Analysis of Flux and Pressure Behavior during Single Pass Tangential Flow Filtration of Monoclonal Antibody Solutions
Open Access
- Author:
- Lipinski, Ann Marie
- Area of Honors:
- Chemical Engineering
- Degree:
- Bachelor of Science
- Document Type:
- Thesis
- Thesis Supervisors:
- Andrew Zydney, Thesis Supervisor
Michael John Janik, Thesis Honors Advisor - Keywords:
- single pass tangential flow filtration
continuous processing
monoclonal antibodies
ultrafiltration - Abstract:
- Antibody treatments can be provided to patients to aid in recovery from diseases such as cancer, psoriatic arthritis, and rheumatoid arthritis, as well as infections such as COVID-19. Current estimates are that antibody-based treatments will result in 172.8 billion dollars of sales in 2022, requiring new innovations in systems to manufacture and purify antibodies efficiently and safely. This has created significant interest in the development of continuous antibody production processes as an alternative to traditional batch processing. For example, the batch ultrafiltration step for antibody concentration can now be achieved in a continuous fashion by using single pass tangential flow filtration (SPTFF). SPTFF modules are comprised of a series of membranes which provide a long path-length channel that can achieve significant concentration of the antibody product in a single pass of the solution through the module. The objective of this thesis was to extend a recently developed theoretical model for the filtrate flux and pressure profiles in traditional ultrafiltration modules to the analysis of SPTFF and to then use this model to understand and predict SPTFF performance. The model accounts for the effects of intermolecular interactions at high protein concentrations on both the osmotic pressure and viscosity of the antibody solution and in turn the pressure profile and filtrate flux through the SPTFF module. The model predictions for the concentration factor as a function of device operating conditions were validated using experimental data obtained with a monoclonal antibody product, with very good agreement obtained over a range of flow rates and protein concentrations for two different SPTFF modules. Future studies will focus on the use of this SPTFF model to evaluate the optimal membrane module design for specific design criteria, including different approaches to minimize the total membrane area required for concentration of an antibody solution to a target level. These results should decrease the cost of antibody production and increase the availability of antibody-based products for treating a wide range of diseases.