Plans underway to prevent future vaccine shortages

The state of vaccines, including an increase in coverage rates, introduction of new vaccines and maintenance of vaccine supplies for routinely recommended childhood vaccines, has come a long way in the past 10 years. The goal now is to not repeat mistakes of the past.

“Most vaccine-preventable diseases in the United States are at record low levels, and we have achieved and sustained high childhood rates, reduced disparities, particularly in childhood coverage, and over the past several years, introduced a number of new vaccines, as well as improved the production, supply and distribution of the influenza vaccine,” Anne Schuchat, MD, director of the CDC’s Center for Global Health, said in February at the National Vaccine Advisory Committee (NVAC) meeting. “Compared to 10 years ago, the situation is pretty remarkable.”

Today, children in the United States are protected against 17 serious diseases and conditions through routine immunization.

“Despite what you read about, most coverage levels in young children are high. ... It’s important to know that less than 1% of toddlers have received no vaccines at all,” Schuchat said. “Vaccinating children remains a social norm in the United States, and the CDC, as a public-private partnership in delivering vaccines, continues to do well, but that doesn’t mean the system hasn’t gone through a lot of changes.”

Infectious Diseases in Children spoke with several experts about a number of entities contributing to vaccine shortages in the United States and what is being done to prevent them.

Past vaccine shortages

Jerome O. Klein, MD, an Infectious Diseases in Children Editorial Board member, cited a 2006 Pediatrics commentary in which he said attention was directed to vaccine supply vulnerability in 2001 when, “eight of the 11 vaccines recommended for universal immunization of infants and children were unavailable or in short supply.”

Most shortages were resolved within the next year; however, there were continued periods of shortages with the pneumococcal conjugate vaccine (Prevnar, Pfizer) until 2004.

“These supply disruptions affected both the public and private sectors, and for a number of these conditions the shortages were severe enough that either the CDC or the Advisory Committee on Immunization Practices and other medical provider groups recommended deferral of certain doses of vaccines and established priorities for high-risk patients until vaccine supply returned to normal,” Melinda Wharton, MD, MPH, who is acting director of the CDC’s National Center for Immunization and Respiratory Diseases, said during the NVAC meeting.

The shortages during that time resulted in NVAC and the US Government Accountability Office to evaluate the situation and make recommendations for prevention and mitigation of future occurrences.

“There were a number of recommendations that came out of this and the GAO recommended the CDC develop a strategic plan for expanding the pediatric vaccine stockpile program, including a time table, consideration of form and storage location for pediatric stockpile vaccines, and procedures to ensure that the stockpile doses were incremental,” Wharton said. “NVAC additionally recommended that additional resources be provided to complete the pediatric vaccine stockpile purchases and that there be a plan for completing, monitoring and maintaining the pediatric vaccine stockpiles.”

Beginning in 2012, there was a shortage of the combined diphtheria-tetanus toxoids-acellular pertussis, inactivated poliovirus and Haemophilus influenzae type b vaccine (DTaP-IPV-Hib; Pentacel, Sanofi-Pasteur) and the diphtheria-tetanus toxoids-acellular pertussis vaccine (DTaP; Daptacel, Sanofi-Pasteur), which led to an increased demand of GlaxoSmithKline’s diphtheria-tetanus toxoids-acellular pertussis, inactivated poliovirus and hepatitis B virus vaccine (DTaP-IPV-HepB), Pediarix.

During the shortage, the CDC recommended that any child who began the vaccine series with Pentacel, then received single-components at one or more visits, could receive Pediarix instead of DTaP, IPV and HepB at subsequent visits when all three vaccines were indicated.

The shortage has since been resolved.

Influenza vaccine supply and demand

The recent history of influenza vaccine provides a clear example of the effect that recommendations and vaccine demand have on supply, according to Bruce G. Gellin, MD, MPH, deputy assistant secretary for health and director of the National Vaccine Program Office (NVPO).

“If you wind the clock forward from the late ’90s to 2008, the incremental expansion of ACIP recommendations for an annual seasonal influenza vaccine ultimately led to our recommendations for routine influenza immunizations for all children aged 6 months or older,” Gellin said.

He said the incremental expansion of these recommendations were important because it allowed manufacturers to gauge the demand for which they would have to meet supply and, at the same time, allowed the practice community to implement these recommendations.

On the supply side, during this same period influenza vaccine supply has also been variable. In 2002, Wyeth decided to drop influenza vaccines in order to focus on other vaccines, that left only a few FDA-approved influenza vaccine suppliers for the United States.

“Then, in 2004, when one of these suppliers had a problem with their production the US influenza vaccine supply was essentially cut in half,” he said.

That was the period when there was increasing attention to pandemic preparedness given the emergence and global spread of the influenza A(H5N1) and heightened awareness of the vulnerability and ability to respond to a pandemic.

“That was a wake-up call for a number of areas where improvements were necessary for influenza vaccines,” Gellin said. “In addition, it highlighted that seasonal influenza vaccine production capacity was going to be the basis on which we had a pandemic vaccination response.”

This led to renewed attention to influenza vaccines, he said, and the recognition that we needed improvements in vaccine production technologies and in the performance of the vaccines themselves. Since then there have been significant public and private investments to make these improvements.

Today, there are six suppliers of seasonal influenza vaccine to the United States and dozens of promising next-generation vaccines in the developmental pipeline.

“With pandemic influenza in mind, we’re in a place now where we have this baseline capacity we could use for a pandemic response,” Gellin said.

Pediatric VFC stockpiling program

In 1983, the first national vaccine stockpiles were started with a congressional appropriation of $4.6 million to the CDC in hopes of establishing a 6-month supply of all recommended childhood vaccines. These first stockpiles included only measles-mumps-rubella, poliovirus and pertussis vaccine, and pediatric diphtheria and tetanus toxoids. The first stockpile delivery took place in December 1983 and included nearly 600,000 doses of MMR vaccine.

According to Wharton, these stockpiles were being funded by annual discretionary appropriations, and in the first 10 or 15 years, stockpiles were used on multiple occasions to alleviate brief disruptions in vaccine supply for both production and non–production-related reasons.

The Omnibus Budget Reconciliation Act (OBRA) of 1993 created the Vaccines for Children program, which allowed stockpile funding to be removed from the annual appropriation.

“The OBRA legislation authorized the CDC to use VFC funds for vaccine purchases and for the stockpiles and charged the CDC with managing the stockpiles for use in outbreaks and vaccines for preventable diseases,” Wharton said. “Initially, the program was envisioned based on vendor-held inventory that was stored and rotated by the manufacturers. The target size was initially a 6-month national supply to adequately serve both public and private sectors. At that point, the feeling was that there was the most vulnerability and the highest risk for vaccines produced by a single manufacturer. The highest priority was placed on well-established vaccines and vaccines that were considered less likely to be replaced by another product. That was the thinking back when the program was first created.”

Number of manufacturers vs. number of vaccines

Even after learning lessons from past vaccine shortages, there remains the potential for future problems. For example, Merck is the only US manufacturer that produces MMR (M-M-R II), the varicella vaccine (Varivax) and the yellow fever vaccine (YF-Vax).

“For me, the biggest issue for shortages and the cost of vaccines is the issue of a single manufacturer,” said Mark H. Sawyer, MD, a former ACIP member and professor of clinical pediatrics and pediatric infectious disease specialist at the University of California, San Diego School of Medicine and Rady Children’s Hospital. “We should try to develop some program, whether it’s incentives or some other approach to augment the number of manufacturers that produce each vaccine so that we have fewer shortages. We haven’t had many shortages of vaccines that are made by more than one manufacturer because another manufacturer can offset a shortage for one that is having a problem.”

Financial issues and changes with the ACA

According to Schuchat, vaccine financing has been a continual issue. In 1990, the cost to fully vaccinate a child through age 18 years was about $90.

“However, it’s important to note the changes since 1990, in how much it costs to fully vaccinate a child through age 18,” Schuchat said “We estimate around $1,723 to fully vaccinate through age 18 in 2013, but we don’t have the contract prices for 2014. Much of that cost is because of new vaccines and diseases that we weren’t able to prevent before. Some of the increase is because of increasing costs of particular antigens.”

Schuchat said when VFC was authorized in 1993, price caps were only kept for vaccines that were already in existence, and any newly licensed or formulated vaccines that came in after VFC authorization, were not subject to a price cap.

“This increased the price that companies charged for vaccines, but it also increased the security of the vaccine supply with manufacturers getting into the market instead of leaving the market, which had been a problem before that,” she said.

Walter A. Orenstein, MD, an Infectious Diseases in Children Editorial Board member, said that changes within the Affordable Care Act (ACA) are good for immunization.

“This goes a long way to removing financial barriers to access,” he said. “It basically allows people to get their vaccines in their medical homes as long as they are in-network providers. This is a great way to try and resolve financing problems.”

The ACA also requires new health insurance plans to provide coverage for all ACIP-recommended vaccines without deductibles or co-pays when delivered by an in-network provider.

“We think that these provisions mean that underinsurance is going to go away, and if you have insurance you should have coverage for all vaccines that ACIP recommends,” Schuchat said. “This is huge in terms of the issues that were front and center for NVAC and states over the past decade, and this problem of underinsurance not addressed by VFC should really be sunsetting.”

National Vaccine Plan Goal 4 accomplishments

The National Vaccine Plan, originally created in 1994 and updated in 2010, was designed to maximize the effect that vaccines have on the health of the US population.

“The plan is focused on ensuring that people have the opportunity to prevent infectious diseases that are vaccine-preventable, and spells out the many elements of the system that need to be in place or that need to happen,” Gellin said.

Goals of the plan include developing new and improved vaccines; enhancing the safety system; supporting communications to make informed decisions about vaccines; ensuring supply, access and better use; and increasing global use of vaccines.

Goal 4 focuses on “ensuring a stable supply of, access to, and better use of recommended vaccines in the United States.” So far, several accomplishments have been made in working toward the goal. Among them is broadening access to vaccines without cost-sharing through the ACA; identifying health care system and provider barriers and facilitators of immunization; expanding the access to vaccines through partnerships with pharmacists and other immunization providers; and accurately tracking vaccine-preventable diseases and disease rates.

A look ahead

According to “The State of the National Vaccine Plan 2013 Annual Report, NVAC plans to implement a number of other aspects to complete the goal.

First, continued support of efforts to decrease missed vaccinations is important, especially those related to HPV vaccine and adolescent and adult immunization. These efforts include systems and services that will support physicians and other immunization providers.

Second, health information technology will continue to be support and encouraged, including 2D barcoding and interactive vaccine finder services in a hope to make it easy for parents and individuals to access recommended vaccines.

Next, all providers will be encouraged to expand and adopt the “best practices” for childhood, adolescent and adult immunization.

Fourth, awareness will be made about all ACIP vaccine recommendations. For example, since January, all vaccines are now accessible without cost sharing to many more people in the United States.

Lastly, strengthening the immunization infrastructure will be done, including to systems and components that exist in both public and private sectors, to provide higher immunization rates.

“The intent is of any national vaccine program … to make sure that you can prevent diseases that are vaccine preventable — and, when possible to transform infectious diseases into vaccine-preventable diseases,” Gellin said.

References:

CDC. Guidance for vaccinated children during the 2013 Pentacel, Daptacel, and Pediarix shortage. May 16, 2013.
CDC. MMWR Recomm Rep. 2008;57:1-60.
Fiore AE. Pediatrics. 2012;129:S54-S62.
Klein JO. Pediatrics. 2006;117:2269-2275.
Lane KS. Clin Infect Dis. 2006;42:S125-129.
Schuchat A. Immunization changes at the state level. Presented at: National Vaccine Advisory Committee Meeting; Feb. 11-12, 2014; Washington, D.C.
US Department of Health and Human Services. The state of the National Vaccine Plan: 2013 annual report. Available at: www.hhs.gov/nvpo/vacc_plan/annual-report-2013/nvpo-annual-report2013.pdf. Accessed Feb. 7, 2014.
Wharton M. VFC pediatric vaccine stockpiles: An overview and update. Presented at: National Vaccine Advisory Committee Meeting; Feb. 11-12, 2014; Washington, D.C.

For more information:

Bruce G. Gellin, MD, MPH, can be reached at National Vaccine Program Office, Room 715-H, 200 Independence Avenue, SW, Washington D.C., 20201; email: bruce.gellin@hhs.gov.
Jerome O. Klein, MD, can be reached at jerome.klein@bmc.org.
Mark H. Sawyer, MD, can be reached at mhsawyer@ucsd.edu.
Walter A. Orenstein, MD, Anne Schuchat, MD, and Melinda Wharton, MD, MPH, declined to provide contact information.

Disclosure: Gellin, Klein, Orenstein, Sawyer, Schuchat and Wharton report no relevant financial disclosures.

With full implementation of the ACA, will vaccine shortages become more common?

Manufacturers will increase vaccine supply.

While the entire impact of the Affordable Care Act (ACA) is not completely clear, health care providers will see advantages and disadvantages with this legislation. I believe that lingering vaccine shortages will occur less frequently and hopefully they disappear. There are multiple reasons to explain vaccine shortages. Fewer pharmaceutical companies provide vaccines in the United States. Manufacturers do not keep "stockpiles" of vaccines. Occasionally there were manufacturing and production issues. I am optimistic that vaccine shortages will occur less often for several reasons.

As a pediatrician, I appreciate that under the ACA all children will have Advisory Committee on Immunization Practices-recommended vaccines covered by commercial insurance and no co-pays. Prior to the ACA, not all children had access to these immunizations. Vaccines for Children (VFC), a federal entitlement program, provides ACIP-recommended vaccines to eligible children. Eligible children include those aged younger than 19 years and Medicaid eligible, those of American Indian or Alaska Native descent, or the uninsured. Underinsured children can quality for VFC, but they may only receive the vaccine at limited locations (Federally Qualified Health Centers and Rural Health Clinics). Access to transportation and high out-of-pocket costs and co-pays formed financial barriers to routine vaccination. The ACA will make it easier to vaccinate children.

Vaccine manufacturers now can better estimate the annual need for vaccine supplies and adjust production accordingly. The new target can be estimated by the birth cohort each year. With the prospect that every child is eligible for vaccines, I anticipate that manufacturers will increase vaccine stock. As potential profits increase, vaccine supply should increase as well.

Dennis J. Cunningham, MD, FAAP, is medical director of epidemiology in the section of infectious diseases at Nationwide Children’s Hospital. Disclosure: Cunningham reports no relevant financial disclosures.

Shortages may occur following more demand.

In the past, children without health insurance or Medicaid were qualified to receive state vaccines, which do not cost the patient anything through the Vaccines for Children program. For this reason, I don’t think the ACA will dramatically increase the vaccine shortages in this age group. As more adults have access to health care, vaccination rates may go up in this age group, creating shortages of adult vaccines.

Children were at a higher risk of not getting other health care issues taken care of if they did not have health insurances and the ACA will help with these issues. Unfortunately, many of the same barriers will continue to exist when it comes to vaccinating children – just as they had before the ACA was enacted.

There are multiple other reasons why parents choose not to vaccinate their children (belief that vaccines are dangerous, lack of regular follow-up, transportation issues, etc.). If these issues are adequately addressed, this may increase the demand for vaccinations and at some point cause shortages.

Josephine Dlugopolski-Gach, MD, FAAP, is assistant professor of general internal medicine and general pediatrics at Loyola Medicine. Disclosure: Dlugopolski-Gach reports no relevant financial disclosures.