As schools re-open their doors and families prepare for the upcoming school year, vaccines are often a part of the back-to-school preparations. In light of this, the public health community recognizes August as National Immunization Awareness Month (NIAM).
During this month, vaccine advocates plan events and activities to raise awareness about the benefits of vaccination for people of all ages. Since everyone benefits from vaccines, understanding a bit about how they are made might be of interest. Therefore, in celebration of NIAM, Parents PACK will address how what’s in the vial gets there.
The first steps for developing a vaccine usually take place in a research laboratory at a university, medical center or small biotech firm. The scientists in these places often spend years researching ideas. As data accumulate, promising projects may be taken over by larger companies, or researchers may take their data to potential partners that would offer the funds to pursue the next level of development.
Initial work is often done using animals. The government or private organizations usually fund these efforts, and their promise is evaluated through publication of peer-reviewed papers in journals and presentations at scientific meetings. This stage can take about five to 10 years.
Phase 1 trials
Phase 1 trials offer the first opportunity to test a potential product in people; the small number of people, usually less than 100, are typically healthy adults. Before a phase 1 trial can begin, the Food and Drug Administration (FDA) must review and approve the study. The goal is to determine whether the candidate vaccine generates an appropriate immune response and whether it is safe.
Research teams will also begin to figure out how to make large quantities (scale up production), ensure the product remains uncontaminated and stable during storage (addition of preservatives and stabilizers), and evaluate whether adjuvants will be needed to increase the level or duration of immunity. Tests must also be developed to ensure production consistency. Only if all of these parameters can be met will the process continue. Many potential vaccines don’t make it past Phase 1 trials. Potential vaccines that show promise will move to phase 2.
Phase 2 trials
Phase 2 trials continue to test the safety of the vaccine by expanding the size of the study to include several hundred volunteers more similar to the group that will receive the vaccine if it gets licensed. Additionally, aspects of product development, such as proper dosage, side effects, and reliability of manufacturing plan are also evaluated.
The dose is determined by figuring out the lowest amount of active ingredient that will induce appropriate levels of immunity. With regard to the manufacturing plan, an important aspect is to establish consistency, so that each batch — or lot — of vaccine is produced with similar results. At this point, the company must be producing the doses in the same facility they would use if this candidate vaccine becomes a product.
Phase 2 trials can last as little as two years, but typically take much longer and represent a large financial commitment toward development of the product. This being said, some candidate vaccines do not move beyond phase 2 trials because of the findings related to safety or manufacturing.
Phase 3 trials
The final stage before a company can request product licensing from the FDA is phase 3 trials. In phase 3 trials, thousands or tens of thousands of volunteers representing the population that will receive the vaccine participate. Safety, efficacy (whether the candidate vaccine works) and manufacturing continue to be monitored.
These studies typically involve hundreds of scientists and doctors and generate thousands and thousands of pieces of data, all of which need to be submitted to the FDA for review before the product can be licensed. In addition, the FDA conducts site evaluations to ensure that the manufacturing facilities are adequate and protocols are being followed according to the specifications. In other words, the FDA licenses both the product and the facility in which the product is manufactured. It can take one to three years for the FDA review to be completed.
Phase 4 trials (post licensure)
Vaccine safety monitoring does not stop once a vaccine has been licensed. The FDA and CDC closely monitor vaccine recipients for possible side effects. This monitoring is done in a variety of ways by hundreds of public health officials, scientists and physicians across the country.
First, in areas of high vaccine distribution, local health departments monitor vaccine recipients. The CDC also monitors data reported by health departments across the country. In addition, programs like the Vaccine Adverse Event Reporting System (VAERS) and the Vaccine Safety DataLink (VSD) provide useful information. Doctors, nurses or consumers can file a report in VAERS if they believe a vaccine has caused a side effect. The VSD includes about 6 million people in six large HMOs; data can quickly be analyzed when vaccine safety concerns arise by comparing people who did and did not receive the vaccine to determine whether a link is present.
As you hear about vaccines during this National Immunization Awareness Month, remember the amount of time and effort that goes into testing them before they are licensed and approved — and check to make sure you and your loved ones are up to date.
VEC: Making Vaccines
CDC: Journey of Your Child’s Vaccine
VAERS: Vaccine Adverse Event Reporting System
VSD: Vaccine Safety Datalink