Stockpiling of H5N1 vaccines Norbert W. Hehme EVM Influenza Pandemic Working Group EU-Commission Workshop on Stockpiling of Medicinal Products February 21/22, 2008
European Vaccine Manufacturers 1 (EVM) Represents major European vaccine producers 2 : - manufacturing 9.7 billions s per year to improve public health around the world - investing in 137 vaccine R&D projects Major partner in improving global public health by targeting all major vaccine preventable disease around the world Largest worldwide suppliers of vaccines (48% of exports goes to developing countries) Europe is at the heart of the world vaccine industry which represents a strategic asset for Europe 1 EVM members are: Baxter, Berna (Crucell), GlaxoSmithkline Biologicals, Novartis Vaccines, Sanofi Pasteur, Sanofi Pasteur MSD, Solvay and Wyeth. 2 EVM data 2006 2
Pandemic preparedness options Three major challenges for effective vaccination Protection throughout Pandemic Protection as early as possible Ensuring sufficient vaccine supply World-wide Pandemic Manufacturing before pandemic and stockpile Vaccine Manufacturing during pandemic Pandemic Vaccine Pre-Pandemic Vaccine 3
Timelines pandemic vaccine production WHO reference centers Producers Week -12.. -1 1 2 3 4 5 6 7 8 9 10 11 12 Declaration of pandemia by WHO Choice of the candidate strain for the production of the vaccine Preparation of the reassortant candidate strain Candidate strain available from the reference centers Reagents for HA quantification available Preparation of production sites Stop production of inter-pandemic vaccine Production of primary seed lot Control of primary seed lot Production of working seed lot Control of working seed lot Production of the first monovalent batch Control of the first monovalent batch Vaccine formulation Control of final monovalent bulk vaccine Filling of the vaccine Control of filled product Packaging Control of final product Local AuthoritiesRelease of final product 12 weeks time gap between arrival of pandemic vaccine strain and availability of first pandemic vaccine s (provided potency test reagents will be available 7 weeks after strain arrival) 4
Key factors for vaccine stockpiles Vaccine stockpiles help Pandemic Preparedness in several ways : Offer the potential for early protection Ease the logistical load therefore establish the logistical systems for large stockpiles Registration of pandemic and pre-pandemic vaccines via 2 regulatory procedures (core dossier, flu vaccines from viruses with the potential to cause a pandemic) Quick availability of strains and reagents is key Many remaining technical issues: Clade changes and requested data (quality, pre-clinical and clinical) How to maintain all clades available with a simple procedure (not having one dossier per strain) Manufacturing yields different per clade Maintaining the annual seasonal production Stability of stockpiles Several countries started stockpiling even without existing registration* 5 * USA, UK, Australia, Finland, France, Italy, Switzerland, Japan
Pathways to pandemic preparedness Human to Human Transmission 0 +/-- + +++ World-wide H5N1 Pandemic Phase 3 Phase 4 Phase 5 Phase 6 : PANDEMIC Advance Purchase Agreement 1 st 2 nd Protection Advance Production Agreement & Stockpile 1 st 2 nd Protection Stockpile and Targeted Use 1 st 2 nd Cross Protection 3 rd Protection Options Pre-Pandemic Vaccine Pandemic Vaccine 6
Logistical aspects Stockpiles will consist of different vaccines Need for harmonized packaging Rules needed to avoid mix-up + allow product identification Variability of presentations (2 vial concept, 1 vial concept, mono, multi- ) Stockpiles must be maintained/updated over time Allow for easy replacement of components Stockpiling of additional components is critical Syringes Needles Packaging materials for distribution Industry needs to deliver vaccine Other components to be provided by parties outside industry 7
Warehouse requirements Warehouses must be Temperature controlled (2-8ºC) cgmp compliant Systems and qualified resources needed for Routine follow up of temperature registrations and GMP conditions Criteria and action in case of deviations Personnel training and qualification To be supervised by a Qualified Person Protection measures mandatory Prevent intrusion of people in panic Prevent damage by the elements (rains, flooding etc) Assure access by authorized persons only Conditions needed to avoid mix up of products Organized to allow stock replacements Depending on shelf life, batches need to be replaced Different replacement of antigen + adjuvant Structured to allow rapid stock deployment 8
Deployment of stockpiled vaccines Rapid distribution is key Need for easy access to transport infrastructure Complete infrastructure to be established up-front Maintaining cold chain during distribution and transport Decision to start distribution To be management centrally (EU vs country level) According to strict rules Final deployment within regions/areas up to administration to patient is not a given Need for development of robust area deployment procedures and systems Appropriate administration of usage for tracking, reporting and follow up in central/national databases Need for adequate communication Development of EU guidelines in collaboration with ECDC and WHO 9
Summary and conclusions Vaccine industry remains committed to work with EU and Member States Continued and intensified communication is mandatory EC / ECDC / WHO / Industry Stockpiling vaccines + antivirals remain only reliable tools to fight against first wave of a pandemic Restrictions to guarantee timely availability of products following declaration of a pandemic alert EU decisions needed on central vs national stockpiles National stockpiling efforts already in place Joined responsibilities on stockpiling Industry in charge of delivering vaccines Syringes, needles etc. to be provided by the public sector Complete infrastructure for building and deploying stocks to be established Free trade of products (keeping borders open) is essential 10