pH Profiles in Continuous Countercurrent Hollow Fiber Dialysis
Open Access
- Author:
- Thoma, Bennett
- Area of Honors:
- Chemical Engineering
- Degree:
- Bachelor of Science
- Document Type:
- Thesis
- Thesis Supervisors:
- Andrew Zydney, Thesis Supervisor
Darrell Velegol, Thesis Honors Advisor - Keywords:
- Diafiltration
- Abstract:
- Pharmaceutical companies are very interested in transitioning their historically batch operations for the production of high-value biological products to continuous processes. Continuous processes can decrease production time, reduce facility sizes, and improve product quality. One critical step for successful continuous biomanufacturing is product formulation to place the product in the desired buffer for storage and delivery. Several recent studies have demonstrated that it can be difficult to control the final pH during batch diafiltration due to Donnan effects and the need to maintain electroneutrality with charged products. The objective of this thesis was to investigate the effectiveness of a continuous dialysis process, as an alternative to batch diafiltration, with a specific focus on evaluating the pH behavior as a function of operating conditions. Experiments were performed using a Polyflux® 17R countercurrent hollow fiber dialyzer, with serum IgG as a model product and histidine as the desired formulation buffer. The countercurrent dialysis was able to achieve high degrees of buffer exchange. The pH of the final product was a function of the dialysate flow rate, with the best performance obtained using a ratio of dialysate to feed flow rate of approximately 1:1. Under these conditions, very small changes in pH were seen over time, which is ideal for a continuous steady-state process. These results provide the first analysis of the pH shifts in countercurrent dialysis of antibody solutions and are the first step towards the development and application of continuous dialysis processes for antibody formulation.