Introduction to Pandemic Influenza Vaccine and Antiviral Decision Issues

1. Introduction to Pandemic Influenza Vaccine and Antiviral Decision Issues

3. Key Vaccine and Antiviral Issues Approach to vaccine purchase and distribution (role of the public and private sectors) Priority groups for receipt of pandemic vaccine Priority groups for antiviral drugs and drug use strategy (chemoprophylaxis & therapy)

4. Pandemic Influenza Vaccine Production Timelines Development of reference strain Use of reverse genetics allows HA and NA from pandemic strain to be combined with other genes from a strain well adapted to growth in eggs Vaccine production (monovalent) Master seed developed from reference strain Growth in eggs and purification Formulation and filling Regulatory process Optimal timing ~3 months (if reference strain and potency testing reagents already developed)

5. Pandemic Spread and Seasonality Spread of a pandemic Months before U.S. community outbreaks for prior pandemic strains 1918 – 0; 1957 – 4-5; 1968 – 2-3; 1977 – 3-4 Spread of the next pandemic More rapid because of increased international travel More warning because of better surveillance Seasonality Fall – Spring seasonality generally preserved Multiple pandemic waves occur – potentially in the same season

6. Asian Influenza in the U.S., July 1957

8. Influenza by Week of Onset in U.S. Counties, Fall 1957

9. Timeline of First and Second Pandemic Waves, 1957-58

10. Pandemic Vaccine Availability in Prior Pandemics

11. Vaccine Availability for the Swine Influenza Program

12. Pandemic Influenza Vaccine Supply Estimates: Current Status Pandemic vaccine supply assumptions Only US produced vaccine will be available (1 mfr) 15 ug antigen/dose and 2 doses/person will be needed for protection Monovalent vaccine production capacity will be 3-fold that of annual vaccine (e.g., similar Ag yield/egg) Current Sanofi production is sufficient to deliver ~250 M monovalent doses/year (~5 million/week) Implication – about 1% of the population can be protected per week

13. Pandemic Vaccine Purchase and Distribution Should vaccine purchase and distribution in the next pandemic be... Similar to 1957 and annual influenza vaccination with most doses distributed in the private sector; or Similar to 1976 Swine influenza program when vaccine was purchased and distributed by the public sector; or Some other model?

14. Pandemic Vaccine Purchase & Distribution: Stakeholder Meetings, 2002 Series of individual discussions and meetings with stakeholders, coordinated by CDC Objective to make recommendations on vaccine purchase and distribution to help state health departments in planning Issues considered included ability to target supply, equity, cost, feasibility of implementation, and others

15. Pandemic Vaccine Purchase & Distribution: Stakeholder Meetings, 2002 Options considered Primarily private sector program similar to inter-pandemic influenza seasons Federal purchase for “traditional” public health care recipients (uninsured, military, children eligible for VFC) – est. 40-50 M Federal purchase for above, HCWs, essential workers, and persons at high risk – est. 130-140 M Federal purchase of all pandemic influenza vaccine

16. Pandemic Vaccine Purchase & Distribution: Stakeholder Meetings, 2002 Most stakeholders preferred the federal purchase option Greatest equity; avoids price inflation; best targeting This option was recommended for the first pandemic year only Recommended negotiating a fair price and providing liability protection to manufacturers and those administering vaccine

17. Vaccine Purchase and Distribution: Potential for Changes Over Time

18. Reconsideration of Vaccine Purchase and Distribution Recommendations Experience since 2002 Release of draft HHS pandemic plan and progress in State pandemic planning Experience with influenza and other vaccine shortages Expansion of influenza vaccine recommendations for inter-pandemic seasons Potential alternate approaches to consider

19. Inter-Pandemic and Pandemic Vaccine Target Groups Inter-pandemic vaccine recommendations Persons at high risk of severe influenza & complications Persons who can transmit disease to those at high risk (HCWs and family members of high risk) Pandemic considerations Pandemic impacts may extend beyond health of infected persons Need to maintain quality health care system Need to maintain essential community services Vaccine supply will be more limited relative to need

20. Potential Vaccine Target Groups and Population

21. Questions in Defining Pandemic Vaccine Priority Groups How should response goals be balanced? Can strata be identified within priority groups? How does one define essential workers? Should priority groups differ in more and less severe pandemics? How should direct vs indirect vaccine effects be considered? How should ethical issues and public preferences be considered?

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23. Goals and Principles of Influenza Antiviral Drug Use Goals of antiviral drug use Decrease health, economic & social impacts (Prevent a pandemic through intensive intervention in a cluster of a less efficiently transmitted strain) (Slow disease spread early in a pandemic) “Overarching principles” Target drug to priority groups Maintain flexibility and responsiveness to local needs Consider efficiency in drug use strategies Use drugs appropriately to limit wastage & resistance

24. Influenza Antivirals Adamantanes – amantadine & rimantadine Effective as prophylaxis; treatment shortens illness H5N1 isolates from human cases in Asia resistant; resistance develops rapidly if used as therapy Adverse events (neurological and GI) common Produced by proprietary & generic manufacturers Neuraminidase inhibitors – oseltamivir & zanamivir Effective as prophylaxis; treatment shortens illness and reduces complications Resistance uncommon Few adverse events Produced by proprietary manufacturers

25. Advantages of NIs for Antiviral Interventions in a Pandemic Documented effectiveness in decreasing influenza complications Low rate of antiviral resistance and less risk of resistance spreading with widespread therapy Low incidence of adverse events Oseltamivir - orally administered, simple dosing, few contraindications (infants <1 year old)

26. Pandemic Antiviral Supply Global NI production capacity insufficient to meet pandemic needs – requirement for stockpiling Antivirals in the Strategic National Stockpile Oseltamivir (~2 million courses) Rimantadine (~4 million courses) Antivirals in the private sector ~1-1.5 million oseltamivir courses pre-influenza season

27. Critical Factors in Defining Drug Use Strategy: Prophylaxis vs Treatment Effectiveness – impact on health outcomes and social & economic function Efficiency – optimal use of a limited antiviral supply Feasibility – can the recommended approach be implemented? Acceptability – is the approach ethical and acceptable to the public?

28. Number of Antiviral Drug Courses for Prophylaxis vs Treatment

29. Prophylaxis vs Therapy In Occupational Settings: Critical Unknowns Need for prevention (vs therapy) to avoid absenteeism From illness From fear of infection Risk of transmission in occupational settings E.g., from HCWs to co-workers and patients Implementation factors Ability to implement early therapy Ability to assure availability of therapy

30. Target Groups for Antiviral Drug Interventions Priority groups are not defined in the draft pandemic plan Establish priorities based on pandemic response goals Draft report developed by an HHS/DoD/VA working group proposes priority groups for antiviral drugs Represents conclusions from the working group and not HHS or its agencies

31. Cumulative Antiviral Courses for Proposed Groups by Pandemic Severity

32. Questions in Defining Pandemic Antiviral Priority Groups Similar questions as for vaccines (balancing goals; stratifying within groups; defining essential workers; ethical issues and public preferences; differences based on pandemic severity) Will treatment be adequate to maintain health care and community services or will prophylaxis be needed? How do implementation issues affect definition of target groups? What drugs should be stockpiled and how does this affect definition of target groups?

33. Conclusions: Products of the Working Group & Subgroups Recommendations on approach to vaccine purchase and distribution, and on vaccine and antiviral strategies and priority groups are important for effective planning Analysis of these issues by the PIWG and recommendations through NVAC and ACIP will facilitate decision-making and an effective pandemic response