BARDA Influenza & Emerging Disease Program:

Topics on this Page:

Mission
Vaccines
Antiviral Drugs
Diagnostics
Other Non-Pharmaceutical Countermeasures

Critical Mission for Influenza Preparedness

The National Strategy for Pandemic Influenza (November 2005) designated the Department of Health and Human Services (HHS) as the lead agency for public health preparedness and medical response to a probable or actual influenza pandemic.

The Biomedical Advanced Research and Development Authority (BARDA), within HHS’ Office of the Assistant Secretary for Preparedness and Response (ASPR), was established by The Pandemic and All-Hazards Preparedness Act (PAHPA, December 2006) to facilitate the research, development, and acquisition of medical countermeasures for chemical, biological, radiological, and nuclear threats, as well as for emerging infectious diseases like pandemic influenza.

BARDA uses a comprehensive portfolio approach to develop and acquire a broad array of medical countermeasures for pandemic flu, including vaccines, therapeutics, diagnostics, and non-pharmaceutical countermeasures and to build and sustain their domestic manufacturing infrastructure.

Bioreactor for influenza
vaccine manufacturing

Vaccines offer pre-exposure protection to individuals who are at risk for contracting influenza. The effective use of vaccines is a key tool for preventing a pandemic or limiting its spread.

Under the HHS Pandemic Influenza Plan (November 2005), the Department’s key goals for vaccine preparedness are:

Stockpile enough pre-pandemic influenza vaccines to cover 20 million persons in the critical workforce;
Develop sufficient domestic manufacturing capacity to produce pandemic vaccine for the entire U.S. population of 300 million persons within six months of pandemic onset.

BARDA’s planning efforts support the advanced development of seasonal and pandemic influenza vaccines toward U.S. licensure. Targeted vaccines include (1) cell-based vaccines, (2) antigen-sparing adjuvanted vaccines, which are designed to conserve antigens by mixing in vaccine-boosting compounds known as adjuvants, and (3) next-generation recombinant vaccines

To establish domestic pre-pandemic influenza vaccine stockpiles, BARDA supports the development and manufacture of vaccines against different H5N1 virus clades (families of closely related strain variants). BARDA supports the secure supply of raw materials including eggs for domestic manufacturing of seasonal and novel influenza vaccines and the development and manufacturing of novel influenza vaccine candidates for clinical evaluation.. BARDA also provides cost-sharing support to expand the domestic influenza vaccine manufacturing infrastructure by retrofitting existing vaccine manufacturing facilities and building new cell-based influenza vaccine manufacturing facilities.

HHS/ BARDA Vaccine Advanced Development Milestones

Awarded contracts totaling over $1.5 billion in 2005-2007 to accelerate development and production of new cell-based and antigen-sparing technologies for influenza vaccines towards U.S.-licensure with manufacturing surge capacities for domestic production of at least 150 M doses of pandemic vaccine per manufacturer within 6 months of pandemic onset.
Provided grants totaling $11 million, as well as technical project management, to support international H5N1 vaccine development with global partners.
Issued an RFP in 2007 for advanced development of recombinant influenza vaccines based on hemagglutinin genes or proteins that may be manufactured in 12 weeks or les post-pandemic onset with the goal of awarding contract(s) towards FDA licensure.
BARDA is leading an HHS interagency – industry partnership to study (Mix-N-Match) whether H5N1 antigens from one manufacturer may be used effectively with adjuvants from other manufacturers to enable extension of the pandemic vaccine supply.

Pre-Pandemic Vaccine Stockpiling

HHS has invested $937 million to date for the establishment of pre-pandemic influenza vaccine stockpiles, resulting in the development and manufacture of egg-based inactivated split monovalent bulk vaccines (bulk batches of ready-to-use single-strain vaccines) against circulating H5N1 avian influenza virus strains. Such emergency stockpiles are essential for immunizing critical personnel upon a pandemic influenza outbreak, pending the production of a vaccine against the actual pandemic strain.
Supported the development and manufacturing of the first licensed H5N1 vaccine
Although the H5N1 avian influenza virus continues to change into new clades, research suggests that the pre-pandemic vaccine developed from an H5N1 clade 1 virus will provide at least partial protection against new virus strains. From 2004-2007, HHS stockpiled sufficient H5N1 clade 1 vaccine to vaccinate 4 million people.
In 2005-2006, as highly pathogenic avian influenza H5N1virus continued to mutate to generate new clades and subclades (a process known as “antigenic drift”), a second clade of H5N1 avian influenza viruses emerged in Asia and Europe. In response, HHS supported the development and manufacture of H5N1 clade 2 vaccine and stockpiled enough doses to immunize at least 3 million persons.
By the end of 2007, the H5N1 vaccine manufacturing campaign produced H5N1 clade 2 vaccine for another 5.5 million persons.

InfrastructureBuilding

HHS awarded a contract totaling $43 million in 2004 to secure year-round vaccine supplies — including embryonated hens’ eggs for influenza vaccine manufacturing — and to provide pandemic-like vaccine candidates for clinical evaluation.
In 2007, HHS awarded two contracts totaling $132.5 million to retrofit existing domestic vaccine manufacturing facilities on a cost-sharing basis and to provide warm-base operations for pandemic vaccine manufacturing; the retrofitted vaccine facilities are expected to produce at least 100 million doses of pandemic influenza vaccine by 2010.

Looking Forward

In Fiscal Year 2008, BARDA plans to solicit contract proposals to establish, on a cost-sharing basis, new domestic vaccine manufacturing facilities for the production of cell-based influenza vaccines that may account for 60%-70% of the U.S. pandemic vaccine supply by 2012.

Antiviral Drugs

Antiviral medications lessen the impact of a virus after an individual has been infected, and are the principal mode of treatment for influenza infections. Under certain circumstances, these drugs can also reduce transmission of the virus or even prevent infection.

Two U.S.-licensed antiviral drugs are effective against the human and H5N1 influenza viruses. Tamiflu is manufactured by Roche as oral capsules or liquid suspension. Relenza®, manufactured by GlaxoSmithKline as a powder, is administered via a respiratory inhaler. Both belong to a class of drugs known as neuraminidase inhibitors, which work by blocking the ability of the virus to multiply beyond the infected host cell.

Under the HHS Pandemic Influenza Plan, HHS must:

Establish national influenza antiviral drug stockpiles to treat 25% of the U.S. population during a pandemic, plus an immediate readiness cache of 6 million treatment courses for containment at pandemic onset;
Support the advanced development of new and promising influenza antiviral drugs toward U.S. licensure; and
Boost U.S.-based production of antiviral drugs.

Accomplishments

To fulfill antiviral drug stockpile goals, BARDA has:

Awarded contracts in 2004-2007 totaling more than $924 million to establish and coordinate the Federal and State pandemic stockpiles of antiviral drugs;
Procured 50 million treatment courses for storage in the Strategic National Stockpile (SNS) by the end of 2007 – completing the federal contribution to the antiviral goal; and
Supported States to purchase 22 M treatment courses of antivirals by the end of 2007 towards the 31 million treatment course goal for State stockpiles under a federal subsidy, with stockpile completion likewise expected in 2008.
Together, the Federal and State stockpiles will comprise the 81 million treatment courses needed to cover 25% of the U.S. population as well as provide the needed cache of courses for the early stages of a pandemic.
To support antiviral development and manufacturing ramp-up, BARDA:
Awarded a contract in 2007 for $102.6 million for advanced development and domestic industrialization of a new influenza neuraminidase inhibitor antiviral drug;
Plans to solicit and award multiple additional contracts for new and combination influenza antiviral drugs in 2008 and beyond.

Diagnostics

Quick and accurate diagnosis of pandemic influenza viruses in humans is essential to early treatment. Currently available tests require specially equipped laboratories, and take as long as one to two weeks to obtain results.

To facilitate the development of “point of care” (POC) rapid diagnostics capable of detecting pandemic flu viruses within 30 minutes in a clinical setting, BARDA and the Centers of Disease Control and Prevention (CDC) awarded four contracts totaling $14.88 million in December 2006 for early prototype device development with the goal of U.S. licensure.

A RFP was issued by CDC with BARDA in 2007 for proposals to develop rapid high-throughput clinical laboratory diagnostics. Contract award(s) are expected in 2008. Plans for support of development of home-based rapid influenza diagnostics are on-going.

Other Non-Pharmaceutical Countermeasures

In 2008, BARDA plans to support the development and/or acquisition of masks, respirators, and ventilators for pandemic influenza and other hazards.