And some can't happen at all. With the agency's reputation at a low point, this is either a very good or a very bad time to
go before the public with Critical Path. In the current political climate, "cooperative research" is likely to sound like
"more cozy deals," and "more efficient" R&D will be heard as "fast and sloppy." But the alternative to taking a risk is the
near certainty of seeing drug development flounder, with companies unable to take advantage of new scientific developments
because the agency just hasn't kept up.
"We have the tools to solve some of these problems," says Woodcock. "We need to get a move on it."
A Science of Development
To explain how drug companies came to their predicament, Woodcock focuses on a key difference between pharma and other industries:
"If you look at electronics, for example, it's standard to have certain basic understandings in the platform from which they
make their innovations," she says. "They don't keep everything secret. They only keep secret the part that's their innovation.
That hasn't happened in biomedicine. Innovations have been kept locked up, and there's no research infrastructure."
There are several reasons for this: Until recently, the biological knowledge to truly explore disease pathways and biomarkers
wasn't available. Then, as bioscience exploded in the 1980s and 1990s, companies—and even academics—tended to treat many discoveries
as intellectual property to be exploited, rather than as science to be shared. The regulatory process, as FDA concedes, has
sometimes discouraged companies from innovating in R&D and manufacturing.
But there are other reasons, says Woodcock. One is rooted in the culture of basic biological research. "When I talk to some
basic research scientists, they say, 'Well, first we have to totally understand the body, molecular level, genetic level,
cellular level, organ system level, the whole organism level, and the disease level.' I don't think they get it: You could
do theoretical physics and understand quantum electrodynamics and still have no Internet or plasma television. You need a
Most important, though, until the past few years, the industry was too successful to seriously contemplate change. "There
would have been no need to talk about this ten years ago," says Woodcock. "It would have fallen on deaf ears if we tried."
Today, with pipelines weak and major patents expiring, companies are more willing to listen.
FDA is getting visible support from its sister agencies, which also advocate a more informed and efficient drug development
process. At NIH, director Elias Zerhouni also is under pressure to demonstrate that the billions the agency spends on basic
and clinical research will pay off in breakthrough treatments for critical diseases. This has generated support for "translational
research" under the NIH Roadmap process.
The connection to translational research—the science of moving new discoveries from the laboratory into clinical development—is
especially important, since FDA's aim is to create a similar science devoted to the motion of drugs from preclinical development
to the patient.
Meanwhile, the Centers for Medicare and Medicaid Services (CMS), headed by former FDA commissioner Mark McClellan, is advocating
increased collaboration with FDA to ensure that new drugs are safe and effective, and that they also provide evidence of value
to justify coverage by Medicare and other programs. McClellan supported the original Critical Path report when he ran FDA;
he considers it vital for the agency to take the lead in spurring new approaches to drug development.
The Critical Path report and opportunities list aim to clarify FDA's involvement in issues that on the surface are problems
for industry and academia to tackle. FDA officials believe that the agency has a responsibility to examine whether regulatory
requirements inhibit drug development.
The main problem, explains Woodcock, is that FDA has to use the science that's available, now 30 years old. She adamantly
wants a better tool kit to reduce the uncertainty of the drug approval process.