Sterile Filtration of Vaccines: The Effect of Formulations and Differences in Hydrophobicity

Open Access
- Author:
- Wee, Alex
- 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:
- Sterile Filtration
Membrane
Nanoparticle
Vaccine
Hydrophobicity - Abstract:
- The recent COVID-19 pandemic demonstrated the importance of vaccine development. Novel vaccine developments and strategies are becoming increasingly important in the pathogenic arms race as the world population continues to rise. One of the critical steps in the production of these vaccines is the final sterile filtration, which is needed to insure the sterility of the injectable product. Despite growing progress in the vaccine field, much of the mechanics and factors behind the sterile filtration process of vaccines are still poorly understood. Recent studies have demonstrated the importance of several factors in the vaccine filtration process, including the surfactant concentration and membrane pore size, both of which affect the filtration efficacy in terms of fouling and vaccine yield. The objectives of this thesis were to: (1) quantify the hydrophobicity for several common sterile filter membranes used in industry, (2) to determine whether relative hydrophobicity differences between surfactants and membranes affects the filtration efficacy of a vaccine products. Experiments investigated the behavior of several sterile filters, including the Sartobran P, Supor EKV, Sterilux, and Stylux, with the surfactants Tween 20, Poloxamer 188, and Cetyltrimethyl ammonium bromide (CTAB). Data were obtained with a nanoparticle suspensions that has previously been shown to have high similarities to the filtration behavior of a live-attenuated virus vaccine formulation. The experimental studies demonstrated that the presence of a surfactant is necessary to reduce membrane fouling and achieve adequate particle transmission. Poloxamer 188 caused higher rates of fouling than either Tween 20 or CTAB. of the best performance was obtained with the Sartobran P membrane using Tween 20, which showed a filter capacity of more than 450 L/m2 in throughput. Hydrophobicity differences between the membrane and surfactant showed minimal correlation with either the fouling rate or particle transmission. The Stylux membrane showed very high rates of particle transmission when used in the presence of Tween 20.. These results provide important insights into some of the factors controlling the sterile filtration of viral vaccine products.