U.S. Policy Regarding Pandemic-Influenza Vaccines
Chapter
5
Options for Modifying HHS’s Plan
The vaccine component of the plan developed by the Department of Health and Human Services in 2005 would provide some amount of immediate insurance against an influenza pandemic, more protection when vaccines produced with cell culture technology are approved and facilities are built, and at some point in the indefinite future a much-reduced risk if next-generation vaccines are successful. This analysis by the Congressional Budget Office indicates that additional spending will be necessary for the indefinite future and that it is unlikely that the objective of providing enough vaccine to immunize 300 million people will be met by 2011. The environment in which the original plans were made has changed in at least one important regard: Policymakers have more information today than they did in 2005 when the plan was formulated. In particular, the likelihood has increased that adjuvants could be used to reduce the amount of antigen needed to provide immunity. That information raises several questions about whether the course of current policy is the most cost-effective and whether it should be altered:
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Does progress in developing adjuvanted vaccines suggest that the current plan supports too much expansion of production capacity? |
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In light of the prospects for adjuvanted vaccines, would providing more support for early and advanced development for next-generation vaccines ultimately provide more protection against an influenza pandemic? |
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Should the United States consider adopting a strategy similar to that of several governments in the European Union? (Instead of giving direct government support to new production facilities, some European governments have entered into advance supply agreements to purchase vaccine in the event of an influenza pandemic.) |
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Does the prospect of successfully developing an adjuvanted vaccine change the optimal size of the stockpile of prepandemic vaccines? |
Adjuvanted Vaccines and Adequate Capacity
One option HHS might consider if adjuvanted vaccines fulfill their promise is to reduce targets for domestic cell-based manufacturing capacity. Such a reduction could initially save $600 million that HHS has budgeted for the construction of the facilities, and it could reduce the spending that will be necessary to keep manufacturers in a state of readiness.1
European regulatory authorities have approved adjuvanted vaccines against seasonal and pandemic influenzas. Drug companies are reporting encouraging results for other adjuvanted influenza vaccines in clinical trials in Europe and the United States. The arithmetic of pandemic vaccination changes dramatically, as discussed in Chapter 2, if adjuvanted vaccines are developed and approved. An extrapolation of the results from clinical trials leads to the preliminary conclusion that, by 2011, domestic egg-based manufacturing could produce enough antigen within six months of the onset of a pandemic to immunize 225 million people with adjuvanted vaccines at 15 micrograms per dose. Data from the most successful clinical trials for adjuvanted vaccines show that the projected U.S. capacity would make it possible to produce enough antigen within six months of the onset of a pandemic to immunize the U.S. population several times over. However, if adjuvanted vaccines were not used, the projected capacity could produce enough antigen only to inoculate about 38 million people (see Table 2-1).
In light of that wide range of estimates of the possible domestic volume of production for egg-based vaccines, it might be prudent for the federal government to slow its support for additional capacity and focus more effort on developing adjuvants. If adjuvant development is successful, the capacity for egg- or cell-based production that is currently available or under construction would be enough to meet HHS’s goal of vaccinating every U.S. resident within six months of the onset of a pandemic. If development is not successful, however, the current plan for $600 million in subsidies would be just a fraction of the $7.6 billion to $11.4 billion needed to build enough cell-based production capacity to meet HHS’s goal.
Current and announced capacity already exceeds what could be supported by demand for seasonal vaccine. Creating additional (possibly unneeded) capacity could compound the risk that the industry would expand too much and then would need to contract, with the result that some companies would exit the market, as has occurred in the past.
Such a change in policy would come with risks, however. The decision not to support the building of new plants for cell-based production would leave the domestic supply still concentrated in a few facilities that are producing egg-based vaccine. Contamination of just one facility or of associated poultry flocks during an influenza pandemic could grievously hamper the federal response and leave the U.S. population at risk. Although manufacturers adhere to strict practices to ensure that their flocks are protected from disease, the risk remains. Adjuvants would lessen that risk, however, because their use would mean there is less capacity and fewer flocks to protect.
Creating additional capacity to produce cell-based vaccines would improve the government’s ability to immunize people who cannot be vaccinated with adjuvanted vaccines. If even a fraction of people required the unadjuvanted vaccine, the supply of antigen could be quickly exhausted. Policymakers could conclude that the side effects from adjuvants, which to date have been minor, are outweighed by the need to immunize a majority of the population. But such a decision would be likely to reduce compliance.
HHS could be optimistic in its goals for manufacturing capacity for cell-based vaccine, in any event. The manufacturers have had incentives to develop adjuvanted prepandemic vaccines in order to win premium-priced contracts from governments around the world for vaccine stockpiling. Absent a market in which to sell the additional seasonal cell-based vaccine, large federal subsidies are likely to be needed to support construction of such facilities, an eventuality that might require additional appropriations.
Next-generation vaccines are needed to reduce the production time required to manufacture the current set of vaccines. Development of adjuvanted vaccines also could have implications for the resources devoted to next-generation vaccines and for the mechanisms the government chooses to accomplish its objectives. Specifically, if adjuvanted vaccines reduce the near-term risk posed by an influenza pandemic by stretching the available and the planned capacity, then resources might be available to support more development of next-generation vaccines. Moreover, there might be enough time to work through markets to use guaranteed purchases or other mechanisms to promote the development of next-generation vaccines, where manufacturers with successful products would be ensured sales into the stockpile.
However, policymakers cannot count on easy and rapid success with next-generation vaccines. Those formulations are, in many cases, based on truly novel concepts and are largely in the early stages of development. It is likely that there will be many failures, which will prolong the process and increase the costs of bringing those products to market.
European governments have chosen to enter into advance supply agreements with companies to provide vaccine in the event of a pandemic. The U.S. approach differs: Policymakers here have chosen to provide direct support to manufacturers for the development of vaccines and the construction of new production facilities. The U.S. government could consider entering into advance supply agreements, which are seen in Europe as economically attractive because each side can concentrate on what it does best: Governments track public health needs, and businesses develop vaccines and manufacturing facilities. Also, with the advance supply agreements, the governments actually purchase some specified amount of vaccine for their populations. The U.S. government, in contrast, would not have a committed supply of vaccine and would need to spend additional funds to acquire vaccine for an influenza pandemic. Companies may have to fulfill the European advance supply agreements first before selling vaccine to the United States, possibly exhausting their supplies. It might be necessary for the United States to structure agreements to recognize that other nations’ governments could temporarily restrict or prohibit exports of pandemic-influenza vaccine until their own populations have been immunized. Even if the United States enters into advance supply agreements, there remains the risk that manufacturers will not have the capacity to fulfill those agreements.
Some analysts question the ability of advance supply agreements to stimulate the development of technology, especially given the lengthy process of ushering vaccines through approval. The European governments, they argue, are beneficiaries of U.S. efforts in technology development. Other analysts point to Sanofi Pasteur’s independent development of an as-yet-unapproved adjuvant as one example of technology development that occurs in response to government demand (in this case for the national stockpiles) but without direct subsidies.
The potential success of adjuvanted vaccines could provide a rationale for HHS to reconsider the size of the stockpile. The current policy calls for building and maintaining a stockpile of prepandemic vaccines large enough to immunize 20 million people. In the event of a pandemic, that supply would be distributed first to health care workers and first responders; to providers of public safety and critical infrastructure; and to infants, young children, and pregnant women.
Determining the optimal size of the stockpile poses a challenge for a variety of reasons that are related to the public health risks that the stockpile is designed to reduce. The current goal of 20 million doses for the stockpile could be too large or too small: If, for example, the strain that causes the pandemic influenza does not respond to the stockpiled vaccine formulation, the stockpile could be wastefully large. But it could be too small if a pandemic were to spread through the population more quickly than new vaccines could be manufactured. The size of the stockpile, moreover, is linked to other elements of the HHS plan that are related to antiviral drugs, medical supplies, and state and local preparedness measures.2
Successful development of adjuvanted vaccines could alter the balance of risks in determining the size of the stockpile and potentially reduce the cost of mitigating those risks. Some recent research indicates that adjuvanted vaccines could provide protection against more than one strain of potential pandemic virus, thereby improving the chances that the vaccines in the stockpile would be effective in a pandemic. Moreover, because adjuvants would reduce the amount of antigen required to immunize any target population, HHS either could retain its current goal of maintaining a stockpile sufficient to inoculate 20 million people while reducing the amount of stockpiled antigen or expand the number of people that could receive the prepandemic vaccine. Doing the latter would reduce the risk that a pandemic would move through the population more quickly than new vaccines could be manufactured, and it might provide enough protection in the population to reduce the severity of the pandemic.
Although HHS has budgeted $600 million to offer capital subsidies to manufacturers to build cell-based production facilities, no contracts have been signed as of this writing.
For a discussion of the likely interactions of various public health policies during a pandemic, see Ferguson and colleagues (2006).
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