ATLANTA — Gail Cassell, a microbiologist and Eli Lilly Distinguished Scholar, played a major role in convincing the FDA that it was in need of an external review, because "all centers should have external review bodies, as other agencies, to encourage improvement."

FDA approval for the report was a coup, because it was only "the second time its science had been reviewed as an entire entity in the agency's 100 years," she said. She collected a review panel of scientists at the highest levels in academia and corporations, a Nobel laureate, and one lawyer, Peter Barton Hutt, formerly chief counsel at the FDA. The task: to investigate areas of research, but not individual programs or individual scientists.

Demands on the FDA had soared, said Cassell during a progress update at the BIO 2009 conference last week, but "resources had not." More than 400 ports of entry in the U.S. relied on only 100 FDA inspectors. The FDA also is currently responsible for over 300 sites in 100 countries. As a consequence, the report found that there is a "fire-fighting" regulatory posture in the agency, vs. "proactive regulatory science," she said. Cassell added, "Individuals are stretched very thin." The review found that agency scientists were unable to keep up with advances within regenerative medicine, genomics, nanotechnology, medical imaging, robotics and wireless healthcare devices.

Peter Barton Hutt was the single regulatory lawyer amid 32 scientist-reviewers. He eventually made the agency cough up budgetary statistics and also performed a review of the agency's responsibilities from a legal standpoint. He found that the FDA's mandates had been amended 225 times since its inception.

When he looked at the last 20 years, he found there were about six new laws a year: six new mandates for the FDA. "There is no other agency that has had this kind of obligation set on them by Congress," he said. In terms of resources; however, he found that in 20 years the FDA's financial support had not even kept up with inflation and "they did not get one extra person" to do the added tasks. He said some congressionally-mandated projects still remain unfinished ... even ones from the 1960s and 1970s

Hutt does not blame the FDA. "You can't expect to tell an agency to do more, with less," he said. "That's hollow government." He added, "This is what happens when you squeeze an agency to death."

The National Institutes of Health (NIH) budget occurs largely due to lobbying by both scientists and nonprofits. People benefit from FDA strength, Hutt said. "Why aren't people marching in the streets for the FDA?"

Garret Fitzgerald, director of the University of Pennsylvania's (Philadelphia) Institute for Translational Medicine and Therapeutics, said he agreed to participate as a reviewer because, "I thought the FDA was a convenient whipping boy when thing go wrong." He added, "I thought I had a fairly developed sense [of the state of the FDA]. I was astonished that things were so much worse."

External reviewer Frank Torti of Wake Forest University (Winston Salem, North Carolina) commented, "So the FDA is not perfect." He said, "However, if you had actually gone to the FDA, you would see that there are many hard-working, dedicated people that usually tend to get it right."

Cassell was said that massive change has occurred in response to the external review, in only about a year's time. To begin to solve the FDA's predicament, the report had recommended the provision by Congress of resources that are "significant and sustainable." Frank Torti reported that a new scientific organization, including a Chief Scientific Officer, has been put in place and funding for the agency has increased.

Torti said the reviewers originally had asked FDA scientists to consider their priorities and develop three projects each, to address them. Following a review of the submissions, the FDA Science Board has already funded some of these projects.

Current FDA scientists have been provided with "Science First" symposia and allowed further career development in their area of interest. To create new employees, a fellowship program was begun in 2008 to attract the "best and brightest" to the agency. It had more than 1,000 applicants for 50 slots.

Torti said it is estimated that about half of the participants will become FDA employees, following this "two-year interview."

Large genomics, biospecimen handling, and informatics initiatives have been created. The informatics transformation will occur over the next four years. Said Torti, "These are tough decisions and expensive ones, so we can't make a mistake." External reviewer recommendations that have not been done so far: the creation of "Centers of Excellence" to tackle problems collaboratively.

Fitzgerald said, "I believed the report would call a spade a spade, and not a digging implement." He said he is sure the agency can become empowered, because its "regulatory science can be enhanced."

He concluded that their external review is already a driving force for FDA revitalization, and that heretofore, "Things are going to change."