Robustness chromatography purification

The development of a qualified down-scale model of a process module is integral to the approach of process validation using bench-scale experiments, as described earlier. We have developed down-scale models of process steps ranging from various types of process chromatography for protein purification to separation by precipitation and filtration. These down-scale models have been utilized to evaluate the effects of relevant process parameters on product-quality attributes. The normal logical sequence of process development, of course, is bench scale to pilot scale to full scale. However, for many plasma protein purification processes, a reverse order needs to be followed. As licensed full-scale processes already exist, the full-scale process steps need to be scaled down to construct small process models in order to evaluate the robustness of process parameters on the product without impacting full-scale production. These models can also be utilized to evaluate process changes, improvements, and optimizations easily and economically. 

Example 1 Robustness of an Affinity Chromatography Step for Purification of a Coagulation Factor... 

Affinity chromatography is based on selective non-covalent interaction between an analyte and specific molecules. It is very specific, but not very robust. It is often used in biochemistry in the purification of proteins bound to tags. These fusion proteins are labeled with compounds such as His-tags, biotin or antigens, which bind to the stationary phase specifically. After purification, some of these tags are usually removed and the pure protein is obtained. 

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