A federal initiative to ensure that the United States can respond to biological threats at home will be put to the test in response to the Ebola outbreak in West Africa.
A Texas site is preparing to manufacture the experimental Ebola drug ZMapp, says Robin Robinson, director of the Biomedical Advanced Research and Development Authority (BARDA), a division within the U.S. Department of Health and Human Services. Robinson adds that Novartis’s (NYSE: NVS) vaccine facility in North Carolina is a possible second site to make the drug. Those sites were developed previously in partnership with a U.S. government effort to establish response centers capable of manufacturing drugs and vaccines in an emergency.
ZMapp, developed by San Diego-based biotech Mapp Biopharmaceutical, is a biological drug. The antibodies that spark the immune system are produced in tobacco plants, then extracted from the plant to make the drug. A Kentucky subsidiary of Reynolds American grew the tobacco plants that made the monoclonal antibodies in ZMapp. Robinson says BARDA is now working with a response center at Texas A&M University to bring the tobacco drug-making technology from Kentucky to Texas. The university and its industry partners will use that technology to make ZMapp.
“They would respond by making that product, then helping us through clinical trials, then taking it to where it’s needed,” Robinson says.
Robinson, who is also deputy assistant secretary for preparedness and response at HHS, was in North Carolina last week for a Novartis event marking the first shipments of seasonal flu vaccine from the company’s Holly Springs, NC, vaccine plant. He says new vaccine production technology that Novartis has implemented to make flu vaccines more quickly could also, if needed, be used to make biological drugs such as ZMapp. The government earlier this month committed up to $42.3 million to help Mapp Bio accelerate development and testing of its Ebola drug.
The idea of creating drug and vaccine manufacturing centers followed the global H1N1 influenza pandemic in 2009. The HHS awarded three contracts in 2012 to establish three centers, called Centers for Innovation and Advanced Development and Manufacturing. These centers, which would address threats from naturally occurring diseases as well as acts of bioterrorism, represent alliances between government, industry, and academia.
Texas A&M recently opened a pandemic influenza vaccine manufacturing facility in Bryan, TX—part of the response center it leads under a five-year $176 million contract. GlaxoSmithKline (NYSE: GSK) is the university’s largest industry partner. Emergent Manufacturing Operations Baltimore, which has Maryland sites in both Baltimore and Gaithersburg, leads another center under a $163 million contract over eight years; Emergent Manufacturing is working with Michigan State University, Kettering University in Flint, MI, and the University of Maryland, Baltimore.
And Novartis leads a response center at its vaccine manufacturing plant in Holly Springs, which was developed under a $60 million contract. This center operates in partnership with NC State University and Duke University. Novartis’s flu vaccine relationship with BARDA predates the formation of the three response centers. In 2006, BARDA awarded Novartis a contract valued at up to $220.5 million to develop a cell-based influenza vaccine.
In conceiving the response centers, the government emphasized both capacity and speed. Each center must be able to produce at least 50 million doses of pandemic flu vaccine within four months. The government also requires that the centers be able to deliver the first doses for distribution within 12 weeks. The reason for three centers is not for geographic diversity. While there is some overlap among the centers, each center has capabilities that set it apart from the others, Robinson explains.
The Novartis Holly Springs site stands apart because of new technology that can produce vaccines in animal cells through a process called cell culture. Flu vaccines have traditionally been produced by growing the virus in chicken eggs, which can take up to six months. Instead, Novartis’s Holly Springs plant makes flu vaccine from animal cells, specifically, a cell line from a dog’s kidney. This cell culture process takes about 30 days.
Novartis broke ground in Holly Springs in 2009. Two years later, the plant was ready for production. In June, the Food and Drug Administration licensed the Novartis facility to produce seasonal flu vaccine made from cell culture. This facility is the first, and so far only, plant in the United States approved by the FDA to manufacture influenza vaccine cultured in animal cells. It will produce about 50 million doses of seasonal flu vaccine annually, but it has the capacity to expand in emergencies. The Novartis site was designed to have the capacity to produce 200 million doses of flu vaccine within six months of the declaration of a flu pandemic.
The ability to quickly manufacture large quantities of medicine would allow the response center to meet government orders for vaccines or drugs during an outbreak of infectious disease, such as flu, or even Ebola.
“That’s what the cell culture [technology] is predominantly about,” says Brent MacGregor, Novartis’s president of U.S. vaccines. “We’re able to scale up more quickly in the event of a pandemic than would otherwise be the case with egg production.”
The Holly Springs plant already has experience responding to a global pandemic threat. When H7N9 influenza emerged in China last year, Novartis scientists in North Carolina received information about the flu strain from health officials in China. Novartis then used its cell culture technology to develop a vaccine. That H7N9 work emerged from research funded by a separate federal grant awarded to Novartis, which supported a collaboration with the J. Craig Venter Institute in San Diego to use synthetic biology to make new influenza vaccines. The H7N9 vaccine produced by Novartis remains stockpiled, for use if needed, in Holly Springs.
In the event of an emerging infectious disease within the United States, the government would take similar steps to respond to the threat. One or more of the response centers could be tasked with making a drug or vaccine for the disease, Robinson says. Those drugs can come from any number of drug companies, including small biotechs such as Mapp Bio. While the Novartis plant in Holly Springs was built for vaccine production, Robinson says its cell culture manufacturing technology makes it capable of manufacturing biological drugs, like ZMapp.
“It’s a biological, a monoclonal antibody,” Robinson says. “So they could make it here.”
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