Few would deny that we are ill-prepared to face a major flu pandemic, in the U.S. or abroad. Its been hard enough to manufacture vaccines quickly and reliably, much less get them to the people who need them, when they need them. And thats been without a real pandemic to speak of.
Some of the leading minds in vaccine development and production, and representatives of the World Health Organization (WHO) and FDA, are meeting at Case Western Reserve in Cleveland this month (April 10-11) to brainstorm Potential Engineering Approaches to a Pandemic, an event sponsored by the National Academy of Engineering and the Institute of Medicine (www.vaccine2006.org). Such gatherings are giving pandemic preparedness a much-needed shot in the arm (pun intended).
But we are still vulnerable. The current system cannot respond to an emerging flu pandemic with large volumes of vaccine in a short amount of time, say University of Michigan professor Dr. Henry Wang and Lyle Lash III, a Ph.D student in Chemical Engineering. Wang, a professor of Chemical and Biomedical Engineering, counts among his research interests the intelligent design and operation of biomanufacturing facilities, as well as the next generation of automated pharmaceutical plants. Together with Lash, he has formulated an unorthodox yet pragmatic response to the current state of vaccine readiness, one that mixes elements of biochemistry, economics and supply chain logistics.
A typical vaccine production cycle is at least six months. Wang and Lash aim to cut this time in half. First, they would forsake antiquated egg-based technologies in favor of cell cultures. This wont reduce actual manufacturing time, they say, but would allow for a consistent available production capacity that can be rapidly scaled-up.
But isnt cell-culture-based manufacturing too expensive? Thats a myth, the researchers argue, and theyve done the economic studies to prove it. The cost lies in manufacturers having to switch from egg-culture to cell-culture manufacturing, an issue that the vaccine community must address, they say.
Use reverse genetics rather than conventional reassortment technology for strain development, Wang and Lash suggest. Experimental bird flu vaccines have been produced this way, and with some cooperation from MedImmune (Gaithersburg, Md.), which holds a key patent, so could vaccines for the common flu.
Another step: Develop non-strain-specific reagents for testing antigen content during development. The reagents could then be stockpiled and made readily available should a pandemic arise. Finally, manufacturers must adopt means of rapid sterility testing to accelerate final lot release, say Wang and Lash. Effective rapid microbiological methods (RMMs) exist (see "Rapid Microbiological Methods for a New Generation," Pharmaceutical Manufacturing, February 2006), but have been slow to take due to perceived regulatory risks.
Production is but half the battle. The other half is delivery. Surge capacity is critical, Wang and Lash believe. The two propose a distributed biomanufacturing network based upon existing cell-culture facilities. In the absence of a pandemic, biomanufacturers would conduct business as usual. Should a widespread virus appear, they would be called into action and shift into vaccine scale-up mode, thus enabling surge capacity. The network would be a sort of national guard for pandemic readiness.
Its a bold plan. Even Wang and Lash admit that it has some holes in it, and would require the cooperation of many parties with disparate interests. We have to start by getting people to support the idea, and to look in-depth at the issues involved in its implementation, they say. That wont be easy. But as the architect Daniel Burnham said, Make no small plans. Ambitious proposals are certainly better than none at all.