) and (D) do need offline analysis only for the model training and enable real-time decision making and real-time release.
In this review, we will elaborate how we can arrive at a system for monitoring and control to run a bioprocess, autonomously; we will mainly on downstream processing. An ideal bioprocess from the point of view of real-time monitoring, control and real-time release is outlined.