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President Obama and HHS eye innovation and countermeasures to protect public health.
To better tackle future biological threats and global pandemics, public-health experts are urging a more efficient approach to producing vaccines and medical treatments. Officials at the US Department of Health and Human Services (HHS), along with research scientists and drug manufacturers, have acknowledged the shortcomings of traditional influenza-vaccine production methods for years, as demonstrated last year during the H1N1 influenza pandemic. The Obama administration is proposing a $2-billion strategy to create a more "nimble and flexible" system that can respond quickly to new pathogens and provide surge capacity for influenza-vaccine production, explained HHS Secretary Kathleen Sebelius at an August press briefing in Washington, DC.
A new HHS report, The Public Health Emergency Medical Countermeasures Enterprise Review, outlines how researchers and biopharmaceutical companies can work with government agencies to produce vaccines and medical countermeasures (MCMs) to meet emergency public-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 biotechnology firms, and modernize influenza-vaccine development and production.
The plan appears to be part of continued efforts to apply lessons learned during the 2009 H1N1 influenza pandemic response to expand the nation's arsenal against bioterrorism and infectious disease. There have been multiple conferences and presentations on what worked, and what went wrong, in the race to produce sufficient quantities of vaccine to combat last year's influenza strain (see the February 2010 Washington Report, "Manufacturers Look to Vaccines for Growth and Innovation").
In Washington this month
Dealing with a global health emergency requires a broad spectrum of activities, from early detection of an outbreak to building a health infrastructure able to provide care. Creating a "21st century countermeasures enterprise," as Secretary Sebelius called the new HHS project, will require even more work.
Faster influenza-vaccine production
The HHS proposals for improving influenza-vaccine production parallel a more detailed plan prepared by the President's Council of Advisors on Science and Technology (PCAST) called "Reengineering the Influenza Vaccine Production Enterprise." This advisory body to the White House Office on Science and Technology Policy assessed the nation's preparedness for the looming H1N1 influenza pandemic in August 2009 and offered recommendations for improvement in May 2010. The final report reiterates the group's proposals for bolstering influenza-vaccine development and production and emphasizes how the proposed changes could serve as a "relevant pathfinder" for modernizing countermeasure production more broadly.
The PCAST review notes that it took 26 weeks to produce pandemic-influenza vaccine after government agencies officially requested it last year, and that most of the US population did not have access to the vaccine for 38 weeks. The pandemic 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, and vaccine manufacturers ended up with unsold product and cancelled government orders that diminished profits. Even so, some entities charged that the pharmaceutical industry hyped the pandemic to sell more vaccines and drugs at high prices. US and international public health officials rejected those accusations, and HHS hopes that improved forecasting and more efficient vaccine production will avoid delays and waste and improve treatment in the future.
Such gains require major improvements in influenza-vaccine production methods, says PCAST. It proposes spending $1 billion a year for three years to shift from egg-based to more modern vaccine-manufacturing methods that use cell-culture and recombinant DNA processes. PCAST also outlines specific strategies that can cut vaccine production by several weeks and can be implemented quickly (see sidebar, "Presidential council aims to streamline influenza-vaccine production").
Presidential council aims to streamline influenza-vaccine production
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 initiatives.
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.
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.
HHS also proposes establishing "Sherpa" teams of government, academic, and industry experts to guide discoverers of promising MCM candidates through the R&D and regulatory processes. National Institutes of Health (NIH) experts provide less experienced researchers with information on preclinical services and clinical-trial support, but the Sherpa teams would offer a more formal effort, explained Anthony Fauci, director of the National Institute of Allergy and Infectious Diseases, at the press briefing.
Probably the most problematic HHS proposal is the provision of $200 million to establish an independent, nonprofit investment entity to fund small innovative firms that are developing novel biodefense technologies. Instead of funding research on specific products, the MCM Strategic Investor would invest in companies, provided Congress authorizes such a plan, which would give money to industry. A priority is to support firms developing new antimicrobials to combat multidrug-resistant organisms, which are spreading globally. The initiative also would fund research on host pathways used by multiple agents of disease, and develop flexible platform technologies for diagnostics, vaccines, and therapeutics.
HHS hopes to support MCM development by better coordinating and integrating its R&D programs internally and with other federal agencies. An efficient and flexible contracting process would encourage private-sector investment, as would a five-year budget and planning process. In addition, Sebelius plans to review current liability protections for private-sector MCM developers to determine whether stronger safeguards are needed to spur product development and manufacture. Lurie emphasizes that the $2-billion program is not "simply a cash infusion to industry." Rather, by eliminating technical and regulatory barriers, the project will reduce the risk for companies that invest their own resources in vaccines and MCMs.
For the upcoming influenza season, the Centers for Disease Control and Prevention hope to vaccinate 160 million Americans with a three-strain influenza vaccine in expectation that H1N1 will return, along with seasonal influenza. The need to produce only one influenza vaccine should avoid many of the problems that occurred in 2009. Yet, a quiet influenza season also could diminish interest on Capitol Hill in increasing spending on countermeasure research and vaccine development and in finding better ways to protect against biological threats.
Jill Wechsler is Pharmaceutical Technology's Washington editor, 7715 Rocton Ave., Chevy Chase, MD 20815, tel. 301.656.4634, firstname.lastname@example.org.