HHS Efforts to Enhance Domestic Production Capacity to Expand the Supply or Accelerate the Availability of Influenza Vaccine

Given its responsibilities for national seasonal influenza and pandemic  preparedness and response, HHS has an interest in enhancing domestic  production capacity—that is, enhancing the nation’s overall infrastructure  for influenza vaccine production—and expanding the supply or  accelerating the availability of influenza vaccine. Specifically,  HHS has funded the development of vaccines using two alternative  production technologies—cell-based and recombinant technologies—and  vaccines using a third alternative technology—antigen-sparing technology  (adjuvants). The Federal Government Has Provided about $2.1 Billion in Funding for the Development of Alternative Technologies that Can Be Used in Producing Influenza Vaccines, and Manufacturers Are Demonstrating Progress Toward Licensure

From fiscal year 2005 through March 2011, the federal government  awarded approximately $2.1 billion in contracts and technology  investment agreements for the research and development of cell-based  and recombinant technologies and adjuvants, which can be used in  producing influenza vaccines. HHS and DOD Have Funded the Research and Development of Recombinant Technology, and One Manufacturer Has Submitted a Licensing Application to FDA

In fiscal year 2009, HHS awarded contracts to manufacturers for the  research and development of recombinant technology. Some Stakeholders Identified Challenges to the Development and Licensure of Influenza Vaccines Using Alternative Technologies

Some stakeholders and federal reports identified three primary challenges  to the development and licensure of influenza vaccines using alternative  technologies: low demand, high research and development costs, and  regulatory challenges. Some Stakeholders Said Low Demand Hinders the Development of Influenza Vaccines Using Alternative Technologies

Some stakeholders told us that low demand because of low vaccination  rates hinders manufacturers’ willingness to develop seasonal influenza  vaccines using alternative technologies. Additionally, despite the increase in influenza vaccine  production and distribution and the United States using more seasonal  vaccine than any other country, 5 of 12 manufacturer representatives, 1 of  3 industry association representatives, and 2 of 12 other experts we  interviewed said that this low demand decreases incentives for  manufacturers to develop new seasonal influenza vaccines using  alternative technologies. Additionally, HHS noted that increased investments in this  area have generated a significant interest in this type of research and  development. Some stakeholders also identified a second challenge, namely that FDA’s  written guidance and consultation with manufacturers on some of the  requirements for licensure of new influenza vaccines using alternative  technologies is not sufficiently comprehensive. FDA officials acknowledged that its guidance documents are high level,  explaining that specific instructions are unique to the product as guidance  documents cannot cover all possible scenarios. Because of their inability to be very specific in guidance documents, FDA  officials told us that they regularly meet with manufacturers developing  vaccines using alternative technologies to discuss various issues and  provide advice. HHS Plans to Assist Manufacturers with High Research and Development Costs by Funding the Establishment of Specialized Facilities to Provide Support and Expertise

HHS plans to assist manufacturers with high research and development  costs by supporting the establishment of two or three privately owned  facilities called Centers for Innovation in Advanced Development and  Manufacturing that will provide support and expertise to manufacturers. HHS Intends to Enhance Regulatory Science at FDA to Facilitate the Review of Licensing Applications for Influenza Vaccines Produced Using Alternative Technologies

HHS has announced plans to spend $170 million available from its fiscal  year 2009 and fiscal year 2010 annual appropriations, in part, to facilitate  FDA’s review of licensing applications for influenza vaccines produced  using alternative technologies and for other medical countermeasures. Agency Comments

HHS, DOD, and the Department of State reviewed a draft of this report. The Department of State did not  provide comments. Appendix I: The Research, Development, and Review of Licensing Applications for New Influenza Vaccine in the United States

The research, development, and review of licensing applications for new  influenza vaccine for the U.S. market involve several stages. Also, the amount of influenza vaccine that can be produced  depends on the manufacturer’s egg supply. Adjuvants were also used with the 2009 H1N1  pandemic vaccine in other countries.
Why GAO Did This Study

Production delays for the 2009 H1N1 pandemic vaccine using the current egg-based production technology heightened interest in alternative technologies that could expand the supply or accelerate the availability of influenza vaccine. Within the federal government, the Department of Health and Human Services (HHS) and the Department of Defense (DOD) support the development of technologies that can be used in producing influenza vaccines. HHS's Food and Drug Administration (FDA) reviews licensing applications for new vaccine, and the Department of State is the U.S. diplomatic liaison to the international entity that declares worldwide pandemics. GAO was asked to review federal activities for the development of alternative technologies used in producing influenza vaccine. This report examines (1) federal funding from fiscal year 2005 through March 2011 for alternative technologies and the status of manufacturers' efforts, (2) challenges to development and licensure identified by stakeholders, and (3) how HHS is addressing those challenges. GAO reviewed HHS and DOD documents and funding data. GAO also interviewed stakeholders, including manufacturer representatives, industry associations, and other experts on challenges to development and licensure. GAO interviewed HHS officials on how they are addressing those challenges.

What GAO Found

From fiscal year 2005 through March 2011, HHS and DOD provided about $2.1 billion in funding for the development of alternative technologies that could potentially expand the supply or accelerate the availability of influenza vaccine. Specifically, HHS and DOD have funded two alternative production technologies--cell-based and recombinant technologies, which produce vaccine in cells instead of eggs--and adjuvants, which can reduce the amount of vaccine needed to stimulate an immune response. HHS's funding supports the development of a new influenza vaccine using alternative technologies with the goal of manufacturers submitting licensing applications to FDA. DOD's funding supports the research and development of a technology that can make various vaccines, including influenza vaccines. HHS awarded $1 billion in contracts to manufacturers to develop cell-based technology, with manufacturers making progress toward licensure. HHS and DOD funded $296.5 million in contracts and $86.9 million in technology investment agreements, respectively, for the development of recombinant technology. HHS also awarded about $152 million in contracts for the development of adjuvanted influenza vaccines. Two manufacturers receiving HHS funds plan to submit licensing applications for their adjuvanted vaccines to FDA within the next 2 years. Some stakeholders said low demand, high research and development costs, and regulatory challenges can hinder the development and licensure of new vaccines using alternative technologies. For example, despite the United States using more seasonal vaccine than any other country, some stakeholders told us that low vaccination rates can decrease incentives for manufacturers to develop new influenza vaccines using alternative technologies because there is not sufficient demand for new products. Some stakeholders said high research and development costs can also decrease manufacturers' incentives; however, HHS noted that increased investments in this area have generated a significant interest in this type of research and development. Some stakeholders also told us that some of FDA's guidance documents are not sufficiently comprehensive. FDA officials told us that their guidance documents cannot cover all possible scenarios; thus, they regularly meet with manufacturers to discuss issues and provide advice. HHS is addressing challenges in the development and licensure of new influenza vaccines using alternative technologies. For example, HHS intends to fund the establishment of specialized facilities that will provide support and expertise to manufacturers. Additionally, through FDA, HHS plans to facilitate the review of licensing applications for new influenza vaccines using alternative technologies and to enhance FDA's staff expertise. HHS, DOD, and the Department of State reviewed a draft of this report. In commenting on a draft of this report, HHS and DOD agreed with GAO on its findings. The Department of State did not provide comments. HHS provided suggestions to clarify the discussion.