Vaccine shortages frustrate everyone

Scarcity leads to calls for stockpiles and campaigns stressing the importance of an uninterrupted immunization schedule.

By Susan J. Landers, AMNews staff. March 4, 2002. Additional information

Washington -- Serious shortages of vaccines for childhood diseases are rocking the foundation of preventive medicine, physicians have warned the Centers for Disease Control and Prevention.

Antigens used in four commonly administered vaccines are in short supply, forcing physicians to postpone necessary immunizations until supplies are available -- a date that is often uncertain.

This latest chapter in the ever-growing saga of vaccine paucity prompted the CDC to gather some key players for a brainstorming session on how to strengthen future supplies.

"Vaccine delayed is vaccine denied," Louis Z. Cooper, MD, professor of pediatrics at Columbia University, told the gathering. The shortages are undermining the trust of families, he said, and leaving pediatricians "frustrated, fearful and anxious."

Calling the shortages "an acute and significant problem," the AMA recently asked Health and Human Services Secretary Tommy Thompson to establish a departmental task force to examine the reasons for recent shortages, which also include diagnostic agents and other drugs.

The task force should include representatives from the Food and Drug Administration, the CDC and the Agency for Healthcare Research and Quality, and it should seek the input of the pharmaceutical industry, distributors, physicians and pharmacy organizations, said the AMA.

The long-term impact on patients should also be considered, L.J. Tan, PhD, senior scientist at the AMA, told meeting participants. When patients are turned away, will they come back, or will they lose their "medical home" to the supermarket that has, for example, received a supply of flu vaccine while the physician has not, he asked.

Serious shortages exist for eight childhood disease antigens: Those used in the measles, mumps and rubella (MMR); invasive pneumococcal disease (pneumococcal 7-valent conjugate); diphtheria, tetanus and pertussis (DTaP); and chicken pox (varicella) vaccines, said Walter Orenstein, MD, director of the CDC's National Immunization Program.

The CDC convened the Feb. 11-12 meeting to bring together pharmaceutical companies, physicians, federal agencies and insurers to air concerns and develop some possible solutions to offer to the agency's National Vaccine Advisory Committee, which was scheduled to meet Feb. 20-21.

Included among the strategies:

• Creating additional stockpiles of vaccines that could be tapped during shortages.
• Increasing funding and liability protection for manufacturers who bear the cost of developing the vaccines and for the physicians who administer them.
• Requiring manufacturers to provide adequate notice before they halt production of a vaccine.

Physicians can also play an important role by doing a better job explaining to parents and policy-makers how crucial it is to resolve the shortages, said Jerome O. Klein, MD, professor of pediatrics at Boston University. "A national advertising campaign is needed on the importance of vaccines," he told the gathering.

While the idea of creating a national vaccine authority was also discussed, the consensus seemed to be that there are enough agencies already empowered to oversee the production of vaccines, said Dr. Klein.

For example, the CDC's advisory committee has acted by releasing guidelines to ration supplies and ensure that patients most in need receive the vaccines.

The committee's revised recommendations for pneumococcal conjugate vaccine, released Dec. 10, 2001, call for high-risk children younger than 5 years to be given top priority.

The committee also continued its earlier recommendations for the DTaP vaccine that called for deferring the fourth dose of the vaccine until supplies are more plentiful. The committee was expected to take up the varicella vaccine shortage during its next meeting. There is a waiting list for 292,000 doses of varicella vaccine, said Dr. Orenstein.

To avert a shortage of MMR vaccine, the CDC allowed its manufacturer, Merck and Co. Inc., to borrow 700,000 doses from a CDC stockpile of 3.1 million doses. All 700,000 doses had been shipped to purchasers as of Jan. 21, Dr. Orenstein reported.

Manufacturing hurdles

Addressing the problem of shortages from the industry's perspective, Wayne Pisano, an executive vice president at Aventis Pasteur, urged the group to consider the complex nature of vaccine manufacturing.

"Vaccines require the use of biological organisms, viruses and bacteria, which will not always grow or respond on demand," he noted. Production time is lengthy and purity and potency tests are strict.

In addition to the complexity of the organism, other reasons have come into play during the past few years that contribute to the shortages, Pisano said. Prime among them are decisions by manufacturers to discontinue production.

For example, Wyeth-Ayerst Laboratories' decision to stop manufacturing the tetanus toxoid prompted ongoing shortages of the tetanus vaccine. The withdrawal of Wyeth left Aventis as the sole manufacturer.

It takes Aventis Pasteur between 27 and 32 weeks to produce a purified bulk lot of Td vaccine, said Pisano. Production is followed by eight to 10 weeks of testing and four to six weeks of packaging and final approvals. "All in all, it takes about 11 months to produce a lot of Td vaccine," he said.

The flu vaccine shortage that has plagued physicians and patients for the past two years was aggravated by factors that arise each year. "It will always be a challenge to provide 80 million doses of flu vaccine by Oct. 31," said Pisano, because manufacturers are essentially producing a new vaccine based on virus strains selected early in the year.

Added complications are contributing to the shortage of DTaP. The requirement that thimerosal be removed as a preservative from all childhood vaccines forced Aventis to repackage its DTaP from multi-dose to single-dose vials to avoid the risk of contamination. This also necessitated additional licensing work.

"The net effect is that we invested approximately two years' development effort to replace an existing product," said Pisano.

A collaborative effort will be needed to resolve the problems, said Pisano. But the effort would be worthwhile to maintain a vaccination enterprise "that has resulted in freedom from disease for millions of children."

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Some vaccines are in short supply. Here's why:

Measles, mumps and rubella (MMR) - Manufacturing difficulties.
Chicken pox (varicella) - Manufacturing difficulties.
Invasive pneumococcal disease (pneumococcal 7-valent conjugate) - Increased demand.
Diphtheria, tetanus and pertussis (DTaP) - One of only two manufacturers of tetanus toxoid stopped production; the remaining manufacturer can't meet demand.

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Drug Shortages page from the FDA's Center for Drug Evaluation and Research (http://www.fda.gov/cder/drug/shortages/)

Drug Products Shortages Management Resource Center from the American Society of Health System Pharmacists (http://www.ashp.org/shortage/)

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Copyright 2002 American Medical Association. All rights reserved.