Early-stage in silico flowsheet analysis for a monoclonal antibody platform

Abstract

In silico frameworks have the potential to improve experimentally designed processes for monoclonal antibody (mAb) manufacturing. In this paper, a framework for the analysis of mAb process alternatives is presented with the objective of realizing process improvements from a flowsheet perspective. The key elements of the proposed method include the generation and decomposition of the design space, the formulation of a flowsheet model, and the simulation and evaluation of alternative designs. An example of an evaluation of a new technology step in mAb manufacturing is given to demonstrate the application of the framework and to illustrate how the design problem is solved using the proposed step-by-step procedure. The methodical approach provides the opportunity to systematically and quantitatively evaluate the impact of different design decisions before selecting a final design. Therefore, it supports the finding of improved process designs that may be ignored using conventional experiment-based methods and sequential optimization of processing steps.