[Upstream bioprocess development] Some notes about recent upstream process characterization approach

This article provides a very brief introduction of some new aspects of biopharmaceutical process development. Implementation of quality by design (QbD) strategy has long been regarded as the paradigm in the development of biopharmaceutical production processes. An essential part of that is to identify the critical quality attributes (CQAs) and their relations between the critical process parameters (CPPs). Intensified design of experiments (iDoE) is a fairly new strategy (proposed during 2017) to efficiently reduce the number experiments required to characterize a bioprocess by bridging different experimental conditions in a more homogeneous way, although cautions might be needed to consider potential cell memory effects and metabolic shifts in mammalian cells. Once the process dynamics is captured, advanced process control techniques such as model predictive control (MPC) can then be adopted for optimal trajectory planning and closed-loop noise rejection during the production phase.

A example of an iDoE planning scheme with two-level Doehlert design (Image taken from DOI: 10.1002/elsc.201600037)