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When developing a manufacturing process for vaccine commercialization, it is prudent to identify a second source vendor for raw materials and supplies used in the process, and to qualify them for inclusion into the regulatory filing. This work describes a quantitative approach to evaluate and compare the performance of several membranes used for the purification of a protein–polysaccharide conjugate vaccine from its unconjugated polysaccharide. To minimize gel layer formation and thereby increasing the efficiency of the membrane operation through reduced fouling, backpulsing was employed in these operations. In order to have a predictive tool for the performance over a broader operating range including different membranes and process conditions, mathematical models of the separation were applied. Backpulsing was found to clear most of the gel layer formed by the conjugate solution and to restore the performance of the fouled membranes. The cleaning efficiency, β , which is defined as the fraction of the membrane surface cleaned by backpulsing, with 1 being maximal was measured to be between 0.2 and 0.4. By evaluating the time constant for cake growth for various purifications, it was determined that polysulfone membranes fouled to a lesser extent than polyethersulfone membrane. Low transmembrane pressure was preferred in the removal of unconjugated polysaccharide while maintaining optimal permeate flux. Through the use of mathematical models to evaluate different membrane performances, a second source vendor was successfully identified to provide an alternate membrane for the proposed manufacturing process. |
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