Rapid vaccine production linchpin of pandemic plan

Will liability waivers lure back domestic firms?

If avian H5N1 influenza emerges as a pandemic strain, no currently available vaccine will be completely protective. Therefore, the thrust of the nation’s pandemic influenza plan is aimed at rapidly producing vaccine and stockpiling effective antivirals.

"We view vaccines to be the foundation of this plan," Michael Leavitt, secretary of the Department of Health and Human Services, said at a recent press conference. "The good news is we have a vaccine that’s been developed by the National Institute of Health. The bad news is we lack capacity to manufacture a vaccine in sufficient volumes and in the time frames necessary."

The pandemic plan contains few surprises in the hospital infection control recommendations, relying on established measures that have proven to prevent transmission of flu within health care facilities.

The pandemic plan calls for the development of a 20 million-dose stockpile of vaccine against the currently circulating avian H5N1 strain. Of course, if the strain mutates to become transmissible between humans that vaccine will not be a perfect match, and the clock will start ticking on the six-month period typically estimated to produce an exact vaccine match.

"[The current avian vaccine] would still produce some level of immune response and would be the best opportunity we have to inoculate early responders and others that would need protection," Leavitt said. "The second overriding objective is to provide the capacity to produce in a six-month period 300 million courses of an appropriate vaccine developed from whatever the strain is that has caused the pandemic."

As part of the plan, President Bush is asking Congress for liability protection to help encourage more domestic vaccine production. "A primary tenet of our effort on vaccines is to assure that all of these are produced domestically," Leavitt emphasized.

Will plan push universal shots?

A massive push on domestic vaccine production for pandemic preparedness could translate to increased capacity to produce the seasonal flu vaccine. As that infrastructure comes into place, public health officials eventually may issue a universal recommendation for annual flu vaccinations. Proponents of such a recommendation argue it would not only save tens of thousands of lives annually but would boost domestic vaccine manufacturing capacity up to pandemic-ready levels. The idea is gaining traction not only because it makes public health sense, but because chronic vaccine shortages and looming pandemic flu have exposed vaccine production vulnerabilities in the United States. Currently, seasonal flu vaccine is recommended for children 6 to 23 months, people older than age 50, and anyone at risk of complications from flu infection.

"For a long period of time we have been expanding the list of indications for influenza vaccine," Julie Gerberding, MD, MPH, director of the Centers for Disease Control and Prevention, said at the pandemic press conference. "We have taken a science-based approach so that when the data are available to indicate there is benefit to a group of people, our advisory committees have recommended expanding vaccine. Of course in theory we would like to expand [recommendations] for influenza because manufacturers will make more flu vaccine if we use more flu vaccine. This is a very good way for us to develop a more robust manufacturing capacity over time."

Anthony Fauci, MD, director of the National Institute for Allergy and Infectious Diseases, said such a recommendation would make the nation ready to gear up rapid production of a pandemic flu vaccine. "You have to have people working on a yearly basis on a seasonal flu to keep them skilled enough to make it happen. The best way to do that is to put them to work on making seasonal flu and increase the number people who [receive flu vaccine]. It would really keep the intellectual and skill capacity warm.’"

Why doesn’t U.S. have vaccine capacity?

Liability concerns are often cited as one of the primary reasons the United States has insufficient flu vaccine production capacity. Current liability woes — which make risk-adverse manufacturers reluctant to produce vaccines — can be traced in part to the disastrous "Cutter incident." It was a vaccine debacle that occurred five decades ago when a different scourge was upon the land: polio.

It’s hard to remember a pre-vaccine time when people feared a disease that could kill or cripple, leaving sad-eyed victims prostrate in iron lung machines. But people were so afraid of polio that in an outbreak in New York City rumors of potions and cures abounded. Desperate citizens took to ingesting "catnip, skullcap, lady’s slipper, earthworm oil, blackberry brandy, and the blood of frogs, snakes and horses," according to new book titled The Cutter Incident: How America’s First Polio Vaccine Led to the Growing Vaccine Crisis.1

In the race to manufacture Jonas Salk’s polio vaccine, quality control measures fell by the wayside at one of the production firms, Cutter Laboratories in Berkley, CA, explains Paul Offit, MD, author of the book and chief of the division of infectious diseases at Children’s Hospital of Philadelphia. In a nutshell, the vaccine virus was not killed down enough to be safe, meaning it could result in actual polio infection rather than merely prompting an immune response.

In 1955, the Cutter polio vaccine was injected into 200,000 people, resulting in 70,000 infections, 200 cases of permanent paralysis and 10 deaths. The disaster created a liability cloud that still hangs over the vaccine industry today. Other factors — not the least of which is profitability — are at play, but the Cutter incident set off a cascade of concerns that still resonate. There is too much money to be made in more marketable products for pharmaceutical companies to run the risks and liabilities of vaccine production.

"If there was a baldness or an impotency pandemic,we could blanket the world with drugs," Offit tells Hospital Infection Control. "The year Cutter went to court in 1957, ironically, was also a pandemic year. That was the only time a pandemic flu was ever predicted and vaccine was successfully made in advance."

Six U.S.-based flu vaccine makers rose to the challenge, turning out 40 million doses and saving tens of thousands of lives.

"Today, if you wanted to call on those six U.S.-based vaccine makers you would find that there are none of them left," he says. "One has a manufacturing facility in the U.S. but [flu vaccine companies] are all based outside the U.S. There has been a tremendous crumbling of the infrastructure over the last 50 years. Certainly, the first big hit was liability. We don’t have the infrastructure to make the hundreds of millions of doses that would be needed [for pandemic flu]. We just don’t have it."

In addition to liability protections, companies must be assured — as they were in the days of polio — that the government will buy their flu vaccine even if is not needed, he says.

Reference

  1. Offit P. The Cutter Incident: How America’s First Polio Vaccine Led to the Growing Vaccine Crisis.New Haven, CT: Yale University Press; 2005.