Monoclonal antibody (mAb) therapeutics have become the majority of drugs being developed by the pharmaceutical industry, due to their ability to target and treat specific diseased cells. In recent years, improvements in bioreactor design and host cell engineering have resulted in much higher titer counts, largely keeping up with the demand for large scale production. Unfortunately, downstream processing, is a large bottleneck in mAb production, and currently accounts for more than 80% of mAb production cost. In addition, high titers can lead to the formation of antibody aggregates, which are known to exhibit antigenic activity and can lead to undesirable immune responses in patients. As such, scalable methods that efficiently improve the purification of mAbs, especially from multimeric aggregates, are highly desired. We propose to demonstrate the purification of mAbs using a high-efficiency nanoporous composite membrane and to demonstrate their superiority to current membranes. These nanoporous composite membranes will offer rapid processing and high purity relative to current membrane processes, thereby dramatically improving purity and reducing the amount of additional time, labor and cost intensive purification needed to achieve purification of mAbs from multimeric aggregates. In Phase I, we will purify a model mAb from multimeric mAb aggregates using a nanoporous composite membrane, which will have a high pore density and a narrow pore size distribution. We will compare the efficacy of this purification, in terms of aggregate removal and recovery of monomeric mAb, to that of selected commercial membranes with similar nominal pore sizes. In Phase II, we will extend this demonstration to a prototype manufacturing process and investigate the effects of filtration conditions and fouling on the purification. We will also work with a commercial partner to integrate our membrane into a complete purification process.
In the last twenty years, improved manufacturing methods have led to a marked improvement in the production of biopharmaceuticals such as monoclonal antibodies (mAbs);however, the resulting high titer streams have greater amounts of impurities which current downstream processing techniques struggle to handle. Consequently, downstream processing has become a huge percentage of mAb production costs, and improvements that reduce these costs and increase efficiency will be able to dramatically improve mAb production, thereby speeding progress through trials and ultimately improving patient health. Membrane separations are one of the least expensive and most efficient purification processes, and improving their purification ability reduces or eliminates the need for other more costly and time consuming processes.
