In 1901, 13 children in St. Louis, Missouri, died of tetanus after being treated for their diphtheria illnesses with a contaminated antitoxin. It was common at that time to use horse’s blood to make antitoxin serum but the blood of a horse that died of tetanus was accidentally collected and used in production. A similar tragedy occurred in Camden, New Jersey, when nine children died from tetanus after being given contaminated smallpox vaccine. These products had been produced in local laboratories with no uniform controls in place to ensure purity and potency and had undergone no inspection or testing of the final product prior to use. This triggered Congress to pass the 1902 Biologics Control Act, which gave the government control over processes used to make biological products and responsibility to ensure their safety. Under this act, the Hygienic Laboratory of the Public Health and Marine Hospital Service mandated that manufacturers of biologics be licensed and that their facilities undergo inspection. Production of biologics had to be overseen by a qualified scientist, and products had to have clear labeling, showing the product name and expiration date. In 1930, the Hygienic Laboratory was renamed the National Institutes of Health (NIH), and oversight of biologics remained under its purview until 1972 when the Food and Drug Administration (FDA) assumed control. Today, the FDAs Center for Biologics Evaluation and Research regulates biological products.¹

In 1955, Jonas Salk’s vaccine held significant promise for preventing the devastation of polio that was ripping across the United States. Salk’s vaccine had been tested on 1.8 million subjects and proved safe and effective.¹ However, once in use, case reports of children contracting polio after being given the inoculation began showing up. It was determined that the affected individuals had received a vaccine that contained live polio virus, which had survived the inactivation process during production at Cutter Laboratories in Berkeley, CA. In what came to be known as the Cutter Incident, more than 40,000 cases of polio were attributed to immunization with the Cutter vaccine, resulting in varying degrees of paralysis in almost 200 children and death in 10.² Vaccine production was halted until every manufacturing facility was inspected and stricter standards for ensuring full inactivation of the polio virus were employed.

Subsequent litigation regarding purported harms by other vaccines contributed to the decision by many vaccine manufacturers in the United States to get out of the business of developing or producing vaccines. The courts’ findings of “liability without fault” meant that vaccine manufacturers were liable for “damage without negligence” even if their product was made using the most current science available and according to industry standards.³

In the mid-1970s and early 1980s, after damages were awarded to groups of patients claiming harm from the diphtheria, pertussis, and tetanus vaccine (DPT)—despite lack of scientific evidence to support those claims—liability insurance costs skyrocketed, several vaccine manufacturers halted production, and vaccine prices soared. The subsequent shortage in the vaccine supply triggered concern by public health officials that we might see a recurrence of epidemic illness as a result. This prompted Congress to pass the National Childhood Vaccine Injury Act (NCVIA) in 1986. Under this act, the National Vaccine Program Office (NVPO) was established to do the following⁴:

As a result of these actions over the years, there has been significant improvement in the monitoring and testing of vaccines for safety and efficacy, and we can place our faith in the fact that our vaccine supply is one of the best in the world.

The exploratory phase begins with monitoring new, persisting, or mutating infections in the population and then moves to the basic science laboratory where infectious viral and bacterial particles, or antigens, are identified. These laboratories are generally run by academic or government scientists who are funded by the federal government, and this step of the process usually lasts between 2 and 4 years.

The Preclinical phase tests the safety and immunogenicity (or ability to induce an immune response) of proposed vaccines, using cell and tissue cultures. Animal subjects (mice and monkeys, for example) are commonly used at this stage of vaccine development, allowing researchers to gauge the type of response they may expect to see in humans. In this stage, the researchers may challenge their test subjects by vaccinating them and then exposing them to the targeted illness. Many candidate vaccines fail to achieve the desired immune response and never make it beyond this stage of development. These researchers are most often from private industry, and this phase of testing typically takes between 1 and 2 years.

An application for an Investigational New Drug is then placed with the FDA that has 30 days to approve or deny the application. At this phase, those putting forth the application are typically from private companies. They are charged with summarizing
the basic science data, describing the manufacturing and testing processes, and putting together a plan for the proposed study which an Institutional Review Board, from the institution where the clinical trials will be conducted, then evaluates for approval. Once this approval takes place, the vaccine candidate is subject to three phases of human testing.

If phase III clinical development trials are successful, the developer will submit a Biologics License Application to the FDA, which will then inspect the manufacturing facilities and approve labeling of the vaccine. The FDA continues oversight after the licensure to assure safety, purity, and potency of the vaccine.

This part of the production process is undertaken by major drug manufacturers. They are equipped with the personnel and infrastructure necessary to make and distribute large quantities of vaccines. They also see the benefit of profit from the sale of successful or widely used vaccines.

After a vaccine is brought to market, the monitoring and oversight do not end. The following organizations participate in ongoing safety and efficacy monitoring of our vaccine supply.