Development of efficient and flexible purification technologies for manufacturing and analyzing biopharmaceuticals

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Biopharmaceuticals such as monoclonal antibodies comprise the fastest growing segment in the pharmaceutical industry. With the emergence of generic biopharmaceuticals or “biosimilars”, this segment is expected to grow even more significantly. Biopharmaceuticals are now used for the treatment of serious viral infections, autoimmune disorders, neurodegenerative diseases and cancer. However, they are very expensive to both develop and to manufacture, and this seriously restricts accessibility, even in developed countries like Canada. The proposed research attempts to address this challenge through the development of efficient separation and purification technologies for manufacturing and analyzing biopharmaceuticals. This is critical for producing affordable, therapeutically active, regulatory-compliant, pure and stable products, which are free from harmful impurities. Resin-based column chromatography which is widely used for separation and purification of biological products requires very expensive capital equipment, suffers from poor-scalability, and gives low-productivity. In recent years, there has been a move away from large bio-manufacturing equipment and facilities towards smaller flexible production, employing single-use equipment. Membrane chromatography, a fast and scalable purification technique, which uses a stack of membranes as chromatographic media has been proposed as a flexible, single-use alternative to column chromatography for biopharmaceutical purification. However, currently available radial-flow membrane chromatography devices give poor resolution and this severely restricts it application. In my group we have designed novel laterally-fed membrane chromatography (LFMC) devices which combine high-resolution with high-speed and scalability, i.e. provides a win-win situation. Resolution obtained with LFMC devices is not only better than that with type of membrane chromatography devices, but also better than resolution obtained with common resin-based columns. Our preliminary studies have shown that bio-similar monoclonal antibodies can be very efficiently purified at a laboratory-scale using LFMC. The objective of the proposed research is to develop the LFMC technology further and take it to the next stage, i.e. demonstrate its effectiveness in larger-scale biopharmaceutical manufacturing. Several case studies involving bio-similar monoclonal antibodies will be undertaken. LFMC has also shown significant promise as an alternative to HPLC for rapid analysis of monoclonal antibodies. The proposed work will also involve understanding the working principles of LFMC based on computational fluid dynamic (CFD) analysis. Overall, the objective is to develop LFMC as an efficient and flexible purification technology for manufacturing biopharmaceuticals.