Novel licensure pathways for expeditious introduction of new tuberculosis vaccines: A discussion of the adaptive licensure concept

Abstract

The ultimate goal of vaccine development is licensure of a safe and efficacious product that has a well-defined manufacturing process resulting in a high quality product. In general, clinical development and regulatory approval 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 TB vaccines, where correlates of protection are not yet identified, phase 2 and 3 efficacy of disease prevention trials are, by necessity, very large. Each trial would span 2-5 years, with full licensure expected only after 1 or even 2 decades of development. Given the urgent unmet need for a new TB vaccine, a satellite discussion was held at the International African Vaccinology Conference in Cape Town, South Africa in November 2012, to explore the possibility of expediting licensure by use of an "adaptive licensure" process, based on a risk/benefit assessment that is specific to regional needs informed by epidemiology. This may be appropriate for diseases such as TB, where high rates of morbidity, mortality, particularly in high disease burden countries, impose an urgent need for disease prevention. The discussion focused on two contexts: licensure within the South African regulatory environment - a high burden country where TB vaccine efficacy trials are on-going, and licensure by the United States FDA --a well-resourced regulatory agency where approval could facilitate global licensure of a novel TB vaccine.

Caregivers' Willingness to Accept Expedited Vaccine Research During the COVID-19 Pandemic: A Cross-sectional Survey

“…32,33 Emergency vaccine preparation and production and a change in risk/benefit ratio due to high morbidity and mortality have been suggested as acceptable. 11,34 While parents are concerned about the adverse events associated with vaccines, perhaps even more than the symptoms of illness itself, 35 more adverse events during a pandemic may be acceptable from a public health perspective. 34 Another important factor that may influence caregivers' willingness is the fact that COVID-19 infection in children is largely a self-limiting, benign disease.…”

“…9 The first COVID-19 vaccine candidate entered human clinical testing with unprecedented speed, on March 16, 2020, 1 and the first Phase III trials were begun just 4 months later. 10 Fast-Tracking the vaccinelicensure process has been explored in the past in other infectious diseases, including tuberculosis, 11 serogroup B meningococcal disease, 12 and Zika virus. 13 In the United States, it has been estimated that only two thirds of people would be willing to undergo COVID-19 vaccination.…”

Novel approaches to vaccine development in lower-middle income countries

“…A regulatory approval would come in stages in parallel with marketing, either by time-limited conditional approval or indication limitation. This regulatory pathway is considered applicable for a novel tuberculosis vaccine with experiences likewise in a new tuberculosis drug and meningococcal group B vaccine (Rustomjee et al, 2014).…”

Tuberculosis vaccines: Time for a global strategy

“…Most recently, adaptive trial designs, which modify ongoing trials in response to interim results and plan accordingly, have been proposed for accelerated clinical development. Adaptive vaccine trials could deliver safety and e& -cacy data more rapidly by allowing iterative modif cations af er participant enrollment in response to interim safety or e& cacy signals (9). For example, participant numbers could be increased or decreased and duration of follow-up modif ed on the basis of new disease incidence data, prognostic clinical surrogate end points, or interven-FOCUS tion regimens.…”