Project Management
Main Activities
  • Develop Company Core Information and leaflet versus Target Product Profile (TPP)
  • Update Product Development Plan (PDP)
  • Set activities, deliverables and criteria to pass Gate H
CRITERIA REQUIRED
  • TPP becomes Company Core Information
  • The updated PDP now focuses on a description and integration of main activities in regulatory and marketing. It contains a planning and budget
  • Activities, deliverables and criteria to pass Gate H agreed and finalised
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Guidance
Guidance

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. Hopefully, efficacy and safety data meet TPP attributes and support the related product information in the leaflet. Additional indications should be sought in the Phase 4 clinical studies.

Business/ Legal/ Market
Main Activities
  • Analyse and update Intellectual property (IP)
  • Establish budget and financial plan to licensure
  • Finalise demand and supply plan
CRITERIA REQUIRED
  • IP obstacles to commercialization resolved
  • Budget for licensure established
  • Demand and supply plan validated
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Guidance
Guidance

The intellectual property is updated, and obstacles to commercialisation addressed. The activities leading to licensure are budgeted and covered. The plan between demand and supply is further defined together with cost of goods assumptions. An initial market plan is developed at this stage. The initial market plan is developed at this stage focusing as a priority on the the early adopter countries.

Product Characterization and quality
Main Activities
  • Release Good Manufacturing Practices (GMP) Phase 3 and consistency batches
  • Evaluate stability data against TPP
CRITERIA REQUIRED
  • No major out-of-specs for the product as listed in the Bill of Testing (BOT). Consistency of batches documented
  • Stability studies completed and data support TPP
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Guidance
Guidance

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.

Production process
Main Activities
  • Manufacture Clinical Trial Material (CTM) for Phase 3
  • Prepare consistency batches of vaccine (final formulation, at market scale) for registration
CRITERIA REQUIRED
  • Phase 3 material produced with no major out-of-specs for the production process
  • Consecutive consistency runs completed and product batches for Phase 3 testing available; consistency between batches documented, confirming process consistency
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Guidance
Guidance

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.

Clinical Development and Operations
Main Activities
  • Complete operations and conduct Phase 3
  • Plan and obtain funding for community engagement for Phase 3, in line with Good Participatory Practice guidelines
  • Initiate planning for Phase 4 studies
CRITERIA REQUIRED
  • Phase 3 completed and data available
  • Community engagement plan and funding in place for Phase 3
  • Product consistency established
  • Draft Phase 4 plan established
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Guidance
Guidance

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.

Clinical Safety
Main Activities
  • Evaluate safety against TPP
  • Draft a post-marketing RMP, including evaluation in specific target studies (i.e. HIV infected individuals)
CRITERIA REQUIRED
  • Pre-licensure safety is acceptable and meets TPP, allow a favourable benefit-risk assessment
  • Post-marketing RMP is updated and includes post_marketing safety evaluation study and specific target studies
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Guidance
Guidance

During the Phase 3 trial biospecimens have been collected. The investigational plan to identify a CoPshould be developed based on the analysis of Phase 3 immunogenicity andefficacy data.

Clinical Immunology
Main Activities
  • Analyse correlates of protection based on Phase 3 immunogenicity and efficacy data
CRITERIA REQUIRED
  • Correlates of protection evaluated
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Guidance
Guidance

During the Phase 3 trial bio specimens have been collected. The investigational plan to identify a CoP should be developed based on the analysis of Phase 3 immunogenicity and efficacy data.

Clinical Efficacy
Main Activities
  • Evaluate clinical efficacy against TPP
  • Establish plan for phase 3 extension
  • Draft a post-marketing evaluation plan for vaccine effectiveness
CRITERIA REQUIRED
  • Protective efficacy meets TPP
  • Plan for phase 3 extension established if needed
  • Draft post-marketing effectiveness evaluation plan (Phase 4, etc.) available
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Guidance
Guidance

Analysis of the data from the Phase 3 trial confirmed 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.

Market Access
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
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Guidance
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.