Clinical vaccine development

Han, Seunghoon

The final step in the clinical evaluation before product license is the 'Phase III' trial. This stage is intended to provide a pivotal conclusion needed for marketing approval, and the efficacy and safety of formulation(s) of the immunologically active component(s) must be assessed in the large-scale target population [18, 21] . The clinical outcome is strongly recommended as a parameter for comparing efficacy (e.g., with placebo/active control groups). Therefore, serological data are usually collected from at least a subset of the immunized population at predefined intervals. The designs of Phase II and Phase III clinical trials are similar, but the size of a Phase III trial is much larger. In consideration of the modern vaccination strategy-administration of multiple vaccines at the same time-interaction and/or interference with other vaccines are evaluated routinely. It is sometimes not possible to conduct a confirmatory study to determine the protective efficacy of products containing the same antigens that are already used commonly and/or whose target disease has a very low incidence [21] . The information obtained during the developmental processes mentioned above are summarized and filed for submission to regulatory authorities in support of an application for marketing approval. The WHO and each regulatory authority have their own guidelines to ensure the quality of the information provided [21, 22] . As an example, the United States Food and Drug Administration (FDA) calls the process 'Biologics License Application' (BLA). The multidisciplinary FDA review team reviews the efficacy and safety information needed to make a risk-benefit assessment and is advise by Vaccines and Related Biological Products Advisory Committee (VRBPAC). The appropriateness of label contents and the reliability of the manufacturing process are also reviewed [23] . Even though a vaccine may be licensed, the safety information provided for licensure is regarded as insufficient, because at that point, only a few thousand people have likely been exposed to the vaccine. Thus, many vaccines undergo postlicensure ('Phase IV') studies. In the United States, the Vaccine Adverse Event Reporting System (VAERS) was established to detect possible signals of adverse events associated with vaccines [24] .