(549a) Evaluating Depth Filtration for Enzyme Removal in Small Molecule Drug Substance Manufacturing

Enzyme mediated reactions are transforming the way pharmaceutical small molecules are synthesized. While enzymes have resulted in greener processes and fewer synthetic steps to make an intermediate or API, removing them from a process can be difficult. In this talk we discuss the evaluation of depth filtration as the enzyme removal unit operation for a complex, multiphase small molecule reaction system composed of immiscible organic and aqueous phases along with precipitated enzymes. Lab scale experiments were performed in a constant-flow mode to evaluate the loading capacity of different depth filter media types: positively charged cellulose fiber with diatomaceous earth (DE), positively charged polyacrylic fiber with silica, and polypropylene+cellulose+DE (Millistak+® and Clarisolve® filters). The loading capacity of filters with the same filter media but different nominal pore size ratings were also studied. Modeling was performed to determine the primary mechanism for filter fouling for all filter types. In this talk we will show that the nominal pore size of the filters had the greatest impact on loading capacity versus the type of filter media. As the nominal pore size increased, the loading capacity increased without any breakthrough. The filter fouling modeling showed that as the nominal pore size increased, the mechanism of fouling transitioned from cake formation to the standard model.