Childhood Vaccines: Challenges in Preventing Future Shortages
Published: 2002-09-17T00:00:00

Fast Facts:

Highlights:
section_title: What GAO Found
paragraphs: Vaccine 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.

section_title: Letter
paragraphs: 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. 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.
subsections: section_title: Background
paragraphs: 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). 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.
section_title: Shortages Prompt Actions to Reduce Immunization Requirements
paragraphs: 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. 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.
section_title: Problems Causing Shortages Largely Resolved, but Shortages Could Recur
paragraphs: 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. While thimerosal  was present in several vaccines, removing it from some vaccines was more  complex than for others. For example, one manufacturer of the diphtheria- tetanus-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.
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.
section_title: No Clear Path Yet to Resolve Ongoing Supply Issues
paragraphs: 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.
subsections: section_title: Expansion of Stockpiles Is under Consideration
paragraphs: 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.