Matthew S. Croughan, PhDIndustry Professor; Founding Professor, Bioprocessing Program
Bioprocessing, Biopharmaceutical Development and Manufacturing
Dr. Croughan earned a B.S. degree from University of California, Berkeley in chemical engineering with High Honors in 1983. He completed his Ph.D. in chemical engineering at the Massachusetts Institute of Technology in 1988. He was subsequently hired by Genentech in South San Francisco as their expert in bioreactor design and scale up. At Genentech, he developed the first licensed, high-density, fed-batch cell culture process. This breakthrough platform technology was first used for Pulmozyme and is now used throughout the biopharmaceutical industry for nearly all antibody products. Dr. Croughan also led the development of a new licensed process for Activase, eliminating all animal-derived raw materials and tripling productivity. Lastly, he served on the design team for Genentech's Vacaville manufacturing facility. In 1993, Dr. Croughan served as the founding Director of Cell Processing and Expansion at Dendreon (formerly Activated Cell Therapy). From 1998 to 2006, Dr. Croughan worked as an independent consultant providing expert guidance on biopharmaceutical process development and manufacturing to more than 50 firms. He also served part-time as the Industrial Liaison Officer for the Biotechnology Process Engineering Center at MIT.
In 2006, Dr. Croughan joined KGI to found and build the Bioprocessing program. From 2006 to 2013, he was the George B. and Joy Rathmann Professor and Director of the Amgen Bioprocessing Center. While at KGI, he still consulted one day per week and maintained very strong connections in industry.
In August 2013, Dr. Croughan joined Sapphire Energy, Inc. as their Chief Technology Officer. He leads the R & D effort, with a staff of ~90 scientist and engineers, to invent, develop, and commercialize methods to economically produce renewable crude oil and animal feed from algae. He maintains a part time role at KGI as Industry Professor. He is a Fellow of the American Institute of Medical and Biological Engineers (top 2% of field).
Croughan MS, Hamel JF, Wang DIC. "Hydrodynamic Effects on Animal-Cells Grown in Microcarrier Cultures". Biotechnology and Bioengineering 1987;29(1):130-141
Croughan MS, Hamel JFP, Wang DIC. "Effects of Microcarrier Concentration in Animal-Cell Culture". Biotechnology and Bioengineering 1988;32(8):975-982
Croughan MS, Wang DIC. "Growth and Death in Overagitated Microcarrier Cell-Cultures". Biotechnology and Bioengineering 1989;33(6):731-744
Croughan MS, Sayre ES, Wang DIC. "Viscous Reduction of Turbulent Damage in Animal-Cell Culture". Biotechnology and Bioengineering 1989;33(7):862-872
Croughan MS, Wang DIC. "Reversible Removal and Hydrodynamic Phenomena in Cho Microcarrier Cultures". Biotechnology and Bioengineering 1990;36(3):316-319
Croughan MS, Chiou T, Wang DIC. "Immobilized Animal Cell Bioreactors". In: Asenjo JA, Merchuk JC, editors. Bioreactor System Design. 1 ed. New York: Marcel Dekker; 1995. p. 377-412
Croughan MS, Hu WS. "From microcarriers to hydrodynamics: Introducing engineering science into animal cell culture". Biotechnology and Bioengineering 2006;95(2):220-5
Warner CM and Croughan MS, Accelerated Manufacturing of Large-Scale, Full-length, Human-like Glycosylated Antibodies for Biodefense, J. Bioterr. Biodef., 2012, 3:3, 1-7
Delfosse S, Sathavipat M, Hsu N, Croughan MS, and LaFond, M, Trends Regarding Viral Barrier Implementation in Animal Cell Culture Processes,, Pharm. Bioprocess., 2013, 1(4), 351-360
Croughan MS, Delfosse S, Svay, K, Microbial Contamination in Industrial Cell Culture Operations, Pharm Bioprocess., 2014, 2(1), 23-25
While a graduate student at MIT studying under Institute Professor Daniel I.C. Wang, Dr. Croughan conducted research on hydrodynamic effects on animal cells in microcarrier bioreactors. His work resulted in a series of nine publications, one of which (#1 below) has been ranked one of the top 20 ever in the field and has been republished twice. At Genentech, his research concentrated for many years on animal cell bioreactor design and scale up. At KGI, Dr. Croughan continues to conduct research in this field and has expanded the scope of his work to include stem cells and algae.
Dr. Croughan also conducts research on biopharmaceutical development, including technology management and strategy. His benchmarking work on 25 years of progress in CHO cell processes has shown that productivity has steadily doubled every 3.4 years; this trend is often referred to as "Croughan's Law." Dr. Croughan continues to consult and conduct research on fed-batch cell culture. His group has invented a novel method to eliminate lactic acid production in fed-batch cell culture.
Current Research Projects
A Novel Method to Control Lactic Acid Production and pH in Animal Cell Culture: The Center has developed a novel method to completely eliminate lactic acid production in animal cell culture, one of the ongoing challenges in industrial animal cell culture. It involves culturing cells at very high (40 mM) lactate levels, which completely inhibits further lactic acid production, and adapting the cells to this otherwise toxic level of lactate. A patent on the technology has been filed.
Scale-Up of Transient Cell Culture for Rapid Production of Antibodies in a Biodefense Emergency: The Amgen Bioprocessing Center aims to produce 3 million doses of protective antibody in less than three months through transient cell culture at the 10,000 to 25,000-liter scale.
Bioprocessing Education: Biofuels, global warming, health care, and bioterrorism are some of the greatest challenges facing mankind. These can be successfully addressed only if a sufficient number of people are skilled in the area of bioprocessing. Successful culturing of living cells to manufacture products (bio-processing) will play an increasingly important role in our future. Even though there is an increasing demand for skilled bioprocessing professionals, there has been limited expansion in educational programs. Many of the current programs have laboratories that are decades behind leading industrial firms in their equipment and development and fail to attract large numbers of students into the field. KGI has developed an innovative bioprocessing curriculum, including many lab courses, and have grown the Bioprocessing focus track up to ~20+ graduates per year, one of the largest Master level bioprocessing programs. As part of this, The Amgen Bioprocessing Center has developed cell lines, medium, and bioreactor protocols that reflect current industry approaches but are not proprietary and can be used in an academic setting.
Future Research Interests
Creation of New Curricular Materials and Textbooks for Bioprocessing Education: KGI hopes to expand the reach of our successful bioprocessing curriculum.
Industrial Cell Culture: Extension of Dr. Croughan's current research on biopharmaceutical process development and manufacturing, including the manufacture of novel biopharmaceuticals.
|Matthew S. Croughan, PhD|