Efficacy is evaluated at this stage, leading to a major decision at Gate H to progress to registration. The PDP is focusing on the performance of Phase 3 and regulatory, anticipating that efficacy and safety data will meet TPP attributes and support the related product information in the leaflet. Potential additional indications should be sought in subsequent Phase 4 clinical studies.

The business plan is consolidated, integrating the latest market assessment and forecasts, refined Cost of Goods assumptions and an initial pricing approach (see function ‘Market, Access and Implementation’ and function ‘Production Process’).

The IP position is further strengthened.

Funding for activities covering the whole stage should be secured.

Stability data have been generated from the first R&D lot and for each manufacturing lot. These stability data should be compared, as part of the characterisation of the product. A sufficient amount of vaccine product from the Phase 3 production has to be stored to serve as a long-term reference standard for QC product assays.

Provided that all pre-set criteria for product and process are confirmed, meaning that no major out-of-specification issues occurred, the production process can be executed for routine manufacturing.

After completion of the Phase 3 study and production of its Clinical Study Report, the CCDS is updated with safety, immunogenicity and efficacy data from Phase 3 and this becomes the Summary of Product Characteristics (SPC). Start compiling data for the Marketing Authorisation Application dossier.

The Phase 3 study has been completed; safety and efficacy data are analysed. The complete study report is prepared. If vaccine consistency has not been established at this stage, a study of safety and immunogenicity consistency of lots should be carried out.

Draft a plan for Phase 4 studies to assess vaccine safety and effectiveness in field conditions and in populations that have not yet been studied during Phase 3 studies.

The review of Phase 3 safety data evaluates further the profile of common and less common reactions induced by vaccination. The pooled analysis of safety data should support an acceptable safety profile in the target population, as per TPP. When available, preliminary data in HIV-infected individuals should not raise a safety concern in this population.

During the Phase 3 trial an appropriate range of biological specimens have been collected. The investigational plan to identify a Correlate of Protection should be developed based on the analysis of Phase 3 immunogenicity and efficacy data.

Analysis of the data from the Phase 3 trial should confirm protective efficacy against the primary case definition endpoint greater or equal to the minimum predefined efficacy as set in the TPP in the target population for licensure.

During Phase 3, the market assessment is completed. It will contribute to fine-tune the demand and supply plan (see also Business development, legal and IP’), Cost of Goods assumptions (see also function ‘Production Process’), pricing and ultimately further build the business plan (see also function ‘Business development, legal and IP’).

At this stage, based upon cost of goods (see also function Production Process) and pricing assumptions, the initial pricing strategy is refined. The strategy is supported by a value-based approach documented by the HEOR rationale and data. It will need to encompass an international vision, taking into account for example specificities of high, middle and low income countries, (multi-tiered pricing strategy). The planning and prioritisation in gathering relevant data to support this value-based approach is crucial because of the timing and costs of these activities.

A formal ‘value dossier’ will support the medical and economic rationale of the vaccination programme. It will contain a summary of the clinical, economic and societal value, and supporting evidence (studies) for the new TB vaccine as well as background and information on TB (i.e., burden of illness, epidemiology, etc.). The value dossier is developed as an evolving document that can serve as a template for customising submissions to local, national and/ or supranational customers and other stakeholders at a later stage.

Based on the access strategy, an initial market access plan is developed, focusing as a priority on the early adopter countries, and describing the in-country activities and operations.

Regular consultations with stakeholders identified earlier (see stage F) are crucial to prepare regulatory submissions, WHO pre-qualification, integration in GAVI VIS (see GAVI vaccine investment strategy) policy recommendation, implementation studies, financing and product launch.

TB vaccine target population considerations

For adolescents/adult vaccines, a tiered pricing strategy should be considered according to potential use in high-risk groups in developed countries.

For neonates/infant vaccines, there is a need to take current BCG pricing and volumes into account.

For therapeutic vaccines, a tiered pricing strategy should be considered taking into account use in TB patients in developed countries. Existing drug pricing and reimbursement mechanisms will be key parameters to analyse and integrate into the analysis