Stage 
H
Perform Ph3
Gate 
H
Progress to licensure
Stage/Gate H
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

With efficacy and safety determined, the TPP develops into the Company Core Information (CCI), also called the Company Core Data Sheet (CCDS – see Regulatory, Stage D for further information), and the leaflet. The PDP now focuses on a description and integration of activities related to regulatory aspects aiming to obtain a Market Authorisation, and to marketing, leading to implementation.

Stage/Gate H
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 IP is updated. Any obstacles to commercialisation must be addressed. Budget and financial plan to licensure have been established and post-market commitments and funding have been secured. The plan between demand and supply is finalised.

Stage/Gate H
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.

Stage/Gate H
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.

Stage/Gate H
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

Phase 3 study has been completed and data are available for analysis. If vaccine consistency has not been established at this stage, a safety and immunogenicity consistency lots study should be planned as well as post-marketing studies committed.

Stage/Gate H
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

At stage H, the review of Phase 3 data confirm the profile of common and less common reactions. The pooled analysis of safety data support an acceptable safety profile in the target population which meets the TPP.

Preliminary data in HIV-infected individuals do not indicate a safety concern in this population and this should be confirmed in a Phase 3 trial.

A post-marketing safety study should address any unexpected event which would have occurred during pre-licensure clinical trials.

Stage/Gate H
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

Evaluate the biomarker samples collected during Phase 3 to detect potential correlates of risk and/ or protection. Evaluate samples from earlier studies utilising advances in the field that may have generated assays or correlates that were not available previously.

Stage/Gate H
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.
Post-marketing studies to confirm vaccine effectiveness should be planned to confirm effectiveness, duration of protection and the need for booster immunisations, as well as effectiveness in specific sub-populations.

Stage/Gate H
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.

A draft of the market access plan should be available at this Stage H.