Action needed on all fronts to prevent future vaccine shortages

The vaccine shortage issue made the list of top stories again this year, as physicians learned to handle shortages, and public health officials worked to prevent them in the future.

Shortages with seven childhood vaccines have been largely resolved with only one vaccine, the pneumococcal conjugate vaccine (PCV7, Prevnar, Wyeth), currently in short supply. However, the questions and reports continued all year.

For physicians, the issue was purely pragmatic. How do I get them? What do I do with kids who cannot be vaccinated now? And how do I get them back into the office when the shortages are over?

The Advisory Committee on Immunization Practices made recommendations to stretch the supply, but otherwise pediatricians were on their own. Most likely no one will ever know how many missed opportunities to vaccinate there were because of the shortage.

“I think it is important for us never to forget that immunization has become the foundation for preventive pediatrics. When you rattle the foundation, you rattle the entire preventive health structure for children in this country,” said Louis Cooper, MD, earlier this year. Cooper is professor of pediatrics at Columbia University and outgoing president of the AAP.

While the vaccine community was quick to respond before irreparable harm was done, we may not be so lucky in the future, several expert panels have warned. Already, there are reports that influenza and polysaccharide vaccines will be in short supply next year, and the PCV7 shortage will probably continue until next year.

Several factors caused the shortages, including manufacturer dropouts, failure to comply with FDA regulations, uncertainty in the market and changes in regulatory requirements. If the underlying causes of those problems are not addressed, experts say, the U.S. vaccine market leaves itself vulnerable to future disruptions in supply.

A report from the National Vaccine Advisory Committee (NVAC) outlined the problem and called for several short- and long-term solutions. A second report by the General Accounting Office (GAO), commissioned by Congress, also called for legislation to address glaring holes in the supply chain.

But the “wheels have been turning slowly,” said Jerome O. Klein, MD, professor of pediatrics at the Boston University School of Medicine and chair of the NVAC working group on vaccine supply. Other government programs compete with vaccines for time and money. Now childhood vaccines may take a back seat as the health system gears up to vaccinate health care workers against smallpox, said Klein, who is also a member of the Infectious Diseases in Children editorial advisory board.

Turning talk into action

One of the most talked about solutions, and probably the quickest to implement, according to Klein, is creating vaccine stockpiles of all childhood vaccines. Congress has allotted money for vaccine reserves since 1983, but the CDC has traditionally only stockpiled vaccines made by a single manufacturer like the inactivated polio vaccine (IPV, IPOL, Aventis) and the measles-mumps-rubella vaccine (MMR, M-M-R-II, Merck), as well as vaccines for emergencies like tetanus.

Several logistical problems have slowed the expansion of stockpiles to include all childhood vaccines, but more importantly, experts say, money is needed to make surplus purchases and to ensure proper storage in the cold chain.

Separate pieces of legislation by Hillary Clinton (D-N.Y.) and William Frist, MD, (R-Tenn.) are now making their way through Congress to earmark money for the creation of stockpiles. While the specifics of stockpiles still need to be ironed out, it is probably easy to get agreement on their necessity, said Klein.

“You want to do the doable and get done what can be done, even if it is not going to directly solve the vaccine shortages,” he said.

The job now is to keep legislative focus on the problems with the vaccine market. Stockpiles would only bridge gaps in supply during shortages and so would only be a short-term solution. There are bigger and more complex problems with vaccine supply that also need correcting to avert future shortages.

Vaccines have traditionally been high-risk, low-profit ventures for pharmaceutical companies. Investors tend to shy away from vaccines because they require extensive and expensive clinical testing before licensure and tend to favor projects on potential blockbuster drugs.

The idea of government owned or sponsored manufacturing has been proposed as one strategy, but the pharmaceutical industry has largely rejected that idea, saying it would be redundant and unnecessary. Instead, several advisory panels have suggested incentives or tax-breaks to manufacturers to keep them interested in making vaccines.

The costs of bringing a new vaccine to market can be astronomical, but they pale in comparison to the risks companies face when those products reach consumers. There has been anecdotal evidence that cost of investment has kept some smaller biotechnology companies from participating in vaccines, but it is a well known fact that fear of liability has caused some pharmaceutical companies to drop out of the market.

Congress created the Vaccine Injury Compensation Program to adjudicate claims of vaccine harm in 1986 after years of contentious litigation led some companies to stop production of vaccines. The program pays claims based on a predesigned table without the need for trial by jury.

But now, trial lawyers have found unique ways to circumvent the process, particularly with thimerosal litigation. Several lawsuits claim thimerosal to be a contaminant, not a preservative, and therefore, not covered by the injury table, while several class-action suits seek money for medical monitoring. However, a new provision to the Homeland-Security Bill will block these claims.

Another suggestion is a review of the regulatory process to make licensing vaccines more predictable and to make sure manufacturers stay compliant with current Good Manufacturing Practices (GMP). Supplies of several vaccines, including MMR and varicella (Varivax, Merck) and some formulations of hepatitis B vaccine became scarce after FDA inspections found issues with manufacturing conditions.

Pharmaceutical companies have complained that the FDA’s current GMP are ambiguous and difficult to interpret. Meanwhile, the FDA has said that its standards are intentionally vague so they can be dynamic and reflect the latest advances in technology.

The FDA’s licensing review process has also come under fire. While not a direct cause of vaccine shortages, regulatory requirements have made it difficult for companies to maintain viability and may be a disincentive for new companies to enter the market.

An undercurrent of the dilemma has been that vaccines are under-appreciated, both by the public and by the public health system. Preventive medicine has proved effective and cost saving, but parents are still turning away vaccination in scores and legislative action to correct supply problems has slowed to a crawl.

Despite all the talk this year, a solution does not seem close, so pediatricians should be prepared to for future shortages. In addition, they must get kids back into their offices over the coming months to help them catch-up on vaccines they missed.

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• Dr. Klein is a paid consultant of Wyeth-Lederle Vaccines and Aventis Vaccines.