investigator-initiated approach, which is generally open ended and not targeted, while BARDA has taken a product-driven approach3 to vaccine development. One example of BARDA’s approach may be found in its June 2009 award of $35 million to a company that is expected to develop “recombinant influenza vaccines based on hemagglutinin genes or proteins (plasmid DNA, virus-vectors, peptides, subunit proteins and virus-like particles) … leading towards FDA-licensure and human usage” (BARDA, 2009).

The vaccine programs under BARDA also offer an example of the regulatory system’s potential for flexibility. Specifically, FDA’s promulgation of the so-called “animal rule”—regulations that describe the conditions under which efficacy data in animals may be submitted in lieu of data from human trials—has allowed BARDA and the companies it supports to evaluate the safety and efficacy of vaccines for biodefense for which human challenge with the pathogen would be unethical or unfeasible (Abdy et al., 2007; FDA, 2009d). (Clinical studies with humans are still needed to demonstrate a vaccine’s safety and immunogenicity.)

Developing and manufacturing most4 vaccines involves using living organisms and presents unique technical and regulatory challenges. Vaccine manufacturers may need to build or renovate a manufacturing facility specifically for the production of a given vaccine before that vaccine has been licensed. This results in a “sunk cost”—a cost that cannot be recovered if the vaccine is not licensed (Coleman et al., 2005). As part of the Biologic License Application, FDA evaluates the manufacturing process and facility (Landry and Heilman, 2005).

The vaccine regulatory process is also complex and difficult, requiring a high level of scientific expertise and sustained funding for its maintenance and enhancement. FDA’s role in recent years has been shaped by two major events. In 2004, the agency announced its Critical Path Initiative, which is intended to bring about an infusion of scientific innovation into its work and spur the same in the companies that develop drugs, vaccines and other biologic products, and devices, with the ultimate goal of translating innovation into safe and effective products (FDA, 2004). FDA’s effort to “modernize the scientific process” that transforms a discovery or proof of concept into a vaccine continues, and the agency publishes yearly compendia of activities it has undertaken or supports, in an effort to bring about the desired changes

3

Requirements for BARDA’s Project Bioshield include “solid clinical experience and/or research data” that support “a reasonable conclusion that the countermeasure will qualify for [FDA] approval or licensure within eight years after the date of a determination” (Hynes, 2007). The term “countermeasure” refers to vaccines, drugs, and other medical products intended to prevent or treat effects of bioterrorism.

4

Newer synthetic sub-unit vaccines are an exception.



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