GAO

United States General Accounting Office

Report to Congressional Requesters

October 2000 INFLUENZA

PANDEMIC

Plan Needed for

Federal and State

Response

GAO-01-4

Page 1 GAO-01-4 Influenza Pandemic

Contents

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
Page 2 GAO-01-4 Influenza Pandemic
Page 3 GAO-01-4 Influenza Pandemic

United States General Accounting Office

Washington, D.C. 20548 Letr

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
Page 4 GAO-01-4 Influenza Pandemic

(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
Page 5 GAO-01-4 Influenza Pandemic

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
Page 6 GAO-01-4 Influenza Pandemic

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.
Page 7 GAO-01-4 Influenza Pandemic

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

May Be Limited in a

Pandemic

Vaccines are considered the first line of defense against influenza to

prevent infection and control the spread of the disease. The ability to

successfully use vaccines to prevent influenza-related illness and death

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
Page 8 GAO-01-4 Influenza Pandemic

vaccine is effective in preventing illness among various sectors of the

vaccinated population.

Problems Related to

Vaccine Production

Annual influenza vaccine production is a complex process involving

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

a

Reagents are substances that laboratories use to help identify or measure other substances.

b

Numbers higher than total because some steps overlap.

Production step Responsible entity Time

Develop reference virus strain for

production

FDA 4−10 weeks

Manufacture test strains Vaccine manufacturers 2−4 weeks

Develop potency test reagentsa FDA 10−12 weeks

Manufacture and test vaccine Vaccine manufacturers/FDA 10−12 weeks

Total production time 6−8 monthsb
Page 9 GAO-01-4 Influenza Pandemic

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

Vaccine Production Compared to

Speed of Infection of Population

While the global influenza surveillance system provides valuable

information for deciding which viral strains to include in the annual

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.
Page 10 GAO-01-4 Influenza Pandemic

Table 2: Months for Newly Detected Influenza Viruses to Reach the 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. NIH5 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.

Influenza virus and year

Country where first

detected

Months to reach

United States

Pandemic year

Spanish flu, 1918 United Statesa 0a

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

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.
Page 11 GAO-01-4 Influenza Pandemic

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

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.

Strain and year Month appeared

Pandemic strain

Spanish flu, 1918 Marcha

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
Page 12 GAO-01-4 Influenza Pandemic

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

Production of Vaccine

One potential production problem is that influenza strains differ in how

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.
Page 13 GAO-01-4 Influenza Pandemic

Problems Related to

Vaccine Effectiveness

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

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.
Page 14 GAO-01-4 Influenza Pandemic

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

Pneumococcal Vaccine

May Be in Limited

Supply During a

Pandemic

Antiviral drugs and vaccine against pneumonia are two additional

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

death until an influenza vaccine becomes available. However, both are

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

production capacity for antiviral drugs and vaccine in response to

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.
Page 15 GAO-01-4 Influenza Pandemic

Problems Related to

Availability of Antiviral

Drugs

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

have immediate availability both as a prophylactic to prevent illness and as

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.

10CDC evaluations have shown antiviral drugs shorten the duration of influenza by about 1

day, with some reduction of severity and prevention of secondary infections.

11These 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.

12Special 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.
Page 16 GAO-01-4 Influenza Pandemic

Table 4: Antiviral Drugs Approved for Influenza by FDA

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

Antiviral drug

Year

approved Approved use

Influenza virus strains

affected by drug

Approved

population

Number of

manufacturers

Cost per

daily dosea

Amantadine 1976 Prophylaxis and

treatment

All A strains Adults and children 9 $0.10b

Rimantadine 1993 Prophylaxis and

treatment

All A strains Adults and

childrenc

1 $1.07d

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
Page 17 GAO-01-4 Influenza Pandemic

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

13The six state pandemic plans we reviewed do not rely on using antiviral drugs, in part

because supplies are expected to be very limited.

14In 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.

15The HHS budget proposal for fiscal year 2001 includes $54 million to continue

development of the National Pharmaceutical Stockpile.
Page 18 GAO-01-4 Influenza Pandemic

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

Pneumococcal Vaccine

Inoculation with pneumococcal vaccine, which helps protect against

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 deaths19—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.

16Combating Terrorism: Chemical and Biological Medical Supplies Are Poorly Managed

(HEHS/AIMD-00-36, Oct. 29, 1999).

17Pneumococcal vaccine provides protection against pneumococcal pneumonia, especially

when other pneumococcal infections such as bacterial meningitis and infection of the

bloodstream are present.

18Influenza 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.

19The 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.
Page 19 GAO-01-4 Influenza Pandemic

Table 5: Excess Influenza-Related Deaths Estimated for Pandemic and

Nonpandemic Periods in the United States, 1918-91

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.

Period Years

Annual average of

excess deaths

Crude death rate

per 100,000

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

Nonpandemica 1981-91 20,000 10.0

20The 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.
Page 20 GAO-01-4 Influenza Pandemic

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

21There 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.

22Immunization: HHS Could Do More to Increase Vaccination Among Older Adults

(GAO/PEMD-95-14, June 8, 1995).
Page 21 GAO-01-4 Influenza Pandemic

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

Purchase, Distribute,

and Administer

Vaccines and Drugs

Federal and state pandemic response plans are in various stages of

completion and do not completely or consistently address the problems

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

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

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.

23A 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)).

24CDC’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.
Page 22 GAO-01-4 Influenza Pandemic

Status of Federal and State

Pandemic Response Plans

The federal government developed the first national pandemic plan in 1978,

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

25A 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).

26In 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.

27Four 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.

28CDC has also provided more general assistance in terms of funding and technical

assistance to enhance public health epidemiologic, laboratory, and communications

capacity more generally.
Page 23 GAO-01-4 Influenza Pandemic

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

Planning Responsibilities

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

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,

Distribution, and Administration

of Vaccines and Antiviral Drugs

HHS has indicated in its interim planning guidance that how vaccines and

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

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
Page 24 GAO-01-4 Influenza Pandemic

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

Population Groups for Limited

Distribution of Vaccines and

Drugs

State officials are particularly concerned that a national plan has not

finalized recommendations for how population groups should be

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

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
Page 25 GAO-01-4 Influenza Pandemic

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

29The 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.
Page 26 GAO-01-4 Influenza Pandemic

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.

30To 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.
Page 27 GAO-01-4 Influenza Pandemic

Recommendations for

Executive Action

To improve the nation’s ability to respond to the emergence of a pandemic

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
Page 28 GAO-01-4 Influenza Pandemic

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
Page 29 GAO-01-4 Influenza Pandemic

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
Page 30 GAO-01-4 Influenza Pandemic

Appendix I

Comments From the Department of Health Apendxies

and Human Services ApendxiI
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

(201048) Letr Page 35 GAO-01-4 Influenza Pandemic
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