Influenza Vaccine: Issues Related to Production, Distribution,	 
and Public Health Messages (31-OCT-07, GAO-08-27).		 
                                                                 
Annual vaccination is the main method for preventing seasonal	 
influenza, which typically occurs in the United States from late 
fall to early spring. Manufacturers produce vaccine through a	 
lengthy and complex process. Manufacturers and medical supply	 
distributors then ship vaccine to providers such as physicians.  
Each year, the Department of Health and Human Services's (HHS)	 
Centers for Disease Control and Prevention (CDC) recommends who  
should be targeted for vaccination, including those at higher	 
risk for influenza-related complications or medical care--for	 
example, adults aged 50 years and older, young children, and some
individuals with chronic medical conditions. CDC bases its	 
recommendations on those made by the agency's Advisory Committee 
on Immunization Practices (ACIP). GAO examined: (1) factors that 
affect the quantity of vaccine produced and when it reaches	 
providers, (2) issues related to making vaccine available to	 
high-risk and other target groups, and (3) public health messages
produced and disseminated by CDC and others to promote		 
vaccination. GAO reviewed relevant documents and interviewed	 
officials from CDC, other public health entities, manufacturers, 
and medical supply distributors, and examined data on vaccine	 
doses produced and shipped.					 
-------------------------Indexing Terms------------------------- 
REPORTNUM:   GAO-08-27						        
    ACCNO:   A77895						        
  TITLE:     Influenza Vaccine: Issues Related to Production,	      
Distribution, and Public Health Messages			 
     DATE:   10/31/2007 
  SUBJECT:   Childhood vaccines 				 
	     Data collection					 
	     Disease control					 
	     Elderly persons					 
	     Emerging infectious diseases			 
	     Immunization programs				 
	     Immunization services				 
	     Infectious diseases				 
	     Influenza						 
	     Locally administered programs			 
	     Medical supplies					 
	     Pharmaceutical industry				 
	     Product evaluation 				 
	     Public health					 
	     Risk assessment					 
	     Risk management					 
	     Vaccination					 
	     Production engineering				 

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GAO-08-27

   

     * [1]Results in Brief
     * [2]Background
     * [3]Manufacturing Challenges, Limitations in Production Capacity

          * [4]Manufacturing Challenges May Limit the Quantity of Seasonal
          * [5]Production Capacity May Limit the Quantity of Seasonal Influ
          * [6]Demand for Influenza Vaccine Affects the Quantity of Seasona
          * [7]Distribution Routes May Affect When Seasonal Influenza Vacci

     * [8]Issues Related to Vaccine Distribution May Affect Vaccine Av

          * [9]High-Risk and Other Target Groups Receive Vaccinations at Va
          * [10]Manufacturers and Medical Supply Distributors Ship Vaccine U
          * [11]CDC Data Indicate State and Local Health Departments General
          * [12]CDC and State Health Officials Have Undertaken Efforts to He

     * [13]CDC and Others Have Produced Public Health Messages, and CDC

          * [14]CDC and Others Have Produced and Disseminated Influenza-Rela
          * [15]CDC Has Taken Some Steps to Assess Its Public Health Message
          * [16]Elements Important for Producing Effective Public Health Mes

     * [17]Agency Comments
     * [18]Appendix I: Scope and Methodology
     * [19]Appendix II: Manufacturers of Seasonal Influenza Vaccine for
     * [20]Appendix III: Advisory Committee on Immunization Practices (
     * [21]Appendix IV: Cumulative Percentage of Vaccine Distributed by
     * [22]Appendix V: CDC's Flu Vaccine Finder
     * [23]Appendix VI: GAO Contact and Staff Acknowledgments

          * [24]GAO Contact
          * [25]Acknowledgments

     * [26]Related GAO Products

          * [27]Order by Mail or Phone

     * [28]PDF6-Ordering Information-Young-10-25-07.pdf

          * [29]GAO's Mission
          * [30]Obtaining Copies of GAO Reports and Testimony

               * [31]Order by Mail or Phone

          * [32]To Report Fraud, Waste, and Abuse in Federal Programs
          * [33]Congressional Relations
          * [34]Public Affairs

Report to the Committee on Oversight and Government Reform, House of
Representatives

United States Government Accountability Office

GAO

October 2007

INFLUENZA VACCINE

Issues Related to Production, Distribution, and Public Health Messages

GAO-08-27

Contents

Letter 1

Results in Brief 4
Background 6
Manufacturing Challenges, Limitations in Production Capacity, and
Fluctuating Demand for Vaccine May Limit the Quantity of Vaccine Produced
or Delay When Vaccine Reaches Providers 16
Issues Related to Vaccine Distribution May Affect Vaccine Availability for
High-Risk and Other Target Groups 22
CDC and Others Have Produced Public Health Messages, and CDC Has Taken
Some Steps to Assess Its Messages 34
Agency Comments 40
Appendix I Scope and Methodology 41
Appendix II Manufacturers of Seasonal Influenza Vaccine for the U.S.
Market, 2000-01 through 2007-08 Influenza Seasons 45
Appendix III Advisory Committee on Immunization Practices (ACIP)
Recommendations 47
Appendix IV Cumulative Percentage of Vaccine Distributed by Provider Type
during 2006-07 Influenza Season 52
Appendix V CDC's Flu Vaccine Finder 53
Appendix VI GAO Contact and Staff Acknowledgments 57
Related GAO Products 58

Tables

Table 1: Number of U.S.-Licensed Manufacturers of Seasonal Influenza
Vaccine and Number of Doses Produced and Distributed, 2000-01 through
2006-07 Influenza Seasons 14
Table 2: Manufacturers of Seasonal Influenza Vaccine for the U.S. Market,
2000-01 through 2007-08 Influenza Seasons 45
Table 3: ACIP Influenza Vaccination Recommendations, 2000-01 through
2007-08 Influenza Seasons 48
Table 4: Target Groups ACIP Recommended for Influenza Vaccination for the
2000-01 Influenza Season, before and after October 2000 49
Table 5: Target Groups ACIP Recommended for Influenza Vaccination for the
2004-05 Influenza Season, before and after October 2004 50
Table 6: Estimates of ACIP Target Group Populations Sizes, 2006 51
Table 7: Percentage of Cumulative Number of Doses Distributed by Month and
Provider Type, 2006-07 Influenza Season 52

Figures

Figure 1: Month of Peak Influenza Activity, 1976 through 2006 7
Figure 2: Seasonal Influenza Vaccine Production Cycle 11
Figure 3: Distribution of Influenza Vaccine Doses in Millions by Month,
2000-01 through 2006-07 Influenza Seasons 19
Figure 4: Potential Impact of Different Distribution Routes of Vaccine
Orders from Manufacturer to Provider 22
Figure 5: Locations Where Adults Aged 65 Years and Older and Aged 50
through 64 Years Reported Receiving Most Recent Influenza Vaccination,
2004 24
Figure 6: Locations Where High-Risk Adults with Certain Chronic Conditions
Reported Receiving Most Recent Influenza Vaccination, 2002 25
Figure 7: Percentage of Cumulative Number of Vaccine Doses Distributed, by
Provider Type and Month, 2006-07 Influenza Season 29

Abbreviations

ACIP: Advisory Committee on Immunization Practices: 
CDC: Centers for Disease Control and Prevention: 
FDA: Food and Drug Administration: 
HHS: Department of Health and Human Services: 

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United States Government Accountability Office
Washington, DC 20548

October 31, 2007

The Honorable Henry A. Waxman: 
Chairman: 
The Honorable Tom Davis: 
Ranking Member: 
Committee on Oversight and Government Reform: 
House of Representatives: 

On average each year in the United States, seasonal influenza--which is
caused by influenza viruses--is associated with more than 200,000
hospitalizations and 36,000 deaths. Particular groups of individuals are
at increased risk for influenza-related complications or at higher risk
for medical care--including those aged 50 years and older, pregnant women,
young children, and individuals with chronic medical conditions. The
primary method for preventing influenza in these groups, and in the
general population, is annual vaccination with influenza vaccine.^1 The
influenza season in the United States generally occurs from late fall to
early spring, with infections typically peaking in January or February.
October through November is considered to be the best time for influenza
vaccination; in most years, however, vaccination in December or later can
still be beneficial. Because circulating influenza virus strains change, a
new vaccine is created each year based on the three influenza virus
strains that the Department of Health and Human Services's (HHS) Food and
Drug Administration (FDA) determines to be likely to cause serious illness
in the United States that year.^2 The vaccine is produced through a
lengthy and complex process that involves growing the influenza virus
strains in millions of chicken eggs.

HHS's Centers for Disease Control and Prevention (CDC) and its Advisory
Committee on Immunization Practices (ACIP) make recommendations on which
groups should be targeted for annual influenza vaccination in the United
States. Individuals in this target population for the 2007-08 influenza
season include those in high-risk groups^3--such as adults aged 50 years
and older, children aged 6 to 59 months, pregnant women, and persons aged
6 months and older with certain chronic medical conditions--and
individuals in other target groups, such as health care workers and others
in close contact with those at high risk. CDC officials have raised
concerns that, should shortages or delays in distribution of vaccine
occur, vaccine would not be available for individuals in high-risk or
other target groups during the time when demand for vaccination among
these groups has traditionally been highest. In addition, these officials
raised concerns, when vaccine has been more plentiful, that not all
individuals in the target population for whom annual vaccination is
recommended have been seeking or receiving vaccination. For example, only
about half of those in groups at higher-risk for influenza-related
complications and only about one-fifth of those in other target groups
received influenza vaccination, according to CDC estimates.^4

^1Influenza vaccination is performed by a diverse group of providers,
including state and local health departments, other medical facilities,
and mass immunizers--visiting nurse agencies or for-profit companies that
contract with and conduct influenza vaccination clinics at workplaces,
retail stores, long-term care facilities, and other locations.

^2FDA's determination of strains to be included in the seasonal influenza
vaccine is based on a review of surveillance data, the availability of
appropriate materials, and consultation with an FDA advisory committee.

We previously reported on manufacturing difficulties experienced during
the 2000-01 influenza season that illustrated the challenges in producing
a new influenza vaccine each year on a timely basis. We reported on the
delays in shipment and resulting initial vaccine shortage experienced for
that season, and we also reported on the vaccine shortage experienced for
the 2004-05 influenza season.^5 You observed that, despite changes since
the 2000-01 season, concerns about the reliability of influenza vaccine
supply and distribution persist. This report discusses (1) factors that
affect the quantity of seasonal influenza vaccine produced and when
vaccine reaches providers who administer vaccine, (2) issues related to
making vaccine available for high-risk and other target groups, and (3)
public health messages produced and disseminated by CDC and others to
promote seasonal influenza vaccination.

^3Throughout this report, we use the term high-risk to refer to those
groups of individuals ACIP has identified for the 2007-08 influenza season
as being at increased risk for influenza-related complications or at
higher risk for medical care--that is, for influenza-associated clinic,
emergency department, or hospital visits. See Centers for Disease Control
and Prevention, "Prevention and Control of Influenza: Recommendations of
the Advisory Committee on Immunization Practices (ACIP), 2007," Morbidity
and Mortality Weekly Report, vol. 56 (June 29, 2007): 1-53.

^4See Centers for Disease Control and Prevention, "Estimates of Influenza
Vaccination Target Population Sizes in 2006 and Recent Vaccine Uptake
Levels,"
[35]http://www.cdc.gov/flu/professionals/vaccination/pdf/targetpopchart.pdf
(downloaded April 2, 2007).

^5See GAO, Flu Vaccine: Supply Problems Heighten Need to Ensure Access for
High-Risk People, [36]GAO-01-624 (Washington, D.C.: May 15, 2001); GAO,
Influenza Vaccine: Shortages in 2004-05 Season Underscore Need for Better
Preparation, [37]GAO-05-984 (Washington, D.C.: Sept. 30, 2005); and see
Related GAO Products at the end of this report.

To address these objectives, we reviewed relevant documents and
interviewed officials from CDC and FDA; national associations representing
state and local health officials,^6 public health officials, medical
supply distributors,^7 physicians, and long-term care providers; and all
five manufacturers of seasonal influenza vaccine for the U.S. market for
the 2007-08 influenza season as of August 31, 2007.^8 We also selected
judgmental samples of (1) medical supply distributors; (2) mass
immunizers--organizations that conduct influenza vaccination clinics at
workplaces, retail stores, long-term care facilities, and other locations;
and (3) state health departments.^9 For each organization in our samples,
we reviewed relevant documents and interviewed officials.

To determine the quantity of seasonal influenza vaccine produced and when
vaccine reaches providers who administer vaccine, we examined data from
CDC regarding the number of influenza vaccine doses produced and
distributed each month for the 2000-01 influenza season through the
2006-07 influenza season. We also reviewed data from CDC on the cumulative
percentage of doses manufacturers and medical supply distributors reported
shipping each month to different types of providers for the 2006-07
influenza season. To identify the locations in which high-risk groups
receive their vaccinations, we reviewed data from CDC's Behavioral Risk
Factor Surveillance System,^10 a poll contracted by CDC, and other surveys
CDC administered on immunization practices. To identify efforts undertaken
by CDC and state health officials to help state and local officials manage
availability of vaccine for high-risk and other target groups, we reviewed
data from and documentation of the Internet-based distribution database
that CDC created--the Flu Vaccine Finder, a component of CDC's Secure Data
Network^11--and interviewed health department officials from our sample of
states. We assessed the reliability of these data and determined they were
sufficiently reliable for our purposes.

^6We also spoke with state and local health officials who are members of
national associations representing state and local health officials.

^7Medical supply distributors purchase vaccine from manufacturers and
resell it to customers such as physicians, hospitals, state and local
health departments, other distributors, and others seeking vaccine in
order to administer vaccinations.

^8For the 2007-08 influenza season, five vaccines were licensed by FDA for
the U.S. market as of August 31, 2007: (1) Fluarix, manufactured by a part
of GlaxoSmithKline plc, GlaxoSmithKline Biologicals, (2) FluLaval,
manufactured by a subsidiary of GlaxoSmithKline plc, ID Biomedical
Corporation of Quebec, (3) FluMist, manufactured by MedImmune Vaccines,
Inc., (4) Fluvirin, manufactured by Novartis Vaccines and Diagnostics
Limited, and (5) Fluzone, manufactured by sanofi pasteur. The policy of
sanofi pasteur is to spell its name without capital letters. We
interviewed officials and obtained information from GlaxoSmithKline
Biologicals regarding both Fluarix and FluLaval; and interviewed officials
and obtained information from MedImmune Vaccines, Inc., Novartis Vaccines
and Diagnostics Limited, and sanofi pasteur regarding FluMist, Fluvirin,
and Fluzone, respectively. On September 28, 2007, FDA approved an
additional influenza vaccine, Afluria, manufactured by CSL Limited, for
the U.S. market for the 2007-08 season.

^9We selected these samples to reflect a mix of distributors, mass
immunizers, and states; however, our samples were not statistically
representative and cannot be generalized. Our judgmental samples included
six medical supply distributors that plan to distribute influenza vaccine
for the 2007-08 season, four mass immunizers, and six state health
departments. For additional information on our scope and methodology, see
app. I.

To examine public health messages that CDC and others have produced and
disseminated to promote seasonal influenza vaccination, we reviewed
influenza vaccination communication plans produced by CDC and research and
surveys conducted by CDC. We conducted our work in accordance with
generally accepted government auditing standards from May through October
2007.

Results in Brief

Several factors--including challenges in manufacturing a new vaccine each
year, limitations in the production capacity of manufacturers, and
fluctuating demand for vaccine by providers and patients--affect the
quantity of vaccine produced for a given influenza season and when it
reaches providers who administer the vaccine. Manufacturing challenges
inherent to the production of seasonal influenza vaccine include the
necessity of adhering to a relatively inflexible and sequential process
involving multiple players including the World Health Organization, CDC,
FDA, and manufacturers; difficulties growing new virus strains; and
problems associated with maintaining safety and quality control practices
to produce a sterile vaccine. Each of these manufacturing challenges has
the potential to affect all manufacturers; however, in any given year, the
degree to which these challenges affect the quantity of vaccine that an
individual manufacturer produces or when that manufacturer's vaccine is
shipped to providers may vary significantly. Overall production
capacity--that is, the maximum amount of vaccine that manufacturers can
produce, package, and ship at any given time--may also limit the quantity
of vaccine produced and can delay when vaccine is available to providers.
Another limiting factor is demand for vaccine throughout the influenza
season. Because demand for vaccine is highest in October and November and
then tapers off in December and later, manufacturers may decide to stop
production if they do not believe there is sufficient demand later in the
season, thereby limiting the quantity produced for that influenza season
and how late in the season it is available. For individual providers who
administer influenza vaccinations, the distribution route the vaccine
takes from the manufacturer to the providers can also affect how much time
elapses before the vaccine reaches them.

^10The Behavioral Risk Factor Surveillance System is a state-based system
of health surveys that collects information on health risk behaviors,
preventive health practices, and health care access primarily related to
chronic disease and injury.

^11The Secure Data Network is an ongoing project sponsored by CDC to allow
CDC field staff, researchers, and public health partners to securely
exchange confidential, proprietary, or sensitive data over the Internet.

Issues related to making vaccine available to high-risk and other target
groups include the locations in which these individuals receive
vaccinations, how vaccine is distributed to providers, and the timing of
vaccine distribution to different types of providers. According to data
from CDC, individuals in high-risk and other target groups have received
influenza vaccinations at various locations where different types of
providers, including physicians, hospitals, pharmacies, state and local
health departments, and mass immunizers, administer vaccine. All
manufacturers we spoke with and more than half of the medical supply
distributors we interviewed reported that, for the 2007-08 influenza
season, they plan to continue or begin distributing vaccine to all types
of providers in multiple shipments--that is, they plan to fill a portion
of each customer's order as vaccine becomes available--so that all
customers may have at least some vaccine available for high-risk or other
target groups. Other medical supply distributors reported shipping vaccine
using a variety of other distribution practices, such as filling vaccine
orders in the order in which they were received. As a result of these
distribution practices, it is possible that some providers receive vaccine
and offer vaccinations to anyone who wants it before other providers have
received enough vaccine to vaccinate their patients in high-risk or other
target groups. In recent years, certain types of providers, such as
physicians and state and local health departments, reported they received
their vaccine orders later than other types of providers, such as mass
immunizers that provide vaccinations at retail stores. National data
collected by CDC for the 2006-07 influenza season indicated that, in
aggregate, most types of providers, including private providers such as
physicians, received vaccine in similar time frames. However, the data
also indicated that state and local health departments received a smaller
percentage of the doses distributed in the early fall than later in the
season. CDC officials acknowledged that individual providers' experiences
at the local level could vary. In an effort to help state and local health
officials manage the availability of vaccine for high-risk and other
target groups, CDC and state health officials have undertaken several
efforts, including the creation of monitoring tools and the implementation
of a state-specific vaccine distribution program.

CDC and others have produced and disseminated public health messages
designed to promote seasonal influenza vaccination and CDC has taken some
steps to assess its messages. Efforts to communicate public health
messages undertaken by CDC and others--including state and local health
departments and provider associations--include production and
dissemination of press releases, educational materials, and public service
announcements designed to promote vaccination, as well as messages aimed
at maintaining public demand later in the season and encouraging
preferential vaccination of certain groups during times of vaccine
shortage or delay. CDC has taken steps to assess its influenza-related
public health messages before disseminating them to the public and has
collected some data afterwards. Although no comprehensive evaluations have
been conducted, CDC and other officials we interviewed identified
elements, such as clear and consistent messages, that are important to
effective public health messages promoting influenza vaccination. However,
there are impediments to effectively implementing these elements, such as
the need to modify messages during the season as circumstances change.

We provided a draft of this report to HHS for comment. The department
provided technical comments, which we incorporated as appropriate.

Background

Influenza is characterized by cough, fever, headache, and other symptoms
and is more severe than some viral respiratory infections, such as the
common cold. Most people who contract seasonal influenza recover
completely in 1 to 2 weeks, but some develop serious and potentially
life-threatening medical complications, such as pneumonia. On average each
year in the United States more than 36,000 individuals die and more than
200,000 are hospitalized from influenza and related complications.

Vaccination, administered annually to provide protection against
particular influenza virus strains expected to be prevalent that year, is
the primary method for preventing seasonal influenza and its more severe
complications. After vaccination, the body takes about 2 weeks to produce
the antibodies that protect against infection. Traditionally CDC has
recommended vaccination begin around October each year. However, because
influenza seasons most often peak in January or February, in most years
vaccination in December or later can still be beneficial. As shown in
figure 1, the influenza season peaked in January or February in nearly
two-thirds of the past 30 seasons.

Figure 1: Month of Peak Influenza Activity, 1976 through 2006

Notes: The peak month of activity was defined as the month with the
greatest percentage of respiratory specimens testing positive for
influenza virus. Percentages do not add to 100 percent due to rounding.

Two types of vaccine are recommended for protection against seasonal
influenza in the United States: (1) an inactivated virus vaccine injected
into muscle or (2) a live attenuated vaccine administered as a nasal
spray.^12 The injectable vaccine--which represents the vast majority of
influenza vaccine administered--can be used to immunize healthy
individuals aged 6 months and older and those at increased risk of
complications or more likely to require medical care, including high-risk
individuals.^13 The live attenuated vaccine, in contrast, is approved for
use only among healthy individuals aged 2 through 49 years who are not
pregnant.^14 This live attenuated vaccine represented less than 3 percent
of the vaccine doses produced for sale in the United States for the
2006-07 influenza season.

^12A live attenuated vaccine contains attenuated, or weakened, influenza
viruses.

Because of fluctuations in the most prevalent virus strains of seasonal
influenza, a new influenza vaccine is produced each year. Seasonal
influenza vaccine is produced by manufacturers each year in a lengthy and
complex process that involves a sequential set of steps (see fig. 2):^15

           1. Virus Strain Selection: In late winter each year, FDA
           determines the three influenza virus strains assessed to be most
           likely to cause serious illness in the United States the following
           influenza season.^16 One or two of the three strains selected for
           inclusion in the vaccine are usually new compared to the prior
           season. For example, for the 2000-01 influenza season and all but
           one of the subsequent seasons, FDA has changed at least one strain
           selected for the vaccine--that is, at least one selected strain
           has differed from the strains included in the previous season's
           vaccine. For one season, the 2003-04 season, FDA selected the same
           three influenza virus strains for the vaccine that were included
           in the prior season's vaccine.
           2. Production and Purification: Manufacturers and FDA obtain
           samples of each of the three selected virus strains from one of
           the World Health Organization Collaborating Centres.^17 The
           manufacturers then inject the virus samples of each selected
           strain into separate batches of fertilized eggs to amplify the
           amount of virus. The viruses grown at this stage are called seed
           viruses and are tested by FDA. After manufacturers develop an
           appropriate seed virus for each of the three virus strains, these
           seed viruses are injected into millions of fertile chicken eggs
           and allowed to replicate.^18 Producing these fertile eggs is more
           difficult than producing eggs grown for human consumption and FDA
           requires that the fertile eggs meet particular sanitation and
           other requirements. Each virus strain is grown separately inside
           the eggs over the course of several days, after which it is
           harvested, inactivated, and purified.^19 
           3. Testing, Filling, and Packaging: Using biological materials
           provided by FDA, manufacturers and FDA test the virus strains
           produced by the manufacturers to determine the purity and yield of
           the virus and to ensure that the potency of the virus is
           sufficient for immunization. The three virus strains are then
           combined to create the vaccine for that season. Once the vaccine
           is created, manufacturers fill vaccine doses into vials and
           syringes. Labels are applied denoting the vaccine lot number and
           expiration date. FDA may conduct additional testing before
           officially releasing each lot for distribution; according to FDA,
           the agency typically releases a lot within 3 weeks, provided the
           lot has satisfied FDA standards.^20 
           4. Shipping to Customers: Manufacturers ship released vaccine to
           customers, which can include medical supply distributors,
           physicians, hospitals, state and local health departments, and
           mass immunizers.^21 The vaccine must be kept refrigerated within a
           prescribed temperature range.^22

^13Manufacturers may produce different formulations of the vaccine, and
formulations are indicated for certain age groups. For example, for the
2006-07 influenza season, only one manufacturer made formulations of its
injectable vaccine that were approved for use in children aged 6 months
through 3 years of age. For that age group, the manufacturer made
formulations in multidose vials that contain a preservative, as well as in
preservative-free single-use prefilled syringes.

^14On September 19, 2007, FDA expanded the group approved for use of the
live attenuated vaccine FluMist from healthy individuals aged 5 through 49
years to those aged 2 through 49 years.

^15These steps describe the manufacturing process for the inactivated
injectable vaccine, which represented over 97 percent of vaccine doses
produced for sale in the United States for the 2006-07 influenza season.
Live attenuated vaccine administered as a nasal spray is produced in a
similar process that follows a similar timeline.

^16FDA conducts this strain selection process in consultation with its
Vaccines and Related Biological Products Advisory Committee. Surveillance
information from the World Health Organization and CDC is evaluated, as is
the availability of materials suitable for commercial production of
vaccine.

^17The four World Health Organization Collaborating Centres are located in
Australia, Japan, the United Kingdom, and the United States. CDC is the
Collaborating Centre in the United States.

^18Manufacturers report that they usually begin production of one virus
strain that they anticipate FDA will select for the following influenza
season's vaccine--for example, a strain that was included in the prior
season's vaccine--in January, prior to FDA's strain selection and
distribution of that influenza season's strains.

^19In contrast, the live attenuated vaccine administered as a nasal spray
is not inactivated.

^20Influenza vaccine is subject to official lot release by FDA.
Manufacturers submit samples of each lot of vaccine, along with summaries
of the history of manufacture and the results of all the tests performed,
to FDA, which may then perform additional tests before officially
releasing the lot for distribution. The manufacturer may not distribute
the vaccine lot until FDA releases it.

^21Some customers may also be members of group purchasing
organizations--entities that help health care providers realize savings
and efficiencies by aggregating purchasing volume and using that leverage
to negotiate discounts with manufacturers, distributors, and other
vendors.

^22For the 2007-08 season, the live attenuated vaccine administered as a
nasal spray also requires refrigeration within a prescribed temperature
range.

Figure 2: Seasonal Influenza Vaccine Production Cycle

Notes: These steps describe the manufacturing process for the inactivated
injectable vaccine, which represented over 97 percent of vaccine doses
produced for sale in the United States for the 2006-07 influenza season.
Live attenuated vaccine administered as a nasal spray is produced in a
similar process that follows a similar timeline.

The months associated with these steps are approximate and may vary from
influenza season to influenza season.

^aThe four World Health Organization Collaborating Centres are located in
Australia, Japan, the United Kingdom, and the United States. CDC is the
Collaborating Centre in the United States.

^bIn contrast, the live attenuated vaccine administered as a nasal spray is
not inactivated.

^cInfluenza vaccine is subject to official lot release by FDA.
Manufacturers submit samples of each lot of vaccine, along with summaries
of the history of manufacture and the results of all the tests performed,
to FDA, which may then perform additional tests before officially
releasing the lot for distribution. The manufacturer may not distribute
the vaccine lot until FDA releases it.

Vaccine production generally takes 6 or more months after virus strains
have been selected, according to vaccine manufacturers, and vaccines for
certain influenza virus strains have been difficult to mass-produce.
Manufacturers are currently pursuing new production technologies, which
may allow for more robust and reliable influenza vaccine production and
may speed up the production process. For example,

           o One such production technology involves growing the influenza
           virus in cells rather than chicken eggs.^23 While eggs must be
           ordered up to 1 year in advance for egg-based production, cells
           used in cell-based production are more readily available, allowing
           for faster start up of vaccine manufacturing--the required amount
           of cells can be produced from frozen cells in a few days to weeks.
           In addition, cell-based production may present fewer contamination
           problems than egg-based production.

           o Another technology under development makes seed viruses using
           genetic techniques rather than through the current trial-and-error
           process in which the virus strains are grown and sampled for the
           desired characteristics. This technology may allow for more
           reliable production of seed viruses--an essential step in the
           vaccine production process.

           o Technology resulting in the development of a universal vaccine
           that would be effective against multiple virus strains would
           eliminate the need for current processes required to reformulate
           seasonal influenza vaccine each year. As a result, vaccine could
           be produced and available at any time of
           the year. However, despite recent increases in funding,^24 a
           completely universal influenza vaccine may be years away.^25
			  
^23While cell-based production methods are new for influenza vaccines,
they have been used for other vaccines such as chickenpox, hepatitis A,
polio, and shingles. HHS has awarded more than $1 billion in contracts to
develop cell-based technologies for influenza vaccines.

^24For example, Dynavax Technologies Corporation was recently awarded a
$3.25 million grant from the National Institutes of Health to continue
development of a universal influenza vaccine.

^25In April 2007, the World Health Organization's Strategic Advisory Group
of Experts on Immunization concluded that it was realistic to expect that
vaccines offering protection against multiple influenza strains could be
developed; however, no specific time frame was given. In May 2007, the
World Health Organization reported that a universal vaccine might not be
available in the next 5 to 10 years.

           Manufacturers aim to make influenza vaccine available before the
           fall vaccination period when demand for vaccination has
           traditionally been the highest. At the end of the influenza season
           unused doses expire and cannot be used in subsequent years.^26 For
           example, more than 18 million doses left over from the 2006-07
           influenza season expired in 2007. Accordingly, manufacturers seek
           to match their vaccine production to expected demand for the
           vaccine so that no doses remain unsold at the end of the influenza
           season.

           Manufacturers sell vaccine directly to providers who administer
           vaccine, including physicians, hospitals, pharmacies, federal
           agencies, state and local health departments, and mass immunizers.
           In addition, manufacturers sell vaccine to medical supply
           distributors, who in turn sell it to providers and other customers
           such as other medical supply distributors. Providers administer
           vaccinations in a variety of locations, including physicians'
           offices, public health clinics, nursing homes, and nonmedical
           locations such as workplaces and retail stores. Millions of
           individuals receive influenza vaccinations through mass
           immunization campaigns in these nonmedical settings, where
           organizations such as visiting nurse agencies under contract
           administer the vaccine.^27
			  
^26According to FDA, the expiration dating period for inactivated virus
vaccine is set so that influenza vaccine for one influenza season cannot
be confused with vaccine for subsequent seasons.

^27According to a Gallup poll conducted for CDC in 2005, adults received
influenza vaccination in the following locations: physicians' offices (39
percent), workplaces (17 percent), other clinics or health centers (10
percent), stores or pharmacies (10 percent), health departments (8
percent), hospitals (6 percent), senior or recreational centers (4
percent), other locations (4 percent), and schools (2 percent).			  

           The number of manufacturers of seasonal influenza vaccine for the
           U.S. market and the number of doses produced and distributed have
           changed over the past seven seasons (see table 1).^28 For the
           2007-08 influenza season, six U.S.-licensed manufacturers are
           expected to produce an estimated 132 million doses of seasonal
           influenza vaccine.

           Table 1: Number of U.S.-Licensed Manufacturers of Seasonal
           Influenza Vaccine and Number of Doses Produced and Distributed,
           2000-01 through 2006-07 Influenza Seasons
			  
                                Total number of                               
Influenza Number of licensed  doses produced         Total number of doses 
season         manufacturers   (in millions)     distributed (in millions) 
2000-01                    3              78                            70 
2001-02                    3              88                            78 
2002-03                    3              95                            83 
2003-04                    3              87                            83 
2004-05                  3^a              61                            57 
2005-06                    4              92                            82 
2006-07                  5^b             121                           103 
			  

           Source: CDC and FDA.

           Notes: Table includes the number of doses produced by
           manufacturers and distributed to customers such as medical supply
           distributors, physicians, or other types of providers.

           ^aOf the three manufacturers of seasonal influenza vaccine for the
           2004-05 influenza season, two produced and distributed vaccine and
           one ceased production and did not distribute any vaccine for the
           U.S. market after its license was suspended by the United Kingdom
           in October 2005. In addition to these three manufacturers, two
           foreign manufacturers' vaccines were purchased by HHS and made
           available in the United States under an investigational new drug
           protocol; however, none of these doses were distributed.

           ^bThe manufacturers of vaccine licensed for the 2006-07 season and
           their vaccines were: GlaxoSmithKline Biologicals, a part of
           GlaxoSmithKline plc (Fluarix), ID Biomedical Corporation of
           Quebec, a subsidiary of GlaxoSmithKline plc (FluLaval), MedImmune
           Vaccines, Inc. (FluMist), Novartis Vaccines and Diagnostics
           Limited (Fluvirin), and sanofi pasteur (Fluzone). The policy of
           sanofi pasteur is to spell its name without capital letters.

           Since influenza vaccine production and distribution are largely
           private-sector activities, HHS and other federal entities have
           limited authority to control influenza vaccine production and
           distribution.^29 CDC administers a number of programs to help make
           vaccines, including influenza vaccine, affordable for low-income
           and other populations. For example, under CDC's Vaccines for
           Children program, vaccines are provided free of charge for certain
           children 18 years of age or younger, including those who are
           Medicaid-eligible, uninsured, or those without insurance coverage
           for vaccinations. CDC also reserves stockpiles of certain vaccines
           for use in the event of a vaccine shortage or disease outbreak.
			  
^28See app. II for a list of U.S.-licensed manufacturers of seasonal
influenza vaccine from the 2000-01 season through the 2007-08 influenza
season.

^29With specified exceptions, the Federal Food, Drug, and Cosmetic Act
prohibits the resale of prescription drugs, including influenza vaccine,
after their purchase by health care entities such as public or private
hospitals. This prohibition does not apply to resale for emergency medical
reasons. In addition, because the term "entity" does not include wholesale
distributors, this prohibition does not apply to resale by wholesale
distributors. See 21 U.S.C. S353(c)(3).			  

           For each influenza season, ACIP, after consulting with CDC, makes
           recommendations on who should be targeted for vaccination and, in
           some years, has modified its annual recommendations after issuing
           them in order to address vaccine shortage, such as during the
           2004-05 season.^30 For the 2007-08 season, ACIP recommends
           vaccination for two categories of individuals: (1) high-risk
           individuals--that is, those persons at increased risk for medical
           complications or more likely to require medical care, such as
           children aged 6 to 59 months, pregnant women, persons aged 50
           years or older, and persons with certain chronic conditions; and
           (2) close contacts of those at high risk--that is, persons who
           live with or care for persons at high risk, such as family members
           and health care workers. According to ACIP, approximately 73
           percent of the U.S. population is included in one or more of these
           target groups. However, not everyone in these recommended target
           groups receives a vaccination each year--only an estimated
           one-third of them received vaccination, according to CDC
           estimates.^31 For the 2007-08 season, in addition to recommending
           that providers vaccinate individuals in high-risk and other target
           groups, ACIP recommends that all persons, including school-aged
           children, who want to reduce the risk of becoming ill with
           influenza or of transmitting influenza to others should be
           vaccinated.
			  
^30See app. III for additional information on ACIP recommendations for
prevention and control of influenza and on the priority groups--comprised
of subsets of the high-risk and other target groups--that ACIP recommended
receive priority for available vaccine during seasons with vaccine delays
or shortage.

^31See app. III for information on the estimated population in each target
group. The vaccination rates among the different high-risk and other
target groups vary. For example, about 65 percent of adults aged 65 years
and older and about 42 percent of health care workers less than 65 years
of age received vaccination, according to CDC estimates. See Centers for
Disease Control and Prevention, "Estimates of Influenza Vaccination Target
Population Sizes in 2006 and Recent Vaccine Uptake Levels."

           Manufacturing Challenges, Limitations in Production Capacity, and
			  Fluctuating Demand for Vaccine May Limit the Quantity of Vaccine
			  Produced or Delay When Vaccine Reaches Providers
			  
			  Manufacturing Challenges May Limit the Quantity of Seasonal Influenza
			  Vaccine Produced or Delay When Vaccine Reaches Providers

           Several factors may affect the quantity of vaccine produced for a
           given season and when it reaches providers who administer the
           vaccine. These factors include: challenges in manufacturing a new
           vaccine each year; limitations in the production capacity of
           manufacturers; and demand for vaccine by providers and patients
           that fluctuates throughout the season. For an individual provider,
           additional factors, including the route the vaccine takes from the
           manufacturer to the provider, can affect how much and when a
           particular provider receives vaccine.

           Manufacturing challenges inherent to the production of a new
           seasonal influenza vaccine each year include the necessity of
           adhering to a relatively inflexible and sequential process
           involving multiple players, difficulties growing new virus
           strains, and problems associated with maintaining safety and
           quality-control practices to produce a sterile vaccine. Each of
           these challenges has the potential to affect all manufacturers;
           however, in any given year the degree that these challenges affect
           the number of doses that an individual manufacturer produces or
           when that manufacturer's vaccine becomes available may vary
           significantly.

           o Adherence to a sequential set of steps involving multiple
           players. Influenza vaccine is produced by manufacturers through a
           relatively inflexible process involving a sequential set of
           critical steps that are undertaken by multiple players including
           the World Health Organization, CDC, FDA, and manufacturers.
           Certain steps in the process must be completed before other steps
           can start and the timing and outcome of these steps can affect
           both the quantity of vaccine produced and when the vaccine reaches
           providers. For example, FDA typically does not have sufficient
           information until late each winter to identify the influenza virus
           strains likely to be prevalent during the upcoming season. As a
           result, FDA selects the three virus strains that will make up the
           vaccine for the upcoming season usually between late February and
           early March; once these selections are made, the manufacturers,
           using samples of each selected virus strain, develop seed viruses
           that are suitable for subsequent vaccine production. Manufacturers
           reported that the timeline for FDA's strain selection and the
           subsequent distribution of samples of strains to develop seed
           viruses does not allow them enough time to produce all three virus
           strains in time for the fall vaccination period. As a result,
           manufacturers consult with CDC and FDA, assess preliminary data,
           and complete their own analyses as to what FDA's choice of virus
           strains for the upcoming season might be. Manufacturers usually
           begin producing one of the influenza virus strains that they
           believe will be included in the vaccine in January in advance of
           FDA's strain selection.^32

           o Difficulties growing a new virus strain. Manufacturers have
           experienced delays in producing and distributing vaccine for
           several recent influenza seasons because of challenges inherent to
           growing influenza virus strains. For example, for the 2000-01
           influenza season, difficulties experienced by two manufacturers
           growing a new virus strain contributed to an overall delay of
           about 6 to 8 weeks in distributing vaccine to most customers and
           an initial shortage of vaccine supply.^33 For the 2006-07
           influenza season, several manufacturers reported problems growing
           one of the two new virus strains that, for one major manufacturer,
           resulted in a delay of about 3 weeks in vaccine production. Since
           this manufacturer was the only producer of vaccine licensed for
           children aged 6 through 47 months, the delay in its production may
           have affected some providers' ability to have vaccine available
           for this population.

           o Problems associated with maintaining safety and quality-control
           practices. Problems associated with maintaining safety and
           quality-control practices to produce a sterile vaccine can limit
           the quantity of seasonal influenza vaccine produced and when it
           reaches providers. In 2002, one manufacturer that had produced
           seasonal influenza vaccine for more than two decades exited the
           U.S. market after it was fined by FDA for failing to correct
           manufacturing deficiencies. In 2004, another manufacturer
           announced that because of potential contamination discovered when
           a small quantity of its vaccine failed sterility tests, it would
           not release any vaccine for the U.S. market. This manufacturer had
           been expected to produce approximately half of the estimated doses
           of influenza vaccine for the 2004-05 season.^34 More recently, in
           May 2007, FDA issued a warning letter to a different manufacturer
           because of deviations from good manufacturing practices, including
           some which could potentially lead to sterility problems.^35 In
           September 2007, the manufacturer reported that it had resolved the
           observances contained in the warning letter.^36
			  
^32If a manufacturer were to begin production of a virus strain in January
that did not end up being one of the strains selected by FDA for the
vaccine--a situation that manufacturers report has yet to occur--it is
possible that the manufacturer would not have enough time to grow a
different virus strain in time to distribute the vaccine for fall
vaccination.

^33 [38]GAO-01-624 .

^34 [39]GAO-05-984 .

^35Good manufacturing practices include requirements applicable to the
entire manufacturing process to help ensure that biological products, such
as vaccines, are safe, pure, and potent.

^36The manufacturer had previously reported that it expected to address
the problem without affecting the quantity of vaccine produced.	
           
           Production Capacity May Limit the Quantity of Seasonal Influenza
			  Vaccine Produced and May Delay When Vaccine Reaches Providers

           Overall production capacity--that is, the maximum amount of
           vaccine that manufacturers can produce, package, and ship at any
           given time--may limit the quantity of seasonal influenza vaccine
           produced and may delay when vaccine reaches providers.
           Manufacturers reported that, even in years with fewer
           manufacturing challenges, they are limited in the number of doses
           that they can produce and fill at a given time, and, therefore,
           not all doses of influenza vaccine are available by the beginning
           of each influenza season. Instead, manufacturers distribute
           vaccine as it becomes available beginning in late summer or in the
           fall and generally continuing into the winter, with the proportion
           of vaccine distributed each month varying from year to year (see
           fig. 3). Because vaccine is produced in batches over the course of
           several months, only a portion of the full year's production is
           available each month to vaccinate individuals against influenza.

           Figure 3: Distribution of Influenza Vaccine Doses in Millions by
           Month, 2000-01 through 2006-07 Influenza Seasons

           More doses of influenza vaccine could be produced for each
           influenza season if either the current manufacturers increased
           their production capacity or if more manufacturers entered the
           U.S. market. All of the manufacturers of seasonal influenza
           vaccine for the U.S. market that we interviewed reported plans to
           increase production capacity for future seasons. In addition, on
           September 28, 2007, a sixth manufacturer, which has reported that
           it will eventually have the capacity to produce as many as 20
           million doses of seasonal influenza vaccine for the U.S. market,
           received FDA approval for the 2007-08 season.^37
			  
^37In October 2007, this manufacturer reported that it will make
approximately 2 million doses immediately available to the U.S. market for
the 2007-08 season.

           Demand for Influenza Vaccine Affects the Quantity of Seasonal
			  Influenza Vaccine Produced

           Since demand for influenza vaccine typically peaks in October and
           November and then tapers off, manufacturers may decide to limit or
           stop production if they do not believe there is sufficient demand
           to sell all of the doses they have the capacity to
           produce--thereby limiting the quantity produced for that season
           and how late in the season it is available. For example, one
           manufacturer reported that it has capacity to produce more doses
           of influenza vaccine than its planned production for the 2007-08
           season, but reported that production of the additional doses would
           be contingent in part on demand for doses later in the season.
           Even in seasons when there were vaccine shortages during the
           traditional fall vaccination period, some doses remained unsold at
           the end of the season. For example, even though there was an
           initial shortage of influenza vaccine for the 2000-01 season,
           after additional doses became available later in the season,
           approximately seven million doses of influenza vaccine went
           unsold.

           In past seasons when demand for influenza vaccine has occurred
           later in the season, supply has not always been available to meet
           it. For example, during the 2003-04 influenza season, there was
           late-season demand for seasonal influenza vaccine after reports of
           influenza-related deaths among children. However, there was not
           enough influenza vaccine available at the time to meet demand and
           individuals that wanted vaccine were not able to obtain it. To
           prevent this scenario from occurring again in subsequent seasons,
           beginning for the 2004-05 season, CDC began contracting with
           manufacturers to produce a small quantity of influenza vaccine to
           be available later in the season to ensure that some vaccine would
           be available in the event of a late-season outbreak of influenza
           and related demand for vaccine.
			  
			  Distribution Routes May Affect When Seasonal Influenza Vaccine
			  Reaches Individual Providers

           In addition to the timing of the production and shipment of
           vaccine from the manufacturer, the distribution route that the
           vaccine takes from the manufacturer to a provider can also affect
           how much time elapses before the vaccine reaches individual
           providers who have ordered it. If, for example, a provider's order
           is routed through a medical supply distributor, it may take longer
           for vaccine to reach that provider than it would if a provider's
           order was routed directly from the manufacturer--a route with no
           stops to reach the provider. For the 2007-08 season, manufacturers
           of two of the five influenza vaccines licensed for the U.S. market
           as of August 31, 2007, reported plans to distribute the majority
           of their vaccine through medical supply distributors. The
           manufacturers of the three other vaccines told us they planned to
           distribute some vaccine through medical supply distributors.
           According to the Health Industry Distributors Association, the
           distribution route for about half of the vaccine sold for the
           2006-07 influenza season was through medical supply distributors,
           8 of every 10 of those doses went to a physician's office or a
           clinic, and medical supply distributors shipped vaccine to
           providers in 1 to 3 days after the distributors received the
           vaccine from the manufacturers. The association also estimated
           that the route for about half of the vaccine sold for the 2006-07
           influenza season was shipped directly from the manufacturer to the
           provider.^38 As shown in figure 4, if it takes from 1 to 3 days
           for manufacturers to distribute vaccine to their customers once it
           is ready for shipment, the route a provider's order takes--that
           is, whether it is routed directly from the manufacturer to the
           provider, which can take as little as 1 day,^39 or whether it is
           routed through multiple medical supply distributors or a central
           location for distribution as is the case for some state health
           departments--affects the time that elapses from the date the
           manufacturer ships the vaccine until an individual provider
           receives it.
			  
^38Health Industry Distributors Association, "2006-07 Influenza Vaccine
Production & Distribution Market Brief," (Alexandria, Va.: Health Industry
Distributors Association, 2007)
[40]http://www.hida.org/attachment.asp?attachment_id=10509 (downloaded
Oct. 3, 2007).

^39An official from the American Medical Association participating in the
National Influenza Vaccine Summit estimated it takes from 1 to 3 days for
a manufacturer to distribute vaccine to customers.

Figure 4: Potential Impact of Different Distribution Routes of Vaccine
Orders from Manufacturer to Provider

Issues Related to Vaccine Distribution May Affect Vaccine Availability for
High-Risk and Other Target Groups

Issues related to making vaccine available for high-risk and other target
groups include the locations where these groups are vaccinated, how
vaccine is distributed to the providers who administer vaccinations, and
the timing of vaccine distribution to different types of providers.
According to data from CDC, individuals in high-risk and other target
groups have received influenza vaccinations at various locations where
different types of providers administer vaccine. Manufacturers and medical
supply distributors we interviewed reported that, for the 2007-08
influenza season, they plan to distribute vaccine using a variety of
distribution practices including shipping vaccine as it becomes available
through multiple shipments and filling vaccine orders in the order in
which they were received. In recent years, certain types of providers,
such as physicians and state and local health departments, reported that
they received their vaccine orders later than other types of providers,
such as mass immunizers. National data collected by CDC for the 2006-07
influenza season indicated that in aggregate most types of providers,
including private providers such as physicians, received vaccine in
similar time frames. However, the data also indicated that state and local
health departments received a smaller percentage of the doses distributed
in the early fall than later in the season. CDC officials acknowledged
that individual providers' experiences at the local level could vary. In
an effort to help state and local health officials manage the availability
of vaccine for high-risk or other target groups, CDC and state health
officials have undertaken several efforts, including the creation of
monitoring tools and the implementation of a state-specific vaccine
distribution program.

High-Risk and Other Target Groups Receive Vaccinations at Various Locations
Where Different Types of Providers Administer Vaccine

Individuals in high-risk and other target groups receive influenza
vaccinations at various locations where different types of providers, such
as physicians, hospitals, pharmacies, and state and local health
departments, administer vaccine. For example, CDC data from 2004 show that
more than half of one population group considered at high-risk for
complications in 2004--adults aged 65 years and older--and about a third
of one target group recommended for vaccination in 2004--adults aged 50
through 64 years--received influenza vaccination at physicians' offices. A
smaller proportion of adults in these groups received influenza
vaccination at other locations, including workplaces and clinics (see fig.
5).^40

^40For the 2007-08 influenza season, ACIP considers both of these
population groups as part of the high-risk groups.

Figure 5: Locations Where Adults Aged 65 Years and Older and Aged 50
through 64 Years Reported Receiving Most Recent Influenza Vaccination,
2004

Notes: Percentages do not add to 100 percent because of rounding. For data
on high-risk adults aged 65 years and older, the category "Other medically
related place" includes hospitals (7.2 percent), pharmacies (6.1 percent),
and other medically related places (3.7 percent); the category "Workplace"
also includes home visits. For data on adults aged 50 through 64 years,
the category "Other medically related place" includes hospitals (9.2
percent), hospital vans or mobile units (2.0 percent), pharmacies (4.7
percent), and other medically related places (3.9 percent); the category
"Other nonmedically related places" includes other nonmedically related
places (8.7 percent) and home visits (0.3 percent).

CDC data from 2002 indicated that about half of individuals included in
another target group recommended for vaccination--adults aged 18 to 64
years with certain chronic conditions--also received vaccinations at
physicians' offices, and the remaining individuals in this target group
reported receiving vaccination at other locations such as workplaces (see
fig. 6).

Figure 6: Locations Where High-Risk Adults with Certain Chronic Conditions
Reported Receiving Most Recent Influenza Vaccination, 2002

Note: Data are for high-risk adults aged 18 through 64 years with chronic
conditions of diabetes or asthma or both. The category "Other" includes
hospitals (5.1 percent), health departments (4.6 percent), other places
(4.6 percent), and community centers (1.1 percent).

Manufacturers and Medical Supply Distributors Ship Vaccine Using a Variety of
Distribution Practices

All manufacturers we interviewed and four of six medical supply
distributors we spoke with reported that for the 2007-08 influenza season
they will continue or begin distributing vaccine as it becomes available
using multiple shipments. This distribution practice allows for all types
of providers to have some vaccine available for their high-risk patients
when vaccine is initially distributed. CDC encouraged distributing vaccine
in multiple shipments--a practice referred to as multiphased
shipments--for the 2005-06 influenza season, stating that this
distribution strategy enables all types of providers to administer vaccine
initially to those persons at high risk, even when supplies are
limited.^41

In addition to the practice of multiphased shipments, one manufacturer and
two medical supply distributors took steps to collect information from
their customers on the number of doses in an order that are intended for
certain priority groups, such as high-risk individuals, so that the
manufacturer and medical supply distributors could, if necessary,
distribute vaccine to customers serving those groups on a priority basis.
However, officials from medical supply distributors and CDC reported
differing perspectives on the utility of this information for prioritizing
distribution to those serving individuals in certain priority groups,
including high-risk groups. For example, two of the six medical supply
distributors we interviewed reported that they routinely collect
information from their customers on the number of doses ordered that are
intended for high-risk individuals and may use this information to
determine distribution of the vaccine. One reported that its distribution
practice is to give priority to those individual providers that are
serving more high-risk individuals; the other medical supply distributor
reported that it intends to use the information to prioritize orders only
in the event of a vaccine shortage.^42 CDC officials, however, reported
that collecting such information from customers on their patients in
priority groups was not useful for prioritizing distribution to those
serving individuals in these groups. For the 2005-06 influenza season, CDC
encouraged manufacturers and medical supply distributors to collect
information from their customers on the number of doses being ordered for
priority groups, but according to CDC officials, the manufacturer that
produced most of the vaccine that season reported such information had
limited utility for prioritizing orders; these officials reported that the
manufacturer found that the vast majority of its customers reported that
nearly all of the doses they ordered were for individuals in priority
groups. As a result, CDC officials said they no longer recommend
collecting such information.^43

^41CDC recommended this strategy because of uncertainty in the production
of vaccine for that season. See CDC, "Influenza Vaccine Prebooking and
Distribution Strategies for the 2005-06 Influenza Season," Morbidity and
Mortality Weekly Report, vol. 54, no. 12 (2005): 307-308.

Other medical supply distributors reported using other distribution
practices. For example, one medical supply distributor stated that it
fills vaccine orders in the order in which it received the orders. Also,
for the 2007-08 season, two of the six medical supply distributors we
interviewed reported guaranteeing delivery of all vaccine ordered by a
specific date to customers. As a result of these distribution practices,
it is possible that some providers receive vaccine and offer vaccinations
to anyone who wants them before other providers have received enough
vaccine to vaccinate their patients in high-risk or other target groups.

^42The other four medical supply distributors we interviewed did not
report that they plan to collect information from their customers on the
number of doses ordered that are intended for high-risk or other target
groups.

^43CDC recommended obtaining information on doses ordered for high-risk
individuals for the 2005-06 season, following the significant and
unexpected shortage of vaccine during the 2004-05 season. When that
shortage occurred, CDC recommended vaccine distribution be prioritized to
certain groups. CDC was only able to successfully facilitate the directed
distribution and redistribution of vaccine so that the vaccine would be
made available to those priority groups through extensive collaboration
and information sharing between multiple parties including the major
manufacturer of vaccine that season, and state and local health officials.
For more information, see [41]GAO-05-984 .

CDC Data Indicate State and Local Health Departments Generally Received a
Smaller Amount of Vaccine Than Other Providers in Early Fall

In recent years, certain types of providers, such as physicians and state
and local health departments, reported they received their vaccine orders
after other types of providers, such as mass immunizers that provide
vaccinations at retail stores. For example, representatives from one
national association representing physicians and one national association
representing state and local public health officials told us that in past
seasons many physicians did not receive their vaccine orders until
November or later but other types of providers--particularly those
providing vaccinations in mass immunization clinics at retail stores--had
vaccine earlier in the fall. As a result, association officials stated
that these other types of providers were able to vaccinate anyone who
wanted a vaccination before physician practices had received a sufficient
number of doses for their patients.

According to CDC, a large percentage of high-risk individuals receive
their annual vaccination at physicians' offices. Some officials from
national associations representing physicians asserted that physicians
should receive priority in vaccine distribution. According to a national
association representing physicians and officials from a state health
department, physicians have reported that if they do not have vaccine when
patients seek it, those patients may not return for vaccination when the
physician has vaccine. According to a national association representing
pediatricians, establishing a reliable place for vaccination is especially
crucial for children, given the ACIP recommendation for the 2007-08
influenza season that children aged 6 months through 8 years receive two
shots 30 days apart in their first year of vaccination. In addition,
according to this association, having unused doses can be a financial
burden to these physicians, as they are responsible for paying for any
vaccine orders they place and receive, regardless of whether they
administer the vaccine or not. While CDC data indicated that most
physicians CDC surveyed intend to continue administering influenza vaccine
as a service to their patients, association officials reported that this
financial burden may serve as an incentive for some individual physicians
to discontinue purchasing and administering the vaccine in the future.

State and local health officials and national associations representing
them also reported that they believe state and local health departments
generally have received their vaccine orders later in the season, and in
some instances, after other types of providers. State and local health
departments are responsible for distributing the influenza vaccine to
those providers who vaccinate high-risk populations through the Vaccines
for Children program, for example. Therefore, officials we spoke with
asserted that state and local health departments should receive vaccine in
the same time frames as other types of providers.

According to CDC officials, with more than 200 million individuals in
high-risk and other target groups who should be vaccinated between late
fall and early spring each influenza season, all types of providers have
an important role to play in providing vaccinations. Therefore, having
multiple opportunities for vaccination available to individuals in
high-risk and other target groups is especially important as ACIP
considers continued expansion of its recommendations on which groups
should be targeted for vaccination for each influenza season. For example,
mass immunization clinics at retail stores play an important role in
increasing influenza vaccination rates because they may provide access to
the vaccine for a population that does not regularly see a physician or
would not otherwise receive the vaccine, according to officials from CDC,
a national association representing physicians, and state and local health
departments.

Despite reports from physicians and other types of providers indicating
otherwise, national data for the 2006-07 influenza season indicate that
most types of providers, including private providers such as physicians,
received vaccine in a similar proportion over the months the vaccine was
distributed (see app. IV and fig. 7).^44 Specifically, CDC analyzed
national data on the percentage of the total vaccine doses distributed as
of each month--these data show that private providers, including
physicians, received about 42 percent of the cumulative number of doses
distributed as of each month, as well as about 42 percent of the total
number of doses distributed for the 2006-07 season. However, the national
data support the testimonies from state and local health officials that
they received a smaller percentage of doses in the early fall than later
in the influenza season.

^44According to CDC, data identifying distribution of vaccine to mass
immunizers were not available within a single provider category; rather,
because these types of providers are classified differently by different
manufacturers and medical supply distributors, doses received by them are
included within a number of provider type categories.

Figure 7: Percentage of Cumulative Number of Vaccine Doses Distributed, by
Provider Type and Month, 2006-07 Influenza Season

Notes: Because a different number of additional doses were distributed
each month, it is possible for one type of provider to receive a higher
percentage of all doses distributed as of the end of one month than the
percentage of cumulative doses the provider received as of the end of the
following month. According to CDC, data identifying distribution of
vaccine to mass immunizers were not available within a single provider
category; rather, because these types of providers are classified
differently by different manufacturers and medical supply distributors,
doses received by them are included within a number of provider type
categories.

^aThe category "Private providers" includes physicians, as well as
outpatient clinics and facilities, health maintenance organizations, and
surgery centers.

^bThe category "Other" includes vaccine doses distributed to medical supply
distributors (15.6 percent), hospitals (9.9 percent), the federal
government (5.1 percent), pharmacies (3.5 percent), other private provider
types (2.9 percent), corporations (2.5 percent), the military (2.2
percent), correctional facilities (0.0 percent), and other public provider
types (1.4 percent). These percentages indicate the total percentage of
all vaccine doses distributed to the provider type during the 2006-07
influenza season. The decrease in the percentage of the cumulative number
of doses distributed to provider types in the "Other" category from
September to October reflects the higher percentage of doses medical
supply distributors received in September, which then decreased later in
the season. See app. IV for complete data on the percentage of the
cumulative number of vaccine doses distributed by month to all types of
providers during the 2006-07 influenza season.

CDC officials acknowledged that the aggregated, national data on vaccine
distribution to private providers such as physicians do not reflect
physicians' testimonies and that individual providers' experiences at the
local level may vary significantly. In addition, several factors, such as
size of order, with whom an order is placed, and the distribution route,
may influence the perception that other types of providers received their
vaccine orders before physicians. For example, the policy of some
manufacturers and medical supply distributors to distribute the vaccine in
multiphased shipments sometimes results in only a small number of vaccine
doses being allocated to an individual provider per shipment. As a result,
providers, including physicians, may choose to ask the medical supply
distributors to delay shipment until a greater number of doses are
available to fill the providers' order so, for example, a physician's
office could hold a vaccination clinic. Manufacturers may also choose to
fill a percentage of larger orders first and delay shipping smaller orders
until later--a practice, according to one manufacturer, that is often
easier to do because of the logistics of shipping. In addition, officials
from one national association representing physicians reported that it is
likely that the route through which smaller physicians' offices receive
vaccine may entail an additional layer of distribution, such as multiple
medical supply distributors, thus extending the time for the vaccine to
reach an individual provider. In contrast, many mass immunizers that hold
clinics in retail stores may receive vaccine more quickly than physicians
if the mass immunizers place, and subsequently receive, large vaccine
orders directly from the manufacturer or a national medical supply
distributor.

Officials from CDC and state health departments had little explanation as
to why state and local health departments received more of their vaccine
orders late in the season. One official from a state health department
stated that her department received its vaccine order for the 2006-07
season late because the manufacturer with whom the department ordered
experienced production problems. However, officials from CDC and two state
health departments we spoke with were unable to speculate as to the reason
for this distribution pattern, and CDC officials reported that the agency
is researching why this occurred.

CDC and State Health Officials Have Undertaken Efforts to Help Monitor the
Availability of Vaccine

In order to help state and local health officials manage the availability
of vaccine for high-risk or other target groups, CDC and state health
officials have undertaken several efforts. These efforts include the
creation of monitoring tools and the implementation of a state-specific
vaccine distribution program.

When faced with a shortage of vaccine for the 2004-05 season, CDC created
a tool, the Flu Vaccine Finder, "to provide information to enhance
visibility of influenza vaccine distribution for state and local health
officials and to assist in their management of influenza vaccine
availability issues and challenges."^45 This tool, which has been modified
for subsequent seasons, continues to be used by CDC and state health
officials. For the 2006-07 season, CDC collected information to be
included in the Flu Vaccine Finder on a weekly basis throughout the
influenza season from all manufacturers and seven major medical supply
distributors on all vaccine distributed. Specifically, the information
collected included a product identifier,^46 state and zip code to which
the vaccine was distributed, number of doses distributed, and type of
provider to whom the vaccine was distributed. For the 2005-06 and 2006-07
influenza seasons, the Flu Vaccine Finder also included a listing of doses
that had been already ordered from a subset of manufacturers and medical
supply distributors.

CDC officials reported that the agency has used the Flu Vaccine Finder
data to conduct a limited amount of routine analyses. Specifically, the
agency routinely conducts two analyses using the data: total distribution
of vaccine by month and total distribution of vaccine by provider type. In
addition, according to CDC, data from the Flu Vaccine Finder have been
used by some state officials to find out information on the number of
vaccine doses distributed to a state or locality by provider type and
vaccine availability by zip code. State health officials have also used
the data to monitor the number of doses of vaccine distributed to certain
types of providers, such as hospitals and local health departments, and to
locate providers following vaccine-related adverse events. For example,
CDC officials stated that one state health department used the Flu Vaccine
Finder data coupled with the state's data on the number of long-term care
beds to determine if the state's long-term care facilities had received
enough vaccine to vaccinate their population. However, according to CDC,
40 of the 56 states and urban areas that are eligible to use the Flu
Vaccine Finder have requested access to it for the 2007-08 influenza
season, suggesting that not all state officials have found this to be a
useful tool or are aware of this resource. To encourage use of the Flu
Vaccine Finder, CDC officials reported that they are designing a Flu
Vaccine Finder guidance document to share with users of the Flu Vaccine
Finder, outlining some of the analyses states have performed using Flu
Vaccine Finder data to help monitor vaccine distribution within states.

^45Jeanne M. Santoli, "Influenza Vaccine Distribution Data and Use of Data
During the 2006-07 Season" (PowerPoint presentation at the 2007 National
Influenza Vaccine Summit, Atlanta, Georgia, April 2007). For more
information on the flu vaccine distribution information collected by CDC
and made available to states through the Flu Vaccine Finder, see app. V.

^46The Flu Vaccine Finder includes the National Drug Code number, a
universal product identifier for human drugs which identifies the labeler,
product, and trade package size. For example, for the influenza vaccine,
the National Drug Code number identifies the manufacturer of the vaccine,
the type of vaccine (preservative-free or preservative-containing), and
the presentation of the vaccine (.25 milliliters, .5 milliliters, etc.,
and single dose syringes or multidose vials).

State health officials suggested changes to the Flu Vaccine Finder, which
they reported would make the Flu Vaccine Finder a more useful tool for
monitoring vaccine distribution. Their suggestions included adding data on
the specific providers receiving the vaccine, county-level data, data
identifying all types of providers, and making the data more timely:

           o Data on specific providers receiving the vaccine. The 2006-07
           version of the Flu Vaccine Finder included data on the zip code to
           which a manufacturer or medical supply distributor delivered a
           vaccine shipment; however, according to state and local health
           officials we spoke with, the Flu Vaccine Finder did not indicate
           the name or address of the particular provider that received the
           vaccine. State health officials reported that the provider who
           administered the vaccine may be in a different zip code from the
           location of where the vaccine was originally shipped. Officials
           also stated that knowing which specific providers have vaccine and
           where the vaccine was administered is helpful for determining
           which populations have access to the vaccine and which areas or
           providers are in need.

           o Addition of county-level data. According to CDC, state health
           officials stated that to make the Flu Vaccine Finder more useful
           to them, data on the number of doses distributed by county, rather
           than by zip code, would be helpful because some state health
           officials reported that public health activities are organized at
           the county level. One state official reported having to create its
           own zip code-to-county crosswalk in order to complete county-level
           data analysis--an imperfect process since some zip codes may cross
           county lines.

           o Data identifying all types of providers. The Flu Vaccine Finder
           does not have a provider type category for mass immunizers;
           rather, because these providers are classified differently by
           different manufacturers and medical supply distributors, doses
           received by them are included within a number of provider type
           categories, according to CDC. As a result, an official from one
           state health department reported being unable to tell how many
           vaccine doses have been shipped to mass immunizers, giving them an
           incomplete picture as to how the available vaccine was distributed
           in their state.

           o More timely data. CDC officials stated that the Flu Vaccine
           Finder data are generally a week old when they become available to
           users because of the time necessary for CDC to collect the data
           from manufacturers and medical supply distributors and upload
           these data into the system. State health officials reported that
           having real-time data would be helpful to effectively determine
           which types of providers are in need of vaccine at a given point
           in time.

           Some state health officials reported that they have utilized other
           mechanisms, such as surveying individual providers in their
           jurisdictions, to determine which providers have received a
           sufficient vaccine supply to vaccinate their high-risk and other
           target groups and which providers are in need. For example, one
           state, Minnesota, created its own database to monitor vaccine
           distribution in the state during the 2004-05 season. State health
           officials surveyed the individual providers in each of the state's
           public health jurisdictions on their vaccine supply, and then
           entered the information into a database. This database then
           provided information for state officials to determine the need for
           and availability of vaccine across the state. Health officials
           from other states have reported administering informal surveys of
           individual providers on their vaccine supply during times of
           shortage. State health officials reported using the information on
           vaccine supply to facilitate voluntary redistribution--that is,
           providers with excess vaccine supply were identified by health
           officials and asked to give their left over doses to providers who
           needed it most, such as occurred during the 2004-05 influenza
           season. According to a representative from a national association
           representing state and territorial health officials, these
           informal surveys were very time and resource intensive, however.

           One state, Rhode Island, created its own vaccine distribution
           program to manage the availability and distribution of vaccine in
           the state. Specifically, Rhode Island is implementing a program
           for the 2007-08 season in which the state health department will
           manage the purchasing and distribution of vaccine among the
           state's providers for vaccination of adults. Specifically, the
           state health department plans to purchase and distribute about
           250,000 influenza vaccine doses among participating providers free
           of charge to vaccinate adults who have health insurance or are
           working for or insured through a Rhode Island company.^47
			  
			  CDC and Others Have Produced Public Health Messages, and CDC Has
			  Taken Some Steps to Assess Its Messages

           CDC and others have produced a variety of public health messages
           designed to promote influenza vaccination, including messages to
           encourage preferential vaccination of certain high-risk and other
           target groups during times of vaccine delay or shortage. CDC has
           also taken some steps to assess its messages. For example, CDC has
           tested its messages prior to dissemination and collected some data
           to give the agency a sense of the impact its messages may be
           having on the public after dissemination. However, CDC and others
           have not conducted comprehensive evaluations on the impact of
           messages after dissemination. Although no comprehensive
           evaluations have been conducted, CDC and other officials we
           interviewed identified key elements, such as clear and consistent
           messages, that they believe are important to producing effective
           public health messages. However, there are impediments to
           effectively implementing these elements.
			  
			  CDC and Others Have Produced and Disseminated Influenza-Related
			  Public Health Messages

           CDC has produced and disseminated public health messages designed
           to promote seasonal influenza vaccination. These messages provide
           information to the public and others--including providers and
           other public health entities--about influenza and aim to motivate
           individuals, particularly those in high-risk and other target
           groups, to receive influenza vaccination. CDC uses diverse means
           to convey its messages to the public, such as press releases,
           information posted on CDC's Web site, print materials, and media
           campaigns. CDC has also created messages designed to reach
           specific populations, such as materials printed in Spanish or
           public service announcements disseminated via Spanish-language
           radio.

           Other public health entities also produce and disseminate their
           own messages to promote seasonal influenza vaccination. For
           example:

           o Some state and local public health departments produce and
           disseminate print material, Web site information, and press
           releases, and inform the public through media and other means
           about the importance of vaccination.
           o Provider associations, such as the American Medical Association
           and the American Academy of Pediatrics, produce and disseminate
           policy statements and other guidelines that adhere to ACIP
           recommendations for influenza vaccination, according to
           representatives of these associations we interviewed.
			  
^47Rhode Island's uninsured residents are eligible to receive influenza
vaccinations through other programs administered by the state.

           o The American Lung Association, in collaboration with one major
           vaccine manufacturer, runs a Web-based educational initiative to
           encourage vaccination.

           o CDC and others participate in an influenza season press kickoff
           event held early each fall. This event, hosted by the National
           Foundation for Infectious Diseases,^48 has involved senior HHS
           officials from CDC and the Centers for Medicare & Medicaid
           Services^49 and has involved the participation of provider
           associations, such as the American Medical Association and the
           American Academy of Pediatrics.

           For the 2006-07 influenza season, CDC and other
           partners--including the Association of State and Territorial
           Health Officials, National Association of County and City Health
           Officials, and Association of Immunization Managers--implemented a
           National Influenza Vaccination Week during the last week of
           November in 2006 to promote influenza vaccination. Throughout the
           week, CDC and other partnering organizations disseminated print
           materials and television and radio public service announcements
           encouraging late-season vaccination. CDC also contacted providers
           of influenza vaccine to encourage them to continue vaccination
           into December and beyond by recommending vaccinations to their
           patients and scheduling additional vaccination clinics and longer
           hours at these clinics. CDC officials reported that the agency
           plans to make National Influenza Vaccination Week an annual event.

           During times of vaccine shortage or delay, CDC has produced and
           disseminated modified public health messages to encourage
           prioritization of available vaccine to allow those groups
           identified by ACIP--including some but not all of ACIP's initial
           target population of high-risk individuals--to be preferentially
           vaccinated before others. For example, during the vaccine shortage
           of the 2004-05 season, CDC held frequent press conferences
           beginning in October 2004 asking individuals who did not belong to
           one of these groups identified by ACIP to step aside and defer
           vaccination so that those in ACIP-identified priority groups would
           have vaccine available to them.^50
			  
^48The National Foundation for Infectious Diseases is a nonprofit
organization whose mission includes educating the public and health care
professionals about infectious diseases, such as influenza.

^49The Centers for Medicare & Medicaid Services administers Medicare, the
government-sponsored insurance program for persons aged 65 years and older
and other qualified persons. The Medicare program pays for influenza
vaccinations for Medicare beneficiaries and the Centers for Medicare &
Medicaid Services partners with CDC to promote influenza vaccination among
Medicare beneficiaries.			

^50See [44]GAO-05-984 and app. III for revisions to groups recommended for
vaccination by ACIP during the 2004-05 influenza season vaccine shortage.

           CDC Has Taken Some Steps to Assess Its Public Health Messages

           CDC has taken steps to assess its influenza-related public health
           messages before disseminating them to the public through focus
           groups and other activities, and has collected some data to give
           the agency a sense of the impact its messages may be having on the
           public after dissemination. For example, CDC has monitored media
           coverage of its messages and--in response to a recommendation we
           made in 2001--collected data to assess the public's recall of the
           content and source of the messages disseminated for the 2000-01
           season. CDC and others have not, however, conducted comprehensive
           evaluations to assess the impact of influenza-related messages
           after they are disseminated to the public.

           CDC officials involved in communicating the agency's
           influenza-related public health messages told us the agency tests
           its messages before they are disseminated to the public using
           focus groups and other similar methods. For example, CDC conducts
           in-depth interviews with providers, and leads focus group
           discussions with target audiences, such as African-American
           seniors, Hispanics, and seniors with chronic conditions. CDC
           officials reported that the goal of these efforts is to help
           determine if the agency's influenza-related public health messages
           are easily understood by these audiences. These officials told us
           the feedback they receive is used to revise the messages as
           necessary before disseminating them to the public.

           CDC officials we interviewed also reported that the agency has
           collected some data to provide a sense of the impact its messages
           may be having on the public. For example, due to the influence
           that media reports can have on public demand for vaccination, CDC
           officials reported that the agency monitors media sources--such as
           newspapers, press releases, and wire services--during the
           influenza season to assess the volume and content of
           influenza-related stories in the news. CDC has also monitored the
           number of calls to the agency's information hotline following
           influenza-related public health campaigns. The agency also
           collected limited information related to its public health
           messages in response to our recommendation that CDC assess the
           relative success of its past outreach and education efforts to
           help the agency prepare for potential delays or shortages of
           vaccine in subsequent seasons.^51 Specifically, CDC conducted a
           mail survey in June 2001 that, in part, assessed the public's
           recall of the content and source of the influenza-related public
           health messages disseminated that year.^52 Based on the survey
           results, CDC officials concluded that the importance of continuing
           to vaccinate persons in December or later should be emphasized
           more strongly in the future, especially when vaccine is not
           available earlier in the season.

           CDC has not conducted comprehensive evaluations to assess the
           impact of the influenza-related messages it uses on promoting
           vaccination after these messages are disseminated to the public.
           CDC officials reported that the agency does not conduct formal
           impact analyses of its influenza-related public health messages
           after these messages are disseminated--such as analyses to
           determine what messages successfully influence changes in
           behavior. These officials, who are responsible for producing and
           disseminating influenza-related messages, commented that it would
           be difficult to discern the impact of public health messages
           disseminated by CDC and others because these messages are just one
           factor among many that can influence vaccination. Given the
           complexity of such an evaluation, these officials noted that CDC
           resources available for influenza-related communications do not
           support formal impact analyses. One of these officials estimated
           that, to complete a post-dissemination evaluation of CDC's
           influenza-related messages, it would cost five times CDC's total
           budgeted amount for seasonal influenza-related public health
           communications. For fiscal year 2007, this budgeted amount was an
           estimated $1.5 million.^53 In addition to CDC officials, officials
           we interviewed representing state and local health departments,
           national associations representing physicians, and a public health
           association reported that they had not conducted, nor were they
           aware of, studies examining the impact of the influenza-related
           public health messages they or others produced.

^51See [45]GAO-01-624 .

^52CDC conducted a mail survey in June 2001 of 3,719 individuals that
assessed vaccination coverage levels, timing of vaccination, place of
vaccination, reasons for not being vaccinated, and messages heard about
vaccination.

^53This $1.5 million for fiscal year 2007 included additional funding for
National Influenza Vaccination Week.

           Elements Important for Producing Effective Public Health Messages
			  Face Impediments to Implementation

           Although no comprehensive evaluations have been conducted to
           assess the impact of influenza-related public health messages on
           vaccination, CDC and other officials identified elements they
           believe, based on their experience, are important to producing
           public health messages regarding seasonal influenza vaccination
           that will have an impact on promoting vaccination. These elements
           included clear and consistent messages, messages encouraging
           late-season vaccination, and the importance of recommendations
           from health care providers in creating public demand for
           vaccination. However, there are impediments to effectively
           implementing these elements.

           o Clear and consistent messages. Officials we interviewed from CDC
           and state and local health departments stressed the importance of
           consistent influenza-related messages disseminated to the public.
           For example, officials from CDC and state health departments
           stressed the importance of consistency in messages coming from
           different public health entities. Similarly, we reported in 2005
           on the importance of clear and consistent messages in averting
           public confusion regarding who should be vaccinated and when they
           should receive the vaccine.^54 For example, we reported that
           during the 2004-05 influenza season, health officials in
           California told us, at one time, local radio stations in the state
           were running two public service announcements--one from CDC
           advising those aged 65 years and older to be vaccinated, and one
           from the California Department of Health Services advising those
           aged 50 years and older to be vaccinated. These officials
           emphasized that these mixed messages created confusion. In
           addition to consistency in messages coming from different public
           health entities, officials we interviewed from CDC, as well as
           national associations representing physicians, stressed the
           importance of consistency in messages sent by any one public
           health entity because inconsistency during an influenza season and
           between seasons may also create confusion. For example, some
           individuals in target groups who heeded CDC's messages to step
           aside during the 2004-05 season still thought it was not
           appropriate for them to get vaccinated after CDC stopped
           disseminating these messages later in the season. CDC has
           recognized the importance of clarity and consistency in
           influenza-related public health messages in its communications
           plans for the 2007-08 influenza season. A CDC official involved in
           communicating the agency's messages acknowledged past
           inconsistencies in messages disseminated by different public
           health entities but noted that many public health entities look to
           CDC to take the lead with public health messages and the result,
           overall, was a high level of consistency in the messages
           disseminated from different entities. This official also stated,
           however, that it is difficult to maintain a consistent message
           during or between influenza seasons, because messages need to
           adapt to the dynamic and complex situations that comprise
           influenza seasons. For example, messages need to be modified to
           account for changes in ACIP recommendations, which could result in
           the public hearing differing messages before and after these ACIP
           revisions are made.
			  
^54 [46]GAO-05-984 .

           o Messages encouraging late-season vaccination. CDC and other
           health officials we interviewed reported that public demand for
           influenza vaccination typically wanes after November. According to
           these and other officials, they believe interest wanes in part
           because the public has been conditioned by prior messages from CDC
           and other public health entities to believe that they must receive
           vaccination before late November for it to be effective. CDC and
           other officials representing state health departments we
           interviewed, as well as national associations representing
           physicians, reported that it is important that public health
           messages effectively encourage late-season vaccination so that as
           many people as possible can be protected against influenza and
           related complications. These efforts are also important to help
           minimize surplus vaccine left over at the end of influenza season.
           The experience by some states during the 2006 National Influenza
           Vaccination Week, however, illustrates the difficulties
           encountered when trying to coordinate promotion of late-season
           vaccination with vaccine availability. Specifically, officials
           from three of the six states we interviewed reported the timing of
           the National Influenza Vaccination Week--which was held from
           November 27 to December 3, 2006--was problematic for their state
           because it occurred before an adequate vaccine supply was
           available. For example, officials from the Minnesota Department of
           Health told us that they were unable to participate in National
           Influenza Vaccination Week because local health departments in the
           state had not yet received vaccine by that week. An official from
           the Texas Department of State Health Services told us the
           department received approximately half of its vaccine in the 2
           weeks immediately preceding National Influenza Vaccination
           Week--probably too late for many providers in the state to
           participate in the initiative, this official said. An official
           from the Washington State Department of Health told us the
           department did not receive the bulk of its vaccine until during
           that week.

           o Recommendations from health care providers influence demand. CDC
           officials we interviewed reported that the agency has consistently
           found that a recommendation from a physician or other health care
           provider is the most important factor in an individual's decision
           to get vaccinated. Officials representing state health departments
           and national associations representing physicians also
           acknowledged the importance of providers' recommendations. CDC
           officials reported that the agency has made efforts to encourage
           providers to recommend vaccination to their patients, including
           providing patient education tools that physicians can use when
           discussing vaccination with their patients. However, despite these
           efforts, available data suggest that getting providers to
           recommend vaccination for their patients has been difficult. For
           example, a January 2007 phone survey of adults conducted for CDC
           by an independent research organization found that less than 40
           percent of respondents reported that their physician or other
           health care worker discussed getting an influenza shot with them.
			  
			  Agency Comments

           We provided a draft of this report to HHS for comment. The
           department provided technical comments, which we incorporated as
           appropriate.

           As arranged with your office, unless you publicly announce the
           contents of this report earlier, we plan no further distribution
           of it until 30 days after its issue date. At that time, we will
           send copies of this report to the Secretary of Health and Human
           Services and other interested parties. We will also provide copies
           to others upon request. In addition, the report will be available
           at no charge on the GAO Web site at [42]http://www.gao.gov . We
           will also make copies available to others upon request.

           If you or your staff members have any questions about this report,
           please contact me at (202) 512-7114 or [43][email protected] .
           Contact points for our Offices of Congressional Relations and
           Public Affairs may be found on the last page of this report. GAO
           staff who made contributions to this report are listed in appendix
           VI.

           Marcia Crosse
			  Director, Health Care
			  
			  Appendix I: Scope and Methodology

           In conducting this study, we reviewed relevant documents and
           interviewed officials from the Department of Health and Human
           Services's (HHS) Centers for Disease Control and Prevention (CDC)
           and Food and Drug Administration (FDA) and manufacturers of all
           five seasonal influenza vaccines licensed for the U.S. market for
           the 2007-08 season as of August 31, 2007.^1 We also reviewed
           relevant documents and spoke with officials from the American
           Public Health Association, the National Foundation for Infectious
           Diseases, and three national associations representing state and
           local public health officials: the Association of Immunization
           Managers, Association of State and Territorial Health Officials,
           and National Association of County and City Health Officials.^2 We
           reviewed relevant documents and spoke with officials from the
           Health Industry Distributors Association, a national association
           representing medical supply distributors, as well from national
           associations representing physicians and long-term care providers,
           including the American Medical Association, American Academy of
           Pediatrics, the National Center for Assisted Living, and the
           American Health Care Association. We also reviewed documents
           related to the 2007 National Influenza Vaccine Summit.^3

           We also selected judgmental samples of (1) medical supply
           distributors; (2) mass immunizers--organizations that conduct mass
           immunization clinics at workplaces, retail stores, long-term care
           facilities, and other locations; and (3) state health departments.
           For each organization in our samples, we reviewed relevant
           documents and interviewed officials. We selected the samples to
           reflect a mix of medical supply distributors, mass immunizers, and
           states; however, our samples were not statistically representative
           and cannot be generalized to all medical supply distributors, mass
           immunizers, or states.
			  
^1For the 2007-08 influenza season, five vaccines were licensed by FDA for
the U.S. market as of August 31, 2007: (1) Fluarix, manufactured by a part
of GlaxoSmithKline plc, GlaxoSmithKline Biologicals, (2) FluLaval,
manufactured by a subsidiary of GlaxoSmithKline plc, ID Biomedical
Corporation of Quebec, (3) FluMist, manufactured by MedImmune Vaccines,
Inc., (4) Fluvirin, manufactured by Novartis Vaccines and Diagnostics
Limited, and (5) Fluzone, manufactured by sanofi pasteur. The policy of
sanofi pasteur is to spell its name without capital letters. We
interviewed officials and obtained information from GlaxoSmithKline
Biologicals regarding both Fluarix and FluLaval; and interviewed officials
and obtained information from MedImmune Vaccines, Inc., Novartis Vaccines
and Diagnostics, Limited, and sanofi pasteur regarding FluMist, Fluvirin,
and Fluzone, respectively. These five manufacturers also produced seasonal
influenza vaccine for the U.S. market for the 2006-07 influenza season. On
September 28, 2007, FDA approved an additional influenza vaccine, Afluria,
manufactured by CSL Limited, for the U.S. market for the 2007-08 season.

^2We also spoke with members of the Association of Immunization Managers
and the National Association of County and City Health Officials who are
state and local health officials.

^3The National Influenza Vaccine Summit participants include stakeholders
interested in influenza prevention such as CDC, the American Medical
Association, manufacturers, medical supply distributors, and others such
as state health departments. The summit meets annually to address
important issues in influenza immunization.

           For our judgmental sample of medical supply distributors, we
           selected six medical supply distributors that plan to distribute
           influenza vaccine for the 2007-08 season.^4 These six distributors
           represented a mix of organizations that distributed seasonal
           influenza vaccine to different markets (i.e., physician offices,
           hospitals, long-term care facilities); distributed different types
           of influenza vaccine products; and varied in whether they
           guaranteed delivery of the vaccine by a specific date, provided
           data to CDC for its Flu Vaccine Finder, and participated in the
           Flu Vaccine Business Practices Initiative.^5 In addition, we
           interviewed one medical supply distributor who distributed the
           influenza vaccine in prior seasons, but has decided not to for the
           2007-08 influenza season.
			  
^4The Health Industry Distributors Association estimated that 25 medical
supply distributors distribute vaccine in the United States in 2007.

^5Members of the Flu Vaccine Business Practices Initiative have
voluntarily committed themselves to adhering to a set of "responsible
business practices" including compliance with all of CDC's guidelines and
initiatives, purchasing vaccine only from manufacturers or
manufacturer-authorized medical supply distributors, and adhering to
manufacturer vaccine storage and handling guidelines. This initiative is
sponsored by the Health Industry Distributors Association.			  

           For our judgmental sample of mass immunizers, we selected four
           mass immunizers who represented a mix of organizations that
           vaccinated individuals in different regions of the country;
           provided seasonal influenza vaccine in a variety of delivery
           locations (i.e., places of work, retail stores, other nonmedical
           settings); and were based on different business models (for-profit
           and nonprofit). We also interviewed representatives from entities
           that contract with mass immunizers to provide vaccinations
           including one retail store, one long-term care and assisted living
           facility, and one workplace.

           For our judgmental sample of state health departments, we selected
           six states that represented a mix of states from different regions
           of the country; with different population sizes; with varied
           influenza vaccination success;^6 and that varied in whether they
           used CDC's Flu Vaccine Finder and have proposed innovative
           approaches for distributing influenza vaccine.^7

           To determine the quantity of seasonal influenza vaccine produced
           and when vaccine reaches providers who administer vaccine, we
           examined data from CDC regarding the number of influenza vaccine
           doses produced and distributed each month for the 2000-01
           influenza season through the 2006-07 influenza season. We also
           reviewed data from CDC on the cumulative percentage of doses
           manufacturers and medical supply distributors shipped each month
           to different types of providers for the 2006-07 influenza season.
           To identify the locations in which high-risk groups receive their
           vaccinations, we reviewed data from CDC's Behavioral Risk Factor
           Surveillance System--a state-based system of health surveys that
           collects information on health risk behaviors, preventive health
           practices, and health care access primarily related to chronic
           disease and injury. We also reviewed data from a Gallup poll
           conducted on behalf of CDC, as well as CDC's National Adult
           Immunization Survey. In addition, to identify efforts undertaken
           by CDC and state health officials to help state and local
           officials manage availability of vaccine for high-risk and other
           target groups, we reviewed data from and documentation of the Flu
           Vaccine Finder, the Internet-based distribution database that CDC
           created to assist state and local health officials in their
           management of influenza vaccine availability issues, and
           interviewed health department officials from our sample of states.
           We assessed the reliability of these data by interviewing
           officials from CDC, manufacturers, and medical supply distributors
           knowledgeable about the data and by reviewing documents related to
           the data. On the basis of our assessment, we determined the data
           were sufficiently reliable for our purposes.

           To identify actions CDC and others have taken to communicate
           public health messages that promote seasonal influenza
           vaccination, we also reviewed influenza vaccination communication
           plans produced by CDC and research and surveys conducted by CDC.
			  
^6To determine vaccination rates, we used immunization rates for adults
aged 65 years and older for 2005 from CDC's Behavioral Risk Factor
Surveillance System.

^7The six states we selected were Colorado, Maryland, Minnesota, Rhode
Island, Texas, and Washington.

           We conducted our work in accordance with generally accepted
           government auditing standards from May through October 2007.
			  
			  Appendix II: Manufacturers of Seasonal Influenza Vaccine for the
			  U.S. Market, 2000-01 through 2007-08 Influenza Seasons

           The manufacturers of seasonal influenza vaccine for the U.S.
           market have changed between the 2000-01 influenza season, when
           there were three manufacturers, and the 2007-08 influenza season,
           for which there were six licensed manufacturers as of September
           28, 2007 (see table 2).

Table 2: Manufacturers of Seasonal Influenza Vaccine for the U.S. Market,
2000-01 through 2007-08 Influenza Seasons

                                        Influenza season
Manufacturer    2000-01 2001-02 2002-03 2003-04 2004-05^a 2005-06 2006-07 2007-08 
sanofi pasteur                                                                    
(Aventis                                                                          
Pasteur Inc.)^b                                                                   
Wyeth                                                                             
Laboratories,                                                                     
Inc.                                                                              
Novartis                                            d                             
Vaccines and                                                                      
Diagnostics                                                                       
Limited (Chiron                                                                   
Vaccines                                                                          
Limited;                                                                          
PowderJect                                                                        
Pharmaceuticals                                                                   
plc; Medeva                                                                       
Pharma Limited;                                                                   
Evans Vaccines                                                                    
Limited)^c                                                                        
MedImmune                                 ^f                                      
Vaccines,                                                                         
Inc.^e                                                                            
GlaxoSmithKline                                     g               ^h      ^h    
Biologicals                                                                       
ID Biomedical                                                        h       h    
Corporation of                                                                    
Quebec                                                                            
CSL Limited                                                                       

Source: CDC and FDA.

Notes: Table shows manufacturers of seasonal influenza vaccine licensed
for the U.S. market for the 2007-08 season as of September 28, 2007.

^aFor the 2004-05 season, in addition to the three manufacturers, two
foreign manufacturers' vaccines were made available by FDA under an
investigational new drug protocol. Although HHS purchased about 1.5
million doses of this vaccine, no doses were distributed that season.

^bAventis Pasteur Inc., became sanofi pasteur in January 2005.

^cIn 2006, Novartis Vaccines and Diagnostics Limited acquired Chiron
Vaccines Limited. In 2003, Chiron Vaccines Limited acquired PowderJect
Pharmaceuticals plc. In 2001, PowderJect acquired Medeva Pharma Limited;
Medeva had previously acquired Evans Vaccines Limited.

^dChiron's license was suspended by the United Kingdom in October 2004
because of contamination at its manufacturing facility there and Chiron
ceased production of the vaccine for the U.S. market for the 2004-05
season.

^eMedImmune Vaccines, Inc. manufactures live attenuated vaccine
administered as a nasal spray, sold under the trade name FluMist. All
other manufacturers produce inactivated virus vaccine administered as an
injection.

^fWyeth Laboratories, Inc. distributed MedImmune's FluMist vaccine during
the 2003-04 season.

^gGlaxoSmithKline Biologicals's vaccine was not licensed for the United
States for the 2004-05 season, but the manufacturer's vaccine was made
available for that season by FDA under an investigational new drug
protocol. Although HHS purchased about 1.2 million doses of
GlaxoSmithKline's vaccine, no doses were distributed that season.

^hID Biomedical Corporation of Quebec, the licensed manufacturer of one
influenza vaccine (FluLaval), is a subsidiary of GlaxoSmithKline plc.
GlaxoSmithKline Biologicals, also part of GlaxoSmithKline plc, is the
licensed manufacturer of another influenza vaccine, Fluarix.

Appendix III: Advisory Committee on Immunization Practices (ACIP)
Recommendations

In spring or summer each year, ACIP, after consulting with CDC, makes
recommendations on which population groups should be targeted for annual
influenza vaccination. Since publishing its recommendations for the
2000-01 season, ACIP has changed its recommendations on who should be
targeted for vaccination, primarily expanding the groups it has
recommended (see table 3).^1 ACIP has also modified its recommendations to
address a vaccine shortage or delay; for two seasons, ACIP published
revised recommendations that narrowed the groups that should receive
priority for available vaccine (see tables 4 and 5). For the 2006-07
season, approximately 73 percent of the U.S. population--an estimated 218
million individuals--were included in ACIP's target groups (see table 6).

^1In addition, for the 2000-01 through 2007-08 seasons, ACIP has advised
that, in addition to the high-risk and other target groups for whom
providers are recommended to provide vaccinations, all persons, including
school-aged children, who want to reduce the risk of becoming ill with
influenza or of transmitting influenza to others, should be vaccinated,
depending on vaccine availability.

Table 3: ACIP Influenza Vaccination Recommendations, 2000-01 through
2007-08 Influenza Seasons

                                           Influenza season
Target group 2000-01^a 2001-02  2002-03    2003-04   2004-05^b 2005-06 2006-07^c 2007-08^c 
Persons at increased risk for influenza-related                                            
complications^d                                                                            
Children                       encouraged encouraged                                       
aged 6 to 23                                                                               
months^e                                                                                   
All women                                                                                  
who will be                                                                                
pregnant                                                                                   
during the                                                                                 
influenza                                                                                  
season                                                                                     
Pregnant                                                                                   
women in                                                                                   
second or                                                                                  
third                                                                                      
trimester                                                                                  
during the                                                                                 
influenza                                                                                  
season                                                                                     
Adults aged                                                                                
65 years and                                                                               
older                                                                                      
Residents of                                                                               
nursing                                                                                    
homes and                                                                                  
other                                                                                      
chronic-care                                                                               
facilities                                                                                 
Persons aged                                                                               
6 months and                                                                               
older with                                                                                 
certain                                                                                    
chronic                                                                                    
medical                                                                                    
conditions                                                                                 
Persons with elevated prevalence of chronic medical conditions, or with increased risk for
influenza-associated clinic, emergency department, or hospital visits^d
Adults aged                                                                                
50 through                                                                                 
64 years^f                                                                                 
Healthy                                                                                    
children                                                                                   
aged 24 to                                                                                 
59 months^f                                                                                
Persons who can transmit influenza to those at high risk^d                                 
Household                                                                                  
contacts of                                                                                
persons at                                                                                 
high risk,                                                                                 
including                                                                                  
those of                                                                                   
children                                                                                   
less than 6                                                                                
months of                                                                                  
age                                                                                        
Health care                                                                                
workers                                                                                    

Source: GAO analysis of CDC's Morbidity and Mortality Weekly Reports, 2000
through 2007.

Notes: A check mark () indicates vaccination was recommended for that
group for that season.

^aThe check marks in this column represent those target groups ACIP
recommended for vaccination for the 2000-01 influenza season prior to ACIP
issuing revised recommendations in October 2000.

^bThe check marks in this column represent those target groups ACIP
recommended for vaccination for the 2004-05 influenza season prior to ACIP
issuing revised recommendations in October 2004.

^cFor the 2006-07 through 2007-08 seasons, ACIP also recommended that
healthy children aged 6 months through 8 years who had not been previously
vaccinated receive two doses of vaccine.

^dACIP generally refers to persons at increased risk for influenza-related
complications as the "high-risk" groups within the target population and
the other persons in the target population for annual vaccination as the
"other target groups." For the 2007-08 influenza season, ACIP also
considers as part of the "high-risk" groups those persons at higher risk
for influenza-associated clinic, emergency department, or hospital
visits--including adults aged 50 through 64 years and children aged 24 to
59 months.

^eFor the 2002-03 and 2003-04 seasons, ACIP encouraged vaccination of
healthy children aged 6 to 23 months when feasible because they are at
increased risk for influenza-related hospitalization. For the 2007-08
season, ACIP recommended vaccination of children aged 6 to 23 months
because they are at increased risk for influenza-related hospitalization.

^fFor the 2000-01 through 2005-06 seasons, adults aged 50 through 64 years
were recommended for vaccination because of an elevated prevalence of
chronic medical conditions in this age group. For the 2006-07 and 2007-08
seasons, adults aged 50 through 64 years and healthy children aged 24 to
59 months were recommended for vaccination because of a higher risk for
medical care--that is an increased risk of influenza-associated clinic,
emergency department, or hospital visits.

Table 4: Target Groups ACIP Recommended for Influenza Vaccination for the
2000-01 Influenza Season, before and after October 2000

Target groups                                  April 2000^a October 2000^b 
Pregnant women in second or third trimester                                
during the influenza season                                                
Adults aged 65 years and older                                             
Residents of nursing homes and other                                       
chronic-care facilities                                                    
Persons aged 6 months through 64 years with                                
certain chronic medical conditions                                         
Health care workers                                                        
Household contacts of persons at high-risk                                 
Adults aged 50 through 64 years                                            

Source: CDC, "Prevention and Control of Influenza: Recommendations of the
Advisory Committee on Immunization Practices (ACIP)," Morbidity and
Mortality Weekly Report, vol. 49, no. RR-3 (2000) and CDC, "Updated
Recommendations From the Advisory Committee on Immunization Practices in
Response to Delays in Supply of Influenza Vaccine for the 2000-01 Season,"
Morbidity and Mortality Weekly Report, vol. 49, no. 39 (2000): 888-892.

Note: Check marks () denote priority groups recommended by ACIP, at the
time shown, for vaccination.

^aACIP advised that in addition to the groups for which vaccination is
recommended, all persons, including school-aged children, who want to
reduce the risk of becoming ill with influenza or of transmitting
influenza to others, should be vaccinated, depending on vaccine
availability.

^bThe revised recommendations, published after a delay in influenza vaccine
availability, also stated that special efforts should be made in December
and later to vaccinate adults aged 50 through 64 years.

Table 5: Target Groups ACIP Recommended for Influenza Vaccination for the
2004-05 Influenza Season, before and after October 2004

Target groups                                    May 2004^a October 2004^b 
Children aged 6 to 23 months                                               
All women who will be pregnant during the                                  
influenza season                                                           
Adults aged 65 years and older                                             
Residents of nursing homes and other                                       
chronic-care facilities                                                    
Persons aged 6 months and older with certain                               
chronic medical conditions                                                 
Health care workers                                                        
Persons aged 2 to 64 years who are household                               
contacts of persons at high-risk^c                                         
Persons aged 2 to 64 years who are household                               
contacts of children younger than 6 months^c                               
Adults aged 50 through 64 years who are not                                
household contacts of high-risk individuals                                

Source: CDC, "Prevention and Control of Influenza: Recommendations of the
Advisory Committee on Immunization Practices (ACIP)," Morbidity and
Mortality Weekly Report, vol. 53, no. RR-6 (2004) and CDC, "Interim
Influenza Vaccination Recommendations, 2004-05 Influenza Season,"
Morbidity and Mortality Weekly Report, vol. 53, no. 39 (2004): 923-924.

Note: Check marks () denote priority groups recommended by ACIP, at the
time shown, for vaccination.

^aACIP advised that in addition to the groups for which vaccination is
recommended, all persons, including school-aged children, who want to
reduce the risk of becoming ill with influenza or of transmitting
influenza to others, should be vaccinated, depending on vaccine
availability.

^bThese revised recommendations were published in response to a shortage of
influenza vaccine.

^cThese groups belonged to a single category in ACIP's May 2004
recommendations.

Table 6: Estimates of ACIP Target Group Populations Sizes, 2006

                                             Population in   Percent of total 
Target group                                   millions    U.S. population 
Persons at increased risk for                                              
influenza-related complications                                            
Children aged 6 to 23 months                        6.0               2.0% 
All women who will be pregnant during                                      
the influenza season                                4.0                1.3 
Adults aged 65 years and older                     37.2               12.5 
Persons aged 24 months through 64 years                                    
with certain chronic medical conditions            44.0               14.8 
Subtotal                                           91.2               30.6 
Persons with elevated prevalence of chronic medical conditions, or with
increased risk for influenza-associated clinic, emergency department, or
hospital visits                         
Adults aged 50 through 64 years                    18.0                6.0 
Children aged 24 to 59 months                       7.1                2.4 
Subtotal                                           25.1                8.4 
Persons who can transmit influenza to                                      
those at high risk                                                         
Household contacts of persons at high                                      
risk or children aged 24 through 59                                        
months                                             94.8               31.8 
Health care workers                                 7.0                2.4 
Subtotal                                          101.8               34.1 
Total target population                           218.1              73.1% 

Source: CDC analysis of United States Census Bureau data.

Note: Population sizes are based on United States Interim population
projections by age, sex, race, and Hispanic origin: 2000 to 2050
(Population Projections Branch, United States Census Bureau, released May
11, 2004). Percentages are based on a total population estimate of about
298 million.

Appendix IV: Cumulative Percentage of Vaccine Distributed by Provider Type
during 2006-07 Influenza Season

For the 2006-07 influenza season, manufacturers distributed 103 million
doses of vaccine to customers such as physicians, state and local health
departments, or other types of providers who administer vaccinations.
Manufacturers distributed vaccine as it became available, with the
proportion of vaccine distributed each month varying. Table 7 shows the
cumulative percentage of vaccine distributed to different types of
providers throughout the 2006-07 influenza season, according to CDC.

Table 7: Percentage of Cumulative Number of Doses Distributed by Month and
Provider Type, 2006-07 Influenza Season

Provider type                  September October November December January 
Corporations                        2.2%    2.5%     2.6%     2.5%    2.5% 
Correctional facilities              0.0     0.0      0.0      0.0     0.0 
Distributors                        24.9    16.2     18.3     15.7    15.6 
Federal government                   1.1     3.9      3.3      5.0     5.1 
Hospitals                            9.2    12.9     10.4      9.9     9.9 
Long-term care facilities            4.7     4.0      3.7      3.1     3.1 
Military                             0.6     1.0      0.8      2.2     2.2 
Other private provider types         3.4     2.9      2.7      2.8     2.9 
Other public provider types          1.3     1.1      1.1      1.4     1.4 
Pharmacies                           5.0     5.1      3.8      3.5     3.5 
Private providers^a                 41.0    43.2     43.1     42.3    42.3 
State and local health               6.6     7.2     10.1     11.6    11.6 
departments                                                                

Source: CDC.

Notes: Percentages do not add to 100 percent because of rounding. Table
indicates the cumulative number of doses distributed to provider types as
of September 29, 2006; October 20, 2006; November 10, 2006; December 22,
2006; and January 12, 2007. According to CDC, there was minimal change in
percentage of doses distributed to provider types after January 12, 2007,
and therefore CDC did not conduct analyses of the percentage of doses
distributed beyond this date. Data identifying distribution of vaccine to
mass immunizers were not available within a single provider category,
according to CDC; rather, because these types of providers are classified
differently by different manufacturers and medical supply distributors,
doses received by them are included within a number of provider type
categories.

^aThe category "Private providers" includes physicians, as well as
outpatient clinics and facilities, health maintenance organizations, and
surgery centers.

Appendix V: CDC's Flu Vaccine Finder

An effort by CDC to provide state and some local health officials with
information to help them monitor where vaccine is distributed is the Flu
Vaccine Finder component of the Secure Data Network.^1 Initially created
to address a severe vaccine shortage that occurred in the 2004-05
influenza season, the Flu Vaccine Finder "provides information to enhance
the visibility of influenza vaccine distribution for state and local
health officials to assist in their management of influenza vaccine
availability issues and challenges."

Fifty-six states, cities, and urban areas that are CDC immunization
grantees--all 50 states and 6 cities and urban areas--are eligible to use
the Flu Vaccine Finder, but to access it, grantees must request and
receive access from CDC.^2 CDC officials reported that for the 2007-08
influenza season, once CDC approval is received, each grantee is allowed
to identify five individuals within their organization to be users of the
Flu Vaccine Finder; these users have access to data for their state or
jurisdiction.

Since its inception, the Flu Vaccine Finder has evolved, specifically in
the number and type of contributors of data and the type of information
available:

           o 2004-05 influenza season. After one of the two major vaccine
           manufacturers exited the market for that influenza season in
           October 2004 because of contamination at its manufacturing
           facility, a severe vaccine shortage occurred. In response, CDC
           developed the Flu Vaccine Finder as part of its plan to help state
           and local health officials direct available vaccine to certain
           high-risk groups. The Flu Vaccine Finder was first available to
           users in November 2004 and included data from the remaining major
           influenza vaccine manufacturer. In addition to providing
           information on where that manufacturer had shipped vaccine, users
           could also order vaccine through the Flu Vaccine Finder.^3 
           o 2005-06 influenza season. According to CDC officials, the Flu
           Vaccine Finder was expanded to include data from two manufacturers
           and seven major medical supply distributors for the 2005-06
           season, and information on the number of doses that had been
           already ordered by users was also available. However, CDC
           discontinued the Flu Vaccine Finder's feature for ordering
           influenza vaccine that had been available during the 2004-05
           influenza season. For this season, the Flu Vaccine Finder was
           available to users beginning in December 2005.
			  
^1CDC's Secure Data Network is an ongoing project sponsored by CDC to
allow field staff, researchers, and public health partners to securely
exchange confidential, proprietary, or sensitive data over the Internet.

^2Immunization grantees are recipients of grants from CDC's National
Center for Immunization and Respiratory Diseases (formerly the National
Immunization Program) that support effective immunization systems and high
rates of coverage through scientific assistance for evaluation, delivery,
communications, and partnership development.

^3For more information about CDC's two-part plan to help state and local
officials direct vaccine to high-risk groups during the vaccine shortage
in the 2004-05 season as well as the inception of the Flu Vaccine Finder,
see [58]GAO-05-984 .

           o 2006-07 influenza season. Before the start of the 2006-07
           season, CDC officials met with manufacturers and major medical
           supply distributors to receive feedback on the Flu Vaccine Finder
           and instruct them on the type of data CDC would be requesting from
           them and the process for submitting this information to CDC during
           the season. For this season, the Flu Vaccine Finder included data
           from seven major medical supply distributors, along with all
           U.S.-licensed manufacturers. Data, including a onetime listing of
           doses ordered in advance from those manufacturers and medical
           supply distributors who submitted the information, were available
           to users from September 2006 until the end of January 2007.

           o 2007-08 influenza season. CDC officials reported that the Flu
           Vaccine Finder will include data from at least the manufacturers
           of five licensed vaccines and six major medical supply
           distributors for this season. CDC officials also reported that
           they expect data will be available to users from September 2007
           until the end of January 2008.

           For the 2007-08 season, CDC officials stated that they requested
           that manufacturers and medical supply distributors submit
           information weekly to CDC for the Flu Vaccine Finder on the
           vaccine doses they distributed for the season so far.^4 The
           requested weekly information includes:

           o National Drug Code number of vaccine distributed,^5
			  
^4According to CDC officials, CDC requested that manufacturers do not
provide data on doses shipped to medical supply distributors participating
in the Flu Vaccine Finder in order to avoid a duplication of information
from that being submitted by the six major medical supply distributors.

^5The National Drug Code number is a universal product identifier for
human drugs which identifies the labeler, product, and trade package size.
For example, for the influenza vaccine, the National Drug Code number
identifies the manufacturer of the vaccine, the type of vaccine
(preservative-free or preservative-containing), and the presentation of
the vaccine (.25 milliliters, .5 milliliters, etc., and single dose
syringes or multidose vials).

           o state where influenza vaccine is distributed,

           o zip code where influenza vaccine is distributed,

           o number of doses distributed,

           o date the vaccine doses were shipped, and

           o type of provider where vaccine is distributed.

           Manufacturers and medical supply distributors do not classify in a
           uniform way the types of providers to whom vaccine is distributed.
           Therefore, for use in the Flu Vaccine Finder, CDC recodes data
           submitted by manufacturers and medical supply distributors on the
           type of provider into one of the following categories:^6

           o corporation/occupational health,

           o correctional facility,

           o distributors,

           o federal government,

           o hospitals/emergency departments/dialysis centers,

           o long-term care,

           o military,

           o other private provider,

           o other public provider,

           o pharmacy,

           o private providers, and
           o state/local health department.
			  
^6According to CDC, data identifying distribution of vaccine to mass
immunizers were not available within a single provider category; rather,
because these types of providers are classified differently by different
manufacturers and medical supply distributors, doses received by them are
included within a number of provider type categories.

           CDC officials reported that it typically takes about a week for
           the information submitted by manufacturers and medical supply
           distributors to be made available by CDC in the Flu Vaccine
           Finder. Users are able to view Flu Vaccine Finder data for their
           state or jurisdiction online as well as download data into a
           spreadsheet format which allows them to then perform their own
           analyses. The spreadsheet contains variables for which
           manufacturers and medical supply distributors submitted data.
           According to CDC officials, CDC does not conduct data reliability
           tests of the data in the Flu Vaccine Finder because the data
           represent a "census" of influenza vaccine distribution data and
           another data source does not exist for reliability testing. In
           addition, CDC officials reported that about 15 percent of doses
           distributed during the 2006-07 season and captured by the Flu
           Vaccine Finder were shipped from manufacturers or medical supply
           distributors to other medical supply distributors for resale. CDC
           officials reported that the Flu Vaccine Finder does not capture to
           which types of providers the medical supply distributors then
           resell these doses.
			  
			  Appendix VI: GAO Contact and Staff Acknowledgments
			  
			  GAO Contact

           Marcia Crosse, (202) 512-7114 or [47][email protected]
			  
			  Acknowledgments

           In addition to the contact named above, Kim Yamane, Assistant
           Director; Ramsey Asaly; George Bogart; Jennifer DeYoung; Jawaria
           Gilani; and Cathleen Hamann made key contributions to this report.
			  
			  Related GAO Products

           Influenza Pandemic: Applying Lessons Learned from the 2004-05
           Influenza Vaccine Shortage. [48]GAO-06-221T . Washington, D.C.:
           November 4, 2005.

           Influenza Vaccine: Shortages in 2004-05 Season Underscore Need for
           Better Preparation. [49]GAO-05-984 . Washington, D.C.: September
           30, 2005.

           Influenza Pandemic: Challenges in Preparedness and Response.
           [50]GAO-05-863T . Washington, D.C.: June 30, 2005.

           Influenza Pandemic: Challenges Remain in Preparedness.
           [51]GAO-05-760T . Washington, D.C.: May 26, 2005.

           Flu Vaccine: Recent Supply Shortages Underscore Ongoing
           Challenges. [52]GAO-05-177T . Washington, D.C.: November 18, 2004.

           Infectious Disease Preparedness: Federal Challenges in Responding
           to Influenza Outbreaks. [53]GAO-04-1100T . Washington, D.C.:
           September 28, 2004.

           Public Health Preparedness: Response Capacity Improving, but Much
           Remains to Be Accomplished. [54]GAO-04-458T . Washington, D.C.:
           February 12, 2004.

           Flu Vaccine: Steps Are Needed to Better Prepare for Possible
           Future Shortages. [55]GAO-01-786T . Washington, D.C.: May 30,
           2001.

           Flu Vaccine: Supply Problems Heighten Need to Ensure Access for
           High-Risk People. [56]GAO-01-624 . Washington, D.C.: May 15, 2001.

           Influenza Pandemic: Plan Needed for Federal and State Response.
           [57]GAO-01-4 . Washington, D.C.: October 27, 2000.

(290620)

To view the full product, including the scope
and methodology, click on [59]GAO-08-27 .

For more information, contact Marcia Crosse at (202) 512-7114 or
[email protected].

Highlights of [60]GAO-08-27 , a report to the Committee on Oversight and
Government Reform, House of Representatives

October 2007

INFLUENZA VACCINE

Issues Related to Production, Distribution, and Public Health Messages

Annual vaccination is the main method for preventing seasonal influenza,
which typically occurs in the United States from late fall to early
spring. Manufacturers produce vaccine through a lengthy and complex
process. Manufacturers and medical supply distributors then ship vaccine
to providers such as physicians. Each year, the Department of Health and
Human Services's (HHS) Centers for Disease Control and Prevention (CDC)
recommends who should be targeted for vaccination, including those at
higher risk for influenza-related complications or medical care--for
example, adults aged 50 years and older, young children, and some
individuals with chronic medical conditions. CDC bases its recommendations
on those made by the agency's Advisory Committee on Immunization Practices
(ACIP).

GAO examined: (1) factors that affect the quantity of vaccine produced and
when it reaches providers, (2) issues related to making vaccine available
to high-risk and other target groups, and (3) public health messages
produced and disseminated by CDC and others to promote vaccination.

GAO reviewed relevant documents and interviewed officials from CDC, other
public health entities, manufacturers, and medical supply distributors,
and examined data on vaccine doses produced and shipped.

Several factors affect the quantity of vaccine produced for a given
influenza season and when it reaches providers who administer the vaccine.
One factor is the difficulty of manufacturing a new vaccine each year,
which includes adherence to a relatively inflexible and sequential
process, challenges of growing new virus strains, and maintaining safety
and quality control practices to produce a sterile vaccine. Other factors
include limitations in the production capacity of manufacturers and demand
for vaccine throughout the influenza season. In addition, the distribution
route the vaccine takes from the manufacturer to the provider can also
affect how much time elapses before the vaccine reaches individual
providers.

Issues related to making vaccine available to high-risk and other target
groups recommended by CDC and ACIP include the locations in which these
individuals receive vaccinations, how vaccine is distributed to providers,
and the timing of vaccine distribution to different types of providers.
According to data from CDC, individuals in high-risk and other target
groups have received influenza vaccinations at various locations where
different types of providers administer the vaccine, including physicians'
offices, workplaces, clinics, or other settings. Certain types of
providers, such as physicians, reported that they received their vaccine
orders after other types of providers, such as mass immunizers that
provide vaccinations at retail stores. Available data for the 2006-07
influenza season indicated, however, that most types of providers received
vaccine in similar time frames. CDC officials acknowledged that individual
providers' experiences at the local level could vary. In an effort to help
state and local health officials manage the availability of vaccine for
high-risk or other target groups, CDC and state health officials have
undertaken several efforts, including the creation of monitoring tools and
the implementation of a state-specific vaccine distribution program.

CDC and others have produced and disseminated public health messages--such
as press releases and public service announcements--designed to promote
seasonal influenza vaccination. These include messages designed to
maintain public demand for vaccination later in the influenza season and
to encourage preferential vaccination of certain groups during times of
vaccine shortage or delay. CDC has taken steps to assess its
influenza-related public health messages before disseminating them to the
public and has conducted limited data collection afterwards. Although no
comprehensive evaluations have been conducted to assess the impact of
influenza-related messages after dissemination, CDC and other officials
GAO interviewed identified key elements, such as clear and consistent
messages, that they believe are important to producing effective public
health messages. However, there are impediments to effectively
implementing these elements, such as the need to modify messages during
the season as circumstances change.

We provided a draft of this report to HHS for comment. The department
provided technical comments, which we incorporated as appropriate.

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References

Visible links
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  36. http://www.gao.gov/cgi-bin/getrpt?GAO-01-624
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  61. http://www.gao.gov/
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  63. http://www.gao.gov/fraudnet/fraudnet.htm
  64. mailto:[email protected]
  65. mailto:[email protected]
  66. mailto:[email protected]
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