Vaccination Education: 2009 H1N1 Lessons Learned

From a public health perspective, there are many insights to be gleaned from the H1N1 pandemic of 2009-10, especially from the development, distribution and administration of the 2009 H1N1 vaccine. While the global impact of the disease was less dire than predicted, more than 17,000 deaths eventually were attributed to H1N1.¹ Amid early stages of panic, public demand for a vaccine was high, but when manufacturing delays caused delivery shortages, initial anger turned to apathy as many people shunned the vaccine when it finally arrived. Was it a case of too little too late? And what could have been done differently to get the vaccine distributed more efficiently?

An Unpredictable Outbreak

From the start, the 2009 H1N1 pandemic did not conform to prior assumptions. For one thing, it began in Mexico, not Asia, which was the anticipated origin of the next influenza pandemic. Second, it was not as deadly as health experts feared (although in the end, it was more communicable than expected, infecting 1,483,520 people worldwide).² Additionally, H1N1 did not follow previous outbreak patterns for influenza, showing up in the spring rather than the typical late fall, catching many public health officials off guard.

Once it surfaced, H1N1 gained notoriety and momentum rapidly, with the most serious and deadly cases noted in otherwise healthy young adults and children, compared with the seniors and infants who typically succumb to seasonal flu complications. It wasn’t long before panic ensued as H1N1 cases spread from state to state and country to country. As the outbreak escalated to pandemic status, the world waited eagerly for word of a vaccine, and everyone from the World Health Organization (WHO) to the Centers for Disease Control and Prevention (CDC) rallied to inform and educate a frightened public about the next steps.

Because the virus was discovered early in humans, response was swift — the virus was characterized, tests were developed and findings were shared at record speed. Vaccine manufacturers collaborated and it was “all systems go” in terms of vaccine development. Confidence was high that a vaccine could be delivered prior to the anticipated flu surge in late fall. In fact, the CDC expected to vaccinate more than half the U.S. population quickly. Health and Human Services Secretary Kathleen Sebelius was quoted as saying, “250 million vaccines have been ordered, and any American who wants to be vaccinated will be able to get a flu shot.”

Unfortunately, things did not go exactly as planned.

Vaccine Production Methods Come Under Scrutiny

While new, streamlined flu vaccine manufacturing techniques were already under development when the 2009 H1N1 hit, none were far enough along to help with a pandemic of this magnitude.As a result, the 2009 H1N1 flu vaccine was produced using fertilized chicken eggs, a method used since the 1930s. The process involves drilling a hole into the eggshell so the virus can be injected into the amniotic cavity (the amniotic cavity provides a sterile and nutrient-rich environment for the influenza virus to replicate). Thereafter, the viruses are recovered by removing the amniotic fluid, which is then used to make the vaccine. At least that’s how it’s supposed to work. True to its unpredictable nature, the H1N1 flu virus did not grow as well as expected in eggs, apparently requiring different conditions to thrive than its seasonal counterpart. As a result, vaccine manufacturers had trouble growing enough of the virus to make the vaccines. Further complicating matters, pharmaceutical companies were producing vaccines for the seasonal flu and 2009 H1N1 at the same time, slowing production timelines even further. Amanda Gardner of U.S. News and World Report stated, “The H1N1 virus did not grow as quickly as expected during a half-century-old — and often-criticized — egg-based production technique used by pharmaceutical companies to make selected vaccines.”³

As delays ensued, concerns about the dated manufacturing process came to light. “Eggs can be very cumbersome to work with,” said John Treanor, MD, the flu expert at the University of Rochester Medical Center. “When you need hundreds of millions of fertilized eggs, you’re dealing with a whole host of agricultural issues, as well as scientific concerns regarding the flu virus itself. Flu viruses can be temperamental, and it’s not always an easy matter to get the virus to grow as you want in eggs.”⁴

Overpromised and Underdelivered

The CDC initially told its Advisory Committee on Immunization Practices in late July that it hoped to have 120 million doses of vaccine for the novel influenza A (H1N1) virus available by October 2009. Unfortunately, the unexpected manufacturing issues made that a difficult promise to keep, and by August, federal officials expected only about 45 million doses to be available by mid-October. In actuality, barely 13 million doses arrived, creating frustration among health practitioners and the general public as supplies were rationed for high-risk patients.

“The final mile of vaccine distribution is always getting it to the patient,” says Chris Ground, senior vice president national accounts, FFF Enterprises Inc. “One of the things they didn’t do this time was to engage the normal seasonal vaccine distribution channels. Mass distribution of flu vaccine is handled very efficiently every year, but because H1N1 went through public health channels, there was a degree of micromanagement that resulted in tons of vaccine being left sitting in warehouses and never reaching patients at all.”

Interestingly, given the timeline of events, vaccine manufacturers actually did a phenomenal job getting the vaccine to market as quickly as they did. The media backlash that resulted from the delay was ironic, since initial outcries claimed the vaccine was not available soon enough. Later, resistance arose when the idea that the vaccine was produced too quickly (and was therefore unsafe) began to surface, fueled by vaccine opponents on the Internet. “One of the lessons we learned is that we had a new level of communication we may not have been used to: social networking,” says Mark B. Johnson, president, American College Preventive Medicine.⁵ “People were spreading messages quickly online — including rumors that the vaccine was unsafe — and many people trusted some of these sources more than they trusted the government. There was a lot of mistrust regarding official messages.”

Overpromising on vaccine delivery became a major public relations problem for both the government and public health agencies — especially when the guidelines for who would be immunized changed. Initially envisioned as a mass vaccination of the general public, the limited vaccine supplies demanded that only those in high-risk groups, such as pregnant women, receive priority access to early batches. In many cases, harried physicians and pharmacists were left holding the bag, having to explain unexpected shortages to a frustrated public. “You had vaccine trickling out to providers who would then advertise that they had [the 2009] H1N1 vaccine, and you’d have a riot on your hands with too many people showing up to get vaccinated,” says Ground. “When you classify high-risk groups, you have to be very careful how you communicate. If you reach out to providers who handle high-risk groups and let them act as the filter to get the word out about vaccine availability, you can hopefully avoid a lot of the problems we saw last fall.

Packaging Problems and Foreign Suppliers

A clear lesson learned during the development of the 2009 H1N1 vaccine was that problems can occur at many points during development. Between the testing, packaging, allocation and distribution, plenty can go awry. For H1N1, unexpected packaging issues arose as officials described a “logjam” at factories attempting to get the completed vaccine into vials.

Another problem highlighted by the 2009 H1N1 pandemic is that America is extremely dependent on European manufacturers for its flu vaccine. The Health and Human Services Department has contracted with five different companies to make influenza immunizations for the U.S. market: Novartis, Sanofi Pasteur, CSL, AstraZeneca unit MedImmune and GlaxoSmithKline. While Sanofi has a flu vaccine plant in Pennsylvania, until recently, remaining flu vaccines for the U.S. market have been made in other countries. Many experts caution that in the event of a serious pandemic, countries would likely prioritize vaccine supplies for their own citizens. Indeed, as the U.S. awaited the arrival of its 2009 H1N1 vaccine last year,Australia’s CSL sent notification that shipments would arrive later than promised because it was providing batches to Australians first (Australia’s winter occurs during our summer months, and their flu season was already in full swing).

U.S. health officials have been actively looking into streamlining vaccine manufacturing methods, while decreasing our dependence on imported vaccines. In November of last year, Novartis opened its first U.S. flu vaccine plant, and it will be the first in the country slated to make flu vaccines out of cells instead of eggs.⁶ In a statement, Novartis said, “If licensed in an emergency, the facility will be ready to respond to a pandemic as early as 2011. The plant is planned to be running at full-scale commercial production in 2013.”

A Fire Drill for Future Pandemics

In many ways, the vaccine challenges that arose during the 2009 H1N1 outbreak served as a fire drill that is hoped will improve our capacity to respond to future pandemics. During a March 2010 webinar titled “Lessons Learned from H1N1,” William Schaffner, MD, FACPM, professor and chairman, Department of Preventive Medicine, noted that despite some unexpected glitches, response to the pandemic was very good at the federal, state and local levels. He also commented that in the absence of widespread vaccination clinics, the American public became quite adept at various nonmedical means of fighting the flu.

“The fundamental way to prevent influenza is to vaccinate as many people as possible,” Shaffner said. “We learned that when you don’t have a vaccine, there are still things you can do to prevent illness — sneezing in your elbow, washing your hands and practicing social distancing can all help. If we didn’t vaccinate as many people as we intended, we certainly did teach America how to sneeze.”