Childhood Vaccines
Challenges in Preventing Future Shortages Gao ID: GAO-02-1105T September 17, 2002Vaccine shortages began to appear in November 2000, when supplies of the tetanus and diptheria booster fell short. By October 2001, the Centers for Disease Control and Prevention (CDC) reported shortages of five vaccines that protect against eight childhood diseases. In addition to diptheria and tetanus vaccines, vaccines to protect against pertussis, invasive pneumococcal disease, measles, mumps, rubella, and varicella were in short supply. In July 2002, updated CDC data indicated supplies were returning to normal for most vaccines. However, the shortage of vaccine to protect against invasive pneumococcal disease was expected to continue through at least late 2002. Shortages have prompted federal authorities to recommend deferring some vaccinations and have caused most states to reduce or suspend immunization requirements for school and day care programs so that children who have not received all mandatory immunizations can enroll. States are concerned that failure to be vaccinated at a later date may reduce the share of the population protected and increase the potential for disease to spread; however, data are not currently available to measure these effects. Many factors, including production problems and unanticipated demand for new vaccines, contributed to recent shortages. Although problems leading to the shortages have largely been resolved, the potential exists for shortages to recur. Federal agencies and advisory committees are exploring ways to help stabilize the nation's vaccine supply, but few long-term solutions have emerged. Although CDC is considering expanding vaccine stockpiles to provide a cushion in the event of a supply disruption, limited supply and manufacturing capacity will restrict CDC's ability to build them.
GAO-02-1105T, Childhood Vaccines: Challenges in Preventing Future Shortages
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United States General Accounting Office:
GAO:
Testimony:
Before the Subcommittee on Public Health, Committee on Health,
Education, Labor, and Pensions, U.S. Senate:
For Release on Delivery:
Expected at 2:30 p.m.
Tuesday, September 17, 2002:
Childhood Vaccines:
Challenges in Preventing Future Shortages:
Statement of Janet Heinrich:
Director, Health Care”Public Health Issues:
GAO-02-1105T:
Mr. Chairman and Members of the Subcommittee:
We are pleased to be here today to discuss recent childhood vaccine
shortages. Today we are releasing our report that you, along with seven
other Members of the Congress, requested on the subject. [Footnote 1]
My statement today highlights some of the key aspects of our report.
The recent incidents of vaccine shortages began in November 2000 when
supplies of the tetanus and diphtheria booster (Td) fell short. By
October 2001, the Centers for Disease Control and Prevention (CDC)
reported shortages of five vaccines that, because some are combination
vaccines, protect against eight childhood diseases. In addition to
diphtheria and tetanus vaccines, vaccines to protect against pertussis,
invasive pneumococcal disease, measles, mumps, rubella, and varicella
were in short supply. In July 2002, updated CDC data indicated supplies
were returning to normal for most vaccines. However, the shortage of
vaccine to protect against invasive pneumococcal disease was expected to
continue through at least late 2002. Concerned about the impact of and
reasons for these shortages, you asked that we examine 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?
In brief, shortages have prompted federal authorities to recommend
deferring some vaccinations and have caused the majority of states to
reduce or suspend immunization requirements for school and day care
programs so that children who had received fewer than the previously
mandatory immunizations could enroll. States are concerned that failure
to be vaccinated at a later date may reduce the share of the population
protected and increase the potential for disease to spread; however,
data are not currently available to measure these effects.
Multiple factors, including production problems and unanticipated
demand for newly approved vaccines, contributed to recent vaccine
shortages. While problems leading to the shortages have largely been
resolved, the potential exists for shortages to recur. The complex
nature and often year-long production schedule of manufacturing a
vaccine will continue to make it difficult for the supply system to
respond rapidly to sudden changes in supply or demand. Additionally, so
few firms make each vaccine (five of the eight recommended childhood
vaccines have only one manufacturer each), that production problems or a
manufacturer‘s decision to withdraw may leave few or no alternative
sources of vaccine. One development that may increase the supply of
vaccines 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. However, completing clinical testing and review by the
Food and Drug Administration (FDA) will likely take several years, as
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. Approaches under consideration include strengthening
manufacturers‘ protection against liability for injuries related to
childhood vaccines and streamlining the regulatory process. While CDC is
considering expanding vaccine stockpiles to provide a cushion in the
event of a supply disruption, limited supply and manufacturing capacity
will restrict CDC‘s ability to build them. CDC also 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. In addition, it is unclear whether
the authority that CDC is using to establish these stockpiles provides
for their use for all children.
Background:
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. 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]
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.
The federal government, primarily through agencies of the Department of
Health and Human Services (HHS), 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,
including those who are eligible for Medicaid or uninsured.
Participating public and private health care providers obtain vaccines
through VFC at no charge. A second program, established under section
317, of the Public Health Service Act, provides project grants for
preventive health services, including immunizations. Currently, CDC
supports 64 state, local, and territorial immunization programs (for
simplicity, we refer to them as state immunization programs). 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 federal government is also responsible for ensuring the safety of
the nation‘s vaccine supply. FDA regulates the production of vaccines.
It licenses all vaccines sold in the United States, requiring clinical
trials to demonstrate that vaccines are safe and effective, and 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.
States also have an important role in immunization efforts. 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. Each state also
established an immunization infrastructure to monitor infectious
disease outbreaks, administer federal immunization grants, manage
centralized supplies of vaccine, and otherwise promote immunization
policies.
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. 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. 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. 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 South Carolina and Washington, reported allowing children to
attend day care or school even if they were not in compliance with
immunization requirements, under the condition that they be recalled
for vaccinations when supplies became available.
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,
therefore, increase the potential for infectious disease outbreaks. The
full impact of vaccine shortages is difficult to measure for several
reasons. For example, none of the national immunization coverage
surveys measures vaccination coverage of children under the age of 18
months”the age cohort receiving the majority of vaccinations. [Footnote
3] While immunization experts generally agree that the residual effects
of historically high immunization rates afford temporary protection for
underimmunized children, missed immunizations could make susceptible
children vulnerable to disease outbreaks. 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 vaccine.
Problems Causing Shortages Largely Resolved, but Shortages Could Recur:
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, as follows.
Production Problems - Manufacturing production problems contributed to
the shortage of certain vaccines. In some cases, production slowdowns or
interruptions occurred when planned maintenance activities took longer
than expected; in other cases, production was affected as manufacturers
addressed problems identified in FDA inspections. Changes over the last
several years in FDA inspection practices may have resulted in the
identification of more or different instances of manufacturers‘
noncompliance with FDA manufacturing requirements. For example, prior
to these changes, biologics inspections tended to focus primarily on
scientific or technical issues and less on compliance with good
manufacturing practices and documentation issues. FDA did take some
steps to inform manufacturers about its inspection program changes;
however, some manufacturers reported problems related to how well the
changes were communicated. FDA issued a compliance program guidance
manual detailing the new protocol for conducting inspections intended
for FDA staff. However, the information in it could have provided
manufacturers a better understanding of the scope of the inspections,
but the manual was not made widely available”only upon request.
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. 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 4] While thimerosal was present in several vaccines, removing
it from some vaccines was more complex than for others. For example,
one manufacturer of the diphtheriatetanus-acellular pertussis vaccine
(DTaP) had to switch its packaging from multidose to single-dose vials
due to the removal of the preservative. This process reduced the
manufacturer‘s output of vaccine by 25 percent, according to the
manufacturer.
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 5]
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, pneumococcal conjugate 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. Company officials said an
extensive education campaign prior to its availability resulted in
record-breaking initial demand for the vaccine. CDC reported shortages
of PCV existed through most of 2001, and the manufacturer was only able
to provide about half the needed doses during the first 5 months of
2002.
Ongoing manufacturing problems limit production, exacerbating the
shortage.
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, involving living
biological organisms, that can take several months to over a year.
Another underlying problem is the limited number of manufacturers”five
of the eight recommended childhood vaccines have only one major
manufacturer each. Consequently, if there are interruptions in supply
or if a manufacturer ceases production, there may be few or no
alternative sources of vaccine.
One situation that may help add to the supply of existing vaccines is
the development of new vaccines. A recent example is a new formulation
of DTaP that recently received FDA approval and has helped ease the
shortage of DTaP. We identified 11 vaccines in development that could
help meet the current recommended immunization schedule. These
vaccines, some of which are already licensed for use in other countries,
are in various stages of development, but all must undergo a rather
lengthy process of clinical testing and FDA review. While FDA has
mechanisms available to shorten the review process, they are not used
for most vaccines under development. FDA policies generally restrict
the use of its expedited review processes to vaccines that offer
protection against diseases for which there are no existing vaccines.
Because childhood vaccines under development often involve new forms or
combinations of existing vaccines, they typically do not qualify for
expedited FDA review.
No Clear Path Yet to Resolve Ongoing Supply Issues:
Federal efforts to strengthen the nation‘s vaccine supply have taken on
greater urgency with the recent incidents of shortages. As part of its
mandate to study and recommend ways to encourage the availability of
safe and effective vaccines, the National Vaccine Advisory Committee
formed a work group to explore the issues surrounding vaccine shortages
and identify strategies for further consideration by HHS. In its
preliminary report, the work group identified several strategies that
hold promise, such as streamlining the regulatory process, providing
financial incentives for vaccine development, and strengthening
manufacturers‘ liability protection, but it concluded that these
strategies needed further study. The work group did express support for
expanding CDC vaccine stockpiles.
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 for 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. Regarding financial incentives for vaccine
development, the Institute of Medicine is currently conducting a study
of vaccine pricing and financing strategies that may address this
issue.
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 compensating individuals for childhood-
vaccine-related injuries from a VICP trust fund. The program 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”that
allege that the lawsuits are not subject to VICP. While the work group
acknowledged that recent vaccine shortages do not appear to be related
to VICP 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 VICP. [Footnote 6]
Expansion of Stockpiles Is under Consideration:
Also consistent with the work group‘s recommendations, CDC is
considering whether additional vaccine stockpiles will help stabilize
the nation‘s vaccine supply. 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”measles-mumps-rubella (MMR) and
inactivated polio vaccine (IPV)”of the eight recommended childhood
vaccines.
Even if CDC decides to stockpile additional vaccines, the limited supply
and manufacturing capacity 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 recommended 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. In addition to these challenges, CDC will also
need to address issues regarding its authority, strategy, and
information needed to use stockpiled vaccines.
Authority - It is uncertain whether stockpiled vaccines purchased with
VFC funds can be used for non-VFC-eligible children. While the 1993
legislation required the Secretary of HHS to negotiate for a 6-month
stockpile of vaccines to meet unanticipated needs, the legislation did
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 all children.
Strategy - Expanding the number of CDC vaccine stockpiles will require a
substantial planning effort”an effort that is not yet complete. For
example, CDC has not made key decisions about 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
represent additional quantities to a manufacturer‘s normal inventory
levels.
Information - 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 information for effective
decision making. Releasing vaccine from a stockpile in a timely manner
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. Through its facility inspections and approvals of production
lots, FDA has important information about manufacturers‘ levels of
vaccine production and plant conditions that could affect production.
This information could help CDC anticipate supply disruptions and
independently assess their potential severity, but it is only available
to CDC by written request. 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.
Concluding Observations:
The vaccine shortages experienced over the last 2 years demonstrate the
vulnerability of the vaccine supply to disruption. Federal agencies are
continually challenged to take a proactive approach within their
existing missions to help mitigate the effects of these potential
future disruptions. Accordingly, our report makes 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
authority to expedite approval of products in development and directing
CDC to address several operational and strategic issues in expanding
childhood vaccine stockpiles. The report also contains a matter for
congressional consideration to amend the VFC program legislation to
address whether vaccines stockpiled under the program are available for
use by all children in the event of a shortage.
This concludes my prepared statement, Mr. Chairman. I will be happy to
respond to any questions that you or Members of the Subcommittee may
have.
Contacts and Acknowledgments:
For future contacts regarding this testimony, please call Janet
Heinrich, Director, Health Care”Public Health Issues, at (202) 512-7119
or Frank Pasquier at (206) 287-4861. Other individuals who made key
contributions include Jennifer Major, Linda McIver, Terry Saiki, and
Leslie Spangler.
[End of section]
Footnotes:
[1] U.S. General Accounting Office, Childhood Vaccines: Ensuring an
Adequate Supply Poses Continuing Challenges, GAO-02-987 (Washington,
D.C.: Sept. 13, 2002).
[2] The CDC recommended immunization schedule combines the
recommendations approved by the Advisory Committee on Immunization
Practices, the American Academy of Pediatrics, and the American Academy
of Family Physicians.
[3] 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.
[4] 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.
[5] 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.
[6] See S. 2053, H.R. 1287, and H.R. 3741.
[End of section]
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