WASHINGTON, D.C. - In 1976, problems with vaccine supply resulted from manufacturing and contractual difficulties and eventually led to a Congressional appropriation beginning in 1983 to support a vaccine stockpile. While that responsibility now falls under the Vaccines for Children program, vaccine stockpiles still exist and continue to aid in similar supply problems.
At a recent National Vaccine Advisory Committee (NVAC) here, Patrick Flaherty, Public Health Prevention Service prevention specialist at the National Immunization Program, outlined the Centers for Disease Control and Prevention (CDC) vaccine stockpile system.
Vaccine stockpiles are maintained to ensure a certain supply of vaccine is available in the event of a short-term supply problems, i.e. problems lasting more than six months; for example manufacturing, lot testing, strikes or natural disasters. Potential long-term supply problems are not addressed by the current stockpile, Flaherty said.
Under these circumstances, children and adults would be at risk without a stockpile because primary immunization would not be initiated and the threat of disease outbreaks increases as a backlog of unimmunized children develops. Recalling children at a later date, once the vaccine becomes available, is also expensive, inefficient and incomplete, he added.
Stockpiling vaccines for supply disruptions have other potential uses. While not maintained expressly for outbreak control, stockpiles can be used to respond to outbreaks if necessary.
"For example, the CDC is currently seeking to establish a stockpile of OPV for the use in the unlikely event of a polio outbreak as global polio eradication nears," Flaherty explained.
NVAC Chairman Georges Peter, MD, expressed the same concern: "After eventually moving to a schedule using only inactivate poliovirus vaccine (IPV, Ipol, Pasteur Mérieux Connaught), this raises the question of 'what would we do for supply of OPV should we have an outbreak?' which is the vaccine of choice for controlling an outbreak. This is obviously a concern until we eradicate the disease."
In such situations, a stockpile may be used to immunize people who are unimmunized or underimmunized, Flaherty said. Stockpiles are held within the different manufacturers storage facilities and the stockpile of vaccine may be held in three forms: labeled, filled or bulk form.
In labeled form simply means that it is ready to be shipped to providers. If in filled form, the vaccine has been put into vials, but is not yet ready for shipping. Bulk form means the vaccine needs to undergo final lot testing, filled and labeled before shipment.
"Vaccine stockpiles often have some doses in all three stages of production," he said.
Once the decision is made to stockpile a vaccine, the CDC establishes a contract with a qualified manufacturer and pays an initial fee to purchase the vaccine, although no excise tax is paid on the product until and unless the product is actually shipped to the provider for use. In addition to the purchase price, the CDC agrees to pay a subsequent fee for rotation, a strategy for incorporating the stockpile inventory into the regular shipping and manufacturing cycle.
"Rotation occurs because manufacturers maintain stockpiles at their facilities. As the expiration data on the stockpiled vaccine nears - usually about one year from the expiration date - manufacturers ship the vaccine to customers and replace it with a supply with a more distant expiration date," Flaherty said.
The quantity of vaccine purchased for the stockpile is usually equivalent to what is used in six months of routine use. This is because it is assumed that supply interruptions would only be temporary. Also, because holding a quantity of vaccine beyond the six-month supply is difficult to rotate through the existing manufacturing process and still get to providers with adequate shelf life remaining to minimize wastage.
The first problems with vaccine supply were recognized in 1976 when temporary shortages of oral polio vaccine (OPV, Orimune, Lederle Labs), measles-mumps-rubella vaccine (MMR, M-M-R II, Merck) and diphtheria-tetanus-pertussis vaccine (DTP) occurred as a result of contractual and manufacturing difficulties. Immunization work groups convened by the Department of Health and Human Services (DHHS) expressed concerns about these shortages in 1976-1977 and the Congressional Office of Technology Assessment added its concerns in 1979.
In 1983, Congress appropriated just over $4.5 million to develop vaccine stockpiles. Line-item appropriations for vaccine stockpiles continued through FY 91, but in 1993, Congress created the Vaccine for Children (VFC) entitlement program and directed the DHHS secretary to negotiate for a six-month supply of vaccine in addition to the quantity otherwise needed for such negotiations.
According to the VFC guidelines, the secretary shall consider the potential for outbreaks of the diseases with respect to which the vaccines have been developed.
Since the legislation was enacted, the CDC has used funds from the VFC program to purchase and maintain stockpiled vaccines.
Since the CDC began stockpiling vaccines in 1983, the stockpiles have been used more than 12 times, often at the request of the manufacturers. Any use of the stockpile must be approved by the CDC and deliveries are made at the direction of the agency. The CDC has developed a decision tree to guide stockpile-use decisions.
In 1986, MMR stockpile was used after a fire in the production facility disrupted the supply. In 1988, DTP was taken from the stockpile after a manufacturing problem, and than in 1990, IPV was used because the U.S. supply of the vaccine was exhausted and at least a six-week delay in production was expected.
In all cases in which stockpile was used by the manufacturer, the supply was replaced by the manufacturer.
Three factors influence CDC decisions of which vaccines to stockpile and how much: the availability of vaccine from multiple manufacturers; vaccine technology changes or changes in the recommended immunization schedule; and cost and contractual considerations.
The number of manufacturers that produce a certain vaccine is an important consideration in stockpiling decisions. Because the intent of vaccine stockpiles is to assure an uninterrupted supply of vaccine, stockpiles of vaccines with multiple manufacturers are less necessary than of vaccines with only a single manufacturer, he explained.
Vaccines produced by a single manufacturer include: Haemophilus influenzae type b/hepatitis B (Hib/HepB, Comvax, Merck), IPV, OPV, varicella (Varivax, Merck), DTaP/Hib (TriHIBit, Pasteur Mérieux Connaught) and MMR.
Changing technology or changing recommendations must also be considered, Flaherty explained. Many manufacturers are developing combination vaccines that protect against multiple diseases, and these advances are expected to continue over the next few years. Using combinations will require some existing stockpiles to be replaced.
"It can be difficult to anticipate new vaccines in production. Technology changes rapidly and if an older vaccine is stockpiled and a superior vaccine is licensed, the CDC could be in the position of having to destroy millions of dollars worth of the older vaccine," he said.
An example would be if DTaP/Hib combination vaccine were licensed for the primary series and adopted into the routine immunization schedule. This would likely result in the destruction of existing stockpiles of individual DTaP and Hib vaccines.
Changes in recommendations also affects stockpiling decisions. The 1999 polio vaccination schedule relies heavily on the use of IPV rather than OPV usage, which affects the amount of IPV and OPV to be stockpiled.
Cost and contractual issues should be considered, because stockpiles are ultimately an insurance policy against supply problems and disease outbreaks which may, or may not, occur, Flaherty explained. The cost of these concerns has to be balanced with other priorities. Regarding contracts, the CDC must have certain guarantees about crucial components of stockpile management, such as prompt delivery in the event of an outbreak.
While the CDC currently stockpiles MMR, IPV and the pediatric formulation of diphtheria and tetanus toxoids, it is also working to include additional vaccines to better ensure against vaccine supply disruptions.
However, vaccines not under consideration for stockpile by the CDC include: DTaP, Hib, DTP/Hib, hepatitis B (adult) and pneumococcal vaccines.
The decision whether to stockpile Varicella and hepatitis A vaccines has been deferred. Despite that there is only one manufacturer, varicella was deferred because of cost considerations, the probability that a combination vaccine containing varicella will be developed, and because a refrigerator-stable product will likely be on the market in the next few years.
CDC believes there is a potential for hepatitis A vaccine stockpile but is unsure to what level. The Advisory Committee on Immunization Practices recommended routine hepatitis A immunization in 11 states with the highest incidence of infection, but the CDC wants to study hepatitis A vaccine usage before making the decision to stockpile.
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