Transcript COCA Conference Call: H1N1Update: Epidemiology and Clinical Features H1N1 Vaccine: Development, Manufacturing and Program Implementation Joseph Bresee, MD Tom Shimabukuro, MD, MPH, MBA Pascale Wortley, MD,

COCA Conference Call:
H1N1Update: Epidemiology and Clinical Features
H1N1 Vaccine: Development, Manufacturing
and Program Implementation
Joseph Bresee, MD
Tom Shimabukuro, MD, MPH, MBA
Pascale Wortley, MD, MPH
July 15, 2009
www.cdc.gov/H1N1flu
Continuing Education Disclaimer
In compliance with continuing education requirements, all
presenters must disclose any financial or other relationships
with the manufacturers of commercial products, suppliers of
commercial services, or commercial supporters as well as any
use of unlabeled product(s) or product(s) under investigational
use.
CDC, our planners, and our presenters wish to disclose they
have no financial interests or other relationships with the
manufacturers of commercial products, suppliers of commercial
services, or commercial supporters. This presentation does not
involve the unlabeled use of a product or product under
investigational use.
There is no commercial support.
www.cdc.gov/H1N1flu
Accrediting Statements

CME: The Centers for Disease Control and Prevention is accredited by the
Accreditation Council for Continuing Medical Education (ACCME) to provide
continuing medical education for physicians. The Centers for Disease Control and
Prevention designates this educational activity for a maximum of 1 AMA PRA
Category 1 Credit. Physicians should only claim credit commensurate with the extent
of their participation in the activity.

CNE: The Centers for Disease Control and Prevention is accredited as a provider of
Continuing Nursing Education by the American Nurses Credentialing Center's
Commission on Accreditation.
This activity provides 1 contact hour.

CEU: The CDC has been approved as an Authorized Provider by the International
Association for Continuing Education and Training (IACET), 8405 Greensboro Drive,
Suite 800, McLean, VA 22102. The CDC is authorized by IACET to offer 0.1 CEU's
for this program.

CECH: The Centers for Disease Control and Prevention is a designated provider of
continuing education contact hours (CECH) in health education by the National
Commission for Health Education Credentialing, Inc. This program is a designated
event for the CHES to receive 1 Category I contact hour in health education, CDC
provider number GA0082.
www.cdc.gov/H1N1flu
Update on the epidemiology and
clinical features of Novel H1N1
Joseph Bresee, MD
Chief, Epidemiology and Prevention Branch
Influenza Division, NCIRD
Centers for Diseases Control and Prevention
July 15, 2009
The contents of this presentation are those of the presenters and
do not necessarily reflect the views of CDC
www.cdc.gov/H1N1flu
Increased swine influenza detection in
humans 2005-9
• January 2007 – “Novel influenza A” made a Nationally
Notifiable Disease but CSTE – part of pandemic
preparedness efforts
• RT-PCR for influenza capabilities developed by public
health labs in U.S.
• Increasing numbers of swine influenza infections in
humans being detected from improved surveillance
• Increasing efforts at states, CDC, and USDA to
investigate human cases of swine influenza
Triple-Reassortant Swine Influenza A (H1) in Humans in the
United States, 2005–2009
Shinde, et al.
N Engl J Med. 2009 Jun 18;360(25):2616-25
www.cdc.gov/H1N1flu
MMWR
Novel Influenza A
(H1N1) Detected

March 2009
• 2 cases of febrile respiratory illness in
children in late March
• No common exposures, no pig contact
• Uneventful recovery
• Residents of adjacent counties in southern
California
• Tested because part of enhanced influenza
surveillancewww.cdc.gov/H1N1flu
Confirmed and Probable Novel H1N1 Cases by Report Date
10 JUN 2009 (N=37,246)
40000
36000
32000
24000
20000
16000
12000
8000
4000
Week Ending Date
www.cdc.gov/H1N1flu
3Ju
l
10
-J
ul
24
-J
un
16
-J
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6Ju
n
10
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ay
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28000
Descriptive Statistics of Novel Influenza A
(H1N1) Cases Reported to CDC by States10 JUL 2009
US TOTALS
CASES
CASES
HOSPS DEATHS
37,246
4,132
211
54
48
24
SLTTs AFFECTED
 Sex: 50% male/female
 Median age:
- all cases 12 years
- hospitalized 20 years
- died 37 years
www.cdc.gov/H1N1flu
International Map
Pandemic H1N1 – 10 JUL 2009
www.cdc.gov/H1N1flu
Epidemiology/Surveillance
Pandemic H1N1 Hospitalizations Reported to CDC
Clinical Characteristics as of 19 JUN 2009 (n=268)
100%
93%
83%
80%
54%
60%
40% 37%
36% 36%
40%
31% 31% 29%
24% 24%
20%
M
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/w
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0%
www.cdc.gov/H1N1flu
Epidemiology/Surveillance
Pandemic H1N1 Cases Rate per 100,000 Population by Age Group
As of 09 JULY 2009 (n=35,860*)
Rate / 100,000 Pop by Age Group
25
21.6
20
n=17829
17.2
n=3621
15
10
5.4
n=5774
5
3
n=1673
0
0-4 Yrs
5-24 Yrs
25-49 Yrs
50-64 Yrs
1.0
n=382
≥65 Yrs
Age Groups
*Excludes 1,386 cases with missing ages.
Rate / 100,000 by Single Year Age Groups: Denominator source: 2008 Census Estimates, U.S. Census Bureau at:
http://www.census.gov/popest/national/asrh/files/NC-EST2007-ALLDATA-R-File24.csv
www.cdc.gov/H1N1flu
Epidemiology/Surveillance
Hospitalizations per 100,000 Population in
Age Group
Pandemic H1N1 Hospitalization Rate per 100,000 Population
by Age Group (n=3,779) as of 09 JULY 2009
4
3.8
3.5
3
n=799
2.5
2
1.7
1.5
n= 1417
1
0.5
1.2
0.8
0.9
n= 906
n=479
25-49 Yrs
50-64 Yrs
n= 178
0
0-4 Yrs
5-24 Yrs
≥65 Yrs
Age Group
*Hospitalizations with unknown ages are not included (n=353)
*Rate / 100,000 by Single Year Age Groups: Denominator source: 2008 Census Estimates, U.S. Census Bureau at:
http://www.census.gov/popest/national/asrh/files/NC-EST2007-ALLDATA-R-File24.csv
www.cdc.gov/H1N1flu
600
500
100
400
80
300
60
200
40
100
20
0
0
0 - 4 Yrs
5 - 49 Yrs
50 - 64 Yrs
Age Group
*Thompson WW, JAMA, 2004
www.cdc.gov/H1N1flu
65+ Yrs
Deaths Per 100,000 Person Years
Hospitalizations Per 100,000 Person Years
Influenza-Associated Hospitalizations
Deaths By Age Group
Epidemiology/Surveillance
Pandemic H1N1 Hospitalizations Reported to CDC
Underlying Conditions as of 19 JUN 2009 (n=268)
35%
27%
32%
25%
32%
30%
20%
hr
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Prevalence, Hospitalized H1H1 Patients
Prevalence, General US Pop
*Excludes hypertension
www.cdc.gov/H1N1flu
4%
3%
1%
6%
1%
6%
0%
7%
0%
7%
8%
8%
9%
A
18%
10%
0%
0%
7%
6%
4%
8%
5%
13%
10%
14%
15%
15%
Pandemic H1N1 Cases by State
Rate / 100,000 State Population
As of 9 JUL 2009
www.cdc.gov/H1N1flu
Epidemiology/Surveillance
Pandemic H1N1 – 9 JUL 2009 EDT
Percentage of Visits for Influenza-like Illness (ILI) Reported by the US Outpatient Influenza-like
Illness Surveillance Network (ILINet),National Summary 2008-09 and Previous Two Seasons
7
6
% of Visits for ILI
5
4
3
2
1
2/
7
2/
21
3/
7
3/
21
4/
4
4/
18
5/
2
5/
16
5/
30
6/
13
6/
27
4
1/
2
0
1/
1
27
12
/
13
29
12
/
11
/
15
1
11
/
11
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18
10
/
10
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4
0
Week Ending Dates
2006-07†
2007-08†
2008-09
National Baseline
† There was no week 53 during the 2006-07 and 2007-08 seasons, therefore the week 53 data point for those seasons is an average of
weeks 52 and 1.
www.cdc.gov/H1N1flu
Epidemiology/Surveillance
A(Pandemic H1N1)
4500
A(Unable to Subtype)
Number of Positive Specimens
76%*
A(H3)
4000
55%*
80%*
A(H1)
3500
37%*
A(Subtyping not performed)
85%*
73%*
B
3000
2500
2000
1500
70
66
62
58
54
50
46
42
38
34
30
26
22
18
14
10
6
2
-2
Percent Positive
81%*
72%*
* Percentage of all
positive influenza
specimens that are
Influenza A
(Pandemic H1N1)
or Influenza A
(unable to subtype)
for the week
indicated
68%*
66%*
1000
500
Week ending
www.cdc.gov/H1N1flu
8/8
8/2
2
7/1
1
7/2
5
6/1
3
6/2
7
5/1
6
5/3
0
4/1
8
5/2
3/2
1
4/4
2/2
1
3/7
1/2
4
2/7
11
/1
11
/15
11
/29
12
/13
12
/27
1/1
0
10
/4
10
/18
0
Percent Positive
Pandemic (H1N1) – 9 JUL 2009
U.S. WHO/NREVSS Collaborating Laboratories Summary, 2008-09
Summary of Antiviral Resistance, U.S. 2008-09
Influenza viruses
Seasonal A Seasonal
Antiviral
Seasonal B
(H1N1)
A (H3N2)
Adamantanes Susceptible
Resistant
No activity
Oseltamivir
Zanamivir
Pandemic
H1N1
Resistant
Resistant
Susceptible Susceptible
Susceptible
Susceptible
Susceptible Susceptible
Susceptible
Oseltamivir-resistance among
Pandemic H1N1 viruses
3 oseltamivir-resistant isolates of Pandemic H1N1 detected
- 2 cases found to have resistant strain while on
oseltamivir chemoprophylaxis
Japan and Denmark
- 1 case detected by Hong Kong Department of
Health reported a resistant virus isolated from
a 16 year-old girl who had a fever upon arrival
at the Hong Kong International airport
 Illness began prior to boarding the plane in San Francisco
 No exposure to
 No illness among close contacts
 No sign of community transmission
- Al recovered uneventfully
No change in recommendations
for treatment or prophylaxis of
www.cdc.gov/H1N1flu
Antiviral Treatment Recommendations
 Priority: Hospitalized Patients with suspected
or confirmed pandemic H1N1 virus infection
• Treatment recommended with Oseltamivir or Zanamivir
• Treat patients as soon as possible (duration: 5 days)
 Outpatients with suspected or confirmed
pandemic H1N1 virus infection who are at
high risk for complications
• Persons with chronic pulmonary, cardiac, renal,
hepatic, metabolic, hematological disorders;
immunosuppression, pregnant women, children <5
years; adults ≥65 years
http://www.cdc.gov/h1n1flu/recommendations.htm
• Treatment
recommended with Oseltamivir or Zanamivir
• Treat patients as soon as possible (duration: 5 days)
www.cdc.gov/H1N1flu
Antiviral Chemoprophylaxis
 Post-exposure chemoprophylaxis with Oseltamivir or
Zanamivir can be considered:
• Close contacts of cases who are at high risk for
complications of influenza
• Health care personnel, public health workers, first
responders with unprotected close contact
exposure to an ill person with pandemic H1N1 virus
infection while in the infectious period
• Chemoprophylaxis: 7-10 days after last known
exposure
http://www.cdc.gov/h1n1flu/recommendations.htm
www.cdc.gov/H1N1flu
Summary of key points
 Once emerged, pandemic H1N1 virus spread to all 5
states and globally quickly
 Some areas more affected than others
 Expect continued summertime circulation with focal
outbreaks
 Elderly seemingly relatively spared
 Capable of causing severe disease and death
 Most severe outcomes among people with
underlying heath problems that are associated
with high risk of influenza complications
 Virus remains sensitive to oseltamivir and zanamvir
www.cdc.gov/H1N1flu
What’s Next
 Disease likely persists
through summer in US,
expected surge in fall
 Severity of Fall epidemic
difficult to predict
 Southern Hemisphere
being monitored for
subtypes, spread, and
severity
 Vaccine being readied
 Surveillance continuing
Northern Hemisphere
Southern Hemisphere
www.cdc.gov/H1N1flu
Pandemic H1N1 Vaccine:
Development and Manufacturing
Tom Shimabukuro, MD, MPH, MBA
Immunization Services Division
Centers for Disease Control and Prevention
July 15, 2009
www.cdc.gov/H1N1flu
New Horizons
H1N1 Vaccines

National Strategy for Pandemic Influenza (Nov. 2005)
goal is to provide vaccine to everyone in U.S. w/in 6
mo. of pandemic onset
 H1N1 Vaccine Strategy follows pandemic playbook
for vaccine development, production, and
administration
 Clinical studies will inform vaccine formulation and
safety profile
 Key decision issues:
 Vaccine product type
 Use of thimerosal preservative
 Use of oil-in-water adjuvant
 Post-vaccination safety monitoring
Courtesy Robin Robinson, PhD, HHS/ASPR/BARDA Director
www.cdc.gov/H1N1flu
Phases of a vaccination program
 Vaccine development
 Commercial scale manufacturing
 Distribution and administration
 Post-launch effectiveness, safety and
utilization monitoring
www.cdc.gov/H1N1flu
Vaccine development
 Vaccine reference strain development
 Master seed strain preparation
 Clinical investigational lot manufacturing
 Clinical studies
 To assess immunologic response and
safety
 Will inform formulation decisions
www.cdc.gov/H1N1flu
Commercial scale production
 Potency assay reagents preparation and
calibration
 Commercial scale bulk antigen manufacturing
without adjuvant
 Commercial bulk antigen manufacturing with
adjuvant
 Bulk adjuvant manufacturing
 Commercial scale syringe/needle manufacturing
 Vaccine formulation fill-finish
www.cdc.gov/H1N1flu
Courtesy Robin Robinson, PhD, HHS/ASPR/BARDA Director
www.cdc.gov/H1N1flu
Vaccine manufacturers
 Novartis (45.7%)
- Also manufactures MF59 adjuvant for potential
pre-formulation with vaccine
 Sanofi Pasteur (26.4%)
 CSL (18.7%)
 MedImmune (5.8%)
 GSK (3.4%)
- Also manufactures ASO3 adjuvant in a separate
vial for potential mixing at the place of
administration
www.cdc.gov/H1N1flu
Vaccine products (general)
 Unadjuvanted multidose vials*
 Unadjuvanted p-free pre-loaded syringes†
 Nasal sprayers (live attenuated)†
Potentially
 Multidose vials pre-formulated with adjuvant
 Multidose vials formulated for adjuvant to be
mixed at the place of administration (separate
antigen and adjuvant vials)
*All
multidose vials will contain thimerosal preservative
†Up
to 20% of vaccine may be p-free pediatric formulation
www.cdc.gov/H1N1flu
Vaccine ancillary supplies
 Needle/syringe units for multidose vials
 Sharps containers
 Alcohol pads
 Mixing syringes if adjuvanted vaccine is
used
www.cdc.gov/H1N1flu
Vaccine products
 Novartis (45.7%)
- Multidose vials: standard unadjuvanted
- Multidose vials pre-formulated with Novartis MF59
adjuvant*
 Sanofi Pasteur (26.4%)
- Multidose vials: standard unadjuvanted and
formulated for GSK ASO3 adjuvant (separate
antigen and adjuvant)*
- P-free pre-loaded syringes
*Decision
to use an adjuvanted vaccine is TBD
www.cdc.gov/H1N1flu
Vaccine products cont.
 CSL (18.7%)
- Multidose vials: standard unadjuvanted
and formulated for GSK ASO3 adjuvant
(separate antigen and adjuvant)*
- P-free pre-loaded syringes
 MedImmune (5.8%)
- Nasal sprayers, p-free
 GSK (3.4%)
*
- Multidose vials: standard unadjuvanted
and formulated for GSK ASO3 adjuvant
Decision to use an adjuvanted vaccine is TBD
(separate antigen and adjuvant)*
www.cdc.gov/H1N1flu
Storage and handling
 Inactivated vaccine
- 2-8°C
 Live attenuated
- 2-8°C
 Oil-in-water adjuvant
- 2-8°C, 2-5 year shelf life
 Inactivated vaccine mixed with adjuvant
- Stable up to 8 hours after mixing
www.cdc.gov/H1N1flu
Emergency Use Authorization
“… use of an unapproved medical product or an
unapproved use of an approved medical product
during a declared emergency …”
- Unadjuvanted pandemic H1N1 vaccine may be
licensed in a manner similar to a seasonal flu
vaccine strain change and therefore would not
need an EUA
- Adjuvanted vaccines, if used (for the 2009-10 flu
season), will be administered under an EUA
www.cdc.gov/H1N1flu
www.cdc.gov/H1N1flu
Pandemic H1N1 Vaccine:
Program Implementation
Pascale Wortley, MD, MPH
Immunization Services Division
Centers for Disease Control and Prevention
July 15, 2009
www.cdc.gov/H1N1flu
Vaccine purchase, allocation, and
distribution
 Vaccine procured and purchased by US
government
 Vaccine will be allocated across states
proportional to population
 Vaccine will be sent to state-designated
receiving sites: mix of local health
departments and private settings
www.cdc.gov/H1N1flu
Vaccine planning assumptions:
 Vaccine available starting mid-October
 Initial amount: 40, 80, or 160 million doses
over one month period
 Subsequent weekly production: 10, 20 or 30
million doses
 2 doses required
 Preservative free single dose syringes for
young children and pregnant women
www.cdc.gov/H1N1flu
Vaccine planning assumptions:
Populations to plan for:
Students and staff (all ages) associated with schools
(K-12) and children (age >6 m) and staff (all ages) in
child care centers
 Pregnant women, children 6m-4yrs, new parents
and household contacts of children <6 months of
age
 Non-elderly adults (age <65) with medical conditions
that increase risk of influenza
 Health care workers and emergency services
personnel
www.cdc.gov/H1N1flu
Delivery model
Public health-coordinated effort that blends
vaccination in public health-organized clinics
and in the private sector (provider offices,
workplaces, retail settings)
Private sector providers who wish
to administer H1N1 vaccine will
need to enter into an agreement
with public health in order to
receive vaccine
www.cdc.gov/H1N1flu
Public Health planning efforts
 Reaching out to private providers (defined broadly) to
assess interest in providing H1N1 vaccine
 Retail sector, pharmacists may be involved
 Planning large scale clinics
- Especially important for school-age children given
limited private sector capacity
www.cdc.gov/H1N1flu
Issues for administration in
provider offices
 Storage capacity
 Administering according to recommended
age groups
 Reporting doses administered early on
 Insurance reimbursement for administration
www.cdc.gov/H1N1flu
Monitoring vaccine coverage
 Initially, states will be required to report doses
administered on a weekly basis
 Transition to assessment via population
surveys (BRFSS, NIS)
www.cdc.gov/H1N1flu
Monitoring vaccine safety
 Vaccine Adverse Event Reporting System
(1-800-822-7967, http://vaers.hhs.gov/contact.htm ) for signal
detection
 Network of managed care organizations
representing approximately 3% of the U.S.
population, the Vaccine Safety Datalink
(VSD) to test signals.
 Active surveillance for Guillain Barre
Syndrome through states participating in
Emerging Infections Program.
www.cdc.gov/H1N1flu
Monitoring vaccine effectiveness (VE)
 VE for prevention of PCR-confirmed medically
attended influenza at 4 community-based sites
 VE for prevention of influenza hospitalizations
diagnosed by provider-ordered clinically available
tests at 10 sites nationwide through the Emerging
Infections Program
 DoD will be assessing VE in active duty service
members
www.cdc.gov/H1N1flu
Continuing Education Credit/Contact Hours
for COCA Conference Calls

Continuing Education guidelines require that the attendance of all
who participate in COCA Conference Calls be properly
documented. ALL Continuing Education credits/contact hours
(CME, CNE, CEU and CECH) for COCA Conference Calls are
issued online through the CDC Training & Continuing Education
Online system http://www2a.cdc.gov/TCEOnline/.

Those who participate in the COCA Conference Calls and who
wish to receive continuing education and will complete the online
evaluation by April 16, 2009 will use the course code EC1265.
Those who wish to receive continuing education and will complete
the online evaluation between April 17, 2009 and March 17, 2010
will use course code WD1265. CE certificates can be printed
immediately upon completion of your online evaluation. A
cumulative transcript of all CDC/ATSDR CE’s obtained through the
CDC Training & Continuing Education Online System will be
maintained for each user.
www.cdc.gov/H1N1flu