U.S. Policy Regarding Pandemic-Influenza Vaccines
Chapter
4
One goal of the Department of Health and Human Services’ plan for an influenza pandemic is to stockpile—as soon as possible and within the constraints of industrial capacity—enough vaccine to immunize 20 million people against the strains that present a pandemic threat (HHS 2005b, p. 24). It is far-fetched to think that a prepandemic vaccine—so called because it is produced before the onset of a pandemic—would be a perfect match for the virus causing the pandemic, but policymakers and public health officials hope that it would offer at least some protection to people who are essential to maintaining security; to health care providers; to those who provide essential products and services; and to infants, young children, and pregnant women before a vaccine specific to the pandemic can be produced.1
Since 2004, HHS has obligated more than $950 million to procure roughly 26 million doses of prepandemic-influenza vaccine (90 micrograms of antigen per dose) for the stockpile (see Table 4-1). The stockpile is intended to meet changing threats to public health; as new influenza strains are identified as having the potential to cause a pandemic, they will be added to the stockpile. So far, HHS has stockpiled vaccines against two variants of the H5N1 virus, the "bird flu." The first variant, called clade 1, consists of the virus that is circulating in Cambodia, Thailand, and Vietnam. The second, clade 2, consists of the virus circulating in China and Indonesia (WHO [no date]). (A clade is a group of viruses descended from a single ancestor.) Although HHS currently is treating the stockpile as one entity, the cost of stockpiling vaccine would rise if it was determined that each strain required a separate stockpile with enough vaccine to immunize 20 million people.
U.S. Stockpile of H5N1 Vaccine, by Year of Purchase
2004 |
2005 |
2006 |
2007 |
Total |
||
Clade 1 |
0.5 |
7.1 |
0.9 |
0 |
8.4 |
|
Clade 2 |
0 |
0 |
6.4 |
11.2 |
17.6 |
|
Total |
0.5 |
7.1 |
7.4 |
11.2 |
26.0 |
|
Source: Congressional Budget Office based on Robinson (2008).
Note: H5N1 is the virus that causes the "bird flu." A clade is a group of viruses descended from a single ancestor. One dose contains 90 micrograms of antigen. (A microgram is one one-millionth of a gram; antigen is the vaccine’s acitve ingredient). Influenza vaccine typically expires after two years; 15 million doses have expired or will expire soon.
At two doses per course (the recommendation for pandemic-influenza vaccine), the stockpile would hold enough to inoculate about 13 million people. Because there already are standards for how long seasonal-influenza vaccines can be stored, HHS has begun studies to determine how long the stockpiled prepandemic vaccines can be counted on to be safe and effective. Currently, HHS assumes a two-year shelf life, which is consistent with industry data for the shelf life of seasonal-influenza vaccine. About 15 million of the 26 million doses in the stockpile have already expired or are now reaching expiration, so the approximately 11 million doses left in the stockpile would be enough to inoculate only about 5.6 million people.
Production of vaccine for the stockpile currently is limited to the three months of the year when the manufacturers are not making seasonal-influenza vaccine. However, HHS has signed a contract with Sanofi Pasteur to retrofit its domestic vaccine-manufacturing facility so it can produce prepandemic-influenza vaccine year-round for the stockpile.
Cost to Complete and Maintain the Stockpile
Several factors drive the cost of completing and maintaining the stockpile: the ability of adjuvants to reduce the amount of antigen needed in a dose of vaccine, the shelf life of stockpiled antigen and adjuvants, and the number of virus strains against which stockpiles must be established.
Stockpiling Adjuvanted Vaccines
Most of the vaccine in the stockpile is being stored in bulk at company sites. From there, it must be put into its final formulation and packaged for shipping to doctors’ offices and clinics. Part of HHS’s plan for a response to an influenza pandemic includes the use of any available adjuvants; the agency wants to be able to consider adjuvanted vaccines as it determines optimal dosage.
If the use of adjuvants substantially reduced the need for antigen, the current stockpile could surpass HHS’s goal of providing enough for 20 million people. If adjuvants made it possible for a dose to consist of 15 micrograms of active ingredient—which would match the amount for each strain of seasonal-influenza vaccine—rather than the 90 micrograms called for with the pandemic-influenza formulation, then the 11 million doses remaining in the stockpile could be stretched to 66 million, or enough to inoculate about 33 million people. In that event, the stockpile would not need to be made larger, although adjuvant would have to be produced and purchased.
Like the vaccines they augment, adjuvants have a limited shelf life—HHS assumes that adjuvants will expire after three years. On the basis of information from the agency, CBO estimates that it would cost $350 million per year to replace expiring antigen and adjuvants with enough new material to maintain a stockpile for 20 million people through 2020, assuming 15 micrograms of antigen per dose. However, the costs would be less if HHS determined that the stockpiled antigen had a longer shelf life: If it lasted three years instead of two, the cost of annual maintenance would drop to about $300 million.
Because adjuvants are not stand-alone drugs, approval by the Food and Drug Administration for adjuvanted versions of the vaccines already in the stockpile would be contingent on completion of additional clinical trials (some are in the planning stages). If the stockpiled vaccines and the adjuvants were made by different companies, however, additional hurdles could arise concerning intellectual property rights (McKenna 2007b). However, if an influenza pandemic were to occur, the FDA could permit the use of unlicensed adjuvanted vaccines even if they had not completed the full cycle of clinical trials. Unlicensed vaccines could be administered under an emergency use authorization or under FDA’s Investigational New Drug provisions (Lister 2007, p. 30).
Stockpiling Vaccines Without Adjuvants
If there is no success in using adjuvants to substantially cut the amount of antigen required, then about 29 million doses of vaccine will be needed to complete the stockpile. Information from HHS indicates that the cost would be about $1.1 billion. However, if HHS found that the stockpiled antigen had a shelf life longer than two years, that cost would be reduced. For example, if antigen could be kept in the stockpile for three years, the cost of completing the stockpile would fall to about $790 million. After completion, it would cost about $1.1 billion annually to replace expired antigen and to maintain a stockpile for 20 million people through 2020.
The vaccine in the stockpile is a combination of vaccines made from different strains of the H5N1 virus. Vaccine made from one strain might not provide protection against viruses from different strains. If HHS maintained a stockpile of vaccine for 20 million people for each circulating strain then the cost of the stockpiles would rise. For example, it would cost about $2.2 billion annually for HHS to maintain a complete stockpile for two circulating strains without adjuvants and about $700 million annually with adjuvants.
The results of recent studies show that adjuvants can increase the ability of influenza vaccines to protect against viruses from different but related virus strains that are not contained in the vaccine (WHO 2008). Thus, if adjuvants can be used with the stockpile, the number of virus strains against which stockpiles must be built can be reduced (WHO 2007b).
The annual cost of maintaining the stockpile would be greater than the cost of funding reserve capacity. Instead of paying $160 million to $870 million per year in subsidies to keep the additional capacity for egg-based or cell-based production ready, most of that excess capacity could be used to produce vaccine for the stockpile, at an additional annual cost of $350 million to $1.1 billion.2 However, not all of the reserve capacity would be suitable for making vaccine for the stockpile (see Chapter 3).
International Efforts to Stockpile Vaccine
The World Health Organization has proposed a global stockpiling plan that would focus on developing nations, mostly those without domestic manufacturing capacity or sufficient resources, to purchase vaccines from abroad (Lewcock 2007d). Several manufacturers (Baxter, GlaxoSmithKline, and Sanofi Pasteur) have pledged to donate or sell at a discount millions of doses of prepandemic vaccine over the next several years. As with the domestic stockpile, the success with adjuvants will determine the number of people who can be immunized. In addition, like policymakers in the United States, WHO will have to decide what to do about stored, but expired, vaccines.
Individual countries are procuring stockpiles, although many more are planning to rely on advance supply agreements (Mounier-Jack, Jas, and Coker 2007, p. 925). The United Kingdom’s Department of Health (2008) has announced that it is stockpiling 3 million doses; France and Italy have announced plans for stockpiling 2 million doses each (Mackenzie 2005). In all, those supplies would contain enough vaccine to inoculate about 2 percent of the populations of those countries. By contrast, Ireland has announced its intention of creating a stockpile of 8.5 million doses, and Austria has signed a contract for 16 million doses; enough in each case to inoculate the entire population of the country (Raymond 2006). The amount in the stockpiles, relative to the size of the population, varies greatly from one nation to another, and different countries could be purchasing vaccine with different amounts of antigen per dose.
For a listing of the priority groups, see "Draft Guidance on Allocating and Targeting Pandemic Influenza Vaccine," www.pandemicflu.gov/vaccine/prioritization.html.
Of the total, $15 million per year would go to subsidize capacity for producing egg-based vaccine; the balance of roughly $140 billion to $850 billion annually would support expanded capacity for production of cell-based vaccine (see Chapter 3).
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