Effects of Solution Ionic Strength and Prefilter Characteristics on the Sterile Filtration of Glycoconjugate Vaccines
Open Access
- Author:
- Dinse, Erica Joy
- Area of Honors:
- Chemical Engineering
- Degree:
- Bachelor of Science
- Document Type:
- Thesis
- Thesis Supervisors:
- Andrew Zydney, Thesis Supervisor
Scott Thomas Milner, Thesis Honors Advisor - Keywords:
- sterile filtration
prefiltration
glycoconjugates
vaccines
membrane fouling - Abstract:
- Sterile filtration is an important step in the production of nearly all biopharmaceuticals, ensuring that the final drug product is completely free of any bacteria. However, membrane fouling can limit the lifetime and effectiveness of the sterile filters, particularly during the filtration of large biotherapeutics like many vaccine products. The aim of this study was to evaluate the effects of ionic strength and prefiltration on the sterile filtration fouling behavior of glycoconjugate vaccines produced by coupling the outer capsular polysaccharide from a bacterium to an immunogenic protein. Two glycoconjugate serotypes were filtered through 0.22 μm pore size sterilizing grade membranes. Constant pressure filtration was carried out at varying buffer solution ionic strength, and the effectiveness of different prefilter characteristics was examined. It was found that Serotype 2 fouled more quickly than Serotype 4, potentially due to greater numbers of large particles in the glycoconjugate generated from Serotype 2. The solution ionic strength had no apparent influence on the fouling behavior. Prefiltration was equally effective at reducing sterile filter fouling when using integral, batch, or inline prefilter configurations. The filter capacities after prefiltration were increased by more than 60%, and in some cases the presence of the prefilter completely eliminated fouling of the sterile filter. For Serotype 2, a prefilter with a 5 μm pore size provided the greatest increase in filter capacity. These results provide important insights into the fouling behavior during sterile filtration of glycoconjugate vaccines and suggest potential strategies to extend the lifetime and improve the performance of sterile filter membranes.