Preventable Disease and Vaccine Supply: Overview

Introduction

Widespread vaccination has produced one of public health’s most impressive success stories: the reduction of vaccine-preventable diseases in the United States by an astonishing 99 percent over just a few decades. In 2001, however, an unprecedented shortage of several vaccines, including those for measles/mumps/rubella (MMR), varicella (chicken pox), and diphtheria/pertussis/tetanus (DPT), frustrated American pediatricians and parents alike. Fearing epidemic outbreaks that could occur in the face of such shortfalls, the Centers for Disease Control and Prevention (CDC) began maintaining a six-month emergency stockpile of many recommended pediatric vaccines in 2002.

Some critics have suggested that one key factor behind the instability of the American vaccine supply is the limited vaccine-manufacturing capacity. Whereas more than two dozen different American companies were in the business of making vaccines in the 1960s, that number steadily dwindled to a mere handful of multinational manufacturers in the twenty-first century. Many pediatric vaccines are produced by a single manufacturer.

The greatest public scrutiny, however, has focused on the nation’s chronic lack of an adequate supply of influenza vaccine. The CDC estimates that in a typical year in the United States, influenza will strike approximately 5 to 20 percent of the population, resulting in more than 200,000 hospitalizations and anywhere from 3,000 to 49,000 deaths. Although vaccination is recommended for all Americans six months and older, especially the elderly, young children, and the immunocompromised, approximately two-thirds of Americans—many of them in these high-risk categories—do not receive an annual flu shot, often because of insufficient supplies. In 2004, the CDC began maintaining a late-season stockpile of influenza vaccinations for children, but this does not guarantee that they will be received.

Experts have attributed the instability of the American vaccine supply to the reality that vaccine production in the United States is a profit-driven enterprise. It is therefore subject to free-market forces that have turned vaccine production into an unattractive business. Vaccines, which are produced from living cells and organisms, are expensive and highly risky investments for pharmaceutical companies. The development of a single vaccine can cost as much as $900 million, and the process can take fifteen years or longer, without any guarantee of success; thousands of subjects are needed to test the vaccine; and the US Food and Drug Administration (FDA) requires the manufacturer to obtain licensure before production can begin. In addition, over the years, private pharmaceutical companies have been forced to discard, at great financial loss, millions of doses of flu vaccine, either because the CDC made an incorrect prediction about the viral strains that were most likely to affect the United States (experts have to make this determination a year in advance, based on epidemiological events in China) or because they incorrectly estimated the demand for that year’s vaccine.

The threat of lawsuits due to vaccine injury used to be another major financial consideration for vaccine manufacturers. However, an increase in the number of lawsuits in the 1980s inspired Congress to pass the National Childhood Vaccine Injury Act of 1986, which established the National Vaccine Injury Compensation Program, thus reducing or eliminating manufacturers’ financial liability in such cases.

Understanding the Discussion

Epidemic: A disease that affects many individuals in a community or a population during a given time period.

Pandemic: An epidemic that occurs over a very wide area, crossing international boundaries and usually affecting a large number of people.

Thimerosal: A mercury-containing preservative that has been used in many vaccines and other products since the 1930s. In 1999, consumer advocates and parents’ groups campaigned to eliminate thimerosal from vaccines as a precautionary measure.

Vaccine: A preparation that contains an antigen (weakened or killed) obtained from a disease-causing organism, used to confer immunity against the disease that the organism causes. Vaccine preparations can be natural, synthetic, or derived using recombinant DNA technology.

History

Chronic vaccine shortages have always posed a deadly threat to public health in the developing world, where poverty and poor infrastructure often inhibit the purchase and distribution of medical resources. Although the first measles vaccine appeared in 1963, measles and measles-related complications killed nearly half a million young children worldwide, primarily in sub-Saharan Africa, and left many others permanently blind or brain damaged as recently as 2004.

In recognition of the potential of aggressive vaccination campaigns to save and improve millions of lives, the World Health Organization (WHO) kicked off its Expanded Programme on Immunization (EPI), aimed at dramatically increasing vaccination rates among children in developing countries, in 1974. The eradication of smallpox, the last naturally occurring case of which was diagnosed in 1977, represented one of the program’s greatest triumphs. Similarly, in 2001, the Measles & Rubella Initiative was founded by WHO, the CDC, the United Nations Foundation (UNF), the United Nations Children’s Fund (UNICEF), and the American Red Cross in order to distribute vaccines to children in developing countries; due in large part to their efforts, the number of measles-related deaths worldwide decreased from 544,200 in 2000 to 145,700 in 2013.

Before 1993, the CDC chose the lowest bidder for each year’s vaccine supply, leading to uncertainty and profit loss for companies that were not selected. Since then, the CDC has divided the contract between suppliers and allowed individual states to choose suppliers. The Vaccines for Children program, created in 1993, set a fixed price on many existing vaccines. Thus, prices do not increase with inflation and may result in little to no profit for the manufacturer, ultimately leading to supply problems. This is significant, as the US government purchases 40 percent to 60 percent of vaccines produced for distribution to the public. Pharmaceutical companies can work around this hurdle by releasing a new vaccine with a different formulation.

Around the turn of the twenty-first century, rich nations such as the United States began grappling with the logistical and ethical issues of how best to respond to the many preventable deaths in the developing world while also having to cope with vaccine supply problems of their own. For a three-year period beginning in 2000, shortages forced the United States to implement rationing programs for a number of key, universally recommended childhood vaccines. Approximately 80 percent of the global vaccine supply was being produced by just five multinational pharmaceutical companies. In many cases, a certain vaccine was only produced by a single company; if that company discontinued production, other manufacturers would struggle to make up the difference. Additionally, foreign companies were reluctant to enter US markets because the US government does not acknowledge clinical trials conducted in other countries.

Vaccine shortfalls could be traced in part to a 1999 decision by the FDA to ban the use of thimerosal, a mercury-based preservative, in childhood vaccines. The decision had significant implications for vaccine manufacturers and for the American vaccine supply. One company, for example, lost a quarter of its production capacity, as it had to repackage DPT in single-dose quantities to maintain the vaccine’s shelf life in the absence of the preservative. A second manufacturer decided to exit the market altogether. This had a strong impact on supply, as the company had been producing about one-third of the American DPT vaccines.

In response to public alarm over the possibility that American children might become vulnerable to as many as eight of eleven preventable infectious diseases for which there existed inadequate supplies of vaccine, federal lawmakers debated a number of proposals. One, introduced in 2001 but never passed, would have permitted the federal government to declare a public-health emergency and seize vaccines from the companies that made them.

Despite continuing concerns over disruptions to the nation’s vaccine supply, vaccine safety rather than supply issues dominated federal legislative proposals. The Mercury-Free Vaccines Act of 2005 (H.R. 881), for example, would have banned mercury from all vaccines given to children and pregnant women. The National Vaccine Injury Compensation Program Improvement Act of 2005 (H.R. 1297) would have extended the statute of limitations, provided a look-back provision for families who missed the filing deadline, increased compensation for injured children, and provided for interim attorney fees and costs. Neither bill was passed.

The September 11, 2001, terrorist attacks urgently refocused attention on the problem of vaccine supply. The Protecting America in the War on Terror Act of 2005 (S. 3) called for sweeping changes in pharmaceutical product liability, vaccine regulation, vaccine policy, vaccine research, and the Vaccine Injury Compensation Act. The Biodefense and Pandemic Vaccine and Drug Development Act of 2005 (S. 1873) would have restricted public access to vaccine regulatory information and required persons injured by vaccines to meet the highest standard of proof in civil law to recover just compensation. Again, neither bill was passed.

Preventable Disease & Vaccine Supply Today

Despite the continued elusiveness of an effective vaccine to prevent diseases such as malaria, dengue, and HIV, which continue to devastate parts of Africa and Asia, world health officials have begun to make significant strides in reducing the rates of vaccine-preventable diseases in the developing world. The Measles & Rubella Initiative set a goal to cut mortality from measles to just 5 percent of 2000 levels by 2015, and measles deaths declined 80 percent worldwide between 2000 and 2017. Following a resurgence of poliomyelitis throughout Africa, the Middle East, and Indonesia between 2002 and 2005, the disease was once again largely curtailed. According to the World Health Organization, by 2018 polio remained endemic only in three countries—Afghanistan, Pakistan, and Nigeria—with just twenty-two cases reported in 2017. In 2013, the WHO began stockpiling two million doses of cholera vaccine annually in order to speed response to emerging outbreaks, particularly in areas experiencing humanitarian crises.

Concerns over vaccine supplies have taken on renewed urgency in the United States as awareness of the risks posed by preventable diseases on a global scale has grown. Fears of bioterrorism have spurred the search for effective vaccines to stockpile against the threat of weaponized forms of the smallpox, anthrax, Ebola, and Marburg pathogens. Research on an Ebola vaccine was further galvanized by the 2014 outbreak of the disease in West Africa, leading to the development of several potential vaccines for evaluation in clinical trials. In addition, the CDC continues to maintain a stockpile of common vaccines in case of supply emergencies or epidemics. However, maintaining an adequate stockpile is challenging, as many manufacturers already produce at peak capacity. The CDC estimated that between 162 million and 169 million doses of influenza vaccine were produced for use in the United States for the 2019–20 influenza season. Waning immunity from some existing vaccines, such as pertussis, and growing antimicrobial resistance further necessitate vaccine development.

Yet, over half of the world's supply goes to waste each year, according to WHO estimates. One is reason is that most vaccines must be kept cold and electric power interruptions to refrigeration systems can jeopardize vaccine safety. This has been a major barrier for rural parts of the developing world, but can also threaten supplies wherever power backups may be lacking. Potential solutions to that particular challenge include the development of new heat-stable vaccines and innovation of solar-powered refrigeration units and other storage devices. Improved monitoring of market supply and demand could also ameliorate the wastage.

Meanwhile, around the world, particularly in middle- and high-income countries, misinformation about and mistrust of childhood vaccines have grown. A 2016 meta-analysis published in the Journal of the American Medical Association found that refusal to vaccinate, whether on religious, philosophical, or safety grounds, led to a dramatic increase in the number of measles and pertussis (whooping cough) cases in the US in the mid-2010s from record lows in 2000 and the 1980s, respectively. In 2019 the US experienced the largest outbreak of measles it had in decades.

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