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entitled 'Childhood Vaccines: Ensuring an Adequate Supply Poses 
Continuing Challenges' which was released on September 13, 2002. 

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United States General Accounting Office: 

Report to Congressional Requesters: 

September 2002: 

Childhood Vaccines: 

Ensuring an Adequate Supply Poses Continuing Challenges: 




Results in Brief: 


Shortages Prompt Actions to Reduce Immunization Requirements: 

Problems Causing Shortages Largely Resolved, but Shortages Could Recur: 

No Clear Path Yet to Resolve Ongoing Supply Issues: 


Matter for Congressional Consideration: 

Recommendations for Executive Action: 

Agency Comments and Our Evaluation: 

List of Requesters: 

Appendix I: Comments from the Department of Health & Human Services: 

Appendix II: GAO Contacts and Staff Acknowledgments: 


Table 1: Functions of Federal Agencies and Committees to Address 
Vaccine Shortages: 

Table 2: Duration of CDC-Reported Childhood Vaccine Shortages: 

Table 3: Modification of Immunization Schedule during Vaccine 

Table 4: Extent of Vaccine Shortages in State Immunization Programs: 

Table 5: Number of Manufacturers Producing Routine Childhood Vaccines 
in the United States: 


AAP: American Academy of Pediatrics: 

ACIP: Advisory Committee on Immunization Practices: 

ASTHO: Association of State and Territorial Health Officials: 

ATSDR: Agency for Toxic Substances and Disease Registry: 

BLA: biologics license application: 

CDC: Centers for Disease Control and Prevention: 

DTaP: diphtheria, tetanus, and acellular pertussis: 

EPA: Environmental Protection Agency: 

FDA: Food and Drug Administration: 

Hep B: hepatitis B: 

Hib: haemophilus influenzae type b: 

HHS: Department of Health and Human Services: 

ICH: International Conference on Harmonisation of Technical 
Requirements for Registration of Pharmaceuticals for Human Use: 

IPV: inactivated polio vaccine: 

MMR: measles, mumps, and rubella: 

NIH: National Institutes of Health: 

NIS: National Immunization Survey: 

NVAC: National Vaccine Advisory Committee: 

NVP: National Vaccine Plan: 

NVPO: National Vaccine Program Office: 

PCV: pneumococcal conjugate vaccine: 

PHS: U.S. Public Health Service: 

Td: tetanus and diphtheria booster: 

VFC: Vaccines for Children: 

VICP: Vaccine Injury Compensation Program: 

[End of section] 

United States General Accounting Office: 
Washington, DC 20548: 

September 13, 2002: 

Congressional Requesters: 

Immunizations are widely considered one of the leading public health
achievements of the 20th century. Mandatory immunization programs have
eradicated polio and smallpox in the United States and reduced the
number of deaths from several childhood diseases, such as measles, to
near zero. A consistent supply of many different vaccines is needed to
support this effort. By 18 months of age, it is recommended that each of
the 11,000 babies born each day in the United States receive up to 20 
doses of vaccine to protect against 11 diseases. 

The federal government plays a variety of roles in immunization 
programs. Although vaccines are made by private companies and 
immunization policies are set at the state level, various agencies of 
the Department of Health and Human Services (HHS) have roles in 
regulating vaccine production, purchasing vaccines and making them 
available to states, and making recommendations for states to consider 
in setting immunization policies, such as those for school and day care 
enrollment. The federal government also plays a central role in 
ensuring the adequacy of the nation’s vaccine supply—a matter of 
increasing concern in recent years. Although sporadic interruptions in 
the supply of vaccines have occurred in the past, these interruptions 
have become much more pronounced in the past 2 years. In late 2001, the 
Centers for Disease Control and Prevention (CDC) reported shortages in 
five of the eight recommended childhood vaccines. Concerned about the 
increasing frequency of these shortages, you asked that we answer the 
following questions: 

1. To what extent have recent childhood vaccine shortages affected 
immunization policies and programs? 

2. What factors have contributed to the recent shortages, and have they
been resolved? 

3. What strategies are federal agencies considering to help mitigate
disruptions in the vaccine supply? 

To assess the effect of vaccine shortages on immunization policies and
programs, we surveyed 64 state, territorial, and local immunization
programs supported by CDC, [Footnote 1] examined recent changes in 
recommended immunization schedules, and reviewed studies of past 
outbreaks. To identify the factors that contributed to shortages and 
determine if they are being resolved, we visited the four primary 
vaccine manufacturers, determined how federal regulatory procedures 
affect vaccine production, and reviewed various analyses of vaccine 
supply problems by HHS agencies and other entities. To identify 
strategies being considered by federal authorities to help prevent or 
mitigate vaccine shortages, we reviewed studies and recommendations to 
strengthen the vaccine supply, attended advisory panel meetings 
examining vaccine shortages, and interviewed agency officials and other 
vaccine experts. We conducted our work from November 2001 through July 
2002 in accordance with generally accepted government auditing 

Results in Brief: 

Recent childhood vaccine shortages have prompted federal authorities to
recommend deferring some immunizations and have caused states to
reduce immunization requirements. The federal Advisory Committee on
Immunization Practices (ACIP) and CDC, which recommend immunization
standards for the nation, have recommended that physicians defer
immunizations for vaccines in short supply, so that the vaccines will
continue to be available to those at highest risk. At the state and 
local levels, 49 state immunization programs reported rationing one or 
more vaccines. Shortages have also prompted the majority of states to 
waive or change immunization requirements for school and day care 
programs so that children who had received fewer than the mandatory 
immunizations could enroll. States reported that vaccine shortages and 
missed make-up vaccinations may reduce coverage and increase the 
potential for disease to spread; however, data are not currently 
available to measure these effects. 

Multiple factors contributed to recent vaccine shortages, and while 
these have largely been resolved, the potential exists for shortages to 
recur. The shortages stemmed from a number of factors that affected 
both supply and demand. On the supply side, for example, some 
manufacturers had production problems that caused them to fall below 
their expected output, while others discontinued making some vaccines 
altogether. On the demand side, one manufacturer could not keep pace 
with the greater-than-expected demand for a new recommended vaccine. 
CDC reported supplies for all but one vaccine were beginning to return 
to normal by July 2002. However, the potential for recurring shortages 
will remain because the complex nature and often year-long production 
schedule of vaccine manufacturing will continue to make it difficult 
for the supply system to respond rapidly to sudden changes in supply or 
demand. Additionally, with so few firms making each vaccine (five of 
the eight recommended childhood vaccines have only one manufacturer 
each), production problems or a manufacturer’s decision to withdraw may 
leave few or no alternative sources of vaccine. One development that 
may help add greater capacity in meeting future needs is that a number 
of new vaccine products that could be used to meet the existing 
childhood immunization schedule are in varying stages of development, 
ranging from clinical testing to review by the Food and Drug 
Administration (FDA). However, the process to complete clinical trials 
and undergo FDA review likely will take several years, and these 
products generally do not qualify for expedited review
under FDA policies. 

Federal agencies and advisory committees are exploring options to help
stabilize the nation’s vaccine supply, but few long-term solutions have
emerged. One option, expanding vaccine stockpiles, is receiving wide
consideration as a short-term strategy that could help cushion 
disruptions in vaccine supply. Stockpiles have been used successfully 
to help mitigate supply disruptions in the past. While CDC is required 
by law to stockpile a 6-month supply of recommended childhood vaccines 
and has the necessary funding, it currently has established partial 
stockpiles for only two—one for measles, mumps, and rubella and one for 
polio. In light of the recent shortages, CDC is now considering plans 
to expand the stockpile to include additional vaccines. Stockpiling 
vaccines, however, has its limitations. While stockpiling can provide a 
cushion in the event of a supply disruption, limited supply and 
manufacturing capacity will restrict CDC’s ability to build certain 
stockpiles in the near term. In addition, it is unclear whether the 
authority that CDC is using to establish these stockpiles provides for 
their use for all children. Another problem in expanding stockpiles is 
that CDC lacks a strategy for determining such things as how much 
vaccine to stockpile, where it should be stored, and how to ensure that 
the stockpile is additional to a manufacturer’s normal inventory. CDC 
also lacks important information from FDA, manufacturers, and states 
needed to anticipate and manage supply disruptions. 

We are making several recommendations to the Secretary of HHS to help
promote the availability of vaccine products. These recommendations
include adding vaccines to the types of products that can be considered
under FDA’s authority to expedite the approval of products in
development trials and directing CDC to address several operational and
strategic issues in expanding childhood vaccine stockpiles. In its 
general comments on a draft of this report, HHS stated that it agrees 
with the report’s findings and has initiated actions to implement the
recommendations. The report also contains a matter for congressional
consideration to address the extent to which currently stockpiled 
vaccines are available for use by all children in the event of a 


CDC currently recommends routine immunizations against 11 childhood
diseases: diphtheria, tetanus, pertussis (whooping cough), haemophilus
influenzae type b (most commonly meningitis), hepatitis B, measles,
mumps, rubella (German measles), invasive pneumococcal disease, polio,
and varicella (chicken pox). [Footnote 2] Some vaccines protect against 
multiple diseases. By combining antigens (the component of a vaccine 
that triggers an immune response), a single injection of a combination 
vaccine can protect against multiple diseases. Examples include the MMR 
vaccine (for measles, mumps, and rubella) and the DTaP vaccine (for 
diphtheria, tetanus, and pertussis). As a result of these combinations, 
eight vaccines are normally used to provide protection against the 11 
childhood diseases. To build and maintain sufficient immunity, multiple 
doses of each of these vaccines are usually needed through infancy and 
early childhood. CDC’s suggested vaccine timetable calls for children 
to receive up to 23 doses of these vaccines through the first 6 years 
of life. An additional tetanusdiphtheria booster is recommended during 
adolescence. When very large shares of the general population are 
immunized, vaccines are successful at preventing major outbreaks of 
disease. Vaccines also offer some degree of protection to individuals 
not immunized, because a high immunization rate in a population gives a 
disease less opportunity to take hold and spread—a concept known as 
“herd immunity.” Development of vaccines and establishment of large-
scale immunization programs have virtually eliminated some diseases and 
drastically reduced the impact of others. Finally, with the ease of 
international travel, wide-scale vaccination programs help protect 
against infected travelers transmitting diseases, such as measles, from 
foreign countries where the diseases are still common. 

Consolidation Resulted in Four Companies Engaged in Vaccine 

Making vaccines is a complicated and time-consuming process. In contrast
to drug manufacturing, vaccine manufacturing entails the use of 
biological organisms, including viruses and bacteria, which requires 
adherence to strict and complex manufacturing controls to ensure that 
they grow and react during processing as expected. Under current 
technology, vaccines typically require long production times. 
Manufacturers report that a typical production schedule, including 
growing the antigen, purifying, testing, packaging, and performing 
final quality checks, can exceed a full year for some vaccines. 

Virtually all routine childhood vaccines are made by commercial
manufacturers. [Footnote 3] Reflecting the challenges of vaccine 
production, the vaccine-manufacturing base in the United States has 
been marked by substantial consolidation over the past three decades. 
According to HHS, there were 26 manufacturers licensed to distribute 
vaccines in 1967. Due in part to acquisitions and mergers, at present 
there are 12 manufacturing entities that hold U.S. licenses, four of 
which produce almost all of the routine childhood vaccines on the U.S. 
market. Two of these companies—Merck & Company and Wyeth—are 
headquartered in the United States, and two—Aventis Pasteur and 
GlaxoSmithKline—are headquartered in Europe. 

Federal and State Governments Play Key Roles: 

The federal government has a role both as a purchaser of vaccines and 
as a regulator of the industry. The federal government is the largest 
purchaser of vaccines in the country. CDC negotiates large purchase 
contracts with manufacturers and makes the vaccines available to public 
immunization programs under the Vaccines for Children (VFC) program. 
Under VFC, vaccines are provided for certain children—Native 
Americans/Alaska Natives, those eligible for Medicaid, those who are 
uninsured, and, when vaccinated in federally qualified health centers 
or rural health clinics, those who are not insured with respect to the 
vaccine. Participating public and private health care providers obtain 
vaccines through VFC at no charge. Under a second program, known as the 
section 317 grant program because it was established under section 317 
of the Public Health Service Act, [Footnote 4] project grants are 
provided for preventive health services including immunization 
programs. Currently, participants include 64 state, local, and 
territorial immunization programs. These grants are intended to help
states maintain immunization infrastructures or purchase vaccines not
covered by private insurance or not available through VFC. In addition,
state immunization programs can use their own funds to buy vaccines
through CDC contracts. In total, about 50 percent of all the childhood
vaccines administered in the United States each year are obtained by
public immunization programs through CDC contracts. 

The cost of the full schedule of recommended vaccines under the CDC
contracts has increased substantially in recent years, with a large 
share attributable to new higher-cost vaccines that have been added to 
the childhood immunization schedule. [Footnote 5] For example, as of 
May 2002, the CDC contract price for vaccine doses needed to complete 
the immunization schedule was about $413. [Footnote 6] Over half of 
this amount is attributable to the most recent ACIP-recommended 
vaccines—varicella (recommended in 1996) and pneumococcal conjugate 
vaccine (recommended in 2001). 

In addition to purchasing vaccines, the federal government is 
responsible for ensuring the safety of the nation’s vaccine supply. 
FDA, an agency within HHS, regulates the production of vaccines. It 
licenses all vaccines sold in the United States, requiring clinical 
trials to demonstrate that a vaccine is safe and effective, and 
thoroughly reviews the manufacturing process to ensure that vaccines 
are made consistently in compliance with current good manufacturing 
practices. Once vaccines are licensed, FDA also conducts periodic 
inspections of production facilities to ensure that manufacturers 
maintain compliance with FDA manufacturing requirements. 

Other HHS agencies and programs also provide support for national, 
state, and local immunization efforts nationwide. The National Vaccine 
Program Office (NVPO), within the Assistant Secretary for Health’s 
office, is responsible for coordinating the efforts of all federal 
agencies, states, providers, industry, and other stakeholders involved 
in immunization activities. CDC’s National Immunization Program, in 
addition to purchasing vaccines for VFC, conducts a number of 
activities to strengthen the nation’s immunization infrastructure, such 
as monitoring the delivery of vaccines to state immunization programs 
and providing technical assistance to help health departments implement 
immunization programs. In times of vaccine shortages, several federal 
agencies and advisory committees play key roles (see table 1). 

Table 1: Functions of Federal Agencies and Committees to Address Vaccine

Agency/committee: ACIP; 
Functions that help avert or mitigate vaccine shortages: Evaluate and 
recommend changes in the immunization schedule to accommodate reduced 

Agency/committee: CDC; 
Functions that help avert or mitigate vaccine shortages: Monitor 
production, monitor inventories of state immunization programs, manage 
distribution of public supplies, administer stockpiles, track back 
orders, and work with ACIP to modify immunization schedules in order to 
respond to vaccine shortages. 

Agency/committee: FDA; 
Functions that help avert or mitigate vaccine shortages: Accelerate 
review of revisions to existing licenses and vaccine lots submitted for 
release. Work with manufacturers to correct violations of good 
manufacturing practices that could disrupt production. 

Agency/committee: NVPO; 
Functions that help avert or mitigate vaccine shortages: Facilitate 
development of contingency plans, identify the reasons for shortages 
and options to address them, and identify strategies to prevent future

Agency/committee: National Vaccine Advisory Committee (NVAC); 
Functions that help avert or mitigate vaccine shortages: Study and make 
recommendations to the HHS Assistant Secretary for Health on ways to 
achieve an adequate supply of safe and effective vaccines. 

Source: ACIP, CDC, FDA, NVPO, and NVAC. 

[End of table] 

States also have an important role in setting immunization policy and
establishing an immunization infrastructure. Policies for immunization
requirements, including minimum school and day care entry requirements,
are made almost exclusively at the state level, although cities 
occasionally impose additional requirements. For example, the state of 
New York requires students to have three doses of DTaP upon entering 
day care or school, while New York City requires an additional fourth 
dose. Each state also establishes an immunization infrastructure to 
monitor infectious disease outbreaks, administer federal immunization 
grants, manage centralized supplies of vaccine, direct professional and 
public education efforts, and otherwise promote immunization policies. 

Vaccine Shortages Have Peaked and Most Supplies Are Returning to 

The recent incidents of vaccine shortages began in fall 2000 when 
supplies of the tetanus and diphtheria booster (Td) fell short. Over 
the course of a year, supplies of other vaccines also declined and by 
fall 2001, CDC reported shortages of five vaccines that, because some 
are combination vaccines, protect against eight childhood diseases (see 
table 2). In July 2002, updated CDC data indicated supplies were 
returning to normal for most vaccines. The shortage of pneumococcal 
conjugate vaccine (PCV), however, was expected to continue through at 
least late 2002. 

Table 2: Duration of CDC-Reported Childhood Vaccine Shortages: 

Vaccine, in short supply: Tetanus and diphtheria booster (Td); 
Approximate start of shortage: November 2000; 
Actual or projected end of shortage: Ended June 2002. 

Vaccine, in short supply: Diphtheria, tetanus, and acellular pertussis 
Approximate start of shortage: January 2001; 
Actual or projected end of shortage: Ended June 2002[A]. 

Vaccine, in short supply: Pneumococcal conjugate vaccine (PCV); 
Approximate start of shortage: September 2001[B]; 
Actual or projected end of shortage: Continue through at least late 

Vaccine, in short supply: Measles, mumps, and rubella (MMR); 
Approximate start of shortage: October 2001; 
Actual or projected end of shortage: Ended June 2002[A]. 

Vaccine, in short supply: Varicella; 
Approximate start of shortage: October 2001; 
Actual or projected end of shortage: Ended July 2002. 

Vaccine, Adequate supply: 
Hepatitis B (Hep B); 
Haemophilus influenzae type b (Hib)[C]; 
Inactivated polio vaccine (IPV). 

[A] Supplies of DTaP and MMR are sufficient to meet demand for routine 
use, but not yet sufficient for extensive make-up initiatives. 

[B] CDC reported shortages of PCV existed throughout most of 2001, but 
intensified in September 2001. 

[C] Not considered a shortage by CDC; however, two of three 
manufacturers reported shipment delays up to 60 days. A third 
manufacturer had product available. 

Source: CDC vaccine shortage reports, July 2002. 

[End of table] 

Shortages Prompt Actions to Reduce Immunization Requirements: 

Recent vaccine shortages have necessitated temporary modifications to
the recommended immunization schedule and have caused states to scale
back immunization requirements. Federal health officials and experts
responsible for the development of immunization guidelines have
temporarily scaled back their recommendations regarding the timing of
immunizations for vaccines in short supply. At the state level,
immunization programs are rationing the amount of vaccines distributed
to providers. Many states have also suspended existing immunization
requirements, allowing children who have received fewer than the
previously recommended number of vaccinations to attend day care or
school. Data to capture the full impact of the shortages on vaccination
coverage are not yet available; however, public health officials are
concerned that shortages raise the potential for disease outbreaks. 

Federal Immunization Recommendations Scaled Back: 

In response to recent vaccine shortages, ACIP and CDC issued temporary
recommendations to defer immunizations for some groups of children, so
that the available supply can be directed to those considered at higher 
risk for contracting vaccine-preventable diseases. [Footnote 7] Five 
vaccines are included: Td, DTaP, PCV, MMR, and varicella (see table 3). 
The revisions give guidance to providers that are facing shortages and 
are intended to help ensure vaccine availability for priority needs. 
For example, the shortage of PCV, which began in 2001, prompted ACIP to 
recommend that the full series of doses be given only to high-risk 
children, such as those with chronic diseases, and that fewer doses be 
given to healthy children. In the case of varicella immunizations, 
where only one dose is generally needed to confer long-term immunity, 
ACIP has recommended that doses be delayed. 

Table 3: Modification of Immunization Schedule during Vaccine 

Vaccine: Td; 
Recommended schedule: Routine booster every 10 years; 
Age at vaccination: 11–15 years and every 10 years thereafter; 
Revised recommendations: Defer routine boosters; prioritize vaccine from
highest to lowest risk groups[A]; 
Date of revision: November 2000. 

Vaccine: DTaP; 
Recommended schedule: 5 doses; 
Age at vaccination: 2 months; 4 months; 6 months; 15–18 months; 4–6 
Revised recommendations: Defer fourth dose; also defer fifth dose, if 
Date of revision: March 2001. 

Vaccine: PCV; 
Recommended schedule: 4 doses; a fifth dose is recommended for certain 
high-risk groups[B]; 
Age at vaccination: 2 months; 4 months; 6 months; 12–15 months; 24–59 
Revised recommendations: Recommendations vary according to severity of
Date of revision: December 2001. 

Vaccine: MMR; 
Recommended schedule: 2 doses; 
Age at vaccination: 12–15 months; 4–6 years; 
Revised recommendations: Defer second dose; 
Date of revision: March 2002. 

Vaccine: Varicella; 
Recommended schedule: 1 dose; 2 doses are recommended for high-risk 
Age at vaccination: 12–18 months; 13 years or older; 
Revised recommendations: Delay until 18–24 months: prioritize to high-
risk groups if shortage persists[E]; 
Date of revision: March 2002. 

[A] Recommendations for use (highest to lowest priority) of Td are 
those traveling to countries where the risk for diphtheria is high, 
those requiring tetanus vaccination for wound management, those who 
have received fewer than three doses of vaccine containing Td, pregnant 
women, those at occupational risk for tetanus-prone injuries, and those 
who have not been vaccinated within the preceding 10 years. 

[B] High-risk children include those with sickle-cell disease, human 
immunodeficiency virus infection, and other immunocompromising or 
chronic medical conditions. 

[C] In December 2001, ACIP issued updated recommendations for PCV use 
for healthy children during moderate and severe shortages. For infants 
who receive their first dose before age 6 months, vaccination with a 
maximum of three doses is recommended during a moderate shortage, and 
two doses are recommended during a severe shortage. All health care 
providers have been asked to reduce the number of doses used and 
ordered, regardless of their current supply, so that vaccine is
more widely available until supplies are adequate. 

[D] Susceptible individuals aged 13 years or older should receive two 
doses spaced at least 4 weeks apart. 

[E] Recommendations for use (highest to lowest priority) of varicella 
vaccine are health care workers, family contacts of immunocompromised 
persons, individuals aged 13 years or older, and adults with high-risk 
children (for example, children infected with human immunodeficiency 
virus and children with asthma or eczema). 

Source: ACIP and CDC recommendations. 

[End of table] 

States Reduce Immunization Requirements: 

The shortages that prompted federal officials to scale back their
immunization recommendations have also affected programs at the state
level. In our survey of 64 state immunization programs, administered
through the Association for State and Territorial Health Officials 
(ASTHO), all 52 responding programs indicated that they had experienced 
shortages of two or more vaccines and had taken some form of action to 
deal with the shortages (see table 4). [Footnote 8] Officials from 31 
of these 52 programs indicated that they had experienced shortages of 
five or more of the vaccines routinely recommended for children. The 
most frequently cited vaccines in short supply—DTaP, Td, varicella, 
MMR, and PCV—protect against eight diseases: diphtheria, tetanus, 
pertussis, varicella, measles, mumps, rubella, and pneumococcal 

Table 4: Extent of Vaccine Shortages in State Immunization Programs: 

Extent of vaccine shortages: Shortages of two or more vaccines; 
Number of state immunization programs reporting: 52. 

Extent of vaccine shortages: Shortages of five or more vaccines; 
Number of state immunization programs reporting: 31. 

Extent of vaccine shortages: Shortages of one or more vaccines for 12 
months or longer; 
Number of state immunization programs reporting: 9. 

Extent of vaccine shortages: Ration vaccines to providers; 
Number of state immunization programs reporting: 49. 

Extent of vaccine shortages: Allow children to attend school with fewer 
than recommended number of vaccinations[A]; 
Number of state immunization programs reporting: 35. 

Note: Information is based on responses from 52 state immunization 

[A] While states set the minimum immunization requirements for school 
and day care entry, local immunization programs have the option to 
establish additional requirements according to local needs. 

Source: GAO survey of 64 state immunization programs. 

[End of table] 

Forty-nine state immunization programs reported taking steps to ration
the vaccines they distribute to providers due to the shortages. Under
normal supply conditions, states maintain vaccine inventories that allow
providers to keep at least a 1-month supply on hand. With a limited 
supply of vaccine available, states reported not receiving enough 
vaccine to maintain ideal inventories, and filling only partial orders 
to ship to providers. For example, in March 2002 officials from the 
immunization program in Arkansas reported that they planned to cut the 
size of vaccine shipments to public and private providers by 50 to 80 
percent, with the percentage reduction depending on the supply of 
vaccine in the state depot. The cuts are made to ensure an even 
distribution of vaccine among providers throughout the state. Officials 
from nine states reported being short of vaccines for 12 months or 
longer, and in some cases states reported having been completely out of 
certain vaccines for months at a time. For example, the immunization 
program in Philadelphia reported it had been unable to supply its 
health care providers with varicella and PCV for a 3-month period, and 
the program in Illinois reported that it had ordered over 70,000 doses 
of PCV since January 2002 but had received no doses as of the end of 
May 2002. 

Vaccine shortages experienced at the state level have, in turn, prompted
cutbacks in immunization requirements for admission to day care or
school. Thirty-five states reported putting into effect new, less 
stringent immunization requirements that allow children who have 
received fewer than the recommended number of vaccinations to attend 
school. [Footnote 9] In general, these states have reduced the 
immunization requirements for day care and/or school entry or have 
temporarily suspended enforcement of those requirements until vaccine 
supplies are replenished. For example, the Minnesota Department of 
Health suspended the school and postsecondary immunization laws for Td 
vaccine for the second year in a row, with the suspension extending 
through the 2002-2003 school year. Other states, including Washington 
and South Carolina, reported allowing children to attend day care or 
school even if they were not immunized in compliance with immunization 
requirements, under the condition that they be recalled for 
vaccinations when supplies became available. 

Deferred Immunizations Likely to Lower Vaccination Coverage and May 
Increase the Risk of Outbreaks: 

While it is too early to measure the effect of deferred vaccinations on
immunization rates, a number of states reported that vaccine shortages
and missed make-up vaccinations may take a toll on coverage and, as
such, increase the potential for infectious disease outbreaks. The full
impact of vaccine shortages is difficult to measure, for several 
reasons. First, none of the surveys that estimate immunization coverage 
at the national level measures the rate of age-recommended immunizations
among children under the age of 18 months—the age cohort receiving the
majority of vaccinations. Second, although the National Immunization 
Survey (NIS) [Footnote 10] measures vaccination coverage among children 
aged 19 to 35 months, it does not inquire why children are not 
immunized. A reported decrease in coverage for any given year may be 
due to a number of factors, such as parental concerns about vaccine 
safety. Third, it would take some time after the shortages have ended 
to determine how many children were not recalled for missed 
vaccinations, a measure that could be useful in evaluating the impact 
of the shortages. [Footnote 11] 

High vaccination rates from recent years could delay the immediate 
effects of deferred immunizations, but underimmunization destabilizes 
population immunity and may lead to outbreaks. Immunization rates for 
children receiving the series of all recommended vaccinations have been 
rising steadily since the inception of the NIS in 1994—from 55 percent 
in 1995 to 74 percent in 2001 for children aged 19 to 35 months. 
[Footnote 12] Coverage with three or more doses of DTaP alone was 
approximately 94 percent in the most recent survey. Immunization 
experts generally agree that the residual effects of such high levels 
of population immunity may afford temporary protection for 
underimmunized children against communicable, vaccine-preventable 
diseases; however, the more numerous the population of susceptible 
individuals becomes, the greater the probability that those who are 
susceptible will come into contact with an infected person. Past 
outbreaks demonstrated this concept and highlight the importance of
giving all recommended doses according to schedule. For example, a CDC
analysis of a 1998 outbreak of measles in an Anchorage, Alaska, school
showed that only 51 percent of the 2,186 children exposed had received
the requisite two doses of measles-containing vaccine. This and other
studies of measles outbreaks cited by CDC underscore the potential
ramifications of deferring the second dose of MMR vaccine. 

In addition to the potential for vaccine shortages to reduce coverage,
public health officials are concerned that the deferment of 
immunizations undermines years of efforts to educate parents and 
physicians about the importance of vaccinating children as recommended. 
Although providers are being asked to set up recall systems for 
children who have been turned away for needed vaccinations, 
immunization officials are concerned that some children will not be 
recalled and therefore will remain underimmunized. 

Problems Causing Shortages Largely Resolved, but Shortages Could Recur: 

The problems causing most of the recent vaccine shortages have largely
been resolved, but the potential exists for other, similar problems to 
bring about a recurrence of shortages. The recent shortages stemmed 
from a number of largely unforeseen factors that affected both supply 
and demand. By July 2002, the supplies for many vaccines were becoming
sufficient to return to the recommended immunization schedule, but the
complex nature of vaccine manufacturing and the limited vaccine
manufacturing base make it difficult to respond rapidly if similar 
problems should occur in the future. Thus, any of the variety of 
technical difficulties that can occur with vaccine production—including 
those that contributed to recent shortages or other problems, such as a 
major product recall or catastrophic event like a vaccine plant 
fire—could trigger shortages again. One prospect that may help 
alleviate the potential for shortages is that several new vaccines 
under development could possibly add to the supply of existing 
childhood vaccines. However, clinical trials and FDA review of these 
products still need to be completed. These steps usually take several
years, and under FDA policies, these products generally do not qualify 
for expedited review. 

Many Factors Affected Supply of and Demand for Vaccine: 

No single reason explains the rash of recent vaccine shortages; rather,
multiple factors coincided that affected both the supply of and demand 
for vaccines. We identified four key factors: production problems, 
calls by immunization policy-making bodies to remove a preservative from
vaccines as a precautionary measure, a manufacturer’s decision to cease
production of some vaccines, and greater-than-expected demand for a
vaccine that had recently been added to the immunization schedule. 

Production Problems: 

Manufacturing production problems contributed to reductions in the
supply of certain vaccines. In some cases, production slowdowns or
interruptions occurred as manufacturers addressed problems identified in
FDA inspections; in other cases, production was affected when planned
maintenance activities took longer than expected. For example, the 
shortages of MMR and varicella vaccines (which are produced by the same
manufacturer) were brought about by two voluntary interruptions to
production. In August 2001, the manufacturer temporarily suspended
operations in one of its manufacturing facilities to address issues 
raised by FDA inspectors during a routine plant inspection. The 
production halt continued while the manufacturer made scheduled 
modifications to its facility. These modifications took longer than 
anticipated and had a substantial impact on production. In the months 
immediately following the interruptions, supply levels of MMR and 
varicella vaccines dropped by about 45 percent. Supplies remained low 
for the next several months, then significantly improved in the spring. 
In late June, CDC announced that the supply of MMR was sufficient to 
return to the recommended immunization schedule, although enough 
vaccine was not available for aggressive efforts to recall children for 
missed vaccinations. In July 2002, CDC announced that supplies of 
varicella were sufficient to return to the recommended immunization 
schedule. Difficulties meeting FDA manufacturing requirements also 
contributed to supply problems with DTaP, Td, and PCV. 

Changes in FDA inspection practices may have resulted in the 
identification of more or different instances of manufacturers’
noncompliance with FDA manufacturing requirements. In 1997, FDA
implemented a new program for inspecting the biologics industry
(including vaccines), called Team Biologics. This new approach
emphasizes a more complete assessment of manufacturers’ compliance
with current good manufacturing practices, which are the agency’s
regulatory requirements for ensuring that biological products remain 
safe, pure, and potent through the entire manufacturing process. These
requirements address a broad range of issues, such as quality assurance,
recordkeeping, personnel qualifications, equipment cleaning, and
laboratory controls. Team Biologics was phased in starting with plasma
fractionation products and moved to vaccines in October 1999. Prior to
this change, biologics inspections were generally shorter and involved
smaller inspection teams, according to FDA officials. The inspections 
also tended to focus primarily on scientific or technical issues and 
less on compliance with good manufacturing practices and documentation 
issues. Several manufacturers confirmed that under this new approach,
inspections have intensified and the emphasis on compliance has
increased, making it more difficult for manufacturers to be considered 
in compliance. 

FDA did take some steps to inform manufacturers about the program
changes; however, some manufacturers reported problems related to how
well the changes were communicated. An official at one company said the
manufacturer was not well informed of the new expectations and officials
at another company said the change in FDA’s inspection approach created
a gap in perception of what was needed to be considered in compliance.
Manufacturers underscored the importance of clear guidance from FDA to
help them understand evolving expectations. FDA’s efforts to inform
manufacturers about the new inspection approach did include numerous
presentations made by agency personnel at a variety of meetings and
conferences since 1997. In addition, in October 1999, when FDA was
beginning to apply Team Biologics to vaccines, FDA issued a compliance
program guidance manual detailing the new protocol for conducting
inspections. Although this manual is intended for FDA’s staff, the
information in it could have provided manufacturers a better
understanding of the scope of the inspections. However, the manual was
not made widely available—only upon request. FDA has made compliance
manuals for other biologic areas available on the Internet, but the 
manual for licensed vaccines is still not available on line, well over 
2 years after its issuance, nor is it included in FDA’s annual 
comprehensive list of guidance documents published in the Federal 

Removal of Thimerosal: 

Calls for the removal of the preservative thimerosal from childhood
vaccines illustrate the effect that policy changes can have on the 
supply of vaccine. Efforts to remove thimerosal affected the production 
of several vaccines and contributed in particular to the shortage of 
DTaP. Thimerosal is a mercury-containing preservative that has been 
used as an additive in vaccines for over 60 years. Its presence in 
vaccines reduces the risk of bacterial contamination when providers 
draw individual doses from multidose vials. Few data are available on 
the effects of exposure to ethyl mercury (the form of mercury in 
thimerosal) at the levels introduced by vaccines. However, exposure to 
mercury-containing compounds, including ethyl and methyl mercury, at 
sufficiently high doses has the potential to produce adverse health 
effects, including effects on the nervous system. [Footnote 13] The 
Food and Drug Administration Modernization Act of 1997 required FDA to 
identify and provide an analysis of foods and drugs containing 
intentionally introduced mercury compounds. As a result of its review, 
in 1999, FDA determined that under the existing recommended immunization
schedule, some children over the first 6 months of life could be 
exposed to a cumulative level of mercury from vaccines exceeding one of 
the three existing federal guidelines for safe exposure to methyl 
mercury. [Footnote 14] As a precautionary measure, in July 1999, the 
American Academy of Pediatrics (AAP) and the U.S. Public Health Service 
(PHS) issued a joint statement advising that thimerosal in vaccines be 
eliminated or reduced as soon as possible. [Footnote 15] 

While thimerosal was present in several vaccines, removing it from some
vaccines was more complex than for others. Thimerosal was introduced in
the latter stages of production in one manufacturer’s hepatitis B 
vaccine, and removing it was fairly straightforward. In contrast, 
thimerosal was used to help stabilize one company’s formulation of 
DTaP, and the manufacturer said it was not able to completely eliminate 
it. This contributed to the manufacturer’s decision to cease production 
of the vaccine, initiating the shortage of DTaP. The shortage was 
exacerbated when one of the remaining manufacturers of DTaP had to 
switch its packaging from multidose to single-dose vials due to the 
removal of the preservative, reducing its output of vaccine by 25 
percent, according to the manufacturer. 

For manufacturers, reformulating existing vaccines without the 
preservative required taking the product through the regulatory approval
process, with the attendant establishment of new procedures, validation,
testing, and labeling. Manufacturers acknowledged that FDA worked hard
to get thimerosal-free vaccines approved, but the process, involving 
both FDA and manufacturers, of getting these products onto the market 
still took about 10 months for one formulation of hepatitis B vaccine 
and approximately 2 years for one manufacturer’s formulation of DTaP. 

Manufacturer’s Decision to Discontinue Production: 

Another major factor in the shortage of DTaP, and also Td, was the
decision of one manufacturer to discontinue production of all products
containing tetanus toxoid. With little advance warning, the company
announced in January 2001 that it had ceased production of these
vaccines. According to the manufacturer, prior to its decision, it 
produced approximately one-quarter of all Td and 25 to 30 percent of 
all DTaP distributed in the United States, so the company’s departure 
from these markets was significant. In the previous year, another 
manufacturer that supplied a relatively small portion of DTaP also had 
stopped producing this vaccine. Together, these decisions decreased the 
number of major manufacturers of DTaP from four to two and of Td from 
two to one. [Footnote 16] 

For the manufacturer involved in the most recent departure, a number of
factors were involved in its decision. According to company officials, 
the manufacturer was already planning to discontinue its DTaP vaccine 
in a few years because it did not think it would be able to compete with
companies developing new DTaP combination vaccines. The company’s
decision was accelerated when it experienced difficulties eliminating
thimerosal from its vaccine, as noted earlier. Company officials said 
the timing of its decision was also triggered by the need to respond to
requirements set forth in a consent decree with the federal government. 
[Footnote 17] To comply with these requirements, the company faced 
making significant upgrades to its facilities where tetanus-toxoid was 
manufactured. For these reasons, the manufacturer had already stopped 
releasing vaccine prior to announcing its decision. The manufacturer 
added that had the company decided to stay in the DTaP and Td market, 
it would have been several years before it could produce vaccines 
meeting FDA requirements. 

Unanticipated Demand: 

The addition of new vaccines to the recommended immunization schedule
can also result in shortages if the demand for vaccine outstrips the
predicted need and production levels. This was the case with a newly
licensed vaccine, PCV, which protects against invasive pneumococcal
diseases in young children. PCV was licensed by FDA in February 2000
and formally added to the recommended schedule in January 2001. CDC 
estimates the monthly national need for this vaccine to be 1.3 million
doses, but the manufacturer was only able to provide about half the
needed doses during the first 5 months of 2002. Company officials said 
an extensive preeducation campaign resulted in record-breaking adoption 
of the vaccine. The company’s production of vaccine was also hampered by
ongoing manufacturing problems. Changes made in the company’s quality
assurance procedures, partly to comply with the terms of a consent 
decree with the federal government, resulted in delays in the release 
of vaccine. Manufacturing equipment problems also affected the 
manufacturer’s ability to meet demand. As of July 2002, both of these 
conditions continued to affect the supply of this vaccine. 

Underlying Factors Could Allow Shortages to Recur: 

While the recent shortages have been largely resolved, the vaccine 
supply remains vulnerable to any number of disruptions that could occur 
in the future—including those that contributed to recent shortages and 
other potential problems, such as a catastrophic plant fire. One key 
reason is that the nature of vaccine manufacturing prevents the quick 
production of more vaccine when disruptions occur. Manufacturing a 
vaccine is a complex, highly controlled process that can take several 
months to over a year. Unlike pharmaceuticals, which are usually 
synthesized from chemicals, most vaccines are produced from or use 
living biological organisms. Strict control is needed over the entire 
manufacturing process, and each lot of vaccine is carefully tested for 
its purity and potency. To illustrate the lengthy production times that 
can be involved, one manufacturer said it takes about 11 months to 
produce Td, including almost 7 to 8 months to produce purified vaccine, 
followed by 8 to 10 weeks of testing, and another 4 to 6 weeks of 
filling, packaging, and final approvals. With such long production 
times, it is difficult for the industry to provide a quick response to 
major disruptions. Some manufacturing plants are dedicated facilities, 
built and maintained to produce a specific vaccine, and cannot be 
easily expanded or switched to produce other vaccines. For example, 
when one of the two major producers of Td ceased production last year, 
both the long production time and fixed capacity left the remaining 
manufacturer unable to meet the unexpected drop in supply. The supply 
of Td only recently returned to levels sufficient to resume routine 
administration, over a year and a half after the shortage began. 

The Td vaccine example illustrates another underlying problem: routine
childhood vaccines are available from a limited number of manufacturers.
Of the eight recommended routine childhood vaccines, five are made by a
single major manufacturer; the remainder are made by two, or in one 
case, three manufacturers (see table 5). Consequently, if there are 
interruptions in supply or if a manufacturer ceases production, there 
may be few or no alternative sources of vaccine. 

Table 5: Number of Manufacturers Producing Routine Childhood Vaccines 
in the United States: 

Vaccine[A]: Hib; 
Number of manufacturers: 3. 

Vaccine[A]: DTaP; 
Number of manufacturers: 2[B]. 

Vaccine[A]: Hep B; 
Number of manufacturers: 2. 

Vaccine[A]: IPV; 
Number of manufacturers: 1. 

Vaccine[A]: MMR; 
Number of manufacturers: 1. 

Vaccine[A]: PCV; 
Number of manufacturers: 1. 

Vaccine[A]: Td; 
Number of manufacturers: 1[C]. 

Vaccine[A]: Varicella; 
Number of manufacturers: 1. 

[A] Not shown are two combination vaccines, which can be used to meet 
the recommended immunization schedule but are generally used much less 
often. DTaP-Hib can be used for booster doses but is not recommended 
for primary immunization in infants; this vaccine is made by one 
company. Hep B-Hib can be used for all but the birth dose of Hep B and 
is made by one company. 

[B] One manufacturer has licenses for two different formulations of 
DTaP vaccine (produced in geographically separate facilities), so there 
are actually three DTaP vaccines currently available on the U.S. 

[C] In addition to the one major nationwide manufacturer of Td, the 
University of Massachusetts produces a small amount of Td vaccine and 
makes some available for nationwide distribution. 

[End of table] 

Vaccines on Horizon May Increase Supply: 

New vaccines in development could potentially add to the supply of
existing vaccines. An example is a new formulation of DTaP that recently
received FDA approval and has helped ease the shortage of DTaP. We
identified 11 routine vaccines in development that could help meet the
current recommended immunization schedule. These vaccines are in
varying stages of development, ranging from clinical testing to FDA
review. Included are the following types of products: 

New brands of existing vaccines: About half of the vaccines in the 
pipeline represent new sources of existing vaccines. If approved, 
several of these vaccines would expand the number of suppliers for 
these products. 

New combinations of existing vaccines: Some of the vaccines under
development represent new combinations of existing vaccines; for 
example, one company is developing a DTaP-IPV-Hib vaccine that protects
against diphtheria, tetanus, pertussis, polio, and haemophilus 
influenzae type b. If approved, how these new combination vaccines will 
be used and whether they will expand supply or simply replace existing 
vaccines depends on several factors. The first determinant will be the 
use for which the company seeks licensure. New vaccines could be 
licensed for use in all doses or just in some doses in an immunization 
series. For example, when one acellular version of diphtheria, tetanus, 
pertussis vaccine was first licensed, the company conducted studies and 
sought licensure for only the fourth and fifth doses of the five-dose 
series. It was eventually licensed for use in all five doses. ACIP has 
encouraged the use of combination vaccines over equivalent component 
vaccines when possible in order to minimize the number of injections 
children receive. In some cases, however, individual vaccines are used 
more often than related combination vaccines. [Footnote 18] Combination 
vaccines also tend to sell at a premium price compared to the 
individual component vaccines, which may affect their market 
acceptance. Provider and parental preferences for vaccines can
also come into play. 

New vaccines for certain age groups: Some vaccines in the pipeline are
vaccines formulated for new age groups. According to a manufacturer, one
vaccine includes a pertussis component for adolescents and adults, which
is not currently available or included in the recommended schedule. 

FDA Policies Restrict Use of Expedited Approval Processes: 

Completing clinical testing and FDA review of these new vaccines can be 
a lengthy process, but FDA has a number of procedures for facilitating 
the development and expediting the review of new pharmaceutical and
biologic products. Clinical testing of a vaccine in humans is typically 
done in three phases to establish the product’s safety and efficacy and 
to determine dosing. Once clinical trials are completed, the 
manufacturer may submit a biologics license application (BLA) to FDA 
that assembles evidence on the vaccine’s safety, purity, and potency 
and whether the manufacturing process can ensure its quality. Based on 
its review of the information in the application and any supplemental 
information it requests, FDA makes a decision on whether to license the 
vaccine. In total, completing clinical trials and FDA review for 
vaccines generally takes over 5 years. However, FDA has a number of 
mechanisms available to help expedite this process for certain 
products, including the following two: 

Fast Track: A manufacturer can request fast track designation if the
product is intended for the treatment of a serious or life-threatening
condition and it demonstrates the potential to address unmet medical
needs. As clinical testing nears completion, and preliminary data 
support a determination that a fast track product may be effective, FDA 
may begin accepting portions of the BLA for review before a complete 
application is submitted. [Footnote 19] 

Priority Review: A product may be eligible for priority review status 
if the product is a significant improvement in the safety or 
effectiveness of the treatment, diagnosis, or prevention of a serious 
or life-threatening disease. [Footnote 20] FDA’s goals are to review 
and take action on priority submissions in 6 months, compared to 10 
months for standard reviews. [Footnote 21] 

These mechanisms are not available for use with many vaccines in the
pipeline because FDA policies preclude their application to products 
that are essentially new forms of existing vaccines. The Food and Drug
Administration Modernization Act of 1997 requires that fast track 
products demonstrate the potential to address unmet medical needs. 
While the statute did not define “unmet medical need” or provide 
criteria for analyzing the need, FDA has established criteria stating 
that an unmet medical need is one that is not adequately addressed by 
existing therapies. FDA officials pointed out that a temporary vaccine 
shortage would not meet the criterion of an unmet medical need, because 
by the time a new source of vaccine was approved (even under expedited 
procedures), the shortage would be expected to be over and the 
condition of unmet need would no longer exist. In addition, because 
many of the products in development are either new brands or new 
combinations of existing vaccines, an FDA official said that under 
current policy they would not meet the agency’s criteria for fast track 
(products address an unmet medical need) or priority review (products 
represent a significant improvement). These expedited processes are 
applicable mainly to vaccines that offer protection against diseases 
for which there are no existing vaccines. This was the case with PCV. 
At the time, no vaccines that protected against invasive pneumococcal 
disease were licensed for use in children under 2 years of age, so PCV 
was eligible to be designated as a fast track product and to receive 
priority review. As a result, the review and approval of PCV took about 
8.5 months, compared with the median time of 18.5 months for vaccines. 

Product Approval Requirements Are Not Standardized among Countries: 

Some of the vaccines in the pipeline are already licensed products in 
other countries, including Canada and various countries in Europe. FDA 
accepts foreign clinical studies in support of U.S. licensure; however, 
agency officials stated that if foreign data are used to support the 
safety, purity, or potency of a vaccine, FDA would need to 
independently assess the information and would usually require 
additional data. For example, the manufacturer might be required to 
provide evidence demonstrating that the product elicits a comparable 
immune response in a U.S. population. These studies can take additional 
time to complete. Part of the problem is that regulatory requirements 
for product registration often differ among countries. Standardizing 
these requirements, a process referred to as “harmonization,” is being 
discussed, but does not appear to be a near-term solution for vaccines. 
Harmonization efforts through the International Conference on 
Harmonisation of Technical Requirements for Registration of 
Pharmaceuticals for Human Use (ICH) involve Europe, Japan, and the 
United States. According to FDA, at the outset of the harmonization 
initiative, all ICH parties agreed to exclude from its scope certain 
biological products, including conventional vaccines, in part because 
of the complex nature of vaccines. [Footnote 22] 

No Clear Path Yet to Resolve Ongoing Supply Issues: 

Federal agencies and advisory committees are exploring options to help
stabilize the nation’s vaccine supply, but few long-term solutions have
emerged. Earlier this year, the National Vaccine Advisory Committee 
(NVAC) convened a meeting of vaccine experts to discuss supply problems 
and develop formal recommendations for further HHS consideration. The 
preliminary conclusion of the NVAC work group was that further study 
was needed of strategies, such as additional financial incentives for 
manufacturers and streamlining the regulatory process. CDC vaccine 
stockpiles have been used successfully to help mitigate temporary 
supply disruptions in the past and were considered a priority strategy 
by workshop participants. While CDC is required by law to stockpile a 6-
month supply of recommended childhood vaccines and has the necessary 
funding to do so, it currently maintains partial stockpiles for only 
two. In light of the recent shortages, CDC is considering expanding the 
stockpiles to include additional vaccines. While stockpiling vaccines
can provide a cushion in the event of a supply disruption, limited 
supply and manufacturing capacity will restrict CDC’s ability to build 
certain stockpiles in the near term. In addition, CDC lacks a 
comprehensive strategy and important information needed to effectively 
plan and manage the stockpile. 

NVAC Studying Strategies to Strengthen Vaccine Supply: 

Federal efforts to strengthen the nation’s vaccine supply have taken on
greater urgency with the recent incidents of shortages. A major effort 
by NVAC has been under way since mid-2001. As part of its mandate to 
study and recommend ways to encourage the availability of safe and 
effective vaccines, NVAC formed a Vaccine Supply Work Group to explore 
the issues surrounding vaccine shortages and identify strategies for 
further consideration by HHS. In February 2002, the work group convened 
a meeting of principal stakeholders—federal and state governments, 
vaccine manufacturers, health care providers, legislators, and academic
researchers—to determine the scope and identify contributing causes of
vaccine shortages and develop strategies to strengthen the vaccine 
supply. The work group presented its preliminary findings and 
recommendations in June 2002. 

In its preliminary report, work group members identified several 
strategies that hold promise, such as providing financial incentives 
for vaccine development, strengthening manufacturers’ liability 
protection, and streamlining the regulatory process, but they concluded 
that these strategies needed further study. In regard to liability 
protections, the work group did make recommendations to strengthen the 
Vaccine Injury Compensation Program (VICP). VICP is a federal program 
authorized in 1986 to reduce vaccine manufacturers’ liability by 
directly compensating individuals for childhood-vaccine-related 
injuries from a VICP trust fund. It was established, in part, to help 
stem the exodus of manufacturers from the vaccine business due to 
liability concerns. Manufacturers, however, reported a recent 
resurgence of childhood-vaccine-related lawsuits—including class action 
lawsuits related to past use of thimerosal—which allege that they are 
not subject to VICP. In the manufacturers’ view, these lawsuits once 
again threaten the stability of the industry by creating disincentives 
to produce vaccines. While the work group acknowledged that recent 
vaccine shortages do not appear to be related to liability issues, it 
indicated that strengthening VICP would encourage manufacturers to
enter, or remain in, the vaccine production business. Legislation has 
been introduced for the purpose of clarifying and modifying the VICP 
program. [Footnote 23] In response to the work group’s finding that 
streamlining the regulatory process needed further study, FDA recently 
announced that it is examining regulations governing manufacturing 
processes in both drugs and vaccine products to determine if reform is 
needed. However, FDA officials told us it is too early to define the 
scope and time frame for this reexamination. 

The NVAC work group expressed little support for constructing 
government-owned production facilities to produce routine childhood
vaccines. One concern raised by the work group was that vaccine
manufacturers might not be able to compete with a government-subsidized
program—potentially causing private manufacturers to withdraw from the
U.S. market, further shrinking the number of manufacturers, and reducing
the level of innovation and introduction of new products. In addition,
government-owned facilities would be subject to many of the same
limitations—such as long production times and stringent quality control
standards—that private manufacturers face. NVAC work group members
concluded that stockpiling vaccines, while having some limitations, 
should receive priority consideration to provide temporary relief during

Expansion of Stockpiles Is under Consideration: 

CDC is considering whether additional vaccine stockpiles will help 
stabilize the nation’s vaccine supply. CDC vaccine stockpiles have been
used to mitigate supply disruptions on at least seven occasions since 
they were first established nearly 20 years ago. In 1993, with the 
establishment of the VFC program, CDC was required to purchase 
sufficient quantities of pediatric vaccines not only to meet normal 
usage, but also to provide an additional 6-month supply to meet 
unanticipated needs. Further, to ensure funding, CDC was authorized to 
make such purchases in advance of appropriations. Despite this 
requirement, to date, CDC has established partial stockpiles for only 
two—MMR and IPV—of the eight routinely recommended pediatric vaccines. 
[Footnote 24] 

CDC’s past decisions to stockpile these two vaccines were based on a
number of factors. First, CDC considered the number of suppliers of each
vaccine—vaccines from a single source were considered at greater risk
and were the highest priority for stockpiling. Second, CDC assessed the
likelihood that changing technology or immunization schedules could
make stockpiled vaccines obsolete—new combination vaccines or revised
ACIP recommendations reduce the priority of stockpiling older vaccines.
CDC officials noted the importance of balancing the cost of 
establishing a stockpile versus the risk that the stockpiled vaccine 
might soon become obsolete. Third, CDC officials stated that because 
the demand for newer vaccines is unknown, manufacturers might not have 
excess capacity to create stockpile inventory. In light of recent 
shortages, CDC is reevaluating its criteria for setting priorities for 
which vaccines to stockpile. For example, limiting stockpiles to 
vaccines produced by sole manufacturers may no longer be appropriate. 

Even if CDC decides to stockpile additional vaccines, the currently 
limited supply of several vaccines will restrict CDC’s ability to build 
certain stockpiles in the near term. CDC estimates it could take 4 to 5 
years to build stockpiles for all the currently recommend childhood 
vaccines—at a cost of $705 million. Past experience also demonstrates 
the difficulty of rapidly building stockpiles. Neither the current IPV 
nor MMR stockpiles have ever achieved target levels because of limited 
manufacturing capacity. As of July 2002, the IPV stockpile stood at 3.7 
million doses, less than half of the 8 million doses on order. 
Similarly, the MMR stockpile has never reached its target of 4 
million—coming as close as 3.1 million doses in late 2001. 

Another issue that will need to be addressed is the extent to which
stockpiled vaccines purchased with VFC funds can be used for non-VFC-
eligible children. In 1993, the Congress passed legislation requiring 
the Secretary of HHS to negotiate for a 6-month supply of vaccines to 
meet unanticipated needs in connection with the VFC program. The 
legislation directed the Secretary to consider the potential for 
outbreaks of vaccine-preventable diseases in carrying out this 
stockpile requirement. [Footnote 25] CDC bases the target levels of its 
current stockpiles on the number of children in the general population 
and has allowed manufacturers to borrow from stockpiled vaccines for 
releases to this population. We note that the legislation does not 
state that the supply of stockpiled vaccines may be made available for 
children not otherwise eligible through the VFC program. CDC officials 
said that the VFC legislation is unclear as to whether stockpiled 
vaccines can be used for these children. 

There are other authorities under which CDC could procure stockpiles of
vaccines for children. CDC may develop vaccine stockpiles under its
authority to respond to public health emergencies and is required to
maintain vaccine stockpiles under the National Vaccine Program (NVP).
NVP is not limited to childhood vaccines, but appropriations were
authorized only through 1995. CDC has identified several other 
provisions of the Public Health Service Act that would authorize 
expenditures for vaccine stockpiles. For example, section 352 
authorizes HHS to produce products for use by the public and private 
sectors when they are unavailable from licensed sources. Section 311 of 
the act authorizes HHS to work closely with the states and provide 
“medical supplies” in the prevention and control of communicable 
diseases and to address other health emergencies. [Footnote 26] 

CDC Lacks a Comprehensive Strategy for Expanded Use of Stockpiles: 

Expanding the number of CDC vaccine stockpiles will require a 
substantial planning effort—an effort that is not yet complete. CDC has
not yet determined key aspects of vaccine stockpiles to ensure their 
ready release, including the quantity of each vaccine to stockpile, the 
form of storage, and storage locations. Also, to ensure that use of a 
stockpile does not disrupt supply to other purchasers, procedures would 
need to be developed to ensure that stockpiles are additional to a 
manufacturer’s normal inventory. CDC’s current approach to stockpiling 
lacks clear direction on the following fronts: 

Quantity to stockpile: CDC officials have not yet determined what 
quantity of vaccine most accurately constitutes a 6-month supply. To 
date, stockpile purchases have been based on estimates of the U.S. 
birth cohort (about 4 million babies per year) and ACIP 
recommendations—but this may not be enough to cover the actual need. 
For example, for each child to receive the recommended two doses of 
MMR, roughly 8 million doses of MMR would be needed annually. However, 
manufacturers report nearly 12.7 million doses were distributed in 
2001. Overvaccination due to lost immunization records, wastage from 
refrigerator outages or multiple dose packaging, and make-up 
immunizations could account for the difference. 

Vaccine experts are also beginning to consider whether stockpiles should
be expanded to include more than a 6-month supply. Recent shortages
have lasted from 9 to 20 months. A catastrophic event, such as a major
plant fire, could disrupt production for several years while a plant is 
being reconstructed. CDC has not yet fully evaluated the logistics of 
maintaining larger stockpiles or developed contingency plans for major 
supply disruptions. 

Form and location of storage: [Footnote 27] Stockpiled vaccines can be 
held in three forms: labeled (ready to ship), unlabeled (in vials, but 
not ready to ship), or bulk (product still must undergo final lot 
testing, filling, and labeling). Stockpiled vaccines requiring 
additional processing or packaging need to be closer to the 
manufacturing facility and require more time for release. Each storage 
method has advantages and disadvantages. For example, while labeled 
vaccine can be stored off site and distributed most rapidly, changes in 
package inserts could require a labor-intensive task of opening all the 
packages to replace the insert. Label changes are less of an issue for
vaccines in unlabeled or bulk form, but these vaccines must still 
undergo additional processing, making them vulnerable to plant 
disruptions. This became apparent in fall 2001, when modifications at 
the manufacturing plant necessitated shutdowns that delayed the release 
of the MMR vaccine held in stockpile. In response, CDC is reevaluating 
the amount of stockpiled vaccines required to be stored in final form 
and the location of storage. 

Maintenance of effort: CDC’s current stockpile program is designed to
ensure a quantity of vaccine in addition to manufacturers’ normal
inventory. However, current CDC stockpile contracts do not contain a
“maintenance of effort” requirement to ensure that production for the
stockpile is additional to normal production levels. Without such a
requirement, CDC efforts to use a stockpile could simply result in stock
being drawn from a manufacturer’s normal deliveries, without an overall
increase in the amount of product being available for release into the
market in times of shortage. [Footnote 28] 

During the MMR shortage, CDC became aware that the manufacturer could 
not release more of the MMR stockpile without affecting its deliveries 
to the private sector. The manufacturer used nearly 1 million doses 
from the stockpile during the winter of 2001-2002 (leaving about 2 
million doses remaining), but was unable to release more vaccine needed
to ease the shortage. The manufacturer had recently adopted additional
quality control procedures that temporarily limited the amount of 
vaccine that could be released during that period. CDC officials said 
that the recent MMR experience points to the need for additional 
contractual assurances that stockpiling represents a ready reserve of 
additional vaccine, and they are considering including maintenance of 
effort provisions in future stockpile contracts. 

Critical Information Needed to Manage Stockpiles Is Lacking: 

Once sufficient quantities of vaccines are stockpiled in the appropriate
form, CDC needs to make wise decisions on when to deploy the 
stockpiles. However, CDC currently lacks important information to help
do so. Timely release of the stockpile requires accurate prediction of a
number of variables related to the early identification, severity, and
duration of the supply disruption. CDC currently has data that it uses 
to screen for disruptions in vaccine supply to state immunization 
programs, but does not have data to anticipate a supply disruption or 
to fully evaluate the potential severity and duration of a supply 
disruption, especially to private providers. With such information, CDC 
could set priorities for or resize states’ orders and determine how 
much stockpiled vaccine to release and when to release it. Timely 
information is important, because releasing vaccine from a stockpile 
can take up to 30 days. Some of this information may already be 
available within HHS, but other information is available only from 
manufacturers or state immunization programs. 

Information from FDA: FDA has important information about 
manufacturers’ levels of vaccine production and plant conditions that
could affect production through its facility inspections and approval of
each production lot. [Footnote 29] On occasion, this information could 
help CDC anticipate supply disruptions and independently assess their 
potential severity, but it is only available to CDC by written request. 
Because of the lack of routine sharing of FDA information, CDC would 
likely be unaware of problems identified in FDA inspections that could 
cause the manufacturer to temporarily shut down a production line, 
unless notified by the manufacturer. This communication may not occur. 
For example, when FDA inspectors identified potential sterility issues 
at one facility, the manufacturer temporarily stopped production during 
the inspection, which eventually led to a shortage. But FDA did not 
inform CDC of the disruption. CDC officials told us they were first 
made aware of the disruption through media reports several weeks later. 

Information from manufacturers: There is no formal mechanism in place
for CDC to obtain critical information from manufacturers on prolonged
vaccine production disruptions, such as shutdowns due to maintenance or
repairs, that could precipitate the need to use the stockpile. CDC 
officials cite the value of having timely information on manufacturers’ 
capacity, current and future production levels, and any circumstances 
that could affect production—information that is often considered 
proprietary by manufacturers. Particularly during shortages, CDC does 
obtain some supply information from manufacturers, but they do not 
always provide it consistently or promptly. In addition, there is no 
requirement for vaccine manufacturers to notify CDC or FDA of business 
decisions to withdraw vaccines from the market. Although the Food and 
Drug Administration Modernization Act of 1997 requires sole 
manufacturers of a drug that is lifesaving or prevents a debilitating 
disease to give FDA a 6-month notification prior to discontinuance, 
[Footnote 30] this requirement does not extend to vaccines. The four 
major vaccine manufacturers told us they would not object to a similar 
requirement that they give FDA a 6-month notification of their intent 
to cease production of a vaccine. [Footnote 31] 

Information from states: To identify critical shortages and manage
distribution of public supplies, CDC needs an accurate, ongoing
accounting of state inventories. State immunization programs can provide
early indications of supply problems if states accumulate back orders.
State immunization programs also maintain working inventories (often a 
3-month or greater supply), which during times of nationwide vaccine
shortages could also help cushion supply disruptions. Prior to the 
recent vaccine shortages, CDC did not routinely monitor the vaccine 
inventory levels in state depots. In response to recent shortages, CDC 
instructed state immunization programs to inventory their stock-on-hand 
and submit monthly reports. CDC program managers are considering 
monitoring states’ inventory levels in nonshortage periods, but 
automated systems to facilitate uniform and timely reporting are still 
under development. In order to help ensure that inventories in excess 
of state needs are not maintained, CDC is also recommending that states 
maintain a 3-month inventory during normal supply situations, 
decreasing to a 1-month inventory during shortages, thus providing a 2-
month cushion. 


A steady and reliable supply of childhood vaccines is critical to 
maintain the substantial U.S. public health achievements in combating 
infectious diseases. However, the vaccine shortages experienced over 
the last 2 years demonstrate the vulnerability of the vaccine supply. 
Long lead times, sometimes a year or more, are needed to produce 
vaccines and alter existing production volumes. Because there are so 
few manufacturers (and increasingly, just one) producing a particular 
vaccine, even short-term disruptions in a manufacturer’s production 
volume can create a shortage. This condition is not likely to change in 
the near term. Therefore, federal agencies are continually challenged 
to take a proactive approach within their existing missions to help 
mitigate the effects of future disruptions to the vaccine supply. 

An often-cited approach that can help provide a cushion against 
disruptive effects of future shortages is to expand CDC’s reserves, or 
stockpiles, of childhood vaccines. While CDC is required to stockpile 
childhood vaccines under the VFC program, authorizing legislation does 
not address the extent that stockpiles can be used to support the needs 
of children not eligible under the program. In addition, stockpiling 
vaccines is not a panacea and, if poorly implemented, may provide 
little in the way of value. Expanding the stockpiles poses operational 
challenges that need to be addressed through strategic planning. For 
example, there is a need to establish a timetable for purchasing 
vaccines in a way that does not disrupt normal distribution, as well as 
a need to make decisions on the most desirable form and storage 
location for each vaccine. Implicit in these efforts to expand and 
manage a stockpile is the need for more timely information on the 
nature and extent of possible shortages. While working with 
manufacturers has shown some promise, opportunities exist to leverage 
other sources of available information, such as the results of FDA
vaccine plant inspections and state vaccine inventory levels. 

Although disruptions in supply can occur when manufacturers must stop
production in order to bring their facilities into compliance with FDA
standards, these standards are critical to helping ensure the safety, 
purity, and potency of vaccines. As FDA strengthens its process for 
measuring compliance with these standards, communication of 
expectations with manufacturers is important. FDA should provide 
manufacturers with available guidance about the expectations of what 
constitutes compliance—a situation that has not always occurred in the 

The prospect of additional vaccine products has potential to help reduce
the intensity of future disruptions to the supply of existing vaccines, 
but introduction of new products faces challenges. On one hand,
manufacturers have economic incentives to bring new childhood vaccines
to market. For example, introduction of new vaccines against additional
childhood diseases or new combinations of existing vaccines 
traditionally sell for higher prices and offer manufacturers new 
opportunities to compete for market share. On the other hand, it is an 
involved and time-consuming process, often taking several years, to 
obtain a license to sell these products in the U.S. market, even if the 
products are licensed for use in other countries. A substantial number 
of vaccines are in the development pipeline. While FDA has mechanisms 
available to shorten the review process, they are not used for most 
vaccines under development. 

FDA’s policy, in effect, applies the expedited processes to address an
unmet medical need for a new product, while childhood vaccines under
development often involve not new products, but existing vaccines or
combinations of existing vaccines. However, the fragility of the vaccine
supply itself demonstrates an unmet medical need because when supplies
are lacking, children may become more vulnerable to the spread of
disease. This possibility warrants FDA’s reconsidering its policy 
regarding expedited review to help prevent or mitigate vaccine 

Matter for Congressional Consideration: 

To help ensure that stockpiled vaccines are available for use by all
children, and in light of CDC’s development of vaccine stockpiles under
the VFC program, the Congress may wish to consider amending the
program legislation to specifically address whether vaccines stockpiled
under this program may be made available to children not otherwise

Recommendations for Executive Action: 

To ensure a well implemented strategy for expanding HHS’s stockpiles of
childhood vaccines, we recommend that the Secretary of HHS direct the
Director of CDC to develop a strategic plan that addresses the 
operational difficulties involved. At a minimum, such a plan should 

* a timetable, developed with manufacturers’ input, for the purchase of
specific quantities of vaccine; 

* a determination of form and location of storage of the vaccine; 

* procedures to ensure that stockpiles of vaccines are incremental to
manufacturers’ normal inventory levels; 

* procedures for systematic interchange of information between FDA and 
CDC on potential childhood vaccine manufacturing interruptions; and; 

* steps for monitoring childhood vaccine inventory in state VFC depots. 

To help strengthen the vaccine supply without compromising standards 
that ensure safety, we recommend that the Secretary direct the 
Commissioner of FDA to: 

* take steps to ensure widespread distribution of all forms of 
compliance guidelines to vaccine manufacturers and ensure that these 
guidelines are kept up-to-date and; 

* consider revising FDA policies for fast track and priority review 
approval of vaccines currently under development to allow their use, 
even in periods of nonshortage, in cases where FDA determines that 
applying them would help address the unmet need of a stable and 
sufficient overall vaccine supply. 

Agency Comments and Our Evaluation: 

We obtained comments on our draft report from HHS. In its general
comments, the department stated that it agrees with the report’s 
findings and that it has initiated action to implement the report’s
recommendations. In regard to our recommendation on the need for HHS
to develop a strategic plan for stockpiling childhood vaccines, HHS 
stated that CDC has arranged site visits to manufacturers for the 
purpose of discussing the specific stockpiling issues raised in the 
report. Further, after these site visits are completed, CDC would 
develop a comprehensive vaccine stockpiling program strategy. HHS also 
cited actions it was taking in regard to our recommendations that FDA 
be directed to ensure the widespread distribution of all forms of 
compliance guidelines to manufacturers. HHS stated that FDA was working 
with a contractor to post all Vaccine Compliance Program guidance on 
its Web site. 

HHS expressed some reservations in its comments about our 
recommendation that the Secretary direct FDA to consider revising FDA
policies for fast track and priority review approval of vaccine products
currently under development. HHS stated that in shortage situations, FDA
has the flexibility to work as expeditiously as possible with 
manufacturers of new or existing vaccines to alleviate the shortage. It 
also stated that critical vaccine shortages could allow for the 
designation of a vaccine as a fast track product. Often, however, 
shortages are temporary and are over before even the most expeditious 
review can be completed. As a result, HHS indicated that formal 
designation for expedited review process would have little impact on 
relieving the shortage. 

We did not intend that our recommendation apply only in times of 
existing vaccine shortages. Rather, the purpose of the recommendation 
is to provide HHS with another option to help prevent or mitigate the 
effects of future shortages. The potential exists to strengthen the 
childhood vaccine supply by selectively using the expedited review 
procedures to increase, as quickly as possible, the number of 
alternative vaccine products and suppliers. As a result of the 
department’s comments, we have modified the wording of our 
recommendation to make it clearer that it is directed at using existing 
expedited review tools as a strategic approach to help strengthen the 
overall vaccine supply. 

HHS did not comment on our matter for congressional consideration
concerning amending legislation under the VFC program, but did provide
technical comments, which we incorporated in the final report where
appropriate. We also provided sections of the draft report on factors 
that contributed to vaccine shortages and new vaccine products under
development to the four major vaccine manufacturers. We incorporated
their technical and clarifying comments where appropriate. 

As agreed with your offices, unless you publicly announce the contents 
of this report earlier, we plan no further distribution until 30 days 
after its issue date. At that time, we will send copies of this report 
to the Secretary of HHS, the Director of CDC, the Deputy Commissioner 
of FDA, and other interested parties. We will also make copies 
available to others on request. Copies of this report will also be 
available at no charge on GAO’s Web site at [hyperlink,]. 

If you or your staffs have any questions, please contact me at (202) 
512-7119. Other contacts and major contributors are included in
appendix II. 

Signed by: 

Janet Heinrich: 
Director, Health Care—Public Health Issues: 

List of Requesters: 

The Honorable Edward M. Kennedy: 
Committee on Health, Education, Labor, and Pensions: 
United States Senate: 

The Honorable Henry A. Waxman: 
Ranking Minority Member: 
Committee on Government Reform: 
House of Representatives: 

The Honorable Jeff Bingaman: 
The Honorable Hillary Rodham Clinton: 
The Honorable Richard J. Durbin: 
The Honorable Bill Frist: 
The Honorable Jack Reed: 
United States Senate: 

The Honorable Gary A. Condit: 
House of Representatives: 

[End of section] 

Appendix I: Comments from the Department of Health & Human Services: 

Department Of Health & Human Services: 
Office of Inspector General: 
Washington, D.C. 20201: 

September 4, 2002: 

Ms. Janet Heinrich: 
Director, Health Care - Public Health Issues: 
United States General Accounting Office: 
Washington, D.C. 20548: 

Dear Ms. Heinrich: 

Enclosed are the department's comments on your draft report entitled, 
"Childhood Vaccines: Ensuring an Adequate Supply Poses Continuing 
Challenges." The comments represent the tentative position of the 
department and are subject to reevaluation when the final version of 
this report is received. 

The department also provided several technical comments directly to 
your staff. 

The department appreciates the opportunity to comment on this draft 
report before its publication. 


Signed by: 

Janet Rehnquist: 
Inspector General: 


The Office of Inspector General (OIG) is transmitting the department's 
response to this draft report in our capacity as the department's 
designated focal point and coordinator for General Accounting Office 
reports. The OIG has not conducted an independent assessment of these 
comments and therefore expresses no opinion on them. 

Comments of the Department of Health and Human Services on the General 
Accounting Office's Draft Report, "Childhood Vaccines: Ensuring an 
Adequate Supply Poses Continuing Challenges" (GAO-02-987): 

The Department of Health and Human Services (department) thanks the 
General Accounting Office (GAO) for undertaking this important study 
and providing the department with the opportunity to comment on the 
draft report. In general, the report calls needed attention to the 
challenges and resource needs of mounting an effective response to 
assure an adequate supply of childhood vaccines. The department agrees 
with the GAO report, which generally presents an accurate and 
informative summary of the key issues that impact on vaccine shortages. 

Immunization is considered one of ten great public health achievements 
of the 20th Century. Indeed, vaccine preventable disease levels are 
currently at or near all-time lows, and childhood immunization coverage 
levels have been at all-time high levels during the last several years. 
This success is in no small part due to the innovative and highly 
effective role of the private sector (often in partnership with 
innovators in academia and government) in vaccine development and 
production in the United States and abroad, and the widespread use of 
licensed vaccines. Many of the childhood vaccines routinely recommended 
in the U.S. and elsewhere in the world, such as Polio, Measles, Mumps, 
and Rubella (MMR), Haemophilia influenzae type b (Hib), hepatitis B, 
and Pneumococcal conjugate vaccines, were first brought to the market 
by private companies. Furthermore, competition among private 
pharmaceutical companies has resulted in substantial innovation, such 
as new and safer vaccines, which saves lives and prevents disease and 

For more than 15 years, our nation's children have had steady access to 
vaccines. The minor disruptions in production that have occasionally 
occurred in the past have been resolved through mobilizing vaccine from 
national stockpiles, and through the department's Food and Drug 
Administration (FDA) and Centers for Disease Control and Prevention 
(CDC), and partners working with manufacturers to increase vaccine 
supplies. Nevertheless, the unprecedented recent disruption in supply 
documents that vaccine supply cannot be taken for granted and that 
critical actions are needed to avert future shortages. 

Below are general comments on the GAO report and specific comments to 
GAO's executive recommendations. 

General Comments: 

The department agrees with the GAO's findings and has initiated actions 
to implement their recommendations. The department agrees that the 
Vaccines for Children (VFC) Stockpile authority in section 1928(d)(6) 
of the Social Security Act (42 U.S.C. I396s(d)(6)), requires that 
stockpiles of childhood vaccines be maintained. Several programmatic 
reasons occurred that have slowed the development of CDC stockpiles. 
These include the following: 

* Implementation of the VFC program took considerable time and 
resources. Priority was given to recruiting providers to serve eligible 
children and establishing new contracts with vaccine manufacturers to 
supply vaccine to the eligible children. 

* The CDC had prioritized acquisition to establish stockpiles in a 
systematic and efficient manner. One year after fully implementing the 
VFC program, CDC began to expand its stockpile program utilizing VFC 
program funds. In the late 1990s, CDC focused its efforts on fully 
establishing single source vaccine stockpiles for highly contagious 
diseases such as polio and measles. Historical experience with multiple 
manufacturers indicated that it might not be efficient to have 
government-funded stockpiles in all instances due to the following: 
changing market shares, evolving vaccine technology (i.e. new 
combination vaccines), and open market. 

* Any changes to the already complicated vaccine schedule or abrupt and 
unanticipated changes to the vaccines themselves, such as removal of 
thimerosal, require concomitant adjustments in stockpiles either by 
stockpiling new vaccines, drawing down existing stockpiles while 
increasing stockpiles of new vaccines, or changing existing stockpiled 
vaccines. Contracts used to establish the stockpiles had previously not 
had the flexibility to rapidly respond to such changes. 

In light of the recent vaccine shortages, as well as the GAO 
recommendations, CDC is undertaking steps to establish and expand 
stockpiles as soon as feasible. 

Comments on Recommendations for Executive Action: 

GAO Recommendation: 

To ensure a well-implemented strategy for expanding HHS's stockpiles of 
childhood vaccines, we recommend that the Secretary of HHS direct the 
Director of CDC to develop a strategic plan that addresses the 
operational difficulties involved. At a minimum such a plan should 

* A timetable, developed with manufacturers' input, for the purchase of 
specific quantities of vaccine; 

* A determination of form and location of storage of vaccine; 

* Procedures for systematic interchange of information between FDA and 
CDC on potential childhood vaccine manufacturing interruptions, and; 

* Steps for monitoring of childhood vaccine inventory in state VFC 

Department Comment: 

The department agrees with GAO's recommendation to develop a strategic 
plan to expand stockpiles of childhood vaccines. Stockpiles have been 
very effective in the past in alleviating brief disruptions in vaccine 
supply and are an important resource to maintain. The CDC has already 
been engaged in a reassessment of its vaccine stockpile and has 
initiated discussions with the manufacturers to determine their 
projections of product availability for establishment/expansion of 
vaccine stockpiles. Site visits to manufacturers have been arranged to 
discuss issues raised in the GAO recommendation related to timetable, 
stockpile form, storage location and maintenance. The CDC will develop 
a comprehensive vaccine stockpile program strategy after the site 
visits are completed. 

GAO Recommendation: 

To help promote the availability of existing and future vaccine 
products without compromising standards that help assure safety, we 
recommend that the Secretary direct the Commissioner of FDA to take 
steps to ensure widespread distribution of all forms of compliance 
guidelines to vaccine manufacturers and ensure that these guidelines 
are kept up-to-date. 

Department Comment: 

Compliance guidance directed to vaccine manufacturers has been made 
available to them through public postings on the FDA website and 
through many outreach meetings held with industry and their trade 
associations. The FDA is working with a contractor to post all 
compliance programs, including the Vaccine Compliance Program, on its 
website. In the meantime, inspectional guidance for FDA investigators 
concerning vaccine-manufacturing inspections will continue to be 
available in the Vaccine Compliance Program through the Freedom of 
Information Act. 

GAO Recommendation: 

To help promote the availability of existing and future vaccine 
products without compromising standards that help assure safety, we 
recommend that the Secretary direct the Commissioner of FDA to consider 
revising FDA policies for fast-tracking and priority review approval of 
vaccine products currently under development to allow their use in 
cases where FDA determines that applying them is in the public health 
interest to address the unmet need of strengthening the overall vaccine 

Department Comment: 

There appears to he some confusion about "fast track" and "priority 
reviews" and how these might or might not speed up the approval time 
for the licensing of new vaccines or existing vaccines that are in 
short supply. 

The department recognizes the seriousness of vaccine shortages or 
potential vaccine shortages and, in either the presence or absence of 
any given formal expedited approval process (i.e., fast track or 
priority review), FDA has reviewed, and will continue to review, 
license applications or their supplements in the most expeditious 
manner possible. The FDA does and will continue to organize priorities 
based on medical need. For example, FDA expedited the review of 
influenza vaccine supplements because of shortage situations or to 
avert potential shortage situations and, recently, the review of 
Daptacel (Aventis Pasteur's diphtheria and tetanus toxoids and 
acellular pertussis vaccine adsorbed [DtaP]) was conducted as 
expeditiously as possible. 

Biologic License Applications (BLA) may be formally designated for a 
priority review. The FDA has 6 months to complete its review for a new 
BLA; in contrast, it has 10 months for a so-called standard review. A 
BLA for vaccines in short supply would qualify for a priority review. 
However, even in the absence of a formal designation for a priority 
review, the application would be reviewed as expeditiously as possible. 
East track, which applies to products that are intended to treat or 
prevent life-threatening or serious conditions, allows for submission 
of a partial application that can be reviewed before the entire license 
application is complete. Most fast track products are eligible for 
priority, 6-month review. Critical vaccine shortages could allow for 
designation of a vaccine as a fast track product. 

It is necessary to consider the practical aspects of priority and fast 
track reviews. Often, shortages are temporary and are over before even 
the most expeditious review can be completed; in such cases, the formal 
designation for the review process has little impact on the shortage. 
Thus, as a practical matter, it will be infrequent that a new vaccine 
will become licensed expressly and in time to alleviate a shortage. 
During the recent shortage of DTaP, Daptacel was approved. The review 
of this application was a priority for the FDA's Center for Biologics 
Evaluation & Research (CBER), and this was consistent with a previous 
determination, stemming from several years ago, that all acellular 
pertussis vaccines would he considered a priority, and reviewed 
expeditiously. The message that we wish to stress is that in a shortage 
situation CBER has the flexibility to work as expeditiously as possible 
with manufacturers of new or existing vaccines to alleviate the 

As an aside, Prevnar, the pneumococcal conjugate vaccine, was 
designated as a fast track drug product and the sponsor was allowed to 
submit a partial application for review before submitting their entire 
marketing application. This was done because there was a clear unmet 
medical need, viz., no existing vaccine for the prevention of invasive 
pneumococcal disease, a serious disease, in infants (< 2 years of age). 


The department appreciates the attention the GAO has brought to the 
issue of childhood vaccine shortages. The GAO's stockpile 
recommendation will he a useful tool in ensuring an adequate supply of 
childhood vaccines. The CDC has begun the planning process to address 
the recommendation regarding stockpiles. 

[End of section] 

Appendix II: GAO Contacts and Staff Acknowledgments: 

GAO Contacts: 

Frank Pasquier, (206) 287-4861: 
Terry Saiki, (206) 287-4819: 

Staff Acknowledgments: 

In addition to those named above, Julian Klazkin, Jennifer Major, Linda
McIver, Leslie Spangler, and Stan Stenersen made key contributions to 
this report. 

[End of section] 


[1] CDC supports 64 immunization programs nationwide—50 states, 8 
territories, 5 cities, and the District of Columbia. For simplicity, 
throughout this report we refer to them as state immunization programs. 
Fifty-two of the 64 state immunization programs responded to our 

[2] The CDC recommended immunization schedule comprises the coordinated
recommendations approved by the Advisory Committee on Immunization 
Practices, the American Academy of Pediatrics, and the American Academy 
of Family Physicians. 

[3] A state-owned facility in Massachusetts produces a limited quantity 
of tetanus and diphtheria booster. 

[4] 42 U.S.C. sec. 247b. 

[5] In 1993, legislation was enacted that established price caps for 
vaccines purchased through existing CDC contracts. Of the eight 
currently recommended vaccines, two (polio and haemophilus influenzae 
type b) are selling below their price caps, one (MMR) is selling at its 
cap, and one (tetanus and diphtheria booster) is not available because
manufacturers are not willing to sell it to CDC at its price cap; the 
remaining four are not subject to price caps because CDC had not 
contracted for them prior to May 1993. 

[6] This total is based on the minimum price of vaccines under CDC 
contracts needed to complete CDC’s suggested normal immunization 
timetable for children through 6 years of age (excludes adolescent 
tetanus and diphtheria booster). 

[7] The guidelines for the prioritization of Td and DTaP were issued by 
CDC and were approved by ACIP. Initially these shortages were 
anticipated to be brief, and therefore no official modifications were 
made to the immunization schedule by ACIP. 

[8] We distributed the survey in February 2002 and conducted follow-up 
on the results through May 2002. 

[9] A CDC survey that was limited to three vaccines and conducted in 
fall 2001 showed comparable results. For example, 48 percent of the 
state immunization programs surveyed reported that they had reduced 
immunization requirements for tetanus and diphtheria boosters in 

[10] NIS is a random-digit-dialing telephone survey sponsored by the 
National Immunization Program and conducted by CDC’s National Center 
for Health Statistics. 

[11] In August 2002, CDC reported that a limited study in Puerto Rico 
found a marked decrease in DTaP coverage consistent with CDC’s 
recommendation to defer the fourth dose of DTaP. See Centers for 
Disease Control and Prevention, “Impact of Vaccine Shortage on 
Diphtheria and Tetanus Toxoids and Acellular Pertussis Vaccine Coverage
Rates Among Children Aged 24 Months-Puerto Rico, 2002,” Morbidity and 
Mortality Weekly Report, vol. 51, no. 30 (2002): 667-668. 

[12] NIS statistics reflect national coverage rates for the following 
immunization series: four or more doses of DTaP, three or more doses of 
IPV, one or more doses or any measles-containing vaccine, three or more 
doses of Hib, and three or more doses of Hep B vaccine. NIS does not 
include varicella or PCV in the combined series. NIS began in 1994; 
however, we only reviewed years 1995 through 2001 because the 1994 
survey did not include coverage of Hep B in the combined series. 

[13] For a review of studies of health effects of ethyl and methyl 
mercury, see Institute of Medicine, Immunization Safety Review: 
Thimerosal-Containing Vaccines and Neurodevelopmental Disorders 
(Washington, D.C.: 2001). 

[14] FDA, the Environmental Protection Agency (EPA), and the Agency for 
Toxic Substances and Disease Registry (ATSDR) have developed guidelines 
for safe exposure to methyl mercury. Thimerosal contains ethyl mercury, 
but since no federal guidelines exist for safe exposure to ethyl 
mercury, FDA used the guidelines for methyl mercury. FDA found that the 
cumulative amount of mercury a child could be exposed to from vaccines 
exceeded EPA’s guidelines for safe exposure to methyl mercury but were 
below those of FDA and ATSDR. 

[15] The joint statement by AAP and PHS also stated that the large risk 
of not vaccinating children far outweighs the unknown and probably much 
smaller risk, if any, of cumulative exposure to thimerosal-containing 
vaccines in the first 6 months of life. 

[16] In addition to the one major nationwide supplier of Td, a second 
manufacturer produces a small amount of Td, primarily for local 
distribution, and makes some available for nationwide distribution. 

[17] The company had entered into a consent decree in October 2000 in 
which it agreed to implement a series of measures aimed at ensuring 
that products manufactured at two of its facilities are in compliance 
with FDA good manufacturing practices regulations. 

[18] For example, in the case of the combination vaccine that protects 
against hepatitis B and Haemophilus influenzae type b (Hep B-Hib), CDC 
data show that about 4.8 million doses of the combination vaccine were 
distributed in calendar year 2000, compared to 23.7 million doses of 
hepatitis B vaccine and 11.4 million doses of Hib vaccine. 

[19] See 21 U.S.C. sec. 356. Acceptance of a portion of the application 
does not necessarily mean that the review will start before a complete 
application is received. According to FDA, when the review is started 
will depend on many factors including staffing, competing priorities, 
and the perceived efficiency of starting the review before the 
submission of the complete application. 

[20] Priority review is ordinarily open to fast track products as well 
as non-fast-track products. 

[21] FDA’s review time is the actual amount of time FDA spends 
reviewing a new drug or BLA. The approval time—from first submission of 
the BLA to BLA approval—could be much longer. The approval time 
includes the sum of FDA review time for the first submission of the 
BLA, plus any subsequent time during which a sponsor addresses 
deficiencies in the BLA and resubmits the application, plus subsequent 
FDA review time. 

[22] At a recent hearing, the Deputy Commissioner of FDA suggested that 
if a vaccine were approved in another country and CDC indicated its use 
would help ameliorate shortages in the United States, FDA would 
consider requests to make these products available as investigational 
vaccines. Under FDA regulations, these vaccines could be administered to
children in the United States with informed consent from their parents. 
However, the Director of the National Immunization Program within CDC 
said the use of investigational vaccines in a routine vaccination 
program could pose problems in achieving public acceptance. 

[23] See S. 2053, H.R. 1287, and H.R. 3741. 

[24] CDC also maintains small stockpiles of pediatric DT and oral polio 
(neither recommended for routine use) for use in the event of 

[25] Td is not available for stockpiling under this mechanism because, 
as previously noted, manufacturers are not willing to sell it to CDC 
under the VFC price cap. 

[26] CDC also identified section 317 of the Public Health Service Act, 
which, as mentioned earlier, authorizes state grants for preventive 
health services, as additional authority to stockpile vaccines. 

[27] To establish a stockpile, CDC contracts with a qualified 
manufacturer to purchase the vaccine. CDC then pays the manufacturer an 
annual fee to store and rotate the stockpile. As portions of the 
stockpile approach 12 months of remaining shelf life, the manufacturer
will rotate the stockpile into normal distribution and replace it with 
stock having a more distant expiration date. Because stockpiled 
vaccines are often stored in unfinished form and are periodically 
rotated with newer lots, stockpiles are typically held at the 
manufacturer’s production location. 

[28] Maintenance of effort requirements are particularly important for 
manufacturers that have multiple products that share the same 
production facilities, because efforts to use a stockpiled vaccine 
during a time of shortage could create or exacerbate a shortage of other
important drugs or vaccines that would be displaced by shifting 
production resources. 

[29] FDA also secures some supply information through reports it 
requires manufacturers to submit on the quantity of vaccines they 
distribute (see 21 C.F.R. sec. 600.81). Currently, such reports are 
required every 6 months. 

[30] The 6-month notification requirement may be reduced if a public 
health problem could result from continued production, manufacturers 
face financial loss, there is a shortage of drug components, or other 
hardship would occur. 21 U.S.C. sec. 356c. 

[31] A bill was recently introduced in the Senate (S. 2049) that would 
amend the notification provision by requiring manufacturers to give FDA 
at least a 12-month notice before discontinuing biological products, 
including vaccines. 

[End of section] 

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