Process Costs and Product Quality
The use of an optimized TFF as a single clarification and partial purification step provides clear advantages over multistage operations for primary recovery. First, reducing the number of process steps lessens product losses that are unavoidable in multiple filtrations, thus increasing overall process efficiency while cutting operational costs. Second, the early depletion of impurities attained by TFF positively impacts the subsequent chromatography sequence in terms of performance and number of chromatography columns.
The use of fewer columns ought to significantly reduce costs; it is well known that the cost of goods for industrial bioprocesses is mainly driven by the number of chromatographic steps. Last, thorough depletion of impurities makes for higher purity of the final product, a key parameter that critically affects product safety.
For instance, the amount of endotoxins that E. coli brings into biopharmaceutical processes is considered the biggest drawback compared to non-E. coli expression technologies. Nearly all API specifications point to residual endotoxin concentration in the product as one key criterion when choosing the administration route.
Endotoxin specifications of Esetec-derived products are often below the LAL-test limit of detection (<0.5 EU/mg) and hence two to three times lower than classical specification set-points from conventional E. coli strains. Therefore, the combination of secretory E. coli expression and simple and efficient primary recovery might be a cost-attractive alternative for producing products otherwise produced in endotoxin-free systems.