# Presentation: 408871

## Canadian Pandemic Influenza Plan: Overview and Update

**Dr. Theresa Tam, Associate Director **
**Immunization and Respiratory Infections Division**

**NVAC Pandemic Influenza Working Group, Washington DC, 19-20 April, 2005**

**Notes:**
Global influenza pandemics have occurred many times in the past and another pandemic will occur again. When it occurs, it will likely be the most devastating health emergency that we are going to face (by orders of magnitude greater than SARS), and it is the most likely of all infectious disease threats to impact national security.

## Outline

- National planning process
- The Canadian Pandemic Influenza Plan
- Underlying assumptions
- components
- Current activities and next steps
- Provincial/Territorial and local planning

**Notes:**
To share information about the status of Pandemic Planning in Canada, including:
an update on preparedness and the Plan

To enhance collaboration on pandemic influenza preparedness, engage front line health care providers

## Pandemic Planning in Canada

- 1988:  First draft plan (planning began in 1983)
- 1996:  Second draft plan
- 1997:  Lessons from Hong Kong “bird flu” incident
- 1998-2000:  Federal-provincial-territorial (F/P/T) planning process began
- Two national planning meetings and working groups established
- 2001:  Political commitment - F/P/T Working Agreement accepted by all provinces and territories

## Pandemic Planning in Canada - II

- 2001:  Multi-year pandemic and annual vaccine contracts signed
- 2002:  Pandemic Influenza Committee (PIC) 	established
- 2002: Input on the Canadian Pandemic Influenza Plan elicited from multiple stakeholder groups and experts
- 07/2003-01/2004:  Lessons from SARS incorporated
- 2003 Dec 12:  Plan approved by Deputy Ministers of Health

## http://www.phac-aspc.gc.ca/cpip-pclcpi/index.html	

**Public Release of the Plan – February 2004**

## Pandemic Influenza Committee (PIC)

- 2 Co-Chairs: Federal and Provincial
- 18 voting members including all provinces and territories, technical experts and an ethicist
- Provides technical advice for pandemic influenza prevention and control
- Provides overall guidance on the Canadian Pandemic Influenza Plan
- Multiple working groups

## Overall Goal of Pandemic Preparedness and Response

-          **First,** to minimize serious illness and overall deaths, and **second** to minimize societal disruption among Canadians as a result of an influenza pandemic.

**Notes:**
Dose not currently include:
Preventing a pandemic through intensive intervention in a cluster of less efficiently transmitted strain
Slow disease spread early in a pandemic

## Canadian Pandemic Influenza Plan

- Based on nationally agreed upon goal
- Organized into components
- Uses WHO Pandemic Phases
*National* plan, outlines roles and responsibilities of all levels of government
- Model for national health emergency response plans
- preparedness, response and recovery sections
- Contains checklists and technical annexes
- Dynamic or “evergreen” document

## Planning: Components

- Surveillance and Laboratory Testing
- Public Health Measures (border measures)
- Vaccine Programs
- Antivirals
- Health Services Emergency Planning
- Infection control, Clinical Care (self care), Resource Management, Mass Fatalities, Non-Traditional Sites and Workers
- Emergency Services
- Communications

## Underlying Assumptions

- Another influenza pandemic is INEVITABLE yet timing and epidemiology UNPREDICTABLE
- SHORT LEAD TIME
- presence in Canada < 3 months (much shorter?)
- 1st peak in illness within 5-7 months
- Outbreaks will occur SIMULTANEOUSLY in multiple locations, in multiple waves
- Limited resources will need to be PRIORITIZED

## Estimated Impact of Pandemic Influenza in Canada

- If vaccine is unavailable, **EXPECT**:
- 11,000 to 58,000 deaths
- 34,000 to 138,000 hospitalizations
- 2 to 5 million outpatients
- economic costs
- health care: $330 million to $1.4 billion
- societal: $5 to $38 billion

**Societal**
**Disruption**

**Health Resource **
**Scarcity**

**Notes:**
- Will affect medical service and essential disease control function
- Will equally affect other essential community services
	Public transport, police, fire brigade, grocery stores, airtraffic control, petrol stations, ..., teachers, politicians, ...
- Social and political disruption
 - Considerable economic losses
– Health consequences of disease and prevention and control efforts
–Indirect disease consequences and impact of travel/trade recommendations/

## Key Strategies for Reducing Spread and Impact

- Public health measures and infection control
- Respiratory etiquette and self care
- Vaccination is the primary means for preventing disease, reducing morbidity and mortality during a pandemic BUT unlikely to be available at start
- Antivirals are the only virus-specific intervention prior to vaccine becoming available
- Maintain public awareness and facilitate acceptance of response strategy
- Maintaining health, emergency and social services

## Key Considerations in Prioritizing Resources

- Effectiveness in reducing impact on health outcomes and societal function
- Efficiency– optimizing use of a limited resource
- Feasibility of implementation
- Acceptability – is the approach ethical (accepted by the public)

## What has been done to increase our preparedness? 

## Pandemic Preparedness Strategy: Building on Annual Influenza Prevention and Control

## What has been done to increase our preparedness? (1)

**Emergency Planning**
**Canadian Pandemic Influenza Plan**
- Developed Respiratory Illness Outbreak Response Protocol (RIORP)
**Surveillance**
- FluWatch weekly surveillance; real time paediatric hospitalization reporting through the IMPACT network
- Intelligence gathering: Global Public Health Intelligence Network (GPHIN)
- Rapid dissemination of information: e-mail and web-based alerts (CIOSC)
**Communications**
- Established F/P/T Communication Network to coordinate messages across the country

**Notes:**
A diversified multi-pronged approach to pandemic planning

Not putting all of our eggs in one basket.

## Pandemic Influenza Vaccine Strategy 
Objective: provide vaccine to all Canadians 

Established 10 yr contract (2001-2011) with ID Biomedical
Production of at least 50% of annual requirement 
Pandemic readiness (production capacity & raw materials)
Manufacturing capacity (8 million monovalent 15 μg HA doses / month) to be attained within 60 months
Manufacturer’s contingency plan to include: the availability of raw materials and supplies (fertilized hen eggs)
National coordinated approach to program & priority groups

*Objective: provide vaccine to all Canadians*
- Established 10 yr contract (2001-2011) with ID Biomedical
- Production of at least 50% of annual requirement
- Pandemic readiness (production capacity & raw materials)
- Manufacturing capacity (8 million monovalent 15 μg HA doses / month) to be attained within 60 months
- Manufacturer’s contingency plan to include: the availability of raw materials and supplies (fertilized hen eggs)
- National coordinated approach to program & priority groups

- What has been done to increase our preparedness? (2)

## Use of Vaccines in Short SupplyUnder review

- Health care providers
- Essential service providers / government leaders
- Persons at high risk of severe or fatal outcomes
- a) persons in nursing homes and long-term care facilities
- b) persons with high-risk medical conditions
- c) persons >65 years
- d) children 6 to 23 months of age
- e) pregnant women
- Healthy adults
- Children 24 months to 18 years old

## What has been done to increase our preparedness? (3)

- Antiviral Stockpiling – 16 million doses
- Antivirals options and priority groups developed by PIC
- Federal contribution of 9.6 million oseltamivir doses ($24M) toward a national stockpile - 2005
- P/Ts are considering, at minimum, purchasing the remaining 6.4 million doses (40% of 16 M) that would represent their respective per capita allocation from the National Stockpile

## Priority Groups for Antivirals 

**Treatment of persons hospitalized for influenza**
**Treatment of ill HCW and ESW**
**Prophylaxis of “front line” HCW and key health decision makers**
**Treatment of high-risk in the community**
- Prophylaxis of remaining HCW
**Control outbreaks in high-risk residents of institutions**
- Prophylaxis of ESW
- Prophylaxis of high-risk persons hospitalized for illnesses other than influenza
- Prophylaxis of high-risk in the community

## Cumulative Doses by Priority Groups

**Doses (Millions)**

**NOTE: THESE PRELIMINARY ESTIMATES HAVE NOT GONE THROUGH SCIENTIFIC OR GOVERNMENT POLICY CHALLENGE.**

**Notes:**
To help visualize where the “jumps” in doses required are with respect to the priority groups.  
Demonstrated here as if you were working down the priority list (I.e. from group 1 to group 9).

## What has been done to increase our preparedness? (4)

**Research**
- influenza immunization program evaluation – request for proposal through the CIHR (phase 1)
- Co-chair and provide secretariat support to the Emerging Infectious Diseases – Clinical Trial Network (EID-CTN)
**Global Collaboration**
- Providing support to WHO, Thailand, Vietnam, China
- Global Health Security Action Group partners (G7 and Mexico):
- Share pandemic plans and joint exercises
- Antivirals (discussion on use in an early global intervention stockpile)
- mock pandemic vaccine development etc.

## Public Health Measures - Background

- Access to vaccines and antivirals will be limited  - non-medical interventions will be important
- Recommendations based on limited scientific evidence and rely on expert opinion
- Tested during SARS but pandemic flu is different
- Effectiveness will depend on the behavior of the virus
- Strategy depends on cost, available resources, ease of implementation, public acceptance, political concerns

## Public Health Measures Guidelines

- Principles and Assumptions
- Uses new WHO phases
- Recommendations
- Public Health Management of Ill Individuals
- Public Health Management of Contacts of Cases
- Community-Based Strategies
- Travel and Border Measures
- Public Education

## Public Health Measures - Challenges

- Effectiveness and objectives will shift with the evolving epidemiology
- Prevent cases before human-to-human spread
- Slow pandemic spread
- Reduce impact of first wave
- How to respond to initial cases in Canada? Global pandemic alert vs pandemic phase

## Community-Based Strategies

- Strongly recommended
- Stay home from public events if ill
- Consider
- School and Day Care Closures
- Not recommended
- Restriction of indoor public gatherings (consider specific events depending on epidemiology)
- Use of masks by well individuals
- Hand sanitizing stations in public settings
- Increase frequency of cleaning surfaces in public places

## Travel and Border Measures

- WHO recommendations
- Providing information to travelers is better use of health resources than formal screening
- Potential value of exit screening from areas with human-to-human transmission
- No entry screening (e.g. thermal scanners) of travelers from affected areas

## Next Steps

- Publish guideline on “Management of Human Health Issues related to Domestic Avian Influenza Outbreaks”
- Finalize and post new Annexes (2004)
- First Nations
- Public Health Measures
- Surveillance
- Pandemic influenza communications working group – communication matrix
- Increase public and professional awareness

## Next Steps

- Update the national Plan to be in line with new WHO guidance documents (including new phase terminology)
- “Exercising” the Plan (e.g. U.K. June 2005)
- Produce mock H5N1 pandemic vaccine and conduct clinical trials - Federal budget 2005 ($34 million)
- Testing domestic vaccine production infrastructure, regulatory processes and clinical trial protocols using the H5N1 vaccine strain Influenza research agenda (2004)
- Determine the optimal H5N1 dosage and schedule
- Investigate antigen sparing strategies e.g. adjuvants, intra-dermal administration, whole cell vaccine

**Notes:**
There are many outstanding issues particularly around Vaccines and Antivirals.

The challenge of responding to a threat of a pandemic must now be supported by clinical trials of a new vaccine manipulated by RG and by large scale manufacturing of the vaccine. 

Produce pilot lots of a candidate/mock pandemic vaccine 
To identify and address issues with production using a vaccine seed generated by reverse genetics; produce clinical trial batch

Establish optimal formulation of mock pandemic vaccine(s) through clinical trials 
include viral antigens to which populations have had little or no previous exposure e.g. H5N1
Safety, dosage and schedule, adjuvants, route of administration
“critical mass” of knowledge on immunogenicity and effect of adjuvants needed...Goal to determine the lowest amount of HA antigen that can be included in an adjuvanted vaccine that will be acceptably immunogenic when given in a 2 dose schedule

Manufacturers would provide the necessary data and pre-register mock-up pandemic vaccine(s) with licensing agencies (e.g. European approach). This is so that at time of a pandemic, only quality data related to the pandemic variation needs to be submitted – rapid approval

Regulatory requirements being addressed
EU (EMEA) and US FDA
Vaccine prototype strain available since April 2004 BUT few clinical trials planned
Jan 2005: US: 2 formulations without adjuvant;
EU: trials planned with adjuvants; 
Japan (summer 2005?)

## Next Steps

- Vaccines
- Allocation plan
- Monitoring usage, effectiveness, adverse effects during a pandemic
- Indemnification
- Role of new technologies
- Antiviral Stockpile
- inventory management and distribution (including First Nations communities)
- guidelines for delivery, monitoring of use

**Notes:**
vaccine strategy options and security of supply 
provide vaccines to all Canadians
domestic capacity
guidelines on use in short supply
strategies for delivery, administration
monitoring of distribution, uptake, wastage 
vaccine adverse events surveillance 
vaccine clinical trials protocols 
Pandemic vaccine production must be based on existing global capacity to produce trivalent vaccines, mostly in egg-based production systems. Current Global distribution is approximately 300 million doses per year (which translates into enough monovalent vaccines in a two dose schedule, for only 450 million persons). Vaccines are produced almost entirely in 9 developed countries (represent only 12% of the global population). We are fortunate that one of the manufacturers is located in Canada. Europe (5 companies) produces over 65% of the annual global supply and 50% of that production is exported outside of Europe. In the event of a pandemic, most countries in the world would be critically short of vaccine.

As you heard yesterday, cell culture technologies may reduce the current dependency on egg based systems and increase capacity.

The key step to increase supply during a pandemic is to increase inter-pandemic vaccine production and utilization. The majority of the world’s countries do not have routine flu vaccine programs. Developed countries that have vaccine programs still have a lot of room for improvement on their vaccine coverage. Canada is the world leader in vaccine distribution per capita but even in this country we are can still improve on coverage for target  populations (see posters by Helen Johanson and Kathryn Haines). 

Antigen sparing stratgies:
Hehme et al 2002: two dose aluminum adjuvanted monovalent vaccine containing reduced HA content (1.9; 3.8; 7.5μg HA) achieved antibody levels that fulfilled European regulatory criteria for annual vaccines
Adjuvants such as Alum salts (MF59) may increase supplies by over 4 fold = 3.5-7 billion doses (enough for 1.75 to 3.5 billion people) Available data show that aluminium salts increase immunogenicity of flu vaccines. Two dose monovalent adjuvanted vaccine at  lower than conventional doses (1.9; 3.8; 7.5microg HA) bring out antibody response that fulfil CPMP criteria. Up-to 8-fold reduction in Ag content could be achieved
1976/77 “swine flu” H1N1 vaccine trials in primed and naïve population. Whole virus vaccine significantly more immunogenic than subunit/split.
Adjuvanted and whole cell vaccines reactogenic but may be acceptable in a pandemic
Route of administration e.g. using intradermal injection, as published in the recent NEJM, may reduce the amount of vaccine dose required and should be further explored.

## Next Steps

- Research
- Develop an Influenza Research Agenda (Sept. 2005)
- International Vaccine Centre (InterVac), U. of Saskatchewan (2005) $24 million
- Mathematical Modelling of the impact of pandemics and potential interventions
- Strengthen collaboration and coordination between animal and human health for surveillance and response to zoonotic/emerging infectious disease

**Notes:**
There are more areas that require research – these are just examples of a few

## Preparedness Activities:

- Provincial/Territorial and Local Levels

## Within Canada...

- Most Provinces and Territories have developed plans for pandemic influenza
- Alberta, BC, Manitoba and Ontario on the web
- Some provinces and territories are at the stage where they are testing their plans
- Local level planning is occurring
- Post-SARS high level of recognition for need for plans to mitigate the impact of pandemic influenza