Who’s Minding the Shop? Ensuring Vaccine Safety and Efficacy

Who’s Minding the Shop? Ensuring Vaccine Safety and Efficacy

The safety of the people shall be the highest law.

—Marcus Tullius cicero

One of the most popular arguments used by the anti-vaccine movement is that vaccines are not studied or monitored thoroughly enough before coming to market. Some people opposed to vaccines will claim that they are “not against vaccines, per se.” They just want them to be “safer.” The reality is that vaccines are among the most thoroughly tested and monitored interventions that we offer in modern medicine. This chapter will review the evolution of vaccine safety regulations and the organizations that enforce them. It will also follow vaccines through their lifecycle, looking at the development of immunizations, their testing, and the postlicensure monitoring that provides highly effective checks and balances for these life-saving interventions.

The assertion is also made that, because pharmaceutical companies (“Big Pharma”) are involved with vaccine production and because pharmaceutical companies are in business to make a profit, there is inherent corruption in the vaccine development process—that somehow vaccines are pushed through without proper regulation just to turn a profit for the “pharmaceutical fat cats.” In the following pages, we will also look at the role that drug companies play in the development of immunizations and offer hope that they are not, after all, pushing through untested vaccines or bilking the medical establishment and patients out of billions of dollars.

We will next look at the alphabet soup of organizations that play a role in vaccine oversight and monitoring. We will gain a better understanding of the organizational structure of vaccine and public health-related governmental programs as well as those privately funded groups that aid their efforts. Finally, we will dive deeper into the Vaccine Adverse Events Reporting System (VAERS), its successes and limitations, and the misconceptions about this system that allow people to think that there is some national conspiracy to offer unsafe medical interventions.


Today, the US vaccine supply is among the safest in the world, thanks to the extensive oversight and regulation that exists to ensure efficacy and safety. However, this was not always the case. Certain unfortunate events in the history of vaccines spurred the development of the highly successful system of checks and balances that we use today. Let’s look at a few of these events and the safety measures that were put in place as a result.

1902 Biologics Control Act

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

Polio and the Cutter Incident

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

National Childhood Vaccine Injury Act

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:

  • 1. Coordinate vaccine-related activities between all Department of Health and Human Services (DHHS) agencies, including the FDA, the Centers for Disease Control and Prevention (CDC), the NIH, and the Health Resources and Services Administration (HRSA).

  • 2. Require health care providers who administer vaccines to give a Vaccine Information Statement, which contains a description of the disease and risks and benefits of the vaccine, to each person receiving a vaccine or to their guardian.

  • 3. Require health care providers to report certain possibly vaccine-related adverse events to the VAERS.

  • 4. Establish the National Vaccine Injury Compensation Program (NVICP) to compensate, on a “no-fault” basis, those persons who were potentially injured by vaccines.

  • 5. Establish a committee from the Health and Medicine Division of the National Academies of Science, Engineering, and Medicine (formerly the Institute of Medicine) to review the literature on potential vaccine reactions.

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 assertion by the anti-vaccine movement that vaccines are not studied thoroughly enough before being brought to market is unfounded. In fact, vaccines are the most thoroughly studied intervention that we have in modern medicine, so much so that it can actually be a problem to address emergent needs in the setting of illness epidemics and pandemics. (See Appendix C: Vaccine Topics Explained to find videos on how vaccines are made.) The development of a vaccine is an involved and highly regulated process that takes years (typically 10-15) to complete. Following is an outline of the phases of prelicensure vaccine development, as well as the postli-censure monitoring that continues after a vaccine is brought to market, that ensures the safety and efficacy of our vaccine supply5 (Figure 5.1).

FIGURE 5.1 Phases of vaccine development. (From George Washington University. Producing prevention: The complex development of vaccines. Milken Institute School of Public Health. February 15, 2017. Accessed December 19, 2018. publichealthonline.gwu.edu/blog/producing-prevention-the-complex-development-of-vaccines/.)

The Exploratory Phase

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

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.

The Clinical Development Phase

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.

Phase I Clinical Trials

The first stage of testing in humans is conducted on a small number of study participants (typically fewer than 100) and may be nonblinded or open-label, meaning that participants and researchers may know who is getting a vaccine and who is getting placebo. If the proposed vaccine is intended for children, testing will first be done on adults and then, as safety and efficacy are established, testing will occur with younger subjects until the target age population is reached. The goal of this phase is to establish safety and determine the kind of immune response that the vaccine may induce.

Phase II Clinical Trials

If phase I testing is promising, a larger number of study participants (on the order of several hundred) will be enrolled in clinical trials. These participants may be people at risk for acquiring the disease (these vaccines are often tested in other countries where illness may be more prevalent). Typically, these trials are randomized, well controlled, and include a placebo group. The goals in this phase are to assess safety, immunogenicity, dosing, scheduling of immunizations, and method of delivery.

Phase III Clinical Trials

If a vaccine makes it to phase III trials, a much larger group of subjects (thousands to tens of thousands) are enrolled for testing. Phase III trials are randomized, doubleblinded, and placebo controlled. The goals here include more of the same. Safety continues to be a primary end point. In these trials, we may expect to find rare side effects that are only detectable in a larger group and may not be seen when fewer subjects are studied. Efficacy is evaluated, looking at whether the vaccine prevents disease, whether it prevents infection with the pathogen, and whether it induces an adequate immune response (measurable antibody response) (Box 5.1).

Regulatory Review and Approval Phase

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.

Quality Control

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.

The Drug Manufacturer

Phase IV clinical trials are optional trials that the vaccine’s manufacturer may choose to conduct after release of the vaccine for general use. These trials monitor effectiveness and safety but also look for other potential uses or applications of the vaccine.

The Vaccine Adverse Events Reporting System

VAERS was established in 1990 as a “national early warning system to detect possible safety problems in US-licensed vaccines.”6 It takes reports of adverse events from any concerned party and investigates the claims to look for any patterns suggesting safety issues with a vaccine. It is managed jointly by the CDC and the FDA.

Mar 16, 2020 | Posted by in GENERAL & FAMILY MEDICINE | Comments Off on Who’s Minding the Shop? Ensuring Vaccine Safety and Efficacy
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