It takes several years to make a vaccine and test it for its safety and utility. There are currently a handful of different approaches used to make vaccines:
To learn more about how some of these vaccines are made, view the "Vaccines and Your Baby" video, and go to the "Click here to learn about specific vaccines" section.
The vaccines made using cell lines originally isolated from two elective abortions performed in the early 1960s include:
The cell lines are maintained in laboratories so that no further abortions need to be performed to make these vaccines. The reasons that fetal cells were originally used included:
So, as scientists studied these viruses in the lab, they found that the best cells to use were the fetal cells mentioned above. When it was time to make a vaccine, they continued growing the viruses in the cells that worked best during these earlier studies.
People critical of vaccines often cite issues related to how a vaccine is made, such as the amount of time a vaccine has been tested, the number of people who received it, and the ingredients in the vaccines. An understanding of how vaccines are made may rest some of these concerns.
Usually a vaccine begins not at a pharmaceutical company, but in a research laboratory in a university, medical center or small biotech company. Scientists in these laboratories are most often funded by grants from the government or private foundations. These scientists often spend years researching whether their ideas work, developing reagents and tests to measure their success (or lack thereof), and finally, using animals to test their ideas. In some cases the ideas are tested in small animals like mice, rats or rabbits and then again in larger animals such as monkeys.
During this time, several different scientists or groups of scientists may be working toward the same goals, e.g., developing a vaccine against a certain virus or bacteria. The progress of these scientists is evaluated by other scientists through presentations at scientific meetings and peer-reviewed papers in journals. Scientists working at pharmaceutical companies often attend these meetings and review journals to see what ideas seem to be working. If any of the work seems promising, the pharmaceutical scientists may approach those working on it about expanding their research toward product development. This process may take 5 to 10 years.
The great majority of university scientists never develop ideas that are turned into products; most enjoy the success of adding to the general body of knowledge that is science.
Once an idea appears promising, it must be tested in a small number of healthy adults. These studies usually include less than one hundred people and answer two main questions: does the vaccine generate the expected immune response and is the vaccine safe?
During phase I trials, scientists at the pharmaceutical company must study how to make the vaccine in a quantity large enough for preliminary trials. They also must determine what preservatives or stabilizers to add so that the vaccine does not break down and whether any adjuvants are necessary to generate a strong enough immune response. Any preservatives, stabilizers or adjuvants that are going to be in the final vaccine must be used in the trials.
In addition, company personnel must develop assays that consistently show positive results when expected and negative results when expected, and they must complete an application to inform the Food and Drug Administration (FDA) of their intentions.
This phase often takes one to two years to complete.
The next phase of trials involves several hundred people. During this phase, scientists try to determine the proper dose of vaccine to be given, and they continue to study the vaccine's safety. They also continue to define methods for manufacturing the vaccine, stabilizing the product, determining packaging vials, and establishing assays necessary for the trials. An important aspect of this phase is to establish manufacturing consistency, so that each lot comes out with similar results.
The manufacture of the vaccine must also be completed in the building that would be used to make the final product. The company must continue to keep the FDA apprised of its progress and results during this time; at any time during this process the company or the FDA can decide against continued development.
While phase II can take as little as two years, it often takes much longer to complete all of the work necessary for this phase of development.
This is the final stage of development before a company requests product licensing, and it takes three to four years to complete.
Studies in this phase of development include thousands of study participants who are similar to the population that will receive the vaccine (e.g., infants for a new infant product). The number of participants is calculated so that statistical differences between the experimental group and control group can be observed. These calculations depend on frequency of disease in the population, estimated participant dropout rates, and ability of the assays being used to show differences. For example, trials on the rotavirus vaccine (RotaTeq® and Rotarix®) required about 130,000 participants because the companies had to determine that these two vaccines did not cause a bowel obstruction caused by an older version of the vaccine (Rotashield®).
During this phase, the company must also continue working on final facility and assay specifications and study how long the vaccine can be used before it expires, taking into account how it will get to the users (doctors' offices, for example) and how it will be stored. Any testing sites (those recruiting patients or testing samples) must be monitored to ensure that protocols are being followed consistently. Samples must be collected and analyzed to study the participants' immune responses, whether they get the disease, and whether they suffer adverse reactions.
During these studies, as with the previous phases, no one working with the patients, testing the samples collected from patients, or calculating the results, knows which participants received the vaccine and which did not.
After completion of these studies, it takes another year and a half to two years for the company to review the data, complete the product license request, and launch the product. The FDA, which does site visits throughout the entire process, then takes about 10 months to further study the data before the product can be offered to the public.
After licensure, experts for the Centers for Disease Control and Prevention (CDC) will also review the data and determine who should be able to get the vaccine. This is essentially the third set of scientists reviewing the same data. Often, the company or healthcare providers who helped run the phase III studies will also publish the results in a scientific journal for review by other scientists.
By the time the product is offered to the public, it has been studied for at least 10 to 15 years (usually longer) in tens of thousands of study participants, by thousands of scientists, statisticians, healthcare providers and other personnel, and has cost about $800 million dollars to produce. There are many products that never reach this stage. Companies are constantly evaluating a product during the trials to determine whether they are worth pursuing. Many ideas are abandoned during the different trial phases.
Because rare side effects may be observed once the vaccine is given to the larger population, the vaccine continues to be studied. In addition to monitoring by the manufacturer, there are two systems of long-term monitoring, the Vaccine Adverse Event Reporting System (VAERS) and the Vaccine Safety Datalink (VSD).
VAERS gathers reports of adverse events. Anyone can report these events; however, because this reporting system is voluntary, it cannot be used to prove there is a problem.
If the reports suggest a potential problem, scientists can examine the Vaccine Safety Datalink, a system that can mine data from a group of eight large managed care organizations, to determine if a group of vaccine recipients has experienced a greater occurrence of the adverse event than a similar group who has not received the vaccine. Scientists can also set up a hypothesis-driven research study to examine whether the vaccine is causing the adverse event. These types of studies have been able to detect adverse events as rare as 1 in 100,000.
Updated: February 2013
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