Immunization Issues

Vaccine Supply and Shortages

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Updated: 10/18/2006

 

• Background
• Causes of vaccine shortages
  • Manufacturing or production problems
  • Companies leave the marketplace
  • Changes in manufacturing recommendations
• Dealing with vaccine shortages
  • Assesing the solutions
  • Insufficient stockpiles
• Summary
• Current number of licensed vaccines and commercial manufacturers in the US

 

Background

Safe and effective vaccines are central to the prevention and control of communicable diseases. As a consequence, any shortage of vaccine places children and adults at risk for vaccine-preventable diseases. Vaccine shortages have been a problem in the past and are likely to be a problem in the future.

For instance, since 2000 the United States has experienced shortages of influenza, diphtheria-tetanus-acellular pertussis (DTaP), tetanus and diphtheria (Td), measles-mumps-rubella (MMR), varicella, and pneumococcal conjugate vaccines. (1,2)

In October 2004, one of two manufacturers of the inactivated influenza vaccine announced that it would not be able to provide trivalent inactivated (killed) virus vaccines (TIV) for that influenza season. This caused both a TIV shortage and an imbalance in the distribution to those who need it the most. Healthcare providers place their vaccine purchase orders well in advance of when vaccine is to be given and in this case before the vaccine became available. Thus some providers had all the vaccine that they would normally need whereas others had none. 

Causes of vaccine shortages

Manufacturing or production problems

• There is only a single US producer of MMR, PCV7, varicella vaccine and now TIV.  (See table below)
• Renovations in the MMR and varicella vaccine manufacturer's vaccine filling suite in 2001 resulted in a temporary interruption of the supply of those vaccines. 
• Complexities in the manufacturing process—particularly when there is more than one vaccine antigen present—can cause delays in vaccine production. Such has been the case with the shortages that have plagued the supply of the 7-valent pneumococcal conjugate vaccine (PCV7) since its licensure. 
• Two of the four influenza vaccine manufacturers during 2000 either withdrew from the market entirely or experienced substantial production delays leading to both a shortage in the supply of vaccine and problems distributing the vaccine equitably to all providers. 
• Problems in complying with industry manufacturing standards (called “current Good Manufacturing Practices” or cGMP)—which evolve over time—is not uncommonly a cause for vaccine to not reach the market, including the current influenza vaccine shortage. For example, failure to assure compliance with cGMP led to the problems with influenza vaccine supply in 2000, noted above.

Companies leave the vaccine marketplace

• When one manufacturer ceased production of DTaP in 2001 and Td in 2000, the other manufacturers couldn’t respond rapidly enough to maintain the vaccines supply because it takes 11 months to produce tetanus toxoid. 
• There are legal barriers that prevent communication between the key stakeholders in the manufacturing industry, federal government agencies, and others. This inability to be able to communicate prevents anticipation of emerging issues. (2) 
• In 2000 there were four manufacturers of inactivated influenza vaccine, one of whom left the market. There were two producers last year and there is but one this year. 
• Vaccine producers are pharmaceutical companies that are compelled to make vaccine production decisions based on profitability: 
  • Vaccines are often cost saving to society. Although everyone wants inexpensive vaccines, all pharmaceutical products compete with all of that company’s other products for corporate resources. Vaccine production must be sufficiently profitable for companies to be able to produce them.
  • Changing cGMP adds manufacturing costs, reducing the producers profit over time.
  • Recent increases in the price of TIV are expected to attract additional producers and new technologies to the US market. 

Changes in manufacturing recommendations

The national recommendation to reduce or eliminate the content of the preservative thimerosal in vaccines given to children less than 6 months of age, required that the manufacturers of DTaP revise their manufacturing process of these vaccines, requiring more vaccine to be produced for the same number of doses and requiring a different packaging system. This contributed to the shortages of these vaccines in addition to the reasons given above. (2)

Dealing with vaccine shortages

Assesing the solutions

In response to severe shortages of a number of vaccines in 2001, both the US General Accounting Office (3) and Department of Health and Human Services’ (DHHS) National Vaccine Advisory Committee (NVAC) (4) considered the causes of the shortages and ways to strengthen the supply of routinely recommended vaccines. They came to similar conclusions.

In conjunction with other groups interested in immunizations, NVAC examined 5 potential solutions: financial incentives to vaccine manufacturers; changes in the regulatory process; government-directed programs; vaccine stockpiles; and liability protections. (4)

NVAC concluded that disruptions to the supply of routinely administered vaccines are likely to continue to occur. Therefore, they proposed both short- and long-term solutions to DHHS. Some of these solutions are:

• Increase funds for vaccine stockpiles to include all routinely administered vaccines in sufficient quantity to be used for amelioration of supply problems or surge demands. 
• Require vaccine manufacturers to provide advance notification to the DHHS regarding intent to withdraw from the marketplace. 
• Increase the availability of accurate information about vaccine supply for opinion leaders and consumers. 
• Enhance the valuation of vaccines by initiating a national campaign to emphasize the safety, efficacy and great benefit of recommended vaccines for the public good.

To address NVAC’s recommendations, CDC completed site visits with the manufacturers, began development of a national vaccine stockpile strategic plan and contracted for additional stockpile purchases of varicella, H. influenzae type b, hepatitis A, hepatitis B and pneumococcal conjugate vaccines, among other things. (2)

Insufficient stockpiles

The Vaccines for Children (VFC) Act mandates vaccine stockpiles be maintained—to provide a six-month supply—of the various childhood vaccines. (1) These stockpiles could be used to mitigate short-term supply disruptions.

Stockpiled vaccines are owned by the federal government but stored by the manufacturer until CDC requests them—this is called a “buy and hold” arrangement. By doing it this way, the manufacturer rotates the stored vaccine by selling the oldest doses in the stockpile (when their shelf life goes below 12 months) and then replaces them with newly manufactured doses. That way the vaccine in the stockpile does not go out of date.

Expanding the stockpiles to include all the recommended childhood vaccines has encountered an unexpected obstacle: an accounting rule published by the Securities and Exchange Commission in 1999. The intent of the rule was to prevent deceptive accounting practices. While the rule may acomplish this in most circumstances, some of the companies that produce vaccines argue that this rule keeps them from classifying payments for stockpiled vaccines as “revenue” on their balance sheets. A solution to this problem may require congressional intervention.

• Currently, there are stockpiles of only two vaccines: VZV and MMR. 
• When there are production problems, there may be insufficient vaccine to place in a stockpile. This may especially be the case with a newly licensed vaccine. 
• Maintaining a stockpile of influenza vaccine is difficult because the vaccine usually changes each year.

Summary

Vaccine shortages repetitively emphasize the fragility and lack of redundancy of the vaccine supply.

Current Number of Licensed Vaccines and Commercial Manufacturers in the US

The following is  list of the 35 FDA-licensed, commercially-distributed, and CDC recommended vaccines in use by US civilians and military during the 1990s.
Number of manufacturers	Number of vaccines	Vaccines
0	7	cholera, plague, rotavirus, smallpox, Lyme, adenovirus Type 4 and adenovirus Type 7
1	21	MMR, polio, varicella, BCG, measles, mumps, MM, rubella, yellow fever, Td, TT, Diphtheria toxoid, anthrax, Japanese encephalitis,  meningococcal, pneumococcal conjugate, Hib-HepB, DTaP-Hib; DTaP-IPV-HepB,  pneumococcal polysaccharide, and LAIV influenza
2	6	DTaP, HepA, HepB, rabies, typhoid, and TIV influenza
3	1	Hib

References

1. CDC (2004). Current Vaccine Delays and Shortages. 

2. Santoli JM, Klein JO, Georges P, and Orenstein WA (2004). Disruptions in the Supply of Routinely Recommended Childhood Vaccines in the United States. The Pediatric Infectious Disease Journal, 23(6):553-554. 

3. General Accounting Office (2002). Childhood vaccines. Ensuring an adequate supply poses continuing challenges. GAO-02-987:1-46. 

4. National Vaccine Advisory Committee (2003). Strengthening the Supply of Routinely Recommended Vaccines in the United States: Recommendations From the National Vaccine Advisory Committee. JAMA, 290:3122-3128.