The Effects of a Prefilter on the Sterile Filtration of Glycoconjugate Vaccines
Open Access
- Author:
- Hillsley, Jordan
- Area of Honors:
- Chemical Engineering
- Degree:
- Bachelor of Science
- Document Type:
- Thesis
- Thesis Supervisors:
- Andrew Zydney, Thesis Supervisor
Ali Borhan, Thesis Honors Advisor - Keywords:
- Sterile Filtration
Glycoconjugate Vaccines
Prefilter
Membrane Fouling - Abstract:
- Glycoconjugate vaccines that are produced from the capsular polysaccharides of pathogenic bacteria can provide strong immune protection against a wide range of bacterial diseases. One of the critical steps in the production of these vaccines is the use of sterile filtration to ensure sterility of the final vaccine product. The objective of this research was to determine how the introduction of a prefilter in the sterile filtration process will affect the capacity of the sterile filter used to process these glycoconjugate vaccines. It is hypothesized that the addition of the prefilter will reduce the fouling of the sterile filter and therefore increase the membrane capacity by removing trace quantities of large species present in the feed. To test this hypothesis, a series of sterile filtration experiments were performed using 0.22 µm Durapore sterilizing grade filters both with and without different prefilters. Data were obtained using two different glycoconjugate serotypes (containing capsular polysaccharides from different bacterial strains) provided by Pfizer. It was found that when the Serotype 3 was processed through a 0.45 µm prefilter prior to the sterile filter, the sterile filter capacity increased from 28 to 80 L/m2 representing nearly a 200% increase in capacity. Corresponding results for Serotype 2 showed an even greater effect, with almost no increase in pressure seen for the sterile filter after prefiltration through the 0.45, 0.65, and 5 µm pore size prefilters. Dynamic light scattering data clearly demonstrated that the prefilters removed a large component present in the glycoconjugate feed that was approximately 5 µm in effective size. These results provide important insights into the potential for improving the performance of the sterile filtration process by employing an appropriate prefilter, although additional studies will be required to optimize the combined prefiltration / sterile filtration process.