Turning uncertainty into a science

Flu vaccine manufacturers and distributors try to predict the unpredictable.
By Laura Thill

Count on it: This flu season, like all others, will be totally up for grabs. “The only thing that is predictable, is that flu season is unpredictable,” says Patrick M. Schmidt, chief executive officer, FFF Enterprises (Temecula, Calif.). Indeed, last year’s H1N1 scare led to an unprecedented demand for seasonal flu vaccine.

The pandemic virus was not detected until April 2009, and by the time an H1N1 vaccine was available, the peak flu season had ended. Furthermore, the H1N1 virus turned out to be much less virulent than expected. That was a good thing, notes Schmidt. Still, there was a surplus of H1N1 vaccine, and the government was left holding the bag, he explains.

With the start of the 2010-2011 flu season, manufacturers and distributors once again attempt to turn uncertainty into a science. And some new factors are at play. First, seasonal flu vaccine will contain an H1N1-like strain. And, second, for the first time, the Advisory Committee on Immunization Practices (ACIP) has issued a universal mass vaccination (UMV) recommendation, which experts expect will lead to greater flu vaccination compliance. “The recommendation means that non-high-risk individuals no longer are encouraged to wait until after October 29 to be vaccinated,” says Schmidt. According to ACIP recommendations, everyone six months old and older should get vaccinated, unless they have a medical condition for which flu vaccine is contraindicated. For children under three years old, it generally will depend on their pediatrician’s discretion, notes Schmidt.

Typically, two-thirds of the American population takes a pass on the flu vaccine, he points out. Because these individuals are not in a high-risk group, they may feel guilty about “taking the vaccine” from those in the high-risk group. With the new guidelines, all of that reasoning falls by the wayside. “Flu vaccine is the first line of defense in flu prevention and therefore one of healthcare’s best values,” he adds. “One of the most common myths is that if an individual was vaccinated last year, they do not need the vaccine this year,” he says. “Each year, the strains change. [This year’s] vaccine will have two new strains in addition to the new H1N1 pandemic strain, so [vaccination] can help protect you and your family.”

Vaccine production
Each year, the viruses used to produce seasonal flu vaccine are selected based on information collected during the previous year about which influenza viruses are spreading and which vaccine strains might offer the best protection, according to the Centers for Disease Control and Prevention (CDC). The World Health Organization (WHO) evaluates viruses gathered by 130 national influenza centers in 101 countries, and typically recommends a trivalent seasonal flu vaccine in order to increase the likelihood that it covers the main circulating flu viruses. “The best predictor of severity and strain in the Northern Hemisphere is the epidemiology of the Southern Hemisphere flu season, which is currently ongoing,” says Vas Narasimhan, president, vaccines, North American Division, Novartis (East Hanover, N.J.).

Due to the seasonal differences, the flu season in the Southern Hemisphere precedes that in the Northern Hemisphere, adds Kristi Kuper, PharmD, BCPS, clinical director, infectious disease, Cardinal Health (Dublin, Ohio). “Experts can extrapolate what will happen in the United States from data they receive from [such] geographic regions as Australia and South America.” Some novel H1N1 is being reported, as well as increased activity of the influenza B strain in parts of Asia, which is considered unusual, she points out. “This year’s flu season likely will mirror a regular flu season. Last year was an anomaly in the sense that the novel H1N1 influenza season began in April, whereas traditional flu seasons begin in the fall. We are not seeing much flu activity right now, which is the complete opposite of what we saw at this time last year.”

Both WHO and the U.S. Food and Drug Administration (FDA) have recommended that the 2010-2011 seasonal flu vaccine contain the following strains:

  • A/California/7 2009 (H1N1) – like virus.
  • A/Perth/16/2009 (H3N2) – like virus.
  • B/Brisbane/60/2008 (B/Victoria lineage) – like virus.

Three factors drive influenza vaccine production plans, according to Narasimhan: vaccine strain yields, pre-book demand for vaccine delivery from the first half of the year and production capacity based on competing demands from other countries. “In a typical year, final determinations of supply can only be made in late June or July, when bulk production is complete,” he says. “Projections [for the current flu season] will be based on historical yield rates and direction from the CDC, European Medicines Agency (EMA) and WHO. Estimated supply by the CDC for the United States is roughly 170 million doses (at press time), which is a record number of doses available.”

Kuper agrees, noting that, according to manufacturers at the National Influenza Vaccine Summit, the five flu vaccine manufacturers are each expected to produce the following number of doses:

  • Sanofi Pasteur – 70 million doses.
  • Novartis – 35-40 million doses.
  • GlaxoSmithKline – 36 million doses.
  • MedImmune – 16 million doses.
  • CSL – Eight million doses.

“Approximately 115 million doses of seasonal influenza vaccine, along with an additional 160+ million doses of the novel H1N1 vaccine, were manufactured for the 2009-2010 season,” says Kuper. While production for 2010-2011 won’t approach those 275+ million doses, it will exceed pre-H1N1 levels, she says. Ideally, flu manufacturers want to get more of their vaccine supply out early, before flu season hits its peak, she adds. “Manufacturers estimate that shipments could begin as early as late July or early August,” she says. And, depending on how much vaccine is produced, shipments may wind down in November 2010.

“[Given] the nature of current flu [vaccine] manufacturing processes, it takes a minimum of six months between strain availability and [the time] the first doses are released,” says Narasimhan. “Because of this, a just-in-time production process is not feasible.” New production processes, such as flu cell culture help minimize the lead time, but lead times are necessary just the same, he adds.

Most manufacturers are able to provide distributors with a vaccine production schedule, according to Schmidt. “We expect to see the majority of flu vaccine (about 75 percent) shipped between August and September,” he says. “About 25 percent will be available between October and December.” But, rarely does the process run smoothly, he adds.

Increased demand?
The fact that the vaccine now incorporates an H1N1 strain may be attractive to some people. However, experts believe a number of factors contribute to vaccine demand. “It is difficult to predict if the incorporation of the 2009 H1N1 flu strain into the seasonal flu vaccine will have an impact on the uptake,” says a spokesperson at GlaxoSmithKline (Philadelphia, Pa.). Other factors come into play, including the severity of the flu season, availability of vaccines and the new universal mass vaccination recommendations, he adds.

“Many people are not educated about how severe influenza can be,” says Narasimhan. “Others are skeptical about the vaccine’s risk/benefit profile. They mistakenly believe the vaccine can cause influenza, or they are concerned about adverse reactions. Historically, there have been roughly 220 million Americans eligible for flu vaccination, but only 100 to 110 million get vaccinated. Currently, less than half of healthcare providers receive an influenza vaccination.”

Kuper cites the CDC, which lists the following barriers to flu vaccination:

  • The belief that previous infection with the H1N1 strain offers immunity to future H1N1 strains.
  • The belief that previous flu vaccination offers immunity for the upcoming season.
  • Myth that the H1N1 vaccine is unsafe or less safe compared with traditional seasonal flu vaccine.
  • Cost of seasonal flu vaccine.
  • Whether or not patients’ providers received the vaccine themselves.
  • Whether or not patients’ physician/healthcare provider recommends they get the vaccine.

As a result of misconceptions about flu vaccine, for the past three years, manufacturers have faced an oversupplied and challenging marketplace, according to Narasimhan. “Immunization rates of the American public only rose 1 percent from 2007 to what was anticipated in 2009, from approximately 107 million to 110 million vaccinations,” he says. “As a result, the market has been oversupplied and prices have dropped by 30 to 40 percent, creating a strong disincentive for manufacturers to maintain or maximize production capacity. In the past this situation has led to manufactures withdrawing from the market. To create a more stable marketplace, vaccination rates need to be driven higher towards this goal through both public and private investment. If demand were to rise to higher levels, supply would likely normalize to a steady level.”

The cost of the vaccine is not expected to increase due to incorporation of the H1N1 strain, although Sanofi Pasteur is expected to release a high-dose flu vaccine this year, which will cost about twice as much as the regular flu vaccine, according to Kuper.

Nor will the inclusion of the H1N1 strain affect the vaccine’s shelf life, which generally is about 9-12 months. As Schmidt notes, flu vaccine is produced specifically for the current season.

Doctors and caregivers should adhere to the manufacturer’s recommendations, says Kuper. Typically, vaccines that are unopened and stored at proper temperatures (usually refrigerated between 2-8 degrees C/ 36-46 degrees F) may be used up to the expiration date on the vial, she explains. “If it is a multi-dose vial and has been opened, it must be stored at the [above] temperature and discarded after the expiration date,” she says. “Unopened single-use vials and syringes should also be stored according to the manufacturer’s recommendation. Once the dose is used, the remainder should be discarded.”

The challenges
Because manufacturers and distributors anticipate “ample supply” of flu vaccine for the 2010-2011 flu season, hospitals and physicians should order as much vaccine as they require, according to Schmidt. “Doctors should encourage their patients to be vaccinated through December,” he says, noting that the upcoming season has been extended. Although patients need to receive the vaccine about six weeks prior to exposure to the virus, they can be vaccinated into January or February if necessary, depending on when the season peaks.

“While flu outbreaks can occur as early as October, they may not peak until February or even later,” says GlaxoSmithKline’s spokesperson.
“The biggest challenge is ensuring adequate supply to serve the market demand,” says Angie Thomas, vice president of Supply Chain Solutions, Cardinal Health. “The manufacturers do their best to have product approved and available for shipping in the early fall, however, in many cases the regulatory approval process can take longer than expected.” Other challenges can arise as well if government agencies decide to sequester vaccine to regulate supply during a crisis, she adds. “Any sequestering can limit what is available to the traditional supply chain.” There is no way to avoid these types of scenarios, she says.
“Each flu season [has] its own challenges that are hard to predict,” adds Kuper.

About Laura Thill

Laura Thill is a contributing editor for The Journal of Healthcare Contracting.

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