INTRODUCTION Influenza viruses have been shown to be capable of causing rapid, widespread morbidity and mortality among infected humans. Pandemics happen when new (novel) influenza A viruses emerge which are able to infect people easily and spread from person to person in an efficient and sustained way. Historically, pandemic outbreaks of influenza viruses have left tens of millions of people dead in their wake and have cost hundreds of billions of dollars in lost lives, wages, productivity and economic devastation. In 1997, highly pathogenic avian influenza (HPAI) A(H5N1) viruses jumped from birds to humans in Hong Kong; six of 18 people with confirmed infections from H5N1 influenza virus died. In 2003, avian influenza A(H5N1) viruses emerged in humans again, this time in Southeast Asia, leading to severe illness and further deaths caused by this virus. Since 1997, over 1826 confirmed human infections and 784 deaths have been caused by avian influenza A(H5N1) around the world. The continual evolution and spillover of avian influenza viruses from birds into humans, coupled with their potential to rapidly spread and cause severe illness and death in people who are immunologically naïve triggered a global assessment of preparedness and response capabilities for a pandemic outbreak caused by influenza. In 2005, the U.S. Department of Health and Human Services (HHS) developed the to prevent, control, and mitigate the effects of influenza HHS Pandemic Influenza Plan A(H5N1) and other influenza viruses assessed to pose high risk to humans. Since their emergence in 1997, A(H5N1) viruses have become enzootic among poultry in many parts of the world, causing sporadic human infections and deaths. Influenza A(H5N1) is not the only animal influenza virus to infect humans. Mammalian influenza viruses (e.g., swine variant viruses H1N1v, H1N2v, H3N2v) and other avian influenza viruses (H5N2, H5N6, H5N8, H7N9) pose threats to humans. For example, since 2013 over one thousand human infections caused by avian influenza A(H7N9) virus have been reported, predominantly in China. In late 2014 and 2015, highly pathogenic avian influenza (HPAI) A(H5N8) viruses spread to birds in the United States from Asia and mixed with North American viruses. The resulting A(H5Nx) virus caused outbreaks in poultry in 15 states (predominantly A/H5N2), affecting 50.4 million birds. An aggressive animal response plan curtailed the outbreak but resulted in the slaughter of 7.5 million turkeys and 42.1 million egg-layer and pullet chickens, costing federal taxpayers more 1 than $950 million. An aggressive public health response that emphasized monitoring of exposed responders and the general public found no human infections with these avian viruses. Over the past decade, the global public health community ramped up pandemic influenza preparedness efforts with an eye toward the emergence of HPAI influenza A(H5N1) viruses in Asia; however the real-life test of pandemic planning came in 2009 following the emergence of a novel H1N1 virus in North America. The 2009 pandemic was caused by a novel reassortant virus designated A(H1N1)pdm09. This pandemic illustrated that pandemic influenza viruses can originate anywhere, vary in severity and 1 Animal and Plant Health Inspection Service. “2016 HPAI Preparedness and Response Plan.” Washington, DC: US Department of Agriculture, 2016. Accessed 7/31/2016. 7