Seminar - Challenges to Centrifugal Separation, the key to Biopharmaceutical Drug Production from Living Organisms by Prof. Wallace Woon-Fong LEUNG
日期：2019 年 05 月 24 日 ( 星期五)
Time：11:00 am – 12:00 pm
A large percentage of therapeutic drugs that are offered to consumers today come from biosynthesis. Monoclonal Antibody, mAb, has been a popular antibody made in the laboratory used for cancer treatment where the antibody is designed to attach as a label to the protein (antigen) on a specific cancer cell so that immune cells can spot and attack the cancer cells, e.g. Leukemia. mAb can also attached to the antigen on breast cancer cells blocking the growth of breast cancer cells. These are two of the many functions of mAb in cancer treatment. Large production of mAb requires cell culture of mammalian cells in huge bioreactors up to 20,000L. At time of harvest, the mAb protein secreted extracellularly from the mammalian cells into the liquid phase is separated from the cells by high-speed centrifugation due to small density difference and micron-size cells which are difficult to be settled from the aqueous phase. Given the mammalian cells do not have cell walls they can be sheared in the centrifuge leaking out cell contents into the broth spoiling the entire batch. Various means of reducing shear during centrifugal separation will be discussed. Today, out of the 19 mAb approved by FDA, 12 are made through the biopharma process and this is growing rapidly over time.
E. coli bacteria is another vehicle that produces protein extracellularly, or intracellularly, in bioreactors and fermenters. Vaccines and enzymes are made from bacteria and virus culture. In one intracellular process, upon harvest the bacteria have to be lysed/homogenized to release the protein trapped in the inclusion bodies 0.2-1.3 micron with cell debris not far too smaller making fractionation mighty difficult. Repeated stages of centrifugation and washing are required resulting in low yield. A more novel way of approach will be presented and simulated to improve the entire process eliminating unnecessary costly downstream purification.
Yeast after fermentation can produces extracellular proteins for making insulin, human serum albumin, and hepatitis vaccines. Insulin is a projected USD 32 billion market in 2018. Clarification and recovery of the protein broth by centrifugation in large quantities is an interesting challenge. Commonly deployed centrifuges used in biopharmaceutical process are disk-stack, tubular and decanter centrifuges. In the past, these have been treated as black boxes. In this presentation, we will discuss the features of these centrifuges and some rather interesting fluid mechanics that also occur in these high-speed rotating machines. New models will also be presented to interpret test data, project performance, and provide machine scale-up.
Wallace Leung has worked on filtration and separation since 1977. Between 1986 and 2004, he was a director of R&D with a major centrifuge company developing various technologies on centrifugal separation. He has developed new technologies awarded by 36 US patents. In 2004-2005, he found his company Advantech Engineering, Sherborn, USA and worked on biotech separation specifically for producing bio-pharmaceutical drug substances made of protein. He has delivered training courses for biopharmaceutical companies, such as Nova Nordisk, Denmark, which is the largest manufacturer of insulin in the world and Amgen, which is a multi-billion biopharma company in California. He has authored an Elsevier book “Centrifugal Separation in Biotechnology” in 2007. Before the book was released in 2007, more than 600 copies have been pre-ordered. After 12 years, on popular demand he is preparing the 2nd edition to this book which quickly became a classic upon the first publication. Wallace Leung is the Chair for the International Delegation on Filtration 2016-2020, which has 13 members around the world. His mission is to promote filtration and separation around the world. He is also the Chair to the World Filtration Congress, April 20-24, 2020, San Diego, USA. Since 2005, he has been Chair Professor of Innovative Products and Technologies in Mechanical Engineering at PolyU. He is a fellow of both ASME (mechanical) and AICHE (chemical). He is also a fellow of the Hong Kong Academy of Engineering Sciences.