Instead of investing in new facilities, the industry should focus on improving manufacturing technology to increase yields,
says Timothy Charlebois, PhD, director of cell and molecular sciences for Wyeth (Madison, NJ,
http://www.wyeth.com/). Charlebois made these remarks in his introduction to the session, "Frontiers and Economics of Mammalian Cell Expression,"
at the BIO 2006 convention."I've seen examples where we took a process that produced 3 grams of protein per liter, and were
able to optimize it so that it produced 9.6 g/L," he said, adding that future yields are likely to be above 10 g/L.
Dana Anderson, PhD, director of late-stage cell culture at Genentech (South San Francisco, CA,
http://www.gene.com/), agreed with Charlebois. Recent increases in cell-culture titers have lowered the motivation to explore alternatives such
as microbial and yeast systems, he said. "Mammalian cell culture is a proven technology; there's a low desire to switch."
Though challenges remain, he said, new tools and technologies will allow the industry to continue to increase yields and efficiencies.
Another approach to improving efficiencies is to establish a company-wide technology platform, like the one that Amgen (Thousand
Oaks, CA,
http://www.amgen.com/) implemented for its monoclonal antibody production. "A main driver of the initiative was to get products into the clinic
faster," said Victor Fung, director of process development at Amgen. After asking each functional group which aspects of their
monoclonal antibody processes could be left untouched, the project team established a platform of standardized elements such
as materials, methods, and process and method architecture. As a result of the initiative, the total number of non-conformances
and planned deviations decreased by 34.5%; staffing needs went down 19%; and cycle times improved by 25%. "I believe single-cycle
development is in reach," Fung concluded.
Wei-Shou Hu, PhD, a professor at the University of Minnesota (Twin Cities, MN,
http://www.umn.edu/), challenged the audience to look far beyond current limitations. Hu charted the evolution of Alexander Fleming's original
penicillin culture into today's highly optimized, low-budget operation that is now carried out only overseas. "We engineered
ourselves out of a job," he quipped. Hu then overlaid the chart with a new graph, suggesting the same could happen with mammalian
cell culture. He envisioned a "dream" cell-culture process with yields and efficiencies many times greater than what we see
today.
Achieving such goals, Hu said, will require many approaches. He compared bioreactors to human systems, noting the major difference
is that a reactor is in a steady state, whereas the human body is not. Exploring such comparisons may be helpful, he said,
to find innovative ways to improve cell and process engineering.
"We don't need hype," Hu concluded. "We must be steadfast and resourceful."
