Cell Culture: Is It Cost-Effective?
Despite the benefits of using cell culture—making more vaccine more quickly in the face of a pandemic—it’s not necessarily a cost-effective process. Any new technology takes substantial research and development costs, for starters. But additionally, the vast testing and assays required by regulatory agencies to prove safety aren’t small change.
For example, Pharmathene has developed assays to characterize the protein, demonstrate vaccine stability, show consistent manufacturing processes, measure immunopotency and toxin neutralization—the list goes on.
“To go through the development and qualification of these assays is a lot of work,” says Tom Fuerst, CSO. “And then you have to establish system suitability criteria around them to make sure that they’re precise and accurate.”
Pharmathene also uses E. coli to culture its vaccines, but its focus is on anthrax. An anthrax vaccine has been licensed since the 1980s, using an attenuated strain. But the current method involves a “crude preparation,” says Fuerst, that is “attenuated with formaldehyde, which is now considered a carcinogen by the NIH”—certainly not an ideal situation.
Pharmathene’s vaccine antigen is a highly conserved recombinant protein from the anthrax bacteria grown instead in E. coli, for which “the cost of manufacturing is very low and production levels are exceptionally high,” says Fuerst.
One of the strengths of its vaccine is that it can be stabilized in an intermediate form, and Pharmathene aims for at least a three-year storage time. This method would allow it to mobilize quickly if another anthrax outbreak occurred.
“In event that there is an emergency, and the demand for an anthrax vaccine is very high, we are able to produce stable production intermediates that then can be polished very quickly and formulated into a vaccine,” says Fuerst.
All the companies mentioned are making vaccines for some diseases that already have vaccines available. Even if they are arguably making better versions of these vaccines, is all the time and money invested worth it?
“By and large what people find is that the cell culture system is cleaner, but a lot more expensive,” says Shaw. “The seasonal flu vaccine is a commodity product…and with cell culture, what you wind up with is a more expensive commodity product that’s not terribly economically interesting.”
But the U.S. government has made its investment clear. Later this year, a $1 billion, 430,000 square foot cell culture-based vaccine-making facility in Holly Springs, North Carolina, is slated for production.
“I don’t know if Novartis is going to break even; it will be more expensive to make than the standard flu vaccines by a factor of two or three I think,” Shaw says. “But enough money has been invested in the cell culture system, at least in the U.S., that they have to use it.”
A big investment, sure; but it is estimated to be able to produce 150 million doses of flu vaccine within six months of a pandemic declaration. This is a far cry from the circumstances surrounding H1N1’s discovery in 2009, when vaccine production didn’t begin until six month after the virus emerged, and even then it was only at a rate of 10 million doses per week.