Processes for monoclonal antibody (mAb) production are often directly scaled up from lab scale to commercial scale to reduce time-to-market, and therefore, more optimal process alternatives are neglected. However, growing economic constraints are driving the development of new processes, which requires a systematic and quantitative evaluation of the design space. Because of the synergistic effects of product-process decisions, it is important to account for process alternatives such as novel flowsheets or new technologies already in the product design phase, hence solving the integrated product-process design problem. The design problem for mAb manufacturing encompasses knowledge in multiple scales: from mechanistic understanding and experimentation, to unit operation, to process flowsheet. Methods and tools need to be developed to build understanding and evaluate alternatives across all scales. Let us consider the evaluation of new technologies and/or approaches for mAb manufacturing that have been developed, including alternative expression systems, non-chromatographic separations, or continuous manufacturing. A flowsheet model represents the production process, including interactions between process steps, which can be used to test ideas for improvement as well as to identify process steps as focus for development. Moreover, flowsheet models allow the evaluation of performance criteria that drives decision making, such as capacity, economics and sustainability. Unit operation models are then used to, at a higher level of resolution, identify values of key variables and parameters to achieve the targets set by testing at the flowsheet level. This is then used to drive experimentation by defining materials and methods, e.g. experimental conditions to be tested. This flow of information across scales applies in both directions. The objective of the presentation is to present an in silico, systematic framework for multi-scale process design and technology evaluation for biopharmaceuticals. The method will be exemplified through a case study for a mAb process starting with the development of a discrete event simulation-based flowsheet model and its application to evaluate and screen ideas for increasing capacity. This leads to the selection of a new technology for upconcentration and drives CFD modelling at the unit operation level, which then drives model-based experimental identification.

In silico framework for multi-scale technology evaluation in monoclonal antibody (mAb) manufacturing

ACS Fall 2021

The official archive and repository for all ACS Meetings & Expositions abstracts and select posters or presentations.