Biotech Companies Gain Support for Vaccine, Countermeasure Production

To better tackle future biological threats and global pandemics, the Obama administration is proposing a $2 billion strategy to create a more "nimble and flexible" system able to respond quickly to new pathogens and to provide surge capacity for vaccine production. Officials at the Department of Health and Human Services (HHS), research scientists, and manufacturers have acknowledged the shortcomings of traditional flu vaccine production methods for years, and the problems were clearly evident in dealing with the H1N1 pandemic last year. Now, a new HHS report ("The Public Health Emergency Medical Countermeasures Enterprise Review," August 2010, available from www.hhs.gov/secretary) outlines initiatives for biopharmaceutical companies to work with federal agencies to produce vaccines and medical countermeasures (MCMs) that meet emergency health needs. The plan proposes to strengthen science at the US Food and Drug Administration, finance multi-use manufacturing operations, provide more assistance to innovative researchers, encourage investment in start-up biotech firms, and modernize influenza vaccine development and production.

SUPPORT FOR FDA SCIENCE

All these approaches aim to spur development of a broad array of medical countermeasures, including antivirals, antibiotics, diagnostics, and vaccines. The current MCM pipeline is full of "leaks, choke points, and dead ends," explained HHS Secretary Kathleen Sebelius at an August press briefing. Countermeasure development has been "slower and more costly than anticipated," under the HHS Project BioShield program, the report notes, and the new HHS plan urges greater investment in infrastructure that can rapidly produce effective MCMs when needed.

Jill Wechsler

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 the FDA $170 million to expand its scientific workforce and infrastructure and to develop additional tools for assessing vaccine and countermeasure safety, efficacy, and quality. The added resources will enable agency staffers to prepare more guidance describing MCM development pathways and to pre-qualify 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 rapidly evaluate high-priority MCM products and platforms. 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.

The FDA also will explore the use of "restricted" or "conditional" licenses for products that could be placed in the national stockpile for emergency use, but not made available on the general market until granted full FDA approval. The agency further hopes to clarify how it may collect clinical data on treatments used during emergencies to support future product approval, along with ways to make the animal efficacy rule more useful.

ADVANCING MANUFACTURING

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 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, jwechsler@advanstar.com