Modeling the Residence Time Distribution of Integrated Continuous Bioprocesses

Area of Science:

• Biopharmaceutical Manufacturing
• Chemical Engineering
• Process Systems Engineering

Background:

• The biopharmaceutical industry is transitioning from traditional batch to continuous manufacturing processes.
• Regulatory bodies like the Food and Drug Administration (FDA) are issuing guidance for continuous integrated biomanufacturing.
• A key requirement for continuous manufacturing is a comprehensive understanding of process mass flows.

Purpose of the Study:

• To develop a computer simulation framework for modeling the residence time distribution (RTD) of integrated continuous downstream bioprocesses.
• To enable a unit-by-unit modeling approach for simulating individual unit operations and integrating them into a comprehensive RTD model.
• To facilitate the evaluation and optimization of continuous biomanufacturing processes.

Main Methods:

• A unit-by-unit computer simulation approach was employed, modeling each unit operation sequentially over the entire processing time.
• The simulated unit operations were combined to create an integrated residence time distribution (RTD) model for the downstream process.
• The framework allows for flexible integration of new unit operations and dynamic adjustment of process parameters.

Main Results:

• The developed RTD model can accelerate the start-up phase to reach steady-state conditions in continuous biomanufacturing.
• The model enables the calculation of the effects of process disturbances at any stage of the manufacturing process.
• Virtual tracking of material flow through the process is possible, enhancing process comprehension.

Conclusions:

• The computer simulation framework provides a robust tool for modeling RTD in continuous downstream bioprocessing.
• This approach supports the implementation of continuous manufacturing by improving process understanding, control, and optimization.
• The framework was successfully demonstrated using a hypothetical antibody manufacturing process.