08/22/2012 - 15:11

The new biological countermeasures program: Will it work?

Leonard A. Cole

Leonard A. Cole

Cole is an expert on bioterrorism and on terror medicine. He is an adjunct professor at the University of Medicine and Dentistry of...

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On June 18, the US Department of Health and Human Services (HHS) announced a new program to protect the population against health threats. Primed by worries about bioterrorism and pandemic flu and other possible epidemics, the department established three centers to more quickly develop and manufacture medical countermeasures. The initial cost of the program is $400 million, with an eventual government outlay projected as high as $2 billion. Described as a "dramatic step forward" by HHS Secretary Kathleen Sebelius, the centers should "help fill gaps in preparedness so that our nation can respond to known or unknown threats."

The three Centers for Innovation in Advanced Development and Manufacturing, as they are called, are to produce vaccines, anti-virals and other medicines, hasten their market availability, and enhance training of the biopharmaceutical workforce. Novel in structure, the centers are public-private consortiums of large pharmaceutical companies, innovative biotech firms, and academic institutions under the oversight of HHS's Biomedical Advanced Research and Development Authority.

While the HHS goals are laudable, whether they are likely to be achieved remains unclear. The development of these centers went widely unnoticed not only by the mainstream press, but also by American bioterrorism experts; thus, much remains unchallenged. And questions about this initiative -- including how the various partners will interact with one another -- are especially poignant in view of the sizeable commitment of government dollars to the program.

Official enthusiasm. The initiative is an outgrowth of HHS's 2009 National Health Security Strategy and two subsequent reviews, one on pandemic flu and the other on emergency medical countermeasures.

When the countermeasures review was released in August 2010, Sebelius publicly identified several deficiencies in US preparedness for health emergencies. She noted, for example, the sluggish pace of vaccine production during the 2009 H1N1 influenza outbreak and the lack of incentive for companies to develop countermeasures for biological or radiation threats. Remediation, she said, should include a "nimble, flexible capacity to produce medical countermeasures rapidly in the face of any attack or threat, known or unknown, including a novel, previously unrecognized, naturally occurring emerging infectious disease."

If exuberance alone were an indicator, the new program seemed assured of success. Nicole Lurie, the HHS assistant secretary for preparedness and response, Thomas Frieden, director of the Centers for Disease Control and Prevention, Margaret Hamburg, commissioner of the Food and Drug Administration, and Eric Lander, who, with Nobel Laureate Harold Varmus, co-chairs the President's Council of Advisors on Science and Technology, all extolled the initiative and celebrated its foresight.

Anthony Fauci, director of the National Institute for Allergy and Infectious Diseases, noted that many scientists formulate concepts, publish their discoveries, and then move on to other ideas; the "acceleration" initiative, he said, will help them realize the potential impact of a concept and how to translate it into a tangible medical countermeasure. These scientists will receive additional funding, guidance in dealing with regulatory agencies, and greater access to NIH reagents, animal models, and expertise.

Fauci also spoke of the program's new "strategic investment fund." Small biotech companies in particular have little incentive to develop products to counter potential threats that have not yet even materialized. The new fund will focus less on the development of a particular product than on a promising innovative company and ways to keep it viable.

These health and science officials were all part of the review process leading to the 2010 countermeasures report, but state and local health departments -- as well as agencies and individuals not directly related to health or science -- also provided input. Among the latter were the Departments of Defense and Homeland Security, the National Security Council, colleagues in academia, and private industry representatives, including those in the investment and venture capital world.

But for all the aforementioned enthusiasm, uncertainties remain about the structure of the enterprise, how success -- or lack thereof -- will be measured, and whether it is worth the cost.

Structure of the new centers. The three centers are scheduled to become operational by 2014, though many of their component firms and institutions have already been named. One center is led by Emergent BioSolutions, a mid-size biotech company in Maryland; the second by Novartis, a large pharmaceutical company based in North Carolina; and the third by Texas A&M University. Each center includes a mix of public and private partners. At a June 18 press conference, leaders of the three centers expressed enthusiasm for the project and pledged fealty to the promise of more nimble, flexible, and rapid approaches to the production of countermeasures.

Brett Giroir, head of the Texas A&M center and also a vice chancellor of the university, later told me that each center will devise its own protocols for decision making. Speaking for his own center, he listed several committees that will deal with influenza, countermeasures, and regulatory practices. After a committee's deliberations, Giroir will share any recommendation with the university's chancellor and other members of his core team. He will then decide whether to submit recommendations to the Biomedical Advanced Research and Development Authority for review and approval.

Aspects of the process still await refinement. Moreover, achieving consensus may be challenging since, as Giroir observes, the mix of big and small pharma concerns, academia, and the government is "completely novel."

Confident in the program's likelihood of success, Giroir acknowledges the inherent inability to be "perfectly prepared," especially for the unknown. But he exhibits near-certainty that defined benchmarks will be reached, such as creation of manufacturing platforms to quickly produce pandemic flu vaccine and other countermeasures. "I would say that the chances of being totally ready by five and one-half years are 90 percent-plus. If you give me seven years, I'd say 99 percent."

Views from outside the process. Though some experts outside the review process, like Peter Palese, chair of the microbiology department at Mount Sinai Hospital in New York City, agree that the HHS initiative is a "superb" investment and that it will greatly enhance the country's ability to respond quickly to a bio-threat, whether of deliberate or natural cause, other knowledgeable observers are less confident. Robert Kadlec, now with a private consulting firm, served from 2007 to 2009 in the White House as principal adviser to the president on bioterrorism and pandemic influenza preparedness. Previously, he was staff director for the Senate Subcommittee on Bioterrorism and Public Health Preparedness, where he helped draft the 2006 Pandemic and All-Hazards Preparedness Act.

Kadlec is sensitive to the need for more effective medical countermeasures, and he applauds the intentions of the HHS initiative. But he is uncertain that the new program will yield the intended results. He is skeptical of how big and small pharmaceutical companies and academic institutions will work together in consortium. "I don't think anybody has an idea of how it's going to work," he said. "The proof will be in the pudding, and I have a lot of questions about it."

For one, he said, he expects there will be issues about protocols, royalties, management, and more, but the manner of governance has not yet been clarified.

He presumes that Novartis and Emergent BioSolutions were chosen as leaders because of innovations they had already demonstrated in developing new influenza vaccines. (Novartis has produced a vaccine based on tissue culture, and Emergent created one based on virus particles.) But he questions this model in relation to other threats, as the platforms to develop vaccine from virus particles or tissue cultures may not be applicable to other biological agents, let alone to chemical, radiological, or nuclear threats.

Even less forgiving is Richard Ebright, a distinguished professor of chemical biology at Rutgers University. He agrees with the need for such a program, but after reviewing HHS's publicly disseminated information, he is doubtful about this one. As he sees it, "there is essentially zero likelihood that individual researchers, or any but the most well-connected, lobbyist-laden businesses, will be able to access the incentives and programs."

In this perspective, he said, Fauci's comments about the program's potential to assist scientists are irrelevant. He rues the absence of information available to individual investigators on interaction with the program: "No websites. No descriptions. No documentation. Nothing." As currently conceived, Ebright believes the program will be a waste of money.

Turning uncertainty into effectiveness. Efforts to enhance medical countermeasures against biothreats of all kinds are surely to be welcomed, but whether HHS's new Centers for Innovation will meet expectations remains uncertain, no matter how exuberant supporters of the moment may be.

Many other federal health and scientific programs have been launched over the years, also with enormous optimism. But for every success, like the 10-year effort to land a man on the moon, there have been disappointments, because the science lagged or the cost proved too high. The government's War on Cancer, declared in 1971, continues 40 years later despite some successful skirmishes. The Superconducting Super Collider was first proposed in 1983, but after unacceptable cost overruns was canceled in mid-construction 10 years later.

To cite these examples in no way diminishes hopes that the Centers for Innovation program will succeed. But obstacles will surely surface along the way, and finding creative paths around them will be essential. Will these challenges be addressed nimbly and flexibly, to borrow terms of aspiration used by program proponents? Or with the bureaucratic rigidity that foretells failure? Creative tweaking will be necessary, along with luck, to keep the process on track.