Influenza Pandemic: Plan Needed for Federal and State Response (Letter
Report, 10/27/2000, GAO/GAO-01-4).

Public health experts have raised concerns about the ability of the
nation's public health system to detect and respond to emerging
infectious disease threats, such as pandemic influenza. Vaccines are
considered the first line of defense to prevent or reduce
influenza-related illness and death, but may be unavailable, in short
supply, or ineffective. Federal and state influenza pandemic plans are
in various stages of completion and do not completely or consistently
address key issues surrounding the purchase, distribution, and
administration of vaccines and antiviral drugs. As a result, state and
federal inconsistencies could contribute to public confusion and weaken
the effectiveness of the public health response.

--------------------------- Indexing Terms -----------------------------

 REPORTNUM:  GAO-01-4
     TITLE:  Influenza Pandemic: Plan Needed for Federal and State
	     Response
      DATE:  10/27/2000
   SUBJECT:  Infectious diseases
	     Health care services
	     Federal/state relations
	     Immunization services
	     Emergency preparedness
	     Health statistics

******************************************************************
** This file contains an ASCII representation of the text of a  **
** GAO Testimony.                                               **
**                                                              **
** No attempt has been made to display graphic images, although **
** figure captions are reproduced.  Tables are included, but    **
** may not resemble those in the printed version.               **
**                                                              **
** Please see the PDF (Portable Document Format) file, when     **
** available, for a complete electronic file of the printed     **
** document's contents.                                         **
**                                                              **
******************************************************************
GAO-01-4

A

Report to Congressional Requesters

October 2000 INFLUENZA PANDEMIC

Plan Needed for Federal and State Response

GAO- 01- 4

Letter 3 Appendix Appendix I: Comments From the Department of Health and
Human

Services 30 Tables Table 1: Annual Vaccine Production Process 8

Table 2: Months for Newly Detected Influenza Viruses to Reach the United
States 10 Table 3: Time of Year Influenza Illness Appeared 11 Table 4:
Antiviral Drugs Approved for Influenza by FDA 16 Table 5: Excess Influenza-
Related Deaths Estimated for Pandemic

and Nonpandemic Periods in the United States, 1918- 91 19

Abbreviations

CDC Centers for Disease Control and Prevention DNA deoxyribonucleic acid FDA
Food and Drug Administration HHS Department of Health and Human Services mg
milligram NIH National Institutes of Health WHO World Health Organization

Lett er

October 27, 2000 The Honorable Tom Bliley Chairman, Committee on Commerce
House of Representatives

The Honorable Fred Upton Chairman, Subcommittee on Oversight and
Investigations Committee on Commerce House of Representatives

Each year influenza viruses cause epidemics somewhere in the world and an
annual average of more than 20, 000 deaths in the United States. New strains
of the virus continually evolve, causing remarkable variability in the
intensity and severity of illness. Periodically, but unpredictably, a major
genetic change in the virus results in a strain that can cause widespread
disease and death. Three such global epidemics- called pandemics- occurred
in the 20th century. The worst occurred in 1918 and killed more than 20
million people worldwide. Recent books and media attention have recounted
the devastation of this pandemic and noted the prospect of a similar
influenza outbreak.

In recent years, public health experts have raised concerns about the
ability of the nation's public health system to detect and respond to
emerging infectious disease threats, such as pandemic influenza. The
response effort would need to include the ability to quickly produce and
distribute a vaccine and antiviral drugs effective against the pandemic
strain, as well as the ability to vaccinate or treat the population against
pneumonia and its complications, which are most often the actual cause of
death. You asked us to examine (1) the capability to develop and produce a
vaccine to protect the nation from a pandemic influenza virus, (2) the
capability to use other measures, such as antiviral drugs and pneumococcal
vaccine, to help protect or treat people exposed to a pandemic virus, and
(3) the status of federal and state plans to address the purchase,
distribution, and administration of vaccines and antiviral drugs in a
pandemic.

To address issues related to the production and use of vaccines and
antiviral drugs, we interviewed officials and reviewed influenza- related
documents from three Department of Health and Human Services (HHS) agencies-
the Centers for Disease Control and Prevention (CDC), the Food and Drug
Administration (FDA), and the National Institutes of Health

(NIH), as well as the Department of Veterans Affairs. We also interviewed
private sector representatives from the 4 manufacturers producing influenza
vaccine for the United States, 4 of 12 manufacturers of antiviral drugs, and
various professional associations representing distributors and
administrators of vaccines and drugs. To gather information on federal and
state influenza pandemic planning efforts, we also interviewed HHS officials
from the Office of the Assistant Secretary for Planning and Evaluation,
Office of Emergency Planning, and National Vaccine Program Office, and
officials in a judgmental sample of 11 of 29 states that either have drafted
a plan or have begun to draft one. Although states have a lead role for
public health response in the United States, state programs vary widely. The
results from our analysis of state efforts are illustrative and cannot be
generalized to other states. We conducted our work in accordance with
generally accepted government auditing standards from April to September
2000.

Results in Brief The results of our review show that vaccines, which are
considered the first line of defense to prevent or reduce influenza- related
illness and death,

may be unavailable, in short supply, or ineffective for certain portions of
the population during the first wave of a pandemic. Experience has shown
that the vaccine production cycle takes at least 6 to 8 months after a virus
strain has been identified. However, new strains of influenza virus
sometimes appear too late to be included in the yearly influenza vaccine
production for the United States. Also, vaccines for some influenza strains
have been difficult to mass- produce, causing further delay. Even if
sufficient quantities of the vaccine are produced in time, studies show that
it is uncertain how well this can help prevent or control the spread of a
pandemic influenza virus. Vaccines against various strains differ in their
ability to produce antibodies to neutralize the virus, and each person's
immune system may respond somewhat differently. Limited studies have shown
that when the vaccine provides a good antibody response to the virus,
approximately 70 to 90 percent of healthy young adults may be protected from
influenza. This protection drops to about 30 to 40 percent for the elderly
and those suffering from chronic illness or disease.

Antiviral drugs and vaccines against pneumonia are expected to be in short
supply if a pandemic occurs and influenza vaccine is unavailable. Antiviral
drugs, which can be used against all strains of influenza, have been as
effective as vaccines in preventing illness from influenza and have the
advantage of being available now. HHS assumes shortages will occur in a
pandemic because demand is expected to exceed current rates of

production and increasing production capacity of antiviral drugs can take at
least 6 to 9 months, according to manufacturers. HHS is studying the
feasibility of stockpiling these drugs to preclude shortages. Among people
who become ill with influenza, prior immunization against pneumococcal
pneumonia, an infection that frequently follows influenza, may help reduce
the number of deaths or the severity of illness. Shortages of this vaccine
are also expected during a pandemic because only about an estimated 7
million doses of vaccine are produced each year as most of the population is
not targeted to receive the vaccine. Increasing immunization rates now,
particularly among high- risk groups, has been suggested by HHS as the
primary strategy to mitigate shortages in a pandemic because the vaccine
provides immunity for at least 5 to 10 years.

Federal and state influenza pandemic plans are in various stages of
completion and do not completely or consistently address key issues
surrounding the purchase, distribution, and administration of vaccines and
antiviral drugs. HHS is working on a national plan, 10 states either have
developed or are developing plans using general guidance from CDC, and 19
more states have plans under development. Outstanding issues remain,
however, because certain key federal decisions have not been made. For
example, HHS has not determined the proportion of vaccines and antiviral
drugs to be purchased, distributed, and administered by the public and
private sectors or established priorities for which population groups should
receive vaccines and antiviral drugs first when supplies are limited. As a
result, policies may differ among states and between states and the federal
government, and in the event of a pandemic these inconsistencies could
contribute to public confusion and weaken the effectiveness of the public
health response. To improve the nation's ability to respond to an influenza
pandemic, we are recommending that HHS determine the capability of the
private and public sectors to produce, distribute, and administer vaccines
and drugs and complete the national response plan. In commenting on a draft
of this report, HHS generally concurred with our recommendations.

Background In almost every year an influenza virus causes acute respiratory
disease in epidemic proportions somewhere in the world. Influenza- also
called “the

flu”- is more severe than some of the other viral respiratory
infections, such as the common cold. Most people who get the flu recover
completely in 1 to 2 weeks, but some develop serious and potentially life-
threatening medical complications, such as pneumonia. People who are age 65
or over or who have severe chronic conditions are much more likely to
develop serious complications than are younger, healthier people. In an
average flu

season (winter months), influenza contributes to as many as 20,000 deaths
and 114,000 hospitalizations in the United States.

Occasionally, worldwide influenza epidemics- called pandemics- occur that
can have successive “waves” of disease and last for up to 3
years. Documented accounts of such pandemics cover the past 300 years, with
three occurring in the 20th century. Notable among these was the pandemic of
1918- called the “Spanish flu”- which killed at least 20 million
people worldwide, including 500,000 in the United States. For reasons still
not completely understood, many of the fatalities during the 1918 pandemic
were young adults, and many people reportedly died within hours after the
first symptoms appeared. The pandemics of 1957 (“ Asian flu”)
and 1968 (“ Hong Kong flu”) caused dramatically fewer
fatalities- 70,000 and 34, 000, respectively, in the United States-
primarily because of antibiotic treatment of secondary infections and more
aggressive supportive care. 1 Nevertheless, both were associated with high
fatality rates and social disruption resulting from high absenteeism among
providers of health care and other essential community services such as
police and firefighters.

The characteristics of influenza viruses make the disease difficult to
control, and its eradication is not a realistic expectation. Influenza
viruses undergo minor but continuous genetic changes from year to year. 2
Periodically, but unpredictably, an influenza virus changes so significantly
that any immunity conferred by previous vaccinations or infections is not
effective, creating the potential for a pandemic. The dramatic genetic
changes that produce variants responsible for widespread illness and death,
such as those that caused the 1957 and 1968 pandemics, probably involve the
mixing of two strains in a single host. For example, strains of the
influenza virus that are found in birds can mix with strains found in other
host animals, such as pigs, to produce a new, and possibly virulent, strain
that infects people. In 1997 a second- never before seen- method for
dramatic change was revealed when an avian influenza virus not previously
known to infect people directly infected humans without an intermediate
host. The virus killed 6 of the 18 people in Hong Kong who became ill.
Although the disease did not readily spread among humans, had it acquired
the ability to do so, it might have become very difficult to

1 The names reflect popular impressions of where the pandemics began,
although many experts believe all three originated in China. 2 Variants of
the influenza B virus and all subtypes of A evolve separately, have distinct
characteristics, and may respond differently to vaccine.

control. Because new influenza viruses will continue to emerge, many experts
believe another pandemic is inevitable.

Public health experts and state and federal officials view influenza vaccine
as the cornerstone of efforts to prevent and control annual epidemic
influenza as well as pandemic influenza. Deciding which viral strains to
include in the annual influenza vaccine depends on data collected from
domestic and international surveillance systems that identify prevalent
strains and characterize their effect on human health. In the United States,
CDC monitors data on the disease and the virus from surveillance that occurs
in all 50 states and the District of Columbia year- round but with
intensified efforts during the October through May flu season. Domestic
surveillance consists of test data from 138 laboratories that receive
specimens year- round, mortality data from 122 cities that account for about
one- third of all deaths, and weekly reports from about 400 physicians and
state epidemiologists regarding the extent and intensity of influenza
illness. In addition, CDC participates in international disease and
laboratory surveillance sponsored by the World Health Organization (WHO),
which operates in 83 countries.

Officials at HHS, WHO, and state public health agencies have begun to
develop strategies to reduce influenza- related illness, death, economic
loss, and social disruption, such as the closure of schools and hospitals
and decreased access to utilities and other essential services. In many
cases, state and federal officials are integrating these strategies with
response plans for such public health emergencies as natural disasters and
bioterrorist events. However, unlike many natural disasters, which often
have fairly localized effects, an influenza pandemic is likely to affect
many locations simultaneously. This widespread nature may preclude the
ability to shift human and material resources from unaffected areas to
locations in great need, a possibility that heightens the importance of
planning during the prepandemic period.

Vaccine Availability Vaccines are considered the first line of defense
against influenza to

May Be Limited in a prevent infection and control the spread of the disease.
The ability to

successfully use vaccines to prevent influenza- related illness and death
Pandemic

during the first wave of a pandemic, however, relies on certain conditions
that have not been realized in the past, and may not occur in the future.
Problems experienced in past influenza pandemics include the inability to
produce a sufficient quantity of vaccine before outbreaks occur in the
United States and variations in the extent to which the manufactured

vaccine is effective in preventing illness among various sectors of the
vaccinated population.

Problems Related to Annual influenza vaccine production is a complex process
involving

Vaccine Production vaccine manufacturers, health care experts, and federal
agencies, primarily

the FDA. The process, which involves growing the virus for vaccine in
fertilized chicken eggs, requires several steps, generally taking at least 6
to 8 months between about January and August each year, as shown in table 1.
Administering the vaccine to the population is estimated to take an
additional 1 to 2 months, or even longer if a second dose of vaccine is
required. After inoculation, it takes about 2 weeks for adults and up to 6
weeks for children to achieve optimal protection under a one- dose regimen,
with an additional 4 weeks if a booster shot is needed a month later.

Table 1: Annual Vaccine Production Process Production step Responsible
entity Time

Develop reference virus strain for FDA 4-10 weeks production Manufacture
test strains Vaccine manufacturers 2-4 weeks

Develop potency test reagents a FDA 10-12 weeks Manufacture and test vaccine
Vaccine manufacturers/ FDA 10-12 weeks

Total production time 6- -8 -- months b

a Reagents are substances that laboratories use to help identify or measure
other substances. b Numbers higher than total because some steps overlap.

Annual production capacity for vaccine is about 80 million doses per year,
which FDA officials and vaccine manufacturers agree can be expanded to
produce vaccine for the entire U. S. population under certain conditions. 3
However, these conditions were not realized during the pandemics of 1957 and
1968, when immunization efforts failed to have any perceptible effect
because too little vaccine was administered too late. HHS officials and
vaccine manufacturers agree that because of the complexity of the vaccine
production cycle, problems are also likely to occur in a future pandemic.
Several factors can hinder timely vaccine production, including (1) the
speed of production compared to the speed at which the virus infects a
population, and (2) how well the virus can be replicated for mass
production.

Problems Related to Speed of While the global influenza surveillance system
provides valuable

Vaccine Production Compared to information for deciding which viral strains
to include in the annual

Speed of Infection of Population influenza vaccine, limits on the speed with
which vaccines can be produced

may hinder pandemic response capability. Because people lack immunity to a
pandemic strain and such a virus may be more virulent, pandemic strains may
spread more quickly. Experts involved in monitoring the identification and
spread of influenza viruses estimate that a pandemic strain originating in a
foreign country could arrive in the United States sooner than vaccine could
be produced. FDA officials and vaccine manufacturers told us that production
of influenza vaccine cannot be shortened to less than the current 6 to 8
months given the existing technology and safety standards. However, as table
2 shows, past pandemics and new strains that might have heralded a pandemic
have generally spread to the United States in less time.

3 The time required to produce vaccines depends, in part, on the number of
viral strains in the vaccine, satisfactory growth and yield of the virus in
chicken eggs, the number of doses required to build immunity, and access to
raw materials. All other things being equal, vaccines that include a single
strain can be produced in less time and in greater quantities than vaccines
containing multiple strains because no additional time is needed to produce
and combine additional strains. For example, current production capacity is
about 80 million doses of a vaccine containing three viral strains; the same
capacity could produce about 240 million doses of a vaccine containing a
single virus in less time. Other factors that affect timing include testing
by FDA and manufacturers to determine vaccine potency and the development of
a standardized serum used for such testing.

Table 2: Months for Newly Detected Influenza Viruses to Reach the United
States Country where first

Months to reach Influenza virus and year detected United States

Pandemic year

Spanish flu, 1918 United States a 0 a Asian flu, 1957 Republic of China 4-5
Hong Kong flu, 1968 Hong Kong 2-3

Year new strains detected

Swine flu, 1976 United States 0 Russian flu, 1977 Russia 3-4 Chicken flu,
1997 Hong Kong Did not reach

United States a It is unknown whether the virus originated in the United
States, China, or Europe. Some researchers suggest that the virus began
circulating in midwestern U. S. military camps.

NIH is developing a library of reagents of all strains known to circulate
among animals that has the potential to shorten the time required to
identify a new virus. 4 More rapid identification could help reduce the time
needed to produce an effective vaccine should these strains appear in
humans. However, more rapid production would not ensure that sufficient
vaccine would be available before the first wave of influenza outbreak
occurs, especially if the pandemic originates in the United States. Even
assuming that the next pandemic originates outside of the United States,
experts estimate the warning time prior to reaching U. S. soil may range
from about 1 to 6 months. NIH 5 and others are sponsoring research to
develop new types of vaccines, but an all- purpose vaccine effective against
a broad spectrum of influenza strains that could be produced in advance of a
pandemic has not materialized.

4 Reagents in this context are materials such as antibodies and purified
proteins that are used by laboratories to measure vaccine potency and
identify new influenza viruses. 5 NIH support for influenza research related
to basic biology, immunology, epidemiology, vaccine and drug development,
and evaluation totaled over $10 million in fiscal year 1999.

The inflexibility of the vaccine production cycle also could contribute to
delays in the availability of an influenza vaccine. To help ensure that
vaccines are ready to be distributed in time for the flu season each fall,
annual influenza vaccine production in the United States routinely occurs
earlier in the year, from January through August. 6 Because no market exists
for vaccine after this period, manufacturers switch their capacity to other
uses between about mid- August and December. This annual vaccine production
cycle may not coincide with the timing needed to respond to an outbreak of a
new influenza strain. For example, in July 1997, public health officials at
CDC determined on the basis of surveillance data from Australia that a new
influenza strain was circulating and would be likely to cause widespread
illness in the United States during the upcoming flu season. But by July,
vaccine production was almost complete, and the new strain could not be
added. As a result, the vaccine for the 1997- 98 flu season in the United
States was, according to CDC reports, less effective in preventing influenza
illness than in previous years. As table 3 shows, other pandemic and newly
detected virus strains have also been identified after the annual vaccine
production cycle had begun.

Table 3: Time of Year Influenza Illness Appeared Strain and year Month
appeared Pandemic strain

Spanish flu, 1918 March a Asian flu, 1957 April Hong Kong flu, 1968 July

New strains with limited effect

Swine flu, 1976 February Russian flu, 1977 November Chicken flu, 1997 August
a Estimates range from spring to early summer.

Manufacturers say they are willing to maintain year- round production
capacity should the government wish to fund the necessary costs of
maintaining unused capacity during nonpandemic periods. To date, HHS

6 In addition, approximately 6 months before vaccine production begins
manufacturers must place their orders for new chicken flocks to support egg
production.

has not developed contingency plans for expanded capacity or analyzed
whether government funding to maintain ongoing manufacturer capacity is
feasible or desirable. Such an analysis would need to consider other
potential production problems that may further preclude vaccine
availability.

Problems Related to Mass One potential production problem is that influenza
strains differ in how

Production of Vaccine well they can be mass- produced for vaccine, which may
negatively affect

the quantity of vaccine that can be produced in a given year. To create a
vaccine, manufacturers first receive the reference strain of virus from FDA.
This reference, or “seed,” virus is generally made up of bits of
the selected influenza virus that have been combined with another influenza
virus that grows more quickly. Manufacturers then mass- produce this
“high- growthreassorted” virus in fertilized chicken eggs and
harvest it to make the vaccine. Problems have occurred when a particular
virus strain either cannot be grown in eggs or grows too slowly. For
example, the strain identified in Hong Kong in 1997 was an avian strain that
killed chick embryos, a factor that complicated U. S. production of a
vaccine. More recently, difficulties replicating and processing one strain
included in the vaccine for the 2000- 01 influenza season have contributed
to lower- thananticipated production yields and delays in distributing
vaccine supplies.

To address this problem, manufacturers and others are studying the
feasibility of switching from an egg- based to a tissue- based production
method, but the latter method has not been licensed by FDA and the overall
benefits are not clear. For example, while some avian strains of influenza
may grow more readily in tissue than in chicken eggs, others may not.
Alternative attempts to grow the 1997 Hong Kong virus in cell substrates
other than eggs were, in some cases, more successful than egg- based
methods, but difficulties still hindered mass vaccine production. Some
manufacturers told us that the cost of switching production methods may not
be worth the investment because tissue- based production may result in lower
yields of vaccine. For example, one manufacturer said that growing the virus
in tissue takes approximately 5 days, while growing the virus in eggs takes
11 days, saving less than 1 week in the total production cycle. New
technology based on a DNA vaccine may resolve these production problems,
while reducing production time. However, researchers estimate it will be at
least 5 to 10 years before this technology is available for vaccine
production.

Problems Related to Vaccinating the entire U. S. population does not
guarantee everyone will be

Vaccine Effectiveness protected from influenza- related illness and death.
Information regarding

the extent to which vaccines have been effective in preventing influenza is
limited, but available studies indicate vaccine effectiveness may vary
significantly from year to year based on both vaccine- related factors and
the demographics of the population receiving the vaccine. For example,
vaccine preparation, dosage, and the degree to which the vaccine matches the
virus circulating in the community all affect vaccine effectiveness.
Demographic factors that influence how well each person's immune system
responds to the vaccine generally include the person's age and extent of
underlying chronic illness or disease.

Although up to about 80 million doses of vaccine are administered each year,
no regular program exists to determine how effectively the vaccine performs.
While HHS officials told us they see some effect from vaccination coverage,
other experts point to national data trends that have not shown a clear
correlation between changes in influenza- related illness and death relative
to changes in the proportion of the population vaccinated. 7 Using data sets
from managed care organizations, CDC intends to continue retrospective
studies of vaccine effectiveness to better determine how well vaccine
prevents influenza or mitigates its severity in various populations.

In the meantime, information on vaccine effectiveness is generally limited
to small studies of primarily vaccinated populations. These studies have
shown that when the vaccine generates a good antibody response to the
circulating virus, influenza vaccine may prevent illness in approximately 70
to 90 percent of healthy persons under 65 years of age. However, vaccine
effectiveness drops sharply for the elderly and people with chronic illness,
who are considered most vulnerable to influenza- related illness and death.
8 For example, studies have shown influenza vaccine may be about 30 to 70
percent effective in reducing hospitalization among the noninstitutionalized
elderly population. Overall effectiveness in preventing influenza among the
elderly has been even lower, often ranging from 30 to

7 One difficulty in comparing effectiveness across years is the growing
number of persons who are at high risk for serious complications. As more
people age and more survive with immune- compromising diseases, this high-
risk group will continue to grow.

8 According to CDC, about 90 percent of influenza- related deaths occur
among people aged 65 and older, with most other deaths occurring in people
suffering from underlying disease.

40 percent. Approaches to improve the effectiveness of the influenza
vaccines include conducting research to develop alternative methods of
administering existing vaccines and new vaccines such as weakened live virus
vaccine or DNA vaccines that, in theory, may produce broader and longer-
lasting protective immune responses.

Antiviral Drugs and Antiviral drugs and vaccine against pneumonia are two
additional

Pneumococcal Vaccine measures that can help prevent or mitigate influenza-
related illness and

death until an influenza vaccine becomes available. However, both are May Be
in Limited

expected to be in short supply during a pandemic, and increasing Supply
During a

production capacity for antiviral drugs and vaccine in response to Pandemic

increased demand could take at least 6 to 9 months. Creating a stockpile of
antiviral drugs is an option to mitigate shortages during a pandemic.
However, HHS officials told us that additional analysis is needed to
determine the feasibility and desirability of such an effort. One option to
minimize shortages of pneumococcal vaccine during a pandemic is to immunize
the population now against possible future infection. However, immunization
rates for elderly and high- risk groups remain below established targets,
and immunization recommendations have not been expanded to include healthy
children and young adults because they are at low risk for pneumococcal
pneumonia during nonpandemic periods.

Problems Related to Antiviral drugs can be used against all strains of
pandemic influenza and

Availability of Antiviral have immediate availability both as a prophylactic
to prevent illness and as

Drugs a treatment if administered within 48 hours of the onset of symptoms.

Studies of these drugs have shown them to be as effective as vaccines in
preventing influenza infection in healthy young adults if taken under the
prescribed regimen, 9 and, when used for treatment, to shorten the duration
and severity of infection. 10

Twelve manufacturers produce antiviral drugs approved by FDA for use against
influenza in the United States. These drugs vary in both their costs and
their benefits, as shown in table 4. For example, the older and less
expensive drugs amantadine and rimantadine have been approved for
prophylaxis of all age groups against the influenza virus strains most
likely to cause a pandemic. However, their side effects, particularly those
of amantadine, include central nervous system disturbances, such as delirium
or behavioral changes, that may preclude their use in certain populations.
11 The newer and more expensive drugs, zanamivir and oseltamivir, have a
lower incidence of side effects and are effective against a broader range of
virus strains. However, as of August 2000 they had FDA approval only for
treatment, not prevention. In addition, they have not been approved for use
in younger age groups, and zanamivir is not recommended for certain other
segments of the population. 12 None of the antiviral drugs have been studied
extensively for long- term use or in large populations.

9 As with vaccine, in studies of healthy young adults antiviral drugs were
generally 70 to 90 percent effective in preventing influenza. For the two
antiviral drugs approved for preventing influenza, the standard adult dosage
is 200 milligrams (mg) per day, taken as two 100- mg tablets or 4
teaspoonfuls of syrup until approximately 1 week after the end of the
outbreak.

10 CDC evaluations have shown antiviral drugs shorten the duration of
influenza by about 1 day, with some reduction of severity and prevention of
secondary infections. 11 These more severe side effects have been associated
with high plasma drug concentrations and observed most often among persons
who have renal insufficiency, seizure disorders, or certain psychiatric
disorders and among elderly persons taking amantadine as prophylaxis at a
dose of 200 mg/ day.

12 Special caution is advised in using zanamivir in patients with underlying
asthma or chronic obstructive pulmonary disease because FDA has received
several reports of deterioration of respiratory function following its use.

Table 4: Antiviral Drugs Approved for Influenza by FDA Year

Influenza virus strains Approved

Number of Cost per Antiviral drug approved Approved use affected by drug
population manufacturers daily dose a

Amantadine 1976 Prophylaxis and All A strains Adults and children 9 $0.10 b
treatment Rimantadine 1993 Prophylaxis and

All A strains Adults and 1 $1. 07 d treatment children c Zanamivir 1999
Treatment only All A and B strains 7 years and older 1 $5. 38

Oseltamivir 1999 Treatment only All A and B strains 18 years and older 1
$6.49 a Cost to federal government based on lowest prices in the federal
supply schedule.

b Cost varies from $0.10 to $0.27 for generic tablets and $1.06 to $1.10 for
brand name tablets. Cost varies from $0.52 to $1.46 for generic syrups and
is $2.26 for brand name syrup. c Rimantadine is approved only for
prophylaxis in children; however, CDC reports that many experts

also consider rimantadine appropriate for treatment in children. d Cost is
for rimantadine tablets. Cost for rimantadine syrup is $1.37.

CDC historically has supported use of antiviral drugs during nonpandemic
periods as an adjunct to vaccine to prevent influenza among high- risk
populations in certain circumstances. Antiviral drugs may be used (1) when
influenza vaccine is unavailable, (2) during the 2 to 6 weeks after
inoculation until the vaccine becomes effective, and (3) for people who
cannot tolerate the vaccine because of allergies or other factors. However,
CDC cautions against the use of antiviral drugs in the face of the vaccine
shortages expected for the 2000- 01 influenza season. CDC states that even
if a vaccine shortage develops, it does not support routine and widespread
use of antiviral drugs to prevent influenza, because it is an untested and
expensive strategy that could result in large numbers of persons
experiencing adverse effects.

While shortages of antiviral drugs have not been a problem in the past, HHS
officials expect the amount produced will be well below demand during a
pandemic. This assumption, supported by drug manufacturers, is based on the
fact that current production levels of antiviral drugs are set in response
to current demand, whereas demand in a pandemic is expected to increase
significantly if vaccines are unavailable as a means to prevent the disease.
Manufacturers told us that expanding supply to meet increased demand is
possible to some extent but that the lead time required to produce at least
one type of antiviral drug can be at least 6 to 9 months. Manufacturers say
that knowing how much drug CDC expects them to produce for a pandemic would
assist them in determining whether their existing surge capacity is
sufficient, and the extent to which they would need to develop contingency

plans to expand capacity even further. Both FDA and CDC started collecting
data on the production capacity of antiviral drug manufacturers in May and
June 2000, but data collection efforts remain incomplete. HHS has not
developed contingency plans with manufacturers to expand production capacity
or analyzed whether government funding to maintain ongoing manufacturer
capacity is feasible or desirable. In the absence of federal decisions about
drug availability and use, state officials are uncertain whether or to what
extent they should include strategies that rely on antiviral drugs to
prevent or treat infection until vaccine becomes available. 13 HHS officials
plan to convene an expert panel to determine how antiviral drugs should be
used in the event of a pandemic or in the face of vaccine shortages.

Creating a stockpile is another option to ensure availability of antiviral
drugs for a pandemic. HHS has not formally evaluated whether creating a
stockpile to preclude shortages is warranted and feasible. 14 CDC officials
have noted several factors that must be addressed in deciding to create a
stockpile. For example, officials need to determine whether to build or rent
storage facilities and where to locate them, develop a distribution system,
assess the feasibility of rotating stock given the shelf- life of the drug
and current market capacity, and determine how to finance the stockpile. The
recent creation of the National Pharmaceutical Stockpile to help prepare for
a bioterrorist attack has provided experience in these areas. This program,
administered by CDC and financed by a federal appropriation of $51 million
in fiscal year 1999 and $52 million in fiscal year 2000, 15 maintains a
medical stockpile considered to be adequate to respond to a bioterrorist
attack but lacks all the pharmaceuticals, supplies, and equipment that may
be necessary to respond to an influenza pandemic. Under this program, the
Department of Veterans Affairs, as CDC's agent, purchases drugs, supplies,
and equipment, which are stored as active

13 The six state pandemic plans we reviewed do not rely on using antiviral
drugs, in part because supplies are expected to be very limited. 14 In
deciding whether stockpiling antiviral drugs is feasible, officials managing
the National Pharmaceutical Stockpile state that someone must look at the
outcome or value- benefit of the costs involved, which would include the
projected lives saved as well as overall decrease in illness and economic
damage. For example, the overall costs of a prevention program for influenza
may be matched against CDC estimates that, if no action is taken in a
moderately severe pandemic, up to 207, 000 people could die, 90 million
could become ill, and economic damages could total $167 billion.

15 The HHS budget proposal for fiscal year 2001 includes $54 million to
continue development of the National Pharmaceutical Stockpile.

inventory in vendor warehouses. In developing the National Pharmaceutical
Stockpile, CDC relied in part on our recent review of two other federally
maintained stockpiles to assess management oversight of items in the
stockpile. 16

Use and Availability of Inoculation with pneumococcal vaccine, which helps
protect against

Pneumococcal Vaccine pneumococcal pneumonia, a type of pneumonia that
frequently follows

influenza infection, may help reduce a substantial number of
influenzarelated deaths. 17 Depending on the severity with which the disease
attacks different population groups, available vaccine supplies might be
needed to help protect groups other than those typically considered at risk,
such as young adults. Although national mortality statistics have directly
attributed about 1, 000 deaths per year to influenza during the last decade,
CDC attributes at least 20,000 more deaths per year to secondary infections
of influenza, such as pneumonia. 18 As shown in table 5, the numbers of
deaths over and above these annual estimates of influenza- related deaths-
called excess deaths 19 -have generally been even higher during pandemics,
especially during the pandemic of 1918, when antibiotics and advanced
medical care to treat secondary infections were unavailable.

16 Combating Terrorism: Chemical and Biological Medical Supplies Are Poorly
Managed (HEHS/ AIMD- 00- 36, Oct. 29, 1999). 17 Pneumococcal vaccine
provides protection against pneumococcal pneumonia, especially when other
pneumococcal infections such as bacterial meningitis and infection of the
bloodstream are present.

18 Influenza by itself is not generally regarded as a fatal disease, but as
a debilitating infection that prepares the way for a secondary invader.
Historically, the most frequent complication has been pneumonia. Over the
years an increasing proportion of excess deaths have been attributed to
other causes, primarily chronic obstructive pulmonary disease.

19 The hallmark of pandemic influenza has been excess mortality, defined in
1847 by William Farr in London, England, as the number of deaths observed
during an epidemic of influenzalike illness in excess of the number
expected.

Table 5: Excess Influenza- Related Deaths Estimated for Pandemic and
Nonpandemic Periods in the United States, 1918- 91

Crude death rate Annual average of

per 100, 000 Period Years excess deaths

persons

Pandemic 1918- 20 225, 000 218. 4 Nonpandemic 1920- 33 28, 338 23. 0
Nonpandemic 1933- 57 10, 108 7.5 Pandemic 1957- 60 38, 567 22. 0 Nonpandemic
1960- 68 14, 363 7.5 Pandemic 1968- 72 27, 982 13. 9 Nonpandemic 1972- 81
22, 089 10. 3 Nonpandemic a 1981- 91 20, 000 10. 0 a Estimated.

Source: W. Paul Glezen, “Emerging Infections: Pandemic
Influenza,” Epidemiologic Reviews, Vol. 18, No. 1 (1996), pp. 64- 76.

CDC officials generally attribute about one- third of the excess deaths each
year to influenza- related pneumonia, and most of these deaths are
attributed to a type of bacterial pneumonia that may be prevented with the
pneumococcal vaccine. The exact number of deaths caused by pneumococcal
pneumonia is unknown, 20 but HHS reports that at least in some epidemics,
the disease has been responsible for up to half of influenza- related
deaths. Because pneumococcal vaccine provides immunity for at least 5 to 10
years, it can provide benefit during nonpandemic as well as pandemic years.
CDC reports that during nonpandemic periods, the populations most at risk
for hospitalization and death due to pneumococcal disease include
approximately 35 million persons aged 65 or older and approximately 33 to 39
million persons of all ages with chronic illness. Therefore, CDC recommends
that pneumococcal vaccine be administered to persons in these groups.

20 The precise incidence of pneumococcal pneumonia is difficult to determine
because routine diagnostic tests are insufficiently specific and sensitive.
Nonetheless, CDC estimates that up to 175, 000 hospitalizations for
pneumococcal pneumonia occur in the United States each year and up to 12,500
deaths, accounting for more deaths than any other vaccinepreventable
bacterial disease. Approximately half of these deaths potentially could be
prevented through use of vaccine, according to CDC.

CDC officials expect shortages of pneumococcal vaccine during a pandemic
because only about 7 to 9 million doses are currently produced each year, 21
the vaccine production process takes about 8 to 9 months, and current
overall immunization rates remain below target. CDC officials say that
manufacturers produce vaccine according to the current demand for the
product. Therefore, increasing the extent that the population is currently
immunized would help preclude shortages of vaccine during a pandemic, not
only by increasing production capacity, but also by reducing the number of
people that remain to be immunized.

In 1995 we reviewed the efforts of HHS to improve pneumococcal vaccination
rates for adults aged 65 and older. 22 As part of its response, CDC and
other HHS agencies developed the Adult Immunization Action Plan, which
focused efforts on raising awareness of the importance of the vaccine among
clinicians, public health professionals, and the public. Specific steps
include encouraging (1) health care provider organizations to revise current
immunization policies and include directives clinicians can use in their
practices to increase immunization, particularly among high- risk groups,
and (2) accrediting organizations to urge requiring hospitals and other care
facilities to adopt directives aimed at immunizing high- risk individuals.
In addition, CDC has developed and disseminated brochures and other
educational material for the public and health care providers that stress
the health benefits of vaccination.

Since CDC initiated these actions, immunization rates have increased,
particularly for adults aged 65 and older. As of 1997, 43 percent of people
aged 65 and older and 11 percent of younger at- risk populations have been
immunized with pneumococcal vaccine. Preliminary data from 1999 indicate
that the rate for those aged 65 and older has increased further to 54
percent. Despite this progress, rates remain below the HHS year 2000 goal of
60 percent for each of these noninstitutionalized populations. Moreover, the
year 2010 goal for people aged 65 and older increases to 90 percent, well
above the current goal. CDC officials cite the continued lack of awareness
about the availability and importance of pneumococcal vaccine

21 There are two manufacturers of the pneumococcal vaccine for the United
States, and CDC officials state that the vaccine has a shelf- life of 2
years. 22 Immunization: HHS Could Do More to Increase Vaccination Among
Older Adults (GAO/ PEMD- 95- 14, June 8, 1995).

as the primary barrier to increasing immunization rates. 23 Officials from
all but one of the 11 states we contacted planned to expand existing
programs to increase nonpandemic use of pneumococcal vaccines by such means
as raising awareness among physicians and public health officials and
educating the public.

Shortages of pneumococcal vaccine could also be exacerbated by the fact that
there may be a high need for it among people under age 65 as well as for the
older population. For example, in the 1918 pandemic the influenzarelated
death rate for young adults was more than 3 times that for people over age
65, just the opposite of the situation in nonpandemic years, when the
influenza- related death rates for those over age 65 were 8 to 15 times
greater than those for younger people. Of the estimated 550, 000 excess
deaths for all age groups in the years 1918 and 1919, over 280,000 pneumonia
deaths were reported in young adults, aged 20 to 39 years. Since 1980, those
under 65 have generally accounted for less than 10 percent of the influenza-
related excess deaths. However, CDC officials have estimated that in a
future pandemic up to 50 percent of deaths may fall within the age group of
0 to 64 years. CDC has not estimated the number of deaths that may be
prevented with pneumococcal vaccine. According to CDC officials, current
recommendations for pneumococcal vaccine are unlikely to be expanded to
include healthy young adults because pandemic scenarios are not considered
when setting immunization policy.

Plans Incomplete to Federal and state pandemic response plans are in various
stages of

Purchase, Distribute, completion and do not completely or consistently
address the problems

related to the purchase, distribution, and administration of supplies of and
Administer

vaccines and antiviral drugs during a pandemic. HHS has provided interim
Vaccines and Drugs

draft guidance to facilitate state plans, but final federal decisions
necessary to mitigate the effects of potential shortages have not been made.
24 Until such decisions are made, the timeliness and adequacy of response
efforts may be compromised.

23 A recent report by the Institute of Medicine notes that without a renewal
and strengthening of the state and federal immunization financial and policy
partnership, gains in immunization rates can be expected to decline
(Institute of Medicine, Calling the Shots: Immunization Finance, Policy, and
Practices( Washington, D. C.: National Academy Press,

June 2000)). 24 CDC's draft interim guidance notes that it has not been
officially approved or endorsed but is intended to guide state planning
efforts until national planning efforts are completed.

Status of Federal and State The federal government developed the first
national pandemic plan in 1978,

Pandemic Response Plans after the threat of a pandemic swine flu in 1976
clearly demonstrated the

need for advance planning to support a mass immunization and response effort
within the United States. Lessons learned from that experience, which was
the government's first attempt at immunization of the entire U. S.
population, included the need for the federal government to reach agreements
with private and public sector entities responsible for the timely purchase,
distribution, and administration of vaccines and drugs. 25 More recent
experience with vaccine shortages also demonstrated the need for federal
guidance in distributing limited quantities of vaccines and drugs to
priority groups within the population. In 1993 the federal government
convened a panel of experts from the public and private sectors to review
and revise the pandemic response plan. As of October 2000, HHS officials
directing the planning effort had not set a date to complete and distribute
a revised national plan.

To foster state and local pandemic planning and preparedness, CDC first
issued interim planning guidance in draft form to all states in 1997,
outlining general federal and state planning responsibilities. As of
September 2000, 28 states were actively preparing a pandemic plan, 10 states
characterized their planning efforts as in the conceptual stage, and 1 state
did not comment on the stage of planning efforts, according to a recent
survey by the Council of State and Territorial Epidemiologists. 26 The
remaining 11 responding officials said their states were not engaged in
pandemic planning. Beginning in 1999, HHS funded 9 states with up to $13,000
each to develop plans. 27 An additional 19 states were developing plans
using other federal and state resources. 28

25 A summary of the response effort to address the 1976 swine flu and
associated problems is discussed in The Swine Flu Program: An Unprecedented
Venture in Preventive Medicine (GAO/ HRD- 77- 115, June 27, 1977).

26 In May 2000, the Council of State and Territorial Epidemiologists
surveyed all 50 states and the District of Columbia about their planning
efforts. By September 2000, they had received 50 responses. For purposes of
this report, the District of Columbia is referred to as a state.

27 Four states- California, Maryland, Minnesota, and South Carolina-
produced draft plans in April 2000, with the remaining five- Florida,
Indiana, Massachusetts, New Hampshire, and New Jersey- to complete plans in
April 2001.

28 CDC has also provided more general assistance in terms of funding and
technical assistance to enhance public health epidemiologic, laboratory, and
communications capacity more generally.

Officials from 32 states said that influenza plans will be integrated with
existing state plans to respond to natural or man- made disasters, such as
flood or bioterrorist attack. Although to a certain extent planning efforts
for other emergencies can be used for pandemic response, additional planning
is important to deal with the specific aspects of pandemic response. This
includes developing plans to address the wide- scale emergency needs of an
entire population, including mass distribution and administration of limited
vaccines and drugs with an uncertain amount of available resources. State
officials say that CDC's financial and technical assistance has greatly
helped in these planning efforts.

Federal Government In the most recent version of its planning guidance for
states, CDC lists

Planning Responsibilities several key federal decisions related to vaccines
and antiviral drugs that

have not been made. These decisions include determining the amount of
vaccines and drugs that will be purchased at the federal level; the division
of responsibility between the public and private sectors for the purchase,
distribution, and administration of vaccines and drugs; and how population
groups will be prioritized and targeted to receive limited supplies of
vaccines and drugs. In each of these areas, until federal decisions are
made, states will not be able to develop strategies consistent with federal
action.

Incomplete Plans for Purchase, HHS has indicated in its interim planning
guidance that how vaccines and

Distribution, and Administration drugs will be purchased, distributed, and
administered by the private and

of Vaccines and Antiviral Drugs public sectors will change during a
pandemic, but some decisions

necessary to prepare for these expected changes have not been made. During a
typical annual influenza response, influenza and pneumococcal vaccines are
purchased through a combination of public and private sector funds. Vaccine
and antiviral drug distribution is primarily handled directly by
manufacturers through private vendors and pharmacies. About 90 percent of
vaccines and antiviral drugs are administered or prescribed to the
population on a first- come, first- served basis by private physicians,
nurses, and other health care providers, with most states and counties
participating to a relatively small extent through publicly funded programs.

During a pandemic, however, HHS draft interim guidance indicates that many
of these private sector responsibilities may be transferred to the public
sector at the federal, state, or local level, and priority groups within the
population should be established for receiving limited supplies of vaccines
and drugs. For example, the draft interim guidance for state pandemic plans
says that resources can be expected to be available from the national level
for federal contracts to purchase influenza vaccine and at

least some antiviral agents, but some state funding may be required. In
addition, federal grants or reimbursement for public sector vaccine
distribution and administration may be provided to states, but the draft
interim guidance contains no recommendations on how the level and nature of
such resources might differ in response to the severity of the pandemic.

Professional organizations representing vaccine manufacturers and
pharmacists have questioned the necessity of moving responsibility for
distribution and administration to the public sector during a pandemic.
According to these organizations, existing private systems are in place and
can operate more smoothly in response to federal direction than an as-
yetto- be- defined public sector system. At least one professional
organization has contacted CDC requesting to assist the federal government
in expanding capacity for private sector vaccine administration. HHS has not
determined the extent to which federal funding will be made available or
developed more guidance for states to use in planning how to use public and
private sector resources to distribute and administer vaccines and antiviral
drugs. In the absence of decisions regarding the extent of federal
responsibility and investment in pandemic response, however, state officials
are uncertain of how much state funding will be required and what level of
state response can be supported. Two say that without more detail and
commitment on federal assistance they plan to respond to the pandemic using
state resources alone.

Incomplete Plans for Prioritizing State officials are particularly concerned
that a national plan has not

Population Groups for Limited finalized recommendations for how population
groups should be

Distribution of Vaccines and prioritized to receive vaccines and antiviral
drugs. In its most recent (1999)

Drugs interim draft guidance sent to states, HHS lists eight different
population

groups that should be considered in establishing priorities among groups for
receiving vaccines and drugs during a pandemic. The list includes such
groups as health care workers and public health personnel involved in the
pandemic response, persons traditionally considered to be at increased risk
of severe influenza illness and mortality, and preschool and schoolaged
children.

The interim guidance states that recommendations on the relative priority of
each group are still under study and will be based on a number of factors,
including the need to maintain community pandemic response capability. Other
factors include limiting mortality among high- risk groups, reducing
mortality in the general population, and minimizing social disruption and
economic losses. HHS officials say they are still committed

to publishing recommendations on the relative priority for each population
group. However, the recommendations need to be flexible to recognize the
different situations that could emerge. For example, officials point out
that the severity with which the pandemic attacks specific population groups
would have to be taken into consideration in setting priorities.

State officials acknowledge the need for flexibility in planning because
many aspects of a pandemic cannot be known in advance. However, these
officials say that the absence of more detail regarding how and when federal
recommendations will be made leaves them uncertain about how to plan for the
use of limited supplies of vaccine and drugs. For example, knowing federal
government recommendations under different conditions allows states to
better estimate the extent to which priority groups can be vaccinated, to
develop strategies to target those groups, and to determine the number of
additional personnel and locations that will be needed for vaccine and drug
administration.

Another concern, particularly for state officials, is that without federal
decisions to establish priorities for which population groups should receive
the limited quantities of vaccines and drugs, inconsistencies could arise
both among states and between states and the federal government. Several
state officials say such policy differences among states and between states
and the federal government in the use and distribution of vaccines and
antiviral drugs may contribute to public confusion and social disruption, as
shown by recent experience. Specifically, in 1998, after 3 of 11 children
who developed meningitis died, one state initiated a mass vaccination
program for people between the ages of 2 and 22 using a strategy of shared
public and private sector responsibility for administering the vaccine. 29
Surrounding states that did not have an increase in reported cases did not
initiate similar programs or recommend vaccination for everyone in this age
group. The differences in state recommendations caused some residents of
bordering states to seek immunization for their children by crossing state
lines. The intense media attention and demand for vaccinations, coupled with
a perceived shortage of meningococcal vaccine, created substantial confusion
in some communities as fearful parents

29 The federal Advisory Committee on Immunization Practices recommends
routine use of meningococcal vaccine only for certain high- risk individuals
in this age group, not the general population.

overwhelmed private providers with phone calls and office visits, according
to officials responsible for the vaccination program. 30

Conclusions While experts consider an influenza pandemic to be inevitable,
no one knows when it will occur or how severe it will be. What is known is
that

traditional response strategies for obtaining, using, and distributing
vaccines and drugs during annual influenza epidemics may be insufficient or
inappropriate to control or minimize the effect of pandemic disease,
particularly in its early stages, on the population and the economy.
Although not much can be known about a pandemic viral strain until it
appears, planning a response that relies on vaccines and drugs depends, at
least in part, on knowing the amounts that can be produced and developing
strategies for reaching various populations that might be at risk. Because
influenza vaccine must be tailored specifically to the pandemic strain that
appears, an effective response plan also depends, in part, on the ability to
rapidly identify the strains that are newly infecting people and to produce
influenza vaccine using alternative methods in the event existing ones
cannot be used. Moreover, acting now to increase the extent to which
vulnerable populations, particularly those aged 65 and older, receive
pneumococcal vaccine can help protect them from the complications of
influenza in the event of a pandemic. Despite recent gains in the use of
vaccines, the rate of pneumococcal immunization among high- risk groups
remains below established goals, indicating the need for HHS to maintain its
efforts to raise awareness about the importance of this vaccine.

Stronger federal leadership is needed to analyze alternative strategies to
increase the availability and relative effect of vaccines and drugs among
various populations. Because new strategies may replace familiar response
patterns to address the unique aspects of a pandemic, advance planning is
particularly important to obtain agreement on how the traditional roles and
responsibilities of the public and private sector response effort are likely
to change. Federal leadership, including development of a national plan that
integrates strategies for the use of vaccines and antiviral drugs, is needed
to address national issues as well as help harmonize the various public and
private sector plans.

30 To relieve the pressure on private providers, allow them to care for ill
patients, and restore order, this state health department assumed full
responsibility for vaccinations and began an aggressive public
communications effort to alleviate public concern. Within 4 weeks,
communities had vaccinated over 90 percent of the targeted population.

Recommendations for To improve the nation's ability to respond to the
emergence of a pandemic

Executive Action influenza virus and help ensure an adequate and appropriate
level of public

protection, we recommend that the Secretary of Health and Human Services
take the following actions. First, we recommend that the Secretary take
steps to fill the knowledge gaps in the capability of the private and public
sectors to produce, distribute, and administer vaccines and antiviral drugs
to various population groups to control the spread and effect of a pandemic.
Specifically, we recommend that HHS

explore and evaluate alternative methods to produce and distribute influenza
vaccine and strategies to help quickly identify newly detected strains of
the influenza virus, identify the capability of all manufacturers to produce
antiviral drugs

and pneumococcal vaccines and their existing “surge capacity” to
expand production as needed during a pandemic, and if existing surge
capacity is insufficient, work with manufacturers to

determine the investment and time required to expand production capacity, or
the feasibility of creating a stockpile against projected shortages.

Second, we recommend that the Secretary establish a deadline for completing
and publishing a federal response plan that will address

how priorities for receiving limited influenza and pneumococcal vaccines and
antiviral drugs during a pandemic will be established among population
groups, and how private and public sector responsibilities might change
during a

pandemic for the purchase, use, and distribution of influenza and
pneumococcal vaccines and antiviral drugs.

Agency Comments In commenting on our draft report, HHS agreed that the
issues surrounding the production, purchase, and distribution of vaccines
and antiviral drugs

merit continued high priority. It discussed several initiatives under way or
planned. HHS generally concurred with our recommendations. It also discussed
several concerns.

HHS concurred with our recommendation to improve estimates of manufacturers'
vaccine and antiviral production capacity and to develop strategies to
ensure adequate production levels in the event of a pandemic. However, HHS
commented that it believed the draft report inappropriately

emphasized the development and use of antiviral drugs and pneumococcal
vaccine over the use of pandemic influenza vaccine. HHS also stated that the
wording of our recommendation in the draft report to fill knowledge gaps
about vaccines and drugs placed undue and potentially misleading emphasis on
the role of antiviral drugs and pneumococcal vaccines in pandemic influenza
preparedness. We agree with HHS that influenza vaccine is the first line of
defense against an influenza virus, but to the extent that it is in short
supply, antiviral drugs and, to a lesser extent, pneumococcal vaccine become
important interventions. Our recommendation was intended to include steps to
enhance all three interventions, including the availability of influenza
vaccine. We have expanded the recommendation to include resolving knowledge
gaps surrounding influenza vaccine production and distribution.

In a related comment, HHS stated that the draft did not convey the
appropriate use of pneumococcal vaccine. HHS said that the availability of
the vaccine will not be a major factor of the federal response plan for
pandemic influenza. Rather, it stated that efforts should be directed toward
increasing pneumococcal vaccination rates among high- risk groups before the
health care delivery system is overwhelmed by a pandemic crisis. We agree
that HHS' strategy has merit and gave it greater prominence in the final
report.

In its general comments HHS stated that the draft report did not address the
full range of activities it considers essential to ensure prepandemic
preparedness and an adequate pandemic response capability. HHS cited as
examples three important aspects of pandemic preparedness that were not
addressed in the report: (1) a robust disease surveillance system, (2) the
presence of community emergency preparedness protocols, and (3) good public
health practices to minimize and control the spread of disease. We recognize
that these factors are important aspects of pandemic preparedness and
response capability. However, our work focused on the production and
distribution of vaccines and drugs, which are also widely regarded as direct
and critical interventions needed to help protect the population from an
influenza pandemic.

HHS concurred with our recommendation to establish a deadline to complete
and publish a federal response plan for pandemic influenza and stated that
it will keep the Congress informed of the proposed timetable and progress
toward the milestones established. HHS also agreed that the plan needs to
include key decisions such as those related to the private and public sector
responsibilities for vaccine purchase and delivery. HHS said

that it is working to create a flexible plan that will accommodate a wide
variety of contingencies.

HHS' comments are reprinted in appendix I. It also provided technical
comments, which we incorporated in the report as appropriate.

As agreed with your offices, unless you publicly release its contents
earlier, we will make no further distribution of this report until 30 days
after its issue date. At that time, we will send copies of this report to
the Honorable Donna E. Shalala, Secretary of Health and Human Services; the
Honorable Jeffrey Koplan, Director, Centers for Disease Control and
Prevention; and other interested parties. We also will make copies available
to others on request.

This report was prepared by Frank Pasquier, Lacinda Baumgartner, Evan Stoll,
and Cheryl Williams. If you or your staffs have any questions, please
contact me at (202) 512- 7119.

Janet Heinrich Director, Health Care- Public Health Issues

Appendi xes Comments From the Department of Health

Appendi xI and Human Services

(201048) Lett er

Ordering Information The first copy of each GAO report is free. Additional
copies of reports are $2 each. A check or money order should be made out to

the Superintendent of Documents. VISA and MasterCard credit cards are
accepted, also.

Orders for 100 or more copies to be mailed to a single address are
discounted 25 percent.

Orders by mail: U. S. General Accounting Office P. O. Box 37050 Washington,
DC 20013

Orders by visiting: Room 1100 700 4th St. NW (corner of 4th and G Sts. NW)
U. S. General Accounting Office Washington, DC

Orders by phone: (202) 512- 6000 fax: (202) 512- 6061 TDD (202) 512- 2537

Each day, GAO issues a list of newly available reports and testimony. To
receive facsimile copies of the daily list or any list from the past 30
days, please call (202) 512- 6000 using a touchtone phone. A recorded menu
will provide information on how to obtain these lists.

Orders by Internet: For information on how to access GAO reports on the
Internet, send an e- mail message with “info” in the body to:
info@ www. gao. gov or visit GAO's World Wide Web home page at: http:// www.
gao. gov

To Report Fraud,

Contact one:

Waste, or Abuse in

Web site: http:// www. gao. gov/ fraudnet/ fraudnet. htm

Federal Programs

e- mail: fraudnet@ gao. gov 1- 800- 424- 5454 (automated answering system)

GAO United States General Accounting Office

Page 1 GAO- 01- 4 Influenza Pandemic

Contents

Page 2 GAO- 01- 4 Influenza Pandemic

Page 3 GAO- 01- 4 Influenza Pandemic United States General Accounting Office

Washington, D. C. 20548 Page 3 GAO- 01- 4 Influenza Pandemic

Page 4 GAO- 01- 4 Influenza Pandemic

Page 5 GAO- 01- 4 Influenza Pandemic

Page 6 GAO- 01- 4 Influenza Pandemic

Page 7 GAO- 01- 4 Influenza Pandemic

Page 8 GAO- 01- 4 Influenza Pandemic

Page 9 GAO- 01- 4 Influenza Pandemic

Page 10 GAO- 01- 4 Influenza Pandemic

Page 11 GAO- 01- 4 Influenza Pandemic

Page 12 GAO- 01- 4 Influenza Pandemic

Page 13 GAO- 01- 4 Influenza Pandemic

Page 14 GAO- 01- 4 Influenza Pandemic

Page 15 GAO- 01- 4 Influenza Pandemic

Page 16 GAO- 01- 4 Influenza Pandemic

Page 17 GAO- 01- 4 Influenza Pandemic

Page 18 GAO- 01- 4 Influenza Pandemic

Page 19 GAO- 01- 4 Influenza Pandemic

Page 20 GAO- 01- 4 Influenza Pandemic

Page 21 GAO- 01- 4 Influenza Pandemic

Page 22 GAO- 01- 4 Influenza Pandemic

Page 23 GAO- 01- 4 Influenza Pandemic

Page 24 GAO- 01- 4 Influenza Pandemic

Page 25 GAO- 01- 4 Influenza Pandemic

Page 26 GAO- 01- 4 Influenza Pandemic

Page 27 GAO- 01- 4 Influenza Pandemic

Page 28 GAO- 01- 4 Influenza Pandemic

Page 29 GAO- 01- 4 Influenza Pandemic

Page 30 GAO- 01- 4 Influenza Pandemic

Appendix I

Appendix I Comments From the Department of Health and Human Services

Page 31 GAO- 01- 4 Influenza Pandemic

Appendix I Comments From the Department of Health and Human Services

Page 32 GAO- 01- 4 Influenza Pandemic

Appendix I Comments From the Department of Health and Human Services

Page 33 GAO- 01- 4 Influenza Pandemic

Appendix I Comments From the Department of Health and Human Services

Page 34 GAO- 01- 4 Influenza Pandemic

Appendix I Comments From the Department of Health and Human Services

Page 35 GAO- 01- 4 Influenza Pandemic

United States General Accounting Office Washington, D. C. 20548- 0001

Official Business Penalty for Private Use $300

Address Correction Requested Bulk Rate

Postage & Fees Paid GAO Permit No. GI00
*** End of document. ***