title: 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.
authors.affiliation: Strategic Health Innovation Partnership, South African Medical Research Council, South Africa; Vaccine Development BioSciences Division, Emergent BioSolutions, Emergent Product Development, United Kingdom, Ltd., United Kingdom. Electronic address: roxana.rustomjee@mrc.ac.za.
authors.forename: Roxana
authors.initials: R
authors.lastname: Rustomjee
authors.affiliation: Vaccine Development BioSciences Division, Emergent BioSolutions, Emergent Product Development, United Kingdom, Ltd., United Kingdom.
authors.forename: Stephen
authors.initials: S
authors.lastname: Lockhart
authors.affiliation: Oxford Emergent Tuberculosis Consortium, United Kingdom, Ltd., United Kingdom.
authors.forename: Jacqueline
authors.initials: J
authors.lastname: Shea
authors.affiliation: Department of Medical Microbiology, University of Pretoria, South Africa.
authors.forename: P Bernard
authors.initials: PB
authors.lastname: Fourie
authors.affiliation: Vaccine Development BioSciences Division, Emergent BioSolutions, Emergent Product Development, United Kingdom, Ltd., United Kingdom.
authors.forename: Zoë
authors.initials: Z
authors.lastname: Hindle
authors.affiliation: Medicines Control Council, South Africa.
authors.forename: Gavin
authors.initials: G
authors.lastname: Steel
authors.affiliation: Vaccines for Africa, Institute of Infectious Diseases and Molecular Medicine, Faculty of Health Sciences, University of Cape Town, South Africa.
authors.forename: Gregory
authors.initials: G
authors.lastname: Hussey
authors.affiliation: Aeras, Rockville, USA.
authors.forename: Ann
authors.initials: A
authors.lastname: Ginsberg
authors.affiliation: Global Affairs, Aeras, Rockville, USA.
authors.forename: Michael J
authors.initials: MJ
authors.lastname: Brennan
mesh_terms: D017277:Drug Approval / Q000458:organization & administration*; D015195:Drug Design; D005260:Female; D017408:Guidelines as Topic; D006801:Humans; D008004:Licensure; D008297:Male; D013019:South Africa; D032581:Tuberculosis Vaccines
chemical_list: D032581:Tuberculosis Vaccines
keywords: Licensure; Regulatory; Strategy; Tuberculosis; Vaccines