Function

The aim of market access activities for a TB vaccine is to secure the introduction of the vaccine into national immunisation programmes (accessibility) together with subsequent funding (affordability) from national and/ or supranational sources as close as possible to market authorisation, to ensure timely and impactful vaccination coverage of the targeted population and therefore meet the vaccination programmes objectives.

This guidance presents the main steps of a comprehensive market access process independent of the company or institution that will perform them. It should help vaccine developers to understand the full approach including the steps that should be initiated in early development stages that could also contribute to a better understanding of the value of the product candidate for potential partners.

There are a number of publicly available general and target-specific references and guidance that should be taken into account when planning market access activities.

For indications in neonates and adolescent/ adults, alignment should be kept with both programmatic suitability and value proposition described in the latest version of WHO PPC for New TB Vaccines. The development of a vaccine for neonates should also be guided by the latest SAGE recommendations / report for BCG (SAGE report BCG).

There is currently no specific guidance for therapeutic TB vaccines, although an advanced draft of the WHO PPC for therapeutic vaccines is available (WHO PPC for Therapeutic vaccines) The Standard of Care (ie drug regimen) in the potential target countries should become a key component of the market access activities, including Health Economics and Outcome Research.

Stage 
E
Perform, First-in-human/Ph1
Gate 
E
Progress to Ph2
Main Activities
  • Based on TPP identify potential list of targeted countries (early, middle and late adopter countries) and considering income (low, average, high)
  • Collect epidemiological, burden of disease data and market data in targeted countries for a preliminary market assessment
CRITERIA REQUIRED
  • Initial list of targeted countries established, with rationale
  • Preliminary market assessments & business strategy available for targeted countries
Plus Icon
Guidance

The objective is to implement as part of or in parallel to Phase 3 the HEOR activities that will enable gathering of key data and the elements to subsequently develop the value dossier to support the medical and economic rationale of the vaccination programme.

A draft of this value dossier should be developed during stage H and 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 core 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.

At this stage, the initial pricing strategy should be drafted and developed. 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.

Regular consultations with stakeholders that were identified in earlier stages are crucial to prepare regulatory submissions, WHO pre-qualification, policy recommendation, implementation studies, financing and product launch.

Target-specific 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.

Stage 
F
Perform Ph2 (including Pre-POC) studies
Gate 
F
Progress to Ph2b Efficacy
Main Activities
  • Establish a multidisciplinary market access team
  • Based upon business strategy, develop understanding of all relevant international stakeholder’s requirements (WHO, GAVI, UNICEF, etc.) and develop mapping
  • Prepare international and national stakeholders mapping, including civil society and TB-affected communities
  • Start to analyse healthcare systems and requirements of countries for integration in National Immunization Program (NIP) and funding
CRITERIA REQUIRED
  • Capacity and expertise to support market access activities available
  • Processes and requirements of international stakeholders understood
  • Map of stakeholders available and engagement underway
  • Countries healthcare systems and requirements analysed
  • Initial identification of early, mid- and late adopters available
Plus Icon
Guidance

A multidisciplinary market access team should be constituted at this stage. The team is comprised of all functions that are necessary to support the process from initiation until completion of a market access plan. This includes, though is not restricted to, Epidemiology, Clinical, Regulatory, Health Economics and Business. Vaccines Europe is currently reviewing 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 and in poor populations, the market access strategy may differ from a European-focused strategy (vaccineseurope.eu) on a case-by-case basis. A dedicated project management tool would facilitate the process of establishing a market access plan.

The major purpose of the activities at this stage is, in alignment with the business strategy, to identify important international (WHO, GAVI, UNICEF) and national (Ministry of Health, Ministry of Finance) stakeholders, including civil society, that will influence the vaccine implementation decision-making processes. The aim is to understand their requirements in terms of data,studies, assessments, including for example Health Economic elements. In addition to desk research, external ad-hoc studies may be worth conducting at this stage 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.

Target-specific considerations

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

Neonate/ infant vaccine: Focus on motivation and evidence for replacing BCG beyond TPP, 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 vaccination implementation need to be identified.

Stage 
G
Perform Ph2b Efficacy
Gate 
G
Progress to Ph3
Main Activities
  • Identify data gaps and options to close them in early (middle, late) adopter countries, aiming to build evidence and meet requirements from stakeholders
  • Identify complementary studies and/or protocol evolution (Phase 3) to close data gaps in early (mid, and late) adopters
  • Define Health Economics, Outcomes Research (HEOR) activities to support health economics (HE) rationale (cost-effectiveness, health and budget impacts, etc.) in early (middle and late) adopters
  • Initiate interactions with major stakeholders (countries, Global Fund, GAVI, UNICEF etc.)
  • Draft market access strategy
CRITERIA REQUIRED
  • Data gaps and options to close them identified
  • Complementary studies and/or protocols evolution (Ph3) to close data gaps identified
  • HEOR activities defined
  • Interactions with major stakeholders initiated
  • Market access strategy drafted
Plus Icon
Guidance

The Market Access team needs to identify the gaps between available data and evidence required by the different stakeholders. A second step is to define in a dedicated plan how 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 novel 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 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 to understand their requirements and the relevance of the gap analysis plan.

Stage 
H
Perform Ph3
Gate 
H
Progress to licensure
Main Activities
  • Develop pricing strategy as per HE outcomes
  • Consult and engage national and international stakeholders
  • Draft a market access plan
  • SSSSS
CRITERIA REQUIRED
  • Draft core value dossier available for international stakeholders and early (priority), mid and late (option) adopters
  • Pricing strategy defined
  • National and international stakeholders engaged
  • Market access plan draft available
Plus Icon
Guidance

The objective is to implement as part of or in parallel to Phase 3 the HEOR activities that will enable gathering of key data and the elements to subsequently develop the value dossier to support the medical and economic rationale of the vaccination programme.

A draft of this value dossier should be developed during stage H and 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 core 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.

At this stage, the initial pricing strategy should be drafted and developed. 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.

Regular consultations with stakeholders that were identified in earlier stages are crucial to prepare regulatory submissions, WHO pre-qualification, policy recommendation, implementation studies, financing and product launch.

Target-specific 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.

Stage 
I
Register vaccine with relevant Regulatory Authorities
Gate 
I
Obtain MA and Progress to launch
Main Activities
  • Continue to consult and engage international stakeholders (WHO) and develop dialogue to include new TB vaccine in GAVI’s “Vaccine Investment Strategy“ (VIS)
  • Execute HEOR activities to close data gaps in early adopter countries
  • Identify and test options for introduction in NIP and for funding of early adopters in low, middle and high income targeted countries
  • Finalise value proposition and core value dossiers for early adopters (priority)
  • Update pricing strategy as per HE outcomes
  • Begin engaging communities and civil society to prepare market entry, including demand generation and education
  • Finalise market access plan
CRITERIA REQUIRED
  • National and international stakeholders engaged
  • Complementary studies to close data gaps implemented; all data to build the rationale of the HEOR are available
  • Product value demonstrated to support introduction in NIP and funding according to identified options
  • Core value dossier for international stakeholders and early (priority), mid and late (option) adopters finalised
  • Pricing strategy updated
  • Communities and civil society engaged
  • Market access plan finalised
Plus Icon
Guidance

During the Regulatory file review, consultations and coordination with WHO, GAVI (see GAVI vaccine investment strategy) and other regional or national decision makers are essential to minimise the delay between vaccine registration and implementation.

Pricing strategy and core value dossier are finalised, complemented by all relevant data gathered in the course of Phase 3 and 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

Target-specific 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 guaranties.

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.

Stage 
J
Launch
Gate 
J
Implement vaccination programs
Main Activities
  • Obtain GAVI programmatic commitment
  • Obtain national immunization program recommendations (and funding) starting by early adopters countries where vaccine is launched
  • Prepare private market
CRITERIA REQUIRED
  • GAVI funding secured
  • NITAG recommendations obtained
  • Funding obtained in early adopters (high income) countries
  • Commercial launch prepared
Plus Icon
Guidance

This stage covers, based on regulatory approval, the WHO pre-qualification, obtainment of SAGE recommendations, funding commitments from GAVI 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.