With the decision to move the vaccine candidate into development, a formal market assessment should be performed at this stage, refining the preliminary data collection  in stage B (as part of the PDP, Project Management). The assessment includes medical need (from epidemiology data, incidence and disease burden), market characteristics and dynamics (economic situation, market size, standard of care (SOC), procurement and delivery processes), and positioning of the vaccine candidate versus the competitive landscape. The selection of the population and of the potential early adopter countries as first priority, and of middle and late adopter countries as second priority should also be made.  It will highlight drivers and barriers that will contribute to the medical and economic value of the vaccine and ensure that a viable market will exist. A comprehensive review of recent literature would be a relevant way to gather data needed for market assessment and business case. This market assessment will contribute to an initial business plan that validates the upcoming investments (see Business, Legal, IP, stage D).

The market assessment is refined according to new data.

At this stage a first market forecast will be developed, also based on a first range of Cost of Goods (CoGs) (with input from Production Process function). This will be instrumental to validate pricing assumptions and ultimately product viability in targeted countries, considering the critical driver of affordability especially in low-income countries.

These elements will also sustain a further development of the business plan (see Business, Legal, IP).

At this stage a multidisciplinary access team is constituted, comprised of all functions that are necessary to support the development of a comprehensive process to successfully introduce a TB vaccine together with an adequate immunization program that will fulfill public health needs. This includes, though not restricted to, Epidemiology, Clinical, Regulatory, Health Economics and Business. Vaccines Europe is currently reviewing the so-called market access best practices focusing on European countries and comparing to non-European countries. The market access approach for novel TB vaccines should be aligned with those practices. However, since TB is a global disease with significant burden in low and middle income countries the market access strategy is likely to differ from a European-focused strategy (vaccineseurope.eu).

In addition, it is important to identify and map international (WHO, GAVI, UNICEF) and national (Ministry of Health, Ministry of Finance) stakeholders, including civil society and communities, that will influence the vaccine implementation decision-making processes. The aim is to understand their requirements and constraints in terms of data and studies, including for example Health Economic or logistics elements. In addition to desk research, external ad-hoc studies may be worth conducting, such as qualitative interviews with international and/ or national key opinion leaders in the TB field. The outcome of this analysis should be a specific mapping of all relevant stakeholders that will also contribute to identify the early countries adopters.

TB vaccine target population considerations

Adolescents/adults vaccine: Gain an initial understanding of vaccination calendars in targeted countries, vaccine coverage rates in such populations, and barriers to vaccine implementation.

Neonate/infant vaccine: Focus on motivation and evidence for replacing BCG and understand national and supranational barriers.

Therapeutic vaccine: Gain initial understanding of Standard of Care in different countries and regions. Stakeholders are likely to be different from preventive vaccination and need to be identified and initial requirements assessed. Specific barriers to implementation need to be identified.

Market assessments are refined for further understanding and identification of potential early, middle or later adopters’ countries. A first demand and supply plan will be drafted, which will also contribute to an update of the business plan (see Business, Legal, IP).

The access team needs to define the data and tools that will be required to sustain the health economic rationale (modelling to support vaccine effectiveness, health and budget impacts, and willingness to pay (WTP) and build the evidence for the full value of vaccine/vaccination. This will identify the gaps between available data and evidence required by the different stakeholders. A second step would be to define a dedicated plan to address existing gaps during clinical Phase 3 development or beyond with the objective to quantify both clinical and economical outcomes of the use of the candidate vaccine. In order to build a gap analysis plan, Health Economic-Outcome Research (HEOR) activities should identify either trials or trial protocol adaptations and/ or modelling approaches to demonstrate the public health value of vaccination and to satisfy the perspective of the ultimate customer in terms of cost effectiveness and budget impact (Knight et al 2014, Bellini et al., 2016). The gap analysis plan will also provide the opportunity to prioritise among countries (feasibility/ cost approach) and draft an initial market access strategy.

Interactions with major stakeholders are key in order to further understand their requirements, gain their support and secure the relevance of the gap analysis plan.

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

During the regulatory file review, updates of the market assessment based on Phase 3 results will be conducted and the market access plan finalised

The value pricing strategy dossier and is finalised, complemented by data from Production Process on Cost of Goods, Clinical operations on Phase 3 and Regulatory. Dissemination at national and international level will be executed to gain support for an early implementation. Assessing barriers to uptake and proposing implementation strategies should be an essential part of the value dossier. National value dossiers also need to be prepared at least for targeted early adopter countries.

Consultations and coordination with WHO, GAVI (see GAVI vaccine investment strategy) and other regional or national decision makers including civil society and communities are essential to minimise time between vaccine registration and implementation.

Global and national marketing plans and activities need to be developed especially for early adopter countries.

TB vaccine target population considerations

For adolescents/adults, the value dossier needs to describe different possible implementation strategies (delivery platform for primary vaccination and for catch up). Co-administration strategies with existing recommended vaccines (HPV) will provide significant public health and economic value. The potential need for implementation studies based on Phase 3 data also has to be addressed.

For neonates/infant vaccines, Market Authorisation Approval will likely be required to convince national authorities to consider BCG replacement. Manufacturers may have to provide supply guarantees.

For prevention of recurrence, the value dossier needs to describe a preferred implementation strategy and be aligned with existing TB treatment infrastructure. Existing drug pricing and reimbursement mechanisms need to be taken into account.

For therapeutic vaccines, the value dossier needs to describe the added value of adjunct vaccination. The implementation strategy needs to be aligned with existing TB treatment infrastructure and practices. Existing drug pricing and reimbursement mechanisms need to be taken into account.

This stage covers, based on regulatory approval, and WHO pre-qualification, obtention of SAGE recommendations, funding commitments through GAVI and/or national mechanisms (recommendations and/or procurement). This requires a general update and regional/national adaptations of the value dossier (including data from Phase 4 clinical studies) and integration of additional requirements from authorities, policy makers and payers.

Pricing negotiations and agreements are finalised.

Commercial launch is achieved in the early adopters’ countries starting potentially with private market with dedicated marketing activities.