Project Management
Main Activities
  • Update PDP
  • Set activities, deliverables and criteria to pass Gate J
CRITERIA REQUIRED
  • PDP updated to include (a) details by functional area to launch and implement vaccination programs; (b) summaries of additional product data collected and (c) updated timelines and budget
  • Activities, deliverables and criteria to pass Gate J approved
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Guidance
Guidance

The PDP is updated to include activities of each functional area to launch and implement vaccination programmes.

Business/ Legal/ Market
Main Activities
  • Validate Business case, demand and supply plan
  • Launch in early adopters countries
CRITERIA REQUIRED
  • Business Case, demand and supply plan validated
  • 1st commercial launch achieved
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Guidance
Guidance

The PDP is updated to include activities of each functional area to launch and implement vaccination programmes.

Production process
Main Activities
  • Routine Manufactory including Quality Management System for trouble shooting, including CAPA
CRITERIA REQUIRED
  • Manufacturing plant operating at initial commercial scale
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Guidance
Guidance

For the routine production of vaccine product for the market, a production plant has to be available. For attenuated live strains of Mtb or BCG it is likely to be a dedicated production facility. For a subunit vaccine product, campaign-wise production after change-over in a multi-purpose facility could be considered, also linked to the required volumes.

All the resources required for sustainable delivery of a sufficient amount of product need to be secured at the correct quality level. This includes trained personnel, approved documentation, released seed stocks, raw materials and disposables, and validated production equipment. In addition, a system to effectively deal with deviations has to be in place (Corrective actions/Preventive actions for all types of failures, CAPA).

Regulatory
Main Activities
  • Register with additional NRAs
  • Submit WHO prequalification (following stringent NRA MAA or EMA Article 58 positive opinion)
CRITERIA REQUIRED
  • NRA additional approvals obtained
  • WHO prequalification obtained
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Guidance
Guidance

When Marketing Authorisation has been obtained from a stringent Regulatory Authority (or scientific opinion from Article 58 procedure with EMA), the WHO prequalification dossier is completed and submitted. WHO prequalification allows supply of the vaccine to the health agencies of GAVI eligible low-income countries, non-GAVI eligible middle-income countries or PAHO countries.

The WHO prequalification process includes a review of production and quality control, testing of consistency lots and audit of the manufacturing facilities. WHO  ensures that vaccine efficacy data and studies are relevant to the target population, that vaccines used in immunisation programmes are safe and effective and meet the specific needs of the programme (programmatic aspects),which are: WHO recommendations and UN tender specifications are met, stability meets the needs of immunisation programmes, the immunisation schedules are compatible with those existing in national immunisation programmes, data on no interference with co-administered vaccines are available, and finally samples, labels, inserts and packaging will suit the UN tender requirements.

A model Package Leaflet (insert) for BCG vaccines (link to BCG model insert) has been prepared by WHO to provide guidance to manufacturers on format and content for preparation of Package Leaflet for their vaccine. It is not intended to provide information specific to any particular vaccine brand. Vaccine manufacturers using this model to prepare their own Package Leaflet, should ensure that the information on their vaccine Package Leaflet is specific to their vaccine. Specific information should be consistent with (does not contradict) the model but can be more comprehensive and detailed.

WHO has published guidelines on international packaging and shipping of vaccines (WHO/IVB/05.23).

The vaccine can then be launched in the countries. Launch involves a number of regulatory activities that depend on countries regulations. For example, after release of commercial batch by the manufacturer, application for official batch release by the Official Medicines Control Laboratory of the country of manufacture should be sought. Another example is the application for export licence. Another is to create, as per national/regional requirements, packaging elements with prescribing information derived from the authorized Summary of Product Characteristics (Package Leaflet, legible, clear and easy to use, labelling, primary and secondary packages). These may require approval by regulatory authorities before launch. Finally, to notify regulatory authorities of initial placing on the market of the product as per national/regional requirements.

Clinical Development and Operations
Main Activities
  • Complete operations and conduct phase 4 studies
CRITERIA REQUIRED
  • Phase 4 studies initiated
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Guidance
Guidance

Phase 4 studies are initiated and carried out.

Clinical Safety
Main Activities
  • Execute pharmacovigilance plan in phase 4 studies
CRITERIA REQUIRED
  • Phase 4 studies initiated
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Guidance
Guidance

Phase 4 safety studies are initiated and performed as planned.

Clinical Safety
Main Activities
  • Evaluate vaccine effectiveness in phase 4 studies
  • Conduct additional co-administration studies
CRITERIA REQUIRED
  • Phase 4 studies initiated
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Guidance
Guidance

Phase 4 studies to determine vaccine effectiveness are initiated and carried out as planned.

Market Access
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
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Guidance
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.