Spurring countermeasures

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.

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 product approval.

Advancing manufacturing

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.