Predictive modeling of single pass tangential flow filtration for continuous biomanufacturing

Area of Science:

• Biopharmaceutical Manufacturing
• Chemical Engineering
• Process Intensification

Background:

• Continuous biomanufacturing offers process intensification opportunities.
• Single-pass tangential flow filtration (SPTFF) enables continuous concentration of biologics.
• Precise control of SPTFF output concentration is crucial in continuous processes.

Purpose of the Study:

• To develop a predictive mechanistic model for SPTFF performance.
• To enable accelerated process development and design flexibility in continuous biomanufacturing.
• To identify SPTFF configurations for desired target concentrations across various feed conditions.

Main Methods:

• Utilized the stagnant film model for mechanistic prediction of SPTFF performance.
• Generated flux excursion data with minimal material consumption and within time constraints.
• Validated model accuracy across a wide design space, particularly at higher feed flow rates.

Main Results:

• The developed model accurately predicts SPTFF performance across a wide design space.
• Model demonstrates higher accuracy at increased feed flow rates.
• Identified limitations of the model at low flow rates (<25 L/m²/h) and high conversions (>0.9).

Conclusions:

• Mechanistic modeling, using the stagnant film model, can accelerate SPTFF process development.
• The model provides a valuable tool for designing continuous biomanufacturing processes.
• Further characterization is needed to address model inaccuracies in low flow rate, high conversion regimes relevant to continuous biomanufacturing.