Strategies for modernizing influenza-vaccine production fit the larger HHS initiative to spur development of a broad array
of MCMs, including antivirals, antibiotics, and diagnostics. The current MCM pipeline is full of "leaks, choke points and
dead ends," said Secretary Sebelius at the press briefing.
The department's plan for fixing these problems, prepared by HHS Assistant Secretary for Preparedness and Response Nicole
Lurie, reflects disappointment with HHS'S Project BioShield program. The US Congress authorized Project BioShield in 2004
to spur MCM development. The project has a $5.6 billion fund for use over 10 years to purchase new vaccines and drugs for
the national stockpile. The idea behind Project BioShield was that the "pull" of a guaranteed market would stimulate private-sector
investment in countermeasure research and development (R&D), but product development has been "slower and more costly than
anticipated," notes Lurie's report.
One solution was to establish the Biomedical Advanced Research and Development Authority (BARDA) within HHS in 2007 to oversee
BioShield activities. Congress transferred approximately $1 billion from the program last year to support pandemic-influenza
preparedness and countermeasure R&D and is looking to shift an additional $2 billion from the program to fund other administration
The new HHS plan continues to de-emphasize MCM procurement in favor of greater investment in infrastructure that can rapidly
produce effective MCMs when needed and to form partnerships with industry to manage product development from laboratory concept
to clinical use.
A key part of the plan is to streamline the regulatory framework for vaccine and MCM development and oversight by bolstering
regulatory science at FDA. HHS proposes to give FDA $170 million to expand its scientific workforce and infrastructure and
to develop additional tools for assessing vaccine and countermeasure safety, efficacy, and quality.
FDA's ability to help bring MCMs to market more quickly is "fundamental" to the success of this enterprise, commented FDA
Commissioner Margaret Hamburg at the HHS briefing. Key challenges for the agency, she noted, are enhancing its review of new
products, strengthening its scientific capacity to develop new standards and policies, and clarifying the legal framework
for MCM regulation. The added resources will enable agency staffers to prepare more industry guidance that describes MCM-development
pathways and to prequalify mobile or convertible manufacturing facilities. Cross-FDA Action Teams will work with sponsors
to identify and resolve scientific issues as early as possible and to evaluate high-priority MCM products and platforms rapidly.
A larger research budget will fund studies to identify and qualify animal models and surrogate measures of product efficacy,
and to improve potency, safety, and stability assays.
In the policy area, FDA will explore the use of "restricted" or "conditional" licenses for products that could be placed in
the national stockpile for emergency use, but that are not available in the general market until granted full FDA approval.
The agency also hopes to clarify how it may collect clinical data on treatments used during emergencies to support future
Effective FDA regulation would support HHS initiatives regarding MCM production methods. Secretary Sebelius proposes a $678-million
program to expand MCM manufacturing capacity, support development of new production technology, and provide manufacturing
services and support to research organizations and small companies. Lurie of HHS plans to contract with pharmaceutical companies
under a competitive bidding process to establish Centers for Innovation in Advanced Development and Manufacturing across the
country. One program goal is to provide a framework for experienced manufacturers to share production expertise with small
biotechnology companies that lack experience and scale-up capacity.
If the program goes forward, the Centers for Innovation in Advanced Development would develop state-of-the-art, modular manufacturing
technologies that could produce multiple vaccines and countermeasures. These facilities would be able to manufacture clinical
investigational lots of candidate vaccines as well as small-market vaccines and small quantities of select treatments against
chemical, biological, radiological, and nuclear agents. In public-health emergencies, the Centers would provide surge-vaccine
and drug-production capacity to augment existing manufacturing infrastructure.
PCAST offered a related strategy for accelerating large-volume vaccine production, which is to develop a network of qualified
fill–finish facilities to package bulk vaccine for distribution to patients. The aim is to overcome a serious bottleneck in
the current influenza-vaccine production process and to provide additional packaging capacity for other MCM products.
The PCAST advisors propose that HHS assess industry's current fill-finish capacity quickly and develop a plan to ensure that
sufficient quantities of prefilled syringes, vials, and nasal sprayers are available to meet the nation's needs. The government
could provide funding for manufacturers to modify existing facilities or to construct new ones to carry out this plan, while
also exploring alternative strategies such as using more multidose vials and stockpiling vaccine containers and delivery devices.
Establishing fill–finish facilities that can process different vaccines at different times would make the project more economical
but also would require further FDA guidance to ensure the safety and quality of drugs produced at multiproduct facilities.