Abstract
Clinical vaccine development and regulatory approval generally occurs in a linear, sequential manner: Phase 1: safety, immunogenicity; Phase 2: immunogenicity, safety, dose ranging, and preliminary efficacy; Phase 3: definitive efficacy, safety, lot consistency; and following regulatory approval, Phase 4: post-marketing safety and effectiveness. For candidate filovirus vaccines, where correlates of protection have not been identified, and phase 2 and 3 efficacy of disease prevention trials untenable, large and/or protracted, each trial may span decades, with full licensure expected only after several decades of development. Given the urgent unmet need for new Marburg virus and Ebola Sudan virus vaccines, the Sabin Vaccine Institute hosted a key stakeholder virtual meeting in May 2021 to explore the possibility of licensure by use of an “animal rule-like” licensure process, based on a risk/benefit assessment specific to regional needs and informed by epidemiology. This may be appropriate for diseases where there are no or limited treatment options, and those prone to sporadic outbreaks with high rates of transmission, morbidity, and mortality. The discussion focused on two contexts: licensure within the Ugandan regulatory environment, a high burden country where Ebola vaccine trials are ongoing, and licensure by the United States FDA—a well-resourced regulatory agency.
Highlights
IntroductionVaccine regulatory processes generally follow similar (often called “traditional”) pathways to licensure; not every disease or every candidate vaccine conforms to traditional standards
Vaccine regulatory processes generally follow similar pathways to licensure; not every disease or every candidate vaccine conforms to traditional standards
The point for concurrence from the Food and Drug Administration (FDA) was how to bridge animal immunogenicity and efficacy to the human immune response. This included defining the appropriate time points for measuring the immune responses and defining an acceptable target antibody level associated with a particular probability of survival. While it took considerable time for the sponsor and the FDA to come to a consensus regarding the appropriate endpoints and bridging mechanism, it is thought that these experiences may be applicable to candidate vaccines being developed against other pathogens that cannot be readily tested for efficacy in human clinical trials [45,48]
Summary
Vaccine regulatory processes generally follow similar (often called “traditional”) pathways to licensure; not every disease or every candidate vaccine conforms to traditional standards. Either human challenge trials for vaccines are not possible due to a high case fatality rate of the challenge pathogen, or disease outbreaks are too infrequent and too small to gather enough efficacy data to support approval through a field trial. Despite the commonalities between traditional and non-traditional pathways, formal animal rule-like regulatory mechanisms are generally uncommon and often do not exist in the countries with endemic diseases against which vaccine efficacy cannot be tested in human trials. Among the meeting goals were gaining insights from participants on regulatory alignment and understanding existing regulatory mechanisms to vaccine licensure in the absence of human efficacy data With these efforts we seek agreement on the need for animal rule-like pathways in countries around the world and alignment on the core requirements of such pathways. The views presented here are those of the Vaccines 2022, 10, 368 authors and are not intended to represent the views of the institutions and organizations with which the authors are affiliated
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