Government effort to produce vaccines on demand raises questions about cost and strategy.
The future of the US government’s biodefence strategy sits in a warehouse in rural Texas. A dozen gleaming-white trailers, each about the length of a bus, hold equipment for producing millions of doses of medical countermeasures against some of the world’s deadliest threats. These mobile clean rooms can be configured to manufacture vaccines against pandemic influenza or antidotes to biological, chemical or radioactive agents. Each room can be unplugged from the pipes that supply sterile air and cell-culture media, pushed across the warehouse, and connected to a new production line — ready in days to make a different product.
The US$286-million site at Texas A&M University in Bryan is one of three new biodefence centres created by the US Department of Health and Human Services (HHS). It will start making its first vaccine this summer. Once completed in 2017, it will be able to make 50 million doses of flu vaccine in just four months — capacity that biosecurity experts say the United States needs to prepare for future pandemics.
Yet some worry that the Texas lab and its counterparts form a system that is too disjointed to deliver as promised. Others argue against expanding capacity to produce countermeasures to biological or chemical threats, in part because few effective antidotes exist. “They’re going to have a lot of challenges,” says Keith Wells, a consultant at BioProcess Technology Consultants in Woburn, Massachusetts.
The $440-million HHS programme, set up in 2012, includes three Centers for Innovation in Advanced Development and Manufacturing (CIADMs): the Texas site; one in Holly Springs, North Carolina, being built by pharmaceutical giant Novartis of Basel, Switzerland; and a facility in Baltimore, Maryland, to be run by biotechnology firm Emergent BioSolutions. Over the next 25 years, the government expects to spend as much as $2 billion on medical countermeasures from the Texas site alone, and up to $23 million per year to stockpile flu vaccines — a cost that could skyrocket if a pandemic strikes.
We need to be prepared for all hazards, not just the last one that hit us.
Gerald Parker, director of the Texas A&M centre, says that the programme’s flexible manufacturing is crucial for US biosecurity. “We need to be prepared for all hazards, not just the last one that hit us,” he says. Other threats could emerge, such as the coronavirus behind Middle East respiratory syndrome, which surfaced in Saudi Arabia in 2012, or the Ebola virus outbreak currently spreading in West Africa. If one of these viruses sparks a pandemic and a vaccine can be developed, the CIADMs will need to produce it quickly and prepare it for the market.
Such capacity is long overdue, and experts contend that it may be possible to achieve only with government funding. Many large companies have stopped developing vaccines because the public often views them with scepticism, says Robert Kadlec, a former White House director for biodefence policy. And small companies often lack the experience to bring such treatments to market.
Government initiatives such as the CIADMs counter this trend by creating an artificial market for specialized vaccines and antidotes, says Amesh Adalja, a physician at the University of Pittsburgh Medical Center in Pennsylvania who studies biosecurity issues. But incentives are not always effective: on 22 April, Novartis announced the sale of its vaccine programme to drug giant GlaxoSmithKline in London. It also plans to sell its government-funded CIADM in North Carolina.
The US biodefence programme also faces the practical challenge of developing and adopting faster methods to make vaccines. Conventional flu-vaccine production, in which each dose is grown in a chicken egg, is notoriously slow; newer methods that culture vaccines in cells are much faster. In 2012, Novartis’ Flucelvax became the first cell-based flu vaccine to gain approval from the US Food and Drug Administration. GlaxoSmithKline and Novartis have developed ways to grow vaccine particles in bird and mammal cells, respectively. And Emergent has partnered with Vaxinnate, a small company in Cranbury, New Jersey, that is working to induce Escherichia coli bacteria to make proteins that will raise an immune response against influenza or other agents. “As we move away from eggs, it makes sense not to put our cell cultures in one basket,” says Richard Ebright, a molecular biologist at Rutgers University in Piscataway, New Jersey.
The three CIADMs are also working to develop countermeasures against bioterror agents such as smallpox that could be produced on demand. Under the current strategy, “we just hope the bad guys attack us with what we stockpiled”, says Brett Giroir, executive vice-president of the Texas A&M Health Science Center, who says that the CIADMs could replenish the existing strategic national stockpile and even expand it over time. The centres’ capacity will be put to the test later this year, when the government will place its first orders for medical countermeasures, according to Robin Robinson, director of the Biomedical Advanced Research and Development Authority in Washington DC, which will oversee the centres.
But some question whether these countermeasures, such as advanced smallpox vaccines, are mature enough to be manufactured and stockpiled — or whether they are even needed. The chance of being attacked with a chemical or biological agent, and then being able to use a vaccine to respond to it effectively, is low, says Ebright.
Others say that the United States does not need multiple biodefence centres, pointing to a 2008 report prepared for the Defense Advanced Research Projects Agency, which recommended the creation of a single development and manufacturing facility to serve both the military and civilians. “Rather than one good operation that meets the government’s needs, we got three operations that spread the money around,” says Philip Russell, a retired major general and former leader of the US Army’s medical research command. The HHS centres’ supporters say that having three sites creates flexibility and leaves backups in case a site is contaminated or attacked.
Despite concerns about duplicated effort, the US Department of Defense (DoD) began building its own $136-million biodefence facility in 2013 in Alachua, Florida. Once the site is completed in 2015, the military expects to spend more than $20 million on it each year. Kendall Hoyt, a biodefence policy specialist at Dartmouth College in Hanover, New Hampshire, says that the separate effort makes sense: the military requires relatively small amounts of a variety of countermeasures, whereas the HHS needs large amounts of a few products. Moreover, the military needs to respond quickly to the wider range of threats that it faces, says James Petro, acting deputy assistant secretary of defence for chemical and biological defence. Such concerns “led us to recognize that it was important we had a facility that was under DoD control”, he adds.
But Petro says that the separation from the HHS is only temporary. “The intent has been and continues to be that once all the centres are up and running, they’ll be operating together as a consortium,” he says.
Either way, because they are the first centres of their kind, the HHS facilities have their work cut out for them, says Leonard Cole, a bioterrorism specialist at Rutgers in Newark, New Jersey. A 31 March report from the US Government Accountability Office concluded that it was still too early to tell whether the billions of dollars that stand to be funnelled into the HHS project are a good investment. Nevertheless, “if there’s the kind of pay-off we’d hope to come from this, it’s worth every nickel”, says Cole.
Related links in Nature Research
Budget forces tough look at biodefence 2013-Apr-10
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Governance plan for the HHS Centers for Innovation in Advanced Development and Manufacturing
Texas A&M Center for Innovation in Advanced Development and Manufacturing
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Reardon, S. US biodefence facilities ramp up. Nature 509, 16–17 (2014). https://doi.org/10.1038/509016a