1. PROJECT MANAGEMENT Influenza Annual Update Weesp, February 22 2011 Dorine Leyssius

2. Agenda Annual Update Influenza, the virus, the disease, the vaccine Manufacturing and Distribution Project Integration Management

3. Annual Update Scope; re-registration of the vaccine Change; adaptations because of strain changes Planning; high level information in detailed plans Management; manage the team and objectives Success; timely registration Monitoring; lessons learned

4. Annual Update Timeline Recommendation by WHO on virus strainsFeb CHMP decision for EU production strainsMar Seed provided by NIBSCApr Reagents produced by NIBSCMay Clinical StudyJun Submission registration dossierJul Approval registration dossierAug Vaccination population Oct/Nov Timelines are very strict!

5. Agenda Annual Update Influenza, the virus, the disease, the vaccine Manufacturing and Distribution Project Integration Management

6. Influenza, the virus and the disease The Influenza A and B Virus Negative strand RNA virus of the orthomyxoviridae family Influenza virus surface proteins: Haemagglutinin (HA) Neuraminidase (NA)

7. Influenza, the virus and the disease Influenza A and B Virus, Antigenic Drift (Seasonal)

8. Influenza, the virus and the disease The Influenza A Virus, Antigenic shift (Pandemic) Can result in a Pandemic

9. Influenza, the virus and the disease Symptoms and Transmission Generally, the major difference between influenza and the common cold and other influenza-like illnesses is the sudden onset and the occurrence of high fever, frequent chills and muscular aching. Influenza is easily transmitted through contact with droplets from the nose and throat of an infected person who is coughing and sneezing. Influenza viruses can generally survive on surfaces for 2-8 hr.

10. Influenza, the virus and the disease Influenza Complications and Risk Groups CommonUncommon PneumoniaEncephalopathy Exacerbation of underlying diseases Myositis SinusitisMyocarditis Acute otitis media (children)Febrile seizures Dehydration (infants)Reye syndrome (children) People at risk for influenza complications: All children <5 yr All elderly people ≥60 yr All pregnant women People of any age with certain (chronic) medical conditions (e.g., asthma, diabetes, immune-deficiencies, renal dysfunction) Source: WHO April 2009

11. Influenza, the virus and the disease Influenza Epidemics Each year in the industrialized world, 3–5 million cases of severe influenza illness result in 250,000–500,000 deaths.

12. Influenza, the virus and the disease Influenza Epidemics, the Influenza Season in US Timing and duration of influenza seasons vary Influenza activity peaks most frequent in February Centers for Disease Control and Prevention (CDC)

13. Influenza, the virus and the disease Influenza Epidemics, Burden of Disease (in the US) Deaths 23,607 Hospitalizations 142,000 Illnesses 40,000,000 Direct costs ($) 4,000,000,000 Indirect costs($) 8,000,000,000 CDC data

14. Influenza, the virus and the disease Influenza Pandemics Asiatic (Russian) Flu H3N8?(1889) Spanish Flu H1N1 (1918) Asian Flu H2N2 (1957) Hong Kong Flu H3N2 (1968) Russian Flu H1N1 (1977) Hong Kong Flu H5N1 (1997) Mexican Flu H1N1 (2009)

15. Agenda Annual Update Influenza, the virus, the disease, the vaccine Manufacturing and Distribution Project Integration Management

16. National Influenza Vaccine Summit 2007

24. Agenda Annual Update Influenza, the virus, the disease, the vaccine Manufacturing and Distribution Project Integration Management

25. Annual Update Regulatory Agencies Activities –Europe (Northern Hemisphere): data requirements according to EU Guideline Apr 1997,Harmonisation of Requirements of Influenza Vaccines –Relates to annual virus strain changes due to WHO recommendation Submission via fast-track Type II variation procedure in 2 parts Administrative data & CMC Clinical (study results) & PSUR –CHMP: annual decision on strains to be used for manufacturing –Ph.Eur.: batch release by national control laboratories & mutual recognition of test results

26. Annual Update Timeline Recommendation by WHO on virus strainsFeb CHMP decision for EU production strainsMar Seed provided by NIBSCApr Reagents produced by NIBSCMay Clinical StudyJun Submission registration dossierJul Approval registration dossierAug Vaccination population Oct/Nov Timelines are very strict!

27. Project Integration Management → Lessons learned Develop Project Charter Develop Project Management Plan Time management Define Activities Sequence Activities Estimate Activity Resources Estimate Activity Durations Develop Schedule Control Schedule Project Communication Management Stakeholder Management Direct and Manage Project Execution Monitor and Control Project Work Perform integrated Change Control Close Project Organizational Process Assets Updates → Lessons learned

28. Project Integration Management Develop Project Charter Develop Project Management Plan Time management Define Activities Sequence Activities Estimate Activity Resources Estimate Activity Durations Develop Schedule Control Schedule Project Communication Management Stakeholder Management Direct and Manage Project Execution Monitor and Control Project Work Perform integrated Change Control Close Project Organizational Process Assets Updates Lessons learned

29. Project Integration Management Develop Project Charter Develop Project Management Plan Time management Define Activities Sequence Activities Estimate Activity Resources Estimate Activity Durations Develop Schedule Control Schedule Project Communication Management Stakeholder Management Direct and Manage Project Execution Monitor and Control Project Work Perform integrated Change Control Close Project Organizational Process Assets Updates Lessons learned

30. Questions