Model-based development and scale-up of chromatographic separation processes

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Biopharmaceutical products such as monoclonal antibodies, enzymes and interferons are increasingly being added to the repertoire of life saving drugs available to physicians for treating life-threatening ailments such as cancer, cardiac diseases and viral infections. As with other pharmaceutical products, these need to be available in highly pure form for their intended therapeutic applications. Biopharmaceuticals are very expensive due to a combination of factors such as high development and manufacturing cost, and relatively low shelf-life. For a typical product such as a monoclonal antibody, purification cost accounts for almost 60-80% of the total manufacturing cost. Most biopharmaceuticals are purified using column or membrane-based chromatography. While chromatography is widely used in the industry, it is quite difficult to scale-up. This is due to the fact that any chromatographic separation involves the complex interplay between adsorption (i.e. thermodynamics) and mass transport of material (i.e. kinetics). Improperly scaled-up processes can be extremely inefficient and this can have a detrimental effect on process economics. The objective of this project is to understand the thermodynamic and kinetic contributions in chromatographic purification of biopharmaceuticals such as monoclonal antibodies. Based on an understanding of these individual contributing factors, models for scale-up of chromatographic purification processes for these products will be developed. Such models will be useful in designing and developing cost-effective purification processes and thereby increase manufacturing efficiency in the biopharmaceutical industry.