A more effective FDA can support HHS efforts to establish flexible and efficient MCM production methods. Secretary Sebelius
proposes a $678 million program to expand MCM manufacturing capacity, encourage development of new production technology,
and provide manufacturing services and funding to independent researchers and small companies. HHS plans to contract with
large manufacturers to establish Centers for Innovation in Advanced Development and Manufacturing across the country. These
will develop state-of-the-art, modular manufacturing technologies able to produce multiple vaccines and countermeasures, while
also providing production expertise for small biotech companies that lack experience and scale-up capacity. These facilities
will be able to produce clinical investigational lots of candidate vaccines, as well as small-market vaccines and small quantities
of select treatments against chemical, biological, and nuclear agents. In public health emergencies, the Centers also would
provide surge vaccine and drug production capacity to augment existing manufacturing infrastructure.
Another strategy for accelerating large-volume vaccine production is to develop a network of qualified fill-and-finish facilities
to package bulk vaccine for distribution to patients. The aim is to overcome a serious bottleneck in the current flu vaccine
production process and to provide additional packaging capacity for other MCM products.
This proposal is spelled out more completely in a report from the President's Council of Advisors on Science and Technology
(PCAST) on "Reengineering the Influenza Vaccine Production Enterprise" (available at
http://www.ostp.gov). This advisory body to the White House Office on Science and Technology Policy proposes that HHS quickly assess industry's
current fill–finish capacity and develop a plan to ensure sufficient quantities of pre-filled syringes, vials, and nasal sprayers
to meet the nation's needs. The plan could include funding for manufacturers to modify existing facilities or to construct
new ones to meet this need, while also exploring alternative strategies, such as using more multi-dose vials and stockpiling
vaccine containers and delivery devices.
The PCAST report is part of continued efforts to parlay the "lessons learned" from the 2009 H1N1 pandemic to expand the nation's
arsenal against bioterrorism and infectious disease. The advisory panel notes that it took 26 weeks to produce pandemic flu
vaccine, and that the disease claimed 13,000 American lives and sickened more than 60 million people, including a disproportionate
number of children and young adults. Fortunately, the H1N1 virus proved to be less lethal than anticipated, but vaccine makers
ended up with unsold product and cancelled orders that diminished profits.
To avoid such problems in the future, PCAST proposes spending $1 billion a year for three years to shift from egg-based to
more modern vaccine manufacturing methods based on cell culture and recombinant DNA processes. HHS should start by assessing
available infrastructure for cell culture flu vaccine production and options and incentives for improving existing facilities
or constructing new ones, including rapid depreciation of plant construction costs, guaranteed purchases, support for idle
plant time, and construction subsidies. Flu vaccine production also could be streamlined through recombinant DNA technology,
which is used now to make vaccines against hepatitis B and human papilloma viruses. The panel recommends an aggressive program
to test and approve at least three recombinant flu vaccines within three years.
Short-term strategies for accelerating flu vaccine production include developing a panel of influenza viral "backbones" that
could generate fast-growth seed viruses, and more efficient potency testing, possibly using mass spectroscopy and molecular
biological techniques; this could replace the two-to-three month process now used to obtain antibodies from sheep for reagents.
And sterility testing, which now takes about two weeks per batch, could become more sensitive and rapid by adapting molecular
biological techniques such as DNA sequencing.
Another approach is to support greater use of live attenuated flu vaccines, which are easier and faster to produce, but require
clinical trials to ensure immunological response. Also, greater use of adjuvants could stretch a limited vaccine supply or
heighten immune response, but requires added investment in adjuvant manufacturing.
ENCOURAGING NEW DISCOVERIES
Innovative manufacturing and testing methods would contribute to efforts to provide assistance and resources for innovative
researchers. HHS plans to establish "Sherpa" teams of government, academic and industry experts to guide discoverers of promising
MCM candidates through the R&D and regulatory processes. HHS also may review current liability protections for private-sector
MCM developers to see if stronger safeguards are needed.
Probably the most controversial proposal is for the government to contribute $200 million to establish an independent, non-profit
investment entity to fund small innovative firms developing novel biodefense technologies. Instead of funding research on
specific products, the MCM strategic investor would invest in companies, provided Congress authorizes the plan. Such investments
would support firms developing new antimicrobials to combat multidrug-resistant organisms and flexible platform technologies.
For this coming flu season, the Centers for Disease Control and Prevention hopes to vaccinate 160 million Americans with a
three-strain influenza vaccine, a one-vaccine campaign that should avoid the problems of 2009. Yet, a quiet flu season could
diminish interest on Capitol Hill in more spending on CMC research and vaccine development or in making major changes in strategies
for protecting against biological threats.
Jill Wechsler is BioPharm International's Washington editor, Chevy Chase, MD, 301.656.4634, firstname.lastname@example.org