Influenza Vaccine
Issues Related to Production, Distribution, and Public Health Messages Gao ID: GAO-08-27 October 31, 2007Annual 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.
GAO-08-27, Influenza Vaccine: Issues Related to Production, Distribution, and Public Health Messages
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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:
Seasonal Influenza Vaccine:
GAO-08-27:
GAO Highlights:
Highlights of GAO-08-27, a report to the Committee on Oversight and
Government Reform, House of Representatives.
Why GAO Did This Study:
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.
What GAO Found:
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.
To view the full product, including the scope and methodology, click on
[hyperlink, http://www.GAO-08-27]. For more information, contact Marcia
Crosse at (202) 512-7114 or crossem@gao.gov.
[End of section]
Contents:
Letter:
Results in Brief:
Background:
Manufacturing Challenges, Limitations in Production Capacity, and
Fluctuating Demand for Vaccine May Limit the Quantity of Vaccine
Produced or Delay When Vaccine Reaches Providers:
Issues Related to Vaccine Distribution May Affect Vaccine Availability
for High-Risk and Other Target Groups:
CDC and Others Have Produced Public Health Messages, and CDC Has Taken
Some Steps to Assess Its Messages:
Agency Comments:
Appendix I: Scope and Methodology:
Appendix II: Manufacturers of Seasonal Influenza Vaccine for the U.S.
Market, 2000-01 through 2007-08 Influenza Seasons:
Appendix III: Advisory Committee on Immunization Practices (ACIP)
Recommendations:
Appendix IV: Cumulative Percentage of Vaccine Distributed by Provider
Type during 2006-07 Influenza Season:
Appendix V: CDC's Flu Vaccine Finder:
Appendix VI: GAO Contact and Staff Acknowledgments:
Related GAO Products:
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 Seasons14:
Table 2: Manufacturers of Seasonal Influenza Vaccine for the U.S.
Market, 2000-01 through 2007-08 Influenza Seasons:
Table 3: ACIP Influenza Vaccination Recommendations, 2000-01 through
2007-08 Influenza Seasons:
Table 4: Target Groups ACIP Recommended for Influenza Vaccination for
the 2000-01 Influenza Season, before and after October 2000:
Table 5: Target Groups ACIP Recommended for Influenza Vaccination for
the 2004-05 Influenza Season, before and after October 2004:
Table 6: Estimates of ACIP Target Group Populations Sizes, 2006:
Table 7: Percentage of Cumulative Number of Doses Distributed by Month
and Provider Type, 2006-07 Influenza Season:
Figures:
Figure 1: Month of Peak Influenza Activity, 1976 through 2006:
Figure 2: Seasonal Influenza Vaccine Production Cycle:
Figure 3: Distribution of Influenza Vaccine Doses in Millions by Month,
2000-01 through 2006-07 Influenza Seasons:
Figure 4: Potential Impact of Different Distribution Routes of Vaccine
Orders from Manufacturer to Provider:
Figure 5: Locations Where Adults Aged 65 Years and Older and Aged 50
through 64 Years Reported Receiving Most Recent Influenza Vaccination,
2004:
Figure 6: Locations Where High-Risk Adults with Certain Chronic
Conditions Reported Receiving Most Recent Influenza Vaccination, 2002:
Figure 7: Percentage of Cumulative Number of Vaccine Doses Distributed,
by Provider Type and Month, 2006-07 Influenza Season:
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:
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.[Footnote 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.[Footnote 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[Footnote 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.[Footnote 4]
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.[Footnote
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.
To address these objectives, we reviewed relevant documents and
interviewed officials from CDC and FDA; national associations
representing state and local health officials,[Footnote 6] public
health officials, medical supply distributors,[Footnote 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.[Footnote 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.[Footnote 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,[Footnote 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[Footnote 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.
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.
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:
This figure is bar chart showing month of peak influenza activity, 1976
through 2006:
November: 3%;
December: 13%;
January: 19;
February: 45;
March: 13;
April: 3;
May: 3.
[See PDF for image]
Source: CDC, "Prevention and Control of Influenza: Recommendations of
the Advisory Committee on Immunization Practices (ACIP), 2007,
"Morbidity and Mortality Weekly Report, vol. 56 (2007): 5.
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.
[End of figure]
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.[Footnote 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.[Footnote 13] The live attenuated
vaccine, in contrast, is approved for use only among healthy
individuals aged 2 through 49 years who are not pregnant.[Footnote 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.
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):[Footnote 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.[Footnote 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.[Footnote 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.[Footnote 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.[Footnote 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.[Footnote 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.[Footnote 21] The vaccine must be kept refrigerated within a
prescribed temperature range.[Footnote 22]
Figure 2: Seasonal Influenza Vaccine Production Cycle:
This figure is a chart with illustrations showing seasonal influenza
vaccine production cycle:
1. Virus Strain Selection:
* FDA‘s Vaccines and Related Biological Products Advisory Committee,
using surveillance information from the World Health Organization and
CDC, recommends three virus strains to include in the annual vaccine
for the following influenza season.
* After receiving the Advisory Committee‘s recommendation, FDA selects
three virus strains that manufacturers must include in the influenza
vaccine for the following influenza season.
* One of the three strains is usually new compared to the prior season.
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.[A]
* The manufacturers then inject the virus sample of each selected
strain into separate batches of fertilized eggs to amplify the amount
of virus. The viruses grown at this step 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.
* Each virus strain is grown separately inside the eggs over the course
of several days.
* The viruses are harvested from the eggs, inactivated, and
purified.[B]
3. Testing, Filling, and Packaging:
* Using biological materials provided by FDA, manufacturers and the FDA
test virus strains to determine the purity and yield of the virus and
to ensure that the potency is adequate for immunization. Once the
potency of each strain is determined to be adequate, manufacturers
combine the three virus strains to create the vaccine for that season.
* Manufacturers fill vaccine doses into vials and syringes,which are
then sealed. 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.[C]
4. Shipping to Customers:
* Vaccine is shipped to customers, which can include medical supply
distributors, physicians, hospitals, state and local health
departments, and mass immunizers.
[See PDF for image]
Source: GAO, Art Explosion.
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.
[A] The 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.
[B] In contrast, the live attenuated vaccine administered as a nasal
spray is not inactivated.
[C] Influenza 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.
[End of figure]
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,
* One such production technology involves growing the influenza virus
in cells rather than chicken eggs.[Footnote 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.
* 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.
* 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,[Footnote 24] a completely universal influenza vaccine may be
years away.[Footnote 25]
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.[Footnote 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.[Footnote 27]
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).[Footnote 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:
Influenza season: 2000-01;
Number of licensed manufacturers: 3;
Total number of doses produced (in millions): 78;
Total number of doses distributed (in millions): 70.
Influenza season: 2001-02;
Number of licensed manufacturers: 3;
Total number of doses produced (in millions): 88;
Total number of doses distributed (in millions): 78.
Influenza season: 2002-03;
Number of licensed manufacturers: 3;
Total number of doses produced (in millions): 95;
Total number of doses distributed (in millions): 83.
Influenza season: 2003-04;
Number of licensed manufacturers: 3;
Total number of doses produced (in millions): 87;
Total number of doses distributed (in millions): 83.
Influenza season: 2004-05;
Number of licensed manufacturers: 3[A];
Total number of doses produced (in millions): 61;
Total number of doses distributed (in millions): 57.
Influenza season: 2005-06;
Number of licensed manufacturers: 4;
Total number of doses produced (in millions): 92;
Total number of doses distributed (in millions): 82.
Influenza season: 2006-07;
Number of licensed manufacturers: 5[B];
Total number of doses produced (in millions): 121;
Total number of doses distributed (in millions): 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.
[A] Of 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.
[B] The 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.
[End of table]
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.[Footnote 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.
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.[Footnote 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.[Footnote 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.
Manufacturing Challenges, Limitations in Production Capacity, and
Fluctuating Demand for Vaccine May Limit the Quantity of 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 May Limit the Quantity of Seasonal Influenza
Vaccine Produced or Delay When Vaccine Reaches Providers:
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.
* 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.[Footnote 32]
* 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.[Footnote 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.
* 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.[Footnote 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.[Footnote 35] In September 2007, the manufacturer reported
that it had resolved the observances contained in the warning
letter.[Footnote 36]
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:
This figure is a line chart showing distribution of influenza vaccine
doses in millions my month, 2000-01 through 2006-07. The X axis
represents the month, and the Y axis represents vaccine doses
distributed in millions.
[See PDF for image]
Source: CDC.
[End of figure]
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.[Footnote 37]
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.[Footnote 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,[Footnote 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.
Figure 4: Potential Impact of Different Distribution Routes of Vaccine
Orders from Manufacturer to Provider:
This figure is a chart showing potential impact of different
distribution routes of vaccine orders from manufacturer to provider.
[See PDF for image]
Source: GAO.
[End of figure]
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).[Footnote 40]
Figure 5: Locations Where Adults Aged 65 Years and Older and Aged 50
through 64 Years Reported Receiving Most Recent Influenza Vaccination,
2004:
This figure is a combination of pie charts showing locations where
adults aged 65 years and older and aged 50 through 64 reported
receiving most recent influenza vaccination in 2004:
Adults aged 65 years and older: Physician's office: 52.6%;
Adults aged 65 years and older: Clinic: 20.55;
Adults aged 65 years and older: Other medically related place: 17.0%;
Adults aged 65 years and older: Other nonmedically related place: 7.4%;
Adults aged 65 years and older: Workplace: 2.0%.
Adults aged 64 years and older: Physician's office: 34.9%;
Adults aged 64 years and older: Clinic: 20.2%;
Adults aged 64 years and older: Other medically related place: 19.85;
Adults aged 64 years and older: Other nonmedically related place: 9.0%;
Adults aged 64 years and older: Workplace: 16.2%.
[See PDF for image]
Source: CDC's National Adult immunization Survey Module, 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).
[End of figure]
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:
This figure is a pie chart showing locations where high-risk adults
with certain chronic conditions reported receiving most recent
influenza vaccination:
Physician's office: 49.05;
Workplace: 19.4;
Other: 15.4;
Clinic: 12.1;
Retail store: 4.1%.
[See PDF for image]
Source: CDC's Behavioral Risk Factor Surveillance System, 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).
[End of figure]
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.[Footnote 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.[Footnote 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.[Footnote 43]
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.
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).[Footnote 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.
Figure 7: Percentage of Cumulative Number of Vaccine Doses Distributed,
by Provider Type and Month, 2006-07 Influenza Season:
This figure is a combination of bar charts showing percentage of
cumulative number of vaccine doses distributed, by provider type and
month, 2006-07 influenza season:
Private providers[A]: Private providers received 42.3 percent of all
vaccine distributed;
Sept.: 41.0;
Oct.: 43.2
Nov.: 43.1;
Dec: 42.3;
Jan.: 42.3.
State and local health departments: State and local health departments
received 11.6 percent of all vaccine distributed;
Sept.: 6.6;
Oct.: 7.2;
Nov.: 10.1;
Dec.: 11.6;
Jan.: 11.6.
Long term care facilities: Long term care facilities received 3.1
percent of all vaccine distributed;
Sept.: 4.7;
Oct.: 4.0;
Nov.: 3.7;
Dec.: 3.1;
Jan: 3.1.
Other[B]: Other providers types received 43.1 percent of all vaccine
distributed;
Sept.: 47.7;
Oct.: 45.6;
Nov.: 43.0;
Dec.: 43.0;
Jan.: 43.1.
[See PDF for image]
Source: CDC.
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.
[A] The category "Private providers" includes physicians, as well as
outpatient clinics and facilities, health maintenance organizations,
and surgery centers.
[B] The 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.
[End of figure]
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."[Footnote 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,[Footnote 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.
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:
* 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.
* 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.
* 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.
* 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.[Footnote 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:
* 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.
* 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.
* The American Lung Association, in collaboration with one major
vaccine manufacturer, runs a Web-based educational initiative to
encourage vaccination.
* 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,[Footnote 48] has involved senior HHS officials
from CDC and the Centers for Medicare & Medicaid Services[Footnote 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.[Footnote 50]
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.[Footnote 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.[Footnote 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.[Footnote 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.
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.
* 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.[Footnote 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.
* 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.
* 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 [hyperlink, 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 crossem@gao.gov. 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.
Signed by:
Marcia Crosse:
Director, Health Care:
[End of section]
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.[Footnote 55] 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.[Footnote 56] 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.[Footnote 57]
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.
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.[Footnote 58] 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.[Footnote 59] 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.
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;[Footnote 60] and that varied in whether they used
CDC's Flu Vaccine Finder and have proposed innovative approaches for
distributing influenza vaccine.[Footnote 61]
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.
We conducted our work in accordance with generally accepted government
auditing standards from May through October 2007.
[End of section]
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:
Manufacturer: sanofi pasteur (Aventis Pasteur Inc.)[B];
Influenza season: 2000-01: [Check];
Influenza season: 2001-02: [Check];
Influenza season: 2002-03: [Check];
Influenza season: 2003-04: [Check];
Influenza season: 2004-05[A]: [Check];
Influenza season: 2005-06: [Check];
Influenza season: 2006-07: [Check];
Influenza season: 2007-08: [Check].
Manufacturer: Wyeth Laboratories, Inc;
Influenza season: 2000-01: [Check];
Influenza season: 2001-02: [Check];
Influenza season: 2002-03: [Check];
Influenza season: 2003-04: [Empty];
Influenza season: 2004-05[A]: [Empty];
Influenza season: 2005-06: [Empty];
Influenza season: 2006-07: [Empty];
Influenza season: 2007-08: [Empty].
Manufacturer: Novartis Vaccines and Diagnostics Limited (Chiron
Vaccines Limited;
PowderJect Pharmaceuticals plc;
Medeva Pharma Limited;
Evans Vaccines Limited)[C];
Influenza season: 2000-01: [Check];
Influenza season: 2001-02: [Check];
Influenza season: 2002-03: [Check];
Influenza season: 2003-04: [Check];
Influenza season: 2004-05[A]: [Check][D];
Influenza season: 2005-06: [Check];
Influenza season: 2006-07: [Check];
Influenza season: 2007-08: [Check].
Manufacturer: MedImmune Vaccines, Inc.[E];
Influenza season: 2000-01: [Empty];
Influenza season: 2001-02: [Empty];
Influenza season: 2002-03: [Empty];
Influenza season: 2003-04: l[F];
Influenza season: 2004-05[A]: [Check];
Influenza season: 2005-06: [Check];
Influenza season: 2006-07: [Check];
Influenza season: 2007-08: [Check].
Manufacturer: GlaxoSmithKline Biologicals;
Influenza season: 2000-01: [Empty];
Influenza season: 2001-02: [Empty];
Influenza season: 2002-03: [Empty];
Influenza season: 2003-04: [Empty];
Influenza season: 2004- 05[A]: [G];
Influenza season: 2005-06: [Check];
Influenza season: 2006-07: [Check][H];
Influenza season: 2007-08: [Check][H].
Manufacturer: ID Biomedical Corporation of Quebec;
Influenza season: 2000-01: [Empty];
Influenza season: 2001-02: [Empty];
Influenza season: 2002-03: [Empty];
Influenza season: 2003-04: [Empty];
Influenza season: 2004-05[A]: [Empty];
Influenza season: 2005-06: [Empty];
Influenza season: 2006-07: [Check][H];
Influenza season: 2007-08: [Check][H].
Manufacturer: CSL Limited;
Influenza season: 2000-01: [Empty];
Influenza season: 2001-02: [Empty];
Influenza season: 2002-03: [Empty];
Influenza season: 2003-04: [Empty];
Influenza season: 2004-05[A]: [Empty];
Influenza season: 2005-06: [Empty];
Influenza season: 2006-07: [Empty];
Influenza season: 2007-08: [Check].
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.
[A] For 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.
[B] Aventis Pasteur Inc., became sanofi pasteur in January 2005.
[C] In 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.
[D] Chiron'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.
[E] MedImmune 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.
[F] Wyeth Laboratories, Inc. distributed MedImmune's FluMist vaccine
during the 2003-04 season.
[G] GlaxoSmithKline 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.
[H] ID 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.
[End of table]
[End of section]
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).[Footnote 62] 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).
Table 3: ACIP Influenza Vaccination Recommendations, 2000-01 through
2007-08 Influenza Seasons:
[See PDF for image]
Source: GAO analysis of CDC's Morbidity and Mortality Weekly Reports,
2000 through 2007.
Notes: A check mark [Check] indicates vaccination was recommended for
that group for that season.
[A] The 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.
[B] The 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.
[C] For 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.
[D] ACIP 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.
[E] For 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.
[F] For 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.
[End of table]
Table 4: Target Groups ACIP Recommended for Influenza Vaccination for
the 2000-01 Influenza Season, before and after October 2000:
Target groups: Pregnant women in second or third trimester during the
influenza season;
April 2000[A]: [Check];
October 2000[B]: [Check].
Target groups: Adults aged 65 years and older;
April 2000[A]: [Check];
October 2000[B]: [Check].
Target groups: Residents of nursing homes and other chronic-care
facilities;
April 2000[A]: [Check];
October 2000[B]: [Check].
Target groups: Persons aged 6 months through 64 years with certain
chronic medical conditions;
April 2000[A]: [Check];
October 2000[B]: [Check].
Target groups: Health care workers;
April 2000[A]: [Check];
October 2000[B]: [Check].
Target groups: Household contacts of persons at high-risk;
April 2000[A]: [Check];
October 2000[B]: [Check].
Target groups: Adults aged 50 through 64 years;
April 2000[A]: [Check];
October 2000[B]: [Empty].
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 [Check] denote priority groups recommended by ACIP,
at the time shown, for vaccination.
[A] ACIP 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.
[B] The 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.
[End of table]
Table 5: Target Groups ACIP Recommended for Influenza Vaccination for
the 2004-05 Influenza Season, before and after October 2004:
Target groups: Children aged 6 to 23 months;
May 2004[A]: [Check];
October 2004[B]: [Check].
Target groups: All women who will be pregnant during the influenza
season;
May 2004[A]: [Check];
October 2004[B]: [Check].
Target groups: Adults aged 65 years and older;
May 2004[A]: [Check];
October 2004[B]: [Check].
Target groups: Residents of nursing homes and other chronic-care
facilities;
May 2004[A]: [Check];
October 2004[B]: [Check].
Target groups: Persons aged 6 months and older with certain chronic
medical conditions;
May 2004[A]: [Check];
October 2004[B]: [Check].
Target groups: Health care workers;
May 2004[A]: [Check];
October 2004[B]: [Check].
Target groups: Persons aged 2 to 64 years who are household contacts of
persons at high-risk[C];
May 2004[A]: [Check];
October 2004[B]: [Empty].
Target groups: Persons aged 2 to 64 years who are household contacts of
children younger than 6 months[C];
May 2004[A]: [Check];
October 2004[B]: [Check].
Target groups: Adults aged 50 through 64 years who are not household
contacts of high-risk individuals;
May 2004[A]: [Check];
October 2004[B]: [Empty].
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 [Check] denote priority groups recommended by ACIP,
at the time shown, for vaccination.
[A] ACIP 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.
[B] These revised recommendations were published in response to a
shortage of influenza vaccine.
[C] These groups belonged to a single category in ACIP's May 2004
recommendations.
[End of table]
Table 6: Estimates of ACIP Target Group Populations Sizes, 2006:
Target group: Persons at increased risk for influenza-related
complications: Children aged 6 to 23 months;
Population in millions: 6.0;
Percent of total U.S. population: 2.0%.
Target group: Persons at increased risk for influenza-related
complications: All women who will be pregnant during the influenza
season;
Population in millions: 4.0;
Percent of total U.S. population: 1.3.
Target group: Persons at increased risk for influenza-related
complications: Adults aged 65 years and older;
Population in millions: 37.2;
Percent of total U.S. population: 12.5.
Target group: Persons at increased risk for influenza-related
complications: Persons aged 24 months through 64 years with certain
chronic medical conditions;
Population in millions: 44.0;
Percent of total U.S. population: 14.8.
Target group: Persons at increased risk for influenza-related
complications: Subtotal;
Population in millions: 91.2;
Percent of total U.S. population: 30.6.
Target group: 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;
Population in millions: 18.0;
Percent of total U.S. population: 6.0.
Target group: Persons with elevated prevalence of chronic medical
conditions, or with increased risk for influenza-associated clinic,
emergency department, or hospital visits: Children aged 24 to 59
months;
Population in millions: 7.1;
Percent of total U.S. population: 2.4.
Target group: Persons with elevated prevalence of chronic medical
conditions, or with increased risk for influenza-associated clinic,
emergency department, or hospital visits: Subtotal;
Population in millions: 25.1;
Percent of total U.S. population: 8.4.
Target group: Persons who can transmit influenza to those at high risk;
Population in millions: Household contacts of persons at high risk or
children aged 24 through 59 months;
Population in millions: 94.8;
Percent of total U.S. population: 31.8.
Target group: Persons who can transmit influenza to those at high risk;
Population in millions: Health care workers;
Population in millions: 7.0;
Percent of total U.S. population: 2.4.
Target group: Persons who can transmit influenza to those at high risk;
Population in millions: Subtotal;
Population in millions: 101.8;
Percent of total U.S. population: 34.1.
Target group: Total target population;
Population in millions: 218.1;
Percent of total U.S. population: 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.
[End of table]
[End of section]
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: Corporations;
September: 2.2%;
October: 2.5%;
November: 2.6%;
December: 2.5%;
January: 2.5%.
Provider type: Correctional facilities;
September: 0.0;
October: 0.0;
November: 0.0;
December: 0.0;
January: 0.0.
Provider type: Distributors;
September: 24.9;
October: 16.2;
November: 18.3;
December: 15.7;
January: 15.6.
Provider type: Federal government;
September: 1.1;
October: 3.9;
November: 3.3;
December: 5.0;
January: 5.1.
Provider type: Hospitals;
September: 9.2;
October: 12.9;
November: 10.4;
December: 9.9;
January: 9.9.
Provider type: Long-term care facilities;
September: 4.7;
October: 4.0;
November: 3.7;
December: 3.1;
January: 3.1.
Provider type: Military;
September: 0.6;
October: 1.0;
November: 0.8;
December: 2.2;
January: 2.2.
Provider type: Other private provider types;
September: 3.4;
October: 2.9;
November: 2.7;
December: 2.8;
January: 2.9.
Provider type: Other public provider types;
September: 1.3;
October: 1.1;
November: 1.1;
December: 1.4;
January: 1.4.
Provider type: Pharmacies;
September: 5.0;
October: 5.1;
November: 3.8;
December: 3.5;
January: 3.5.
Provider type: Private providers[A];
September: 41.0;
October: 43.2;
November: 43.1;
December: 42.3;
January: 42.3.
Provider type: State and local health departments;
September: 6.6;
October: 7.2;
November: 10.1;
December: 11.6;
January: 11.6.
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.
[A] The category "Private providers" includes physicians, as well as
outpatient clinics and facilities, health maintenance organizations,
and surgery centers.
[End of table]
[End of section]
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.[Footnote 63]
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.[Footnote 64] 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:
* 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.[Footnote
65]
* 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.
* 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.
* 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.[Footnote 66] The requested weekly information
includes:
* National Drug Code number of vaccine distributed,[Footnote 67]
* state where influenza vaccine is distributed,
* zip code where influenza vaccine is distributed,
* number of doses distributed,
* date the vaccine doses were shipped, and:
* 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:[Footnote 68]
* corporation/occupational health,
* correctional facility,
* distributors,
* federal government,
* hospitals/emergency departments/dialysis centers,
* long-term care,
* military,
* other private provider,
* other public provider,
* pharmacy,
* private providers, and:
* state/local health department.
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.
[End of section]
Appendix VI: GAO Contact and Staff Acknowledgments:
GAO Contact:
Marcia Crosse, (202) 512-7114 or crossem@gao.gov:
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.
[End of section]
Related GAO Products:
Influenza Pandemic: Applying Lessons Learned from the 2004-05 Influenza
Vaccine Shortage. GAO-06-221T. Washington, D.C.: November 4, 2005.
Influenza Vaccine: Shortages in 2004-05 Season Underscore Need for
Better Preparation. GAO-05-984. Washington, D.C.: September 30, 2005.
Influenza Pandemic: Challenges in Preparedness and Response. GAO-05-
863T. Washington, D.C.: June 30, 2005.
Influenza Pandemic: Challenges Remain in Preparedness. GAO-05-760T.
Washington, D.C.: May 26, 2005.
Flu Vaccine: Recent Supply Shortages Underscore Ongoing Challenges. GAO-
05-177T. Washington, D.C.: November 18, 2004.
Infectious Disease Preparedness: Federal Challenges in Responding to
Influenza Outbreaks. GAO-04-1100T. Washington, D.C.: September 28,
2004.
Public Health Preparedness: Response Capacity Improving, but Much
Remains to Be Accomplished. GAO-04-458T. Washington, D.C.:
February 12, 2004.
Flu Vaccine: Steps Are Needed to Better Prepare for Possible Future
Shortages. GAO-01-786T. Washington, D.C.: May 30, 2001.
Flu Vaccine: Supply Problems Heighten Need to Ensure Access for High-
Risk People. GAO-01-624. Washington, D.C.: May 15, 2001.
Influenza Pandemic: Plan Needed for Federal and State Response. GAO-01-
4. Washington, D.C.: October 27, 2000.
[End of section]
Footnotes:
[1] Influenza 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.
[2] FDA'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.
[3] Throughout 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.
[4] See Centers for Disease Control and Prevention, "Estimates of
Influenza Vaccination Target Population Sizes in 2006 and Recent
Vaccine Uptake Levels," [hyperlink,
http://www.cdc.gov/flu/professionals/vaccination/pdf/targetpopchart.pdf]
(downloaded April 2, 2007).
[5] See GAO, Flu Vaccine: Supply Problems Heighten Need to Ensure
Access for High-Risk People, GAO-01-624 (Washington, D.C.: May 15,
2001); GAO, Influenza Vaccine: Shortages in 2004-05 Season Underscore
Need for Better Preparation, GAO-05-984 (Washington, D.C.: Sept. 30,
2005); and see Related GAO Products at the end of this report.
[6] We also spoke with state and local health officials who are members
of national associations representing state and local health officials.
[7] Medical 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.
[8] For 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.
[9] We 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.
[10] The 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.
[11] The 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.
[12] A live attenuated vaccine contains attenuated, or weakened,
influenza viruses.
[13] Manufacturers 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.
[14] On 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.
[15] 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.
[16] FDA 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.
[17] The 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.
[18] Manufacturers 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.
[19] In contrast, the live attenuated vaccine administered as a nasal
spray is not inactivated.
[20] Influenza 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.
[21] Some 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.
[22] For the 2007-08 season, the live attenuated vaccine administered
as a nasal spray also requires refrigeration within a prescribed
temperature range.
[23] While 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.
[24] For 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.
[25] In 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.
[26] According 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.
[27] According 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).
[28] See 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.
[29] With 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. §353(c)(3).
[30] See 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.
[31] See 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."
[32] If 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] GAO-01-624.
[34] GAO-05-984.
[35] Good manufacturing practices include requirements applicable to
the entire manufacturing process to help ensure that biological
products, such as vaccines, are safe, pure, and potent.
[36] The manufacturer had previously reported that it expected to
address the problem without affecting the quantity of vaccine produced.
[37] In 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.
[38] Health Industry Distributors Association, "2006-07 Influenza
Vaccine Production & Distribution Market Brief," (Alexandria, Va.:
Health Industry Distributors Association, 2007) [hyperlink,
http://www.hida.org/attachment.asp?attachment_id=10509] (downloaded
Oct. 3, 2007).
[39] An 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.
[40] For the 2007-08 influenza season, ACIP considers both of these
population groups as part of the high-risk groups.
[41] CDC 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.
[42] The 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.
[43] CDC 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 GAO-05-984.
[44] 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.
[45] Jeanne 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.
[46] The 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).
[47] Rhode Island's uninsured residents are eligible to receive
influenza vaccinations through other programs administered by the
state.
[48] The 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.
[49] The 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.
[50] See GAO-05-984 and app. III for revisions to groups recommended
for vaccination by ACIP during the 2004-05 influenza season vaccine
shortage.
[51] See GAO-01-624.
[52] CDC 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.
[53] This $1.5 million for fiscal year 2007 included additional funding
for National Influenza Vaccination Week.
[54] GAO-05-984.
[55] For 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.
[56] We 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.
[57] The 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.
[58] The Health Industry Distributors Association estimated that 25
medical supply distributors distribute vaccine in the United States in
2007.
[59] Members 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.
[60] To determine vaccination rates, we used immunization rates for
adults aged 65 years and older for 2005 from CDC's Behavioral Risk
Factor Surveillance System.
[61] The six states we selected were Colorado, Maryland, Minnesota,
Rhode Island, Texas, and Washington.
[62] In 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.
[63] CDC'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.
[64] Immunization 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.
[65] For 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 GAO-05-984.
[66] According 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.
[67] The 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).
[68] 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.
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