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A “Public Private Partnership-PPP” on European Pandemic Influenza by pharmphresh24


									EU influenza pandemic
preparedness plan – sufficiency in
vaccine supply and link to annual
vaccine uptake

Franz Karcher
Health Threats Unit
European Commission
EVM pandemic influenza proposals

Sent to Commission February 2004
HSC mandate discussed in Council
HS WG reviewed proposals in two
meetings -> report with comments
HSC adopted report in October 2004
Meeting HSC - EVM December 2004
 Follow up:
    Technical Brainstorm January 2005
    Drafting Group Meeting February 2005
             December 2004
             HSC – EVM Meeting
Vaccination Coverage Increase
    but there is a red line
Consider Pandemic Flu Vaccine
Development “PPP”
    3MSs (UK, NL, DEN) -> Underpinning ?
Follow Up
    Technical Expert Brainstorm meeting
    with EVM on “PPP” to identify elements
    -> 26-27 January
                   January 2005
                   Technical Meeting
EVM reaction “lukewarm”:
    Involve WHO ?
    Re-iterated need for financial support
    Endorsed APC concept
Vaccine Coverage:
    VCR studies needed
Continue dialogue:
    on basis of a written working document (WD)
Funding to be established
                      Drafting Group
                      Meeting 23 Feb.
(WD) Document to contain:

 Mission / concept “PPP”
 Key elements
   include “underpinning”
   include vaccination coverage increase
 Actors and their contributions
                          vaccination coverage in
                          Western Europe in 2000
                              No. of doses distributed / 1000 population

            Belgium                                                 223
         Netherlands                                          204
           Germany                                        186
                    UK                                    185
                 Spain                                   178
                  Italy                                 174
               France                                  170
              Iceland                                  170
         Switzerland                            127
            Portugal                            125
             Austria                           120
               Ireland                         119
             Finland                          115
              Greece                         110
           Denmark                         104
             Norway                       96
             Sweden                       92

                          0       50     100     150      200         250   300
DS Fedson, unpublished observations
                 Interface between pandemic
                 preparedness plans and pandemic
                 vaccine development
     Phase 0                    Phase 0                 Phase 0                 Phase 0
                          Preparedness Level 1    Preparedness Level 2    Preparedness Level 3

Interpandemic period      Appearance of a new     Human infection         Human transmission
No indications of any     influenza strain in a   confirmed: 2 or more    confirmed
new virus type have       human case              cases in human case     Seed distribution
been reported.                                    definition              starts
                                                                          Reagent preparation

- Anticipate the          - Development and        - Development and      - Adaptation of the
  pharmaceutical and        adaptation of the        adaptation of the      vaccine strain to the
  clinical development      pandemic stain to        pandemic stain to      production process;
  of pandemic-like          production process       production process   - Preparation of the
  vaccines, including                                                       license variation
  marketing                                                               - Start production
- Anticipate production
- Adapt production
- Develop monitoring
  systems for signal
- Adapt vaccination

Interpandemic Period                              Pre-Pandemic Period
         Interface between pandemic
         preparedness plans and pandemic
         vaccine development
    Phase 1              Phase 2               Phase 3               Phase 4             Phase 5

Confirmation of       Worldwide spread      End of first         Second or later     End of the
onset of pandemic                           pandemic wave        waves of the        pandemic
Several outbreaks                                                Pandemic            (Back to Phase 0)
in at least one
country and
spread to others

- Production starts   - Maximize            - Production         - Estimate           - Back to
- File variation        production effort     planning             remaining needs      “business as
- Conduct clinical    - Ensure vaccine        (remaining         - Production of        usual”
  trial with            distribution          needs)               inter-pandemic
  pandemic vaccine    - Monitor vaccine     - Monitor              vaccine
- Define                safety,               possibility of a
  implementation        effectiveness and     second phase
  strategies and        immunogenecity      - Re-start
  supply                                      interpandemic
                                            - Monitor safety

                                   Pandemic Period                                   Post-Pandemic
                                Proposals for Action Plan
         Proposals                          EVM Members
                                            EVM Members                            MSs & EC
                                                                                   MSs & EC
1 To prepare a flu pandemic
1 To prepare a flu pandemic                                                    EC to contribute through technical
     vaccine                              To develop, register and produce
      vaccine                                                                  & financial support

                                                                               MSs to increase vaccine
2 To increase the potential
2 To increase the potential                   To increase their production     interpandemic recommendations to
     influenza vaccination coverage
      influenza vaccination coverage
     of the EU population                            capabilities              populations aged 50 and over, and
      of the EU population                                                     children
3 To define supply agreements            To switch & to develop best efforts   MS to plan for their pandemic needs
      To define supply agreements        to maximise pandemic production       and adapt their interpandemic use;EC
     between MS and EVM members
      between MS and EVM members
     for flu pandemic vaccine             capacities versus interpandemic      to propose a framework;
      for flu pandemic vaccine
4                                         To respect commitments inside &      EC coordination to ensure
     To ensure equitable distribution
      To ensure equitable distribution
                                                     outside EU                management of public health needs
                                                                               inside (MS) & outside (WHO) EU
5                                                                              To anticipate price attribution &
    To anticipate pricing issues          To accelerate time to market and
     To anticipate pricing issues                                              encourage for a homogenous
                                              avoid supply disruption
                                                                               European price

6                                                                              To exempt manufacturers from
6 To provide liability protection
   To provide liability protection       To comply with quality requirements   liability & MSs to establish a
                                                                               national vaccine injury
                                                                               compensation program
     In order to protect 450 M EU inhabitants in case of a pandemic,
     an increase of the vaccination coverage from 20 to 33 % is needed
        = Need to increase # vaccinees from 90 to 150 M per year

Million doses
                                                                                         100      Maxi 100
                                                                                          70     for
        270                                                                               60
Million doses                                                                            50       Mini 50 %
                        x3                                                               40
Million doses X 3 / 2

Million doses

         Years x 3 Switching from a trivalent to a07
                     04        05       06
                                                   monovalent vaccine
                                                          08      09         10
                        Inter Pandemic
                        Pandemic (1 dose)                    Source : EVM modeling, Proposal for Action Plan, 2004
                        Pandemic (2 doses)
             A PPP to underpin the
              vaccine industry for
              pandemic influenza

Problems in case of pandemic influenza
at present

Total time of vaccine production is too long
Production capacity falls short
Protection of existing vaccines is not sufficient (60% in elderly)
A single dose will be less protective against a new pandemic
         A PPP to underpin the
          vaccine industry for
          pandemic influenza
Objective: Underpin the vaccine industry in preparing
           plans to manufacture influenza vaccine in an

Specific objectives:
  Production of seed stocks
  Testing candidate vaccines for protection in animal models
  Immunological testing to prove efficacy in humans
                       A PPP to underpin the
                        vaccine industry for
                        pandemic influenza
Production of seed stocks
1. Setting up a definitive, on-going library of wild type influenza strains

  In co-operation with the WHO collaborating laboratories in the partner nations.

   The collection will include representatives of all the major types and sub-
   types, selected using the expertise of the WHO.

2. Identification of potential risks and production of PR8 based reassortments

   Representative strains from each major type will be held as PR8 based
   reassortants (vaccine reference strains).

3. Production of seed stock (master seed banks) of selected strains

  Seed stocks will be made to GMP from a sub-set of the PR-8 collection, for
  those strains of which there is evidence of possible human infection.
             A PPP to underpin the vaccine
                 industry for pandemic
Production of seed stocks

4. Safety testing of seed stocks in chickens and ferrets

  Influenza PR8 reassortants are tested for safety, using a standard protocol of
  challenging chickens and ferrets, before they can be released.

5. Small scale production in eggs and cell culture

  A small number of seed stocks will be tested in representative egg and cell
  culture systems to determine suitability for production.
                  A PPP to underpin the
                   vaccine industry for
                   pandemic influenza

Testing candidate vaccines for protection in animal models
A small number of vaccine strains will be tested for protection in animal
models, in order to investigate the degree of cross-protection of seed
stocks and existing vaccine candidates against relevant wild type strains.

The ferret model of influenza:
              Well established, correlates well with human

              Indicators of infection: fever, virus load in lung
              A PPP to underpin the
               vaccine industry for
               pandemic influenza

Immunological testing to prove efficacy in humans

There is a clear need to establish an immune response that is a reliable
predictor of vaccine efficacy, as there is no clear correlation between HI
titers and protection.

For determining parameters that predict the efficacy of a pandemic
vaccine, further activities are needed
                                      A PPP to underpin the
                                       vaccine industry for
                                       pandemic influenza
                                Vaccine production for pandemic influenza
 Criteria for                Causing             Causing serious                      Potentially                        Pandemic
increasing to               disease in           human disease                         causing                             virus
 next phase               animals or man                                              pandemic

Phase                             I                     II                                III                                IV

Time scale
                            3 months                  1 month                          1 month                          3-4 months

 Vaccine            Bank               Produce PR8                Assemble                          Master seed stock                    Vaccine
production      collection of          reassortants          continuous library of                   ready to go to                     ready for
                  viruses                                        seed-stocks                           producers                           use

                                                                 Start basic trial                      Start trials          Start cross-
                                                             investigating 1.1-1.4                       1.1-1.4          protection studies
                                                              for one H5, H7 and                        using the         with pandemic virus
  Human and Animal
                                                             H9 prototype virus for                     candidate          using ferrets and
       trials                                                 licensing purposes                         vaccine           sera from human

Role of industry
  Manufacture trial lots of vaccine
  Submit core pandemic dossiers for different mock up
  vaccine strains in accordance with EMEA guidelines

Role of public sector
  Develop a library of seed strains
  Support clinical trials for mock up vaccine
  Assist in clinical trials
  Undertake serological and animal challenge studies for
  efficacy testing

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