Tremendous changes are underway at FDA headquarters in Rockville, Maryland. Whole sections of biologics review moving from one center to another. Regulatory activities being refocused on risk. Restructured roles for agency field inspectors. And a variety of other reforms, many driven by the specter of bioterror. Despite operating for almost two years without a commissioner, FDA is moving full speed ahead with a major reorganization and a new regulatory philosophy.

An interview with Deputy Commissioner Lester M. Crawford, who has served as acting commissioner for the past nine months, reveals the purpose, status, and prognosis for those changes-which may accomplish the most sweeping transformation of the agency in decades. (For a look at Crawford's background and accomplishments, see "Sweet Home Alabama," page 40.)

Complementing PE's conversation with Crawford is a preview of newly confirmed FDA Commissioner Mark McClellan's view on FDA policies. It includes McClellan's responses to questions from members of the Senate's Health, Education, Labor and Pensions (HELP) Committee that has jurisdiction over confirmation of the FDA commissioner. The new FDA leader reveals familiarity with many health policy issues and political skill in side-stepping controversial topics-something he may not do so easily once he is in the driver's seat.

Sweet Home, Alabama

We have traditionally rewarded inspectors by the number of inspections they make. That's not the way to do it. It may have been right years ago, but now we need to focus on high-risk products that threaten human health and also raise concerns about bioterrorism.

In the drug approval process, the same thing holds true. We need to be doing risk-assessment across the board. We need to inform the public that although there will always be risk, some things are riskier than others. The FDA commissioner is really the risk manager of food and drugs in the United States. No more, no less. In fact, as a deputy commissioner, I wouldn't mind being called deputy risk manager. That would be great because it would convey what we are trying to do.

PE: So, risk-based regulation means, for example, that you might choose to reduce inspections for a certain class of manufacturing plants?

Crawford: That's possible. Our biggest challenge in risk assessment has been managing field operations. We are ready to rethink how we want to organize the Office of Regulatory Affairs, because it now has approximately 4,500 personnel. That's big news for two reasons. First, it's the largest number we've ever had. Second, we finally have parity again between regulatory affairs and the rest of the agency. Until recently, we had only half as many people in field operations as we did in the centers.

PE: What was the ratio historically?

Crawford: When I first got here in 1975, it was half and half. Then, during the Carter administration, there was a cutback of about 1,000 FTEs. Later, there was some more bleeding, and the field took the cuts for a complicated set of reasons. I believe we are getting more even now, and last year's increases have been impressive.

PE: Does that come from the bioterrorism threat?

Crawford: It does, and a lot of it comes from the sheer force of Secretary Thompson, because he picked FDA as something that needed to function fully. His support for the supplemental bio-terrorism legislation got us a big influx of funds and personnel, and that became permanent with the bioterrorism bill.

PE: How would field operations work under a risk management approach?

From the Heart of Texas

Also, contaminants and microbiological concerns must be examined on a risk basis. When I was at USDA's Food Safety and Inspection Service, any chemical in the environment, whether it was cyanide or table salt, was treated the same way. We spent just as much time and got just as much credit for controlling table salt as we did cyanide. Every year we had to go before Congress and explain why we were doing so few inspections of some of those compounds.

So we set up a simple matrix, which is rudimentary for risk assessment. Along the abscissa, we labeled the most toxic compounds A; we labeled the least toxic D. Across the ordinate, there was a numerical system of 1-4 for increasing availability in the environment. If the compound was a D-4, it wasn't very toxic or very available, so why spend time trying to find it? But an A-1 was something that would kill birds in flight, so we had to spend a lot of time on it. We were able to convince Congress and the American people that we shouldn't worry about the Ds or spend much time on the Cs. And, if they cut our budget any more, we would be dealing only with the As, and they would have to accept that.

PE: Traditionally, the field force has been involved with plant inspections and border controls, and CDER [the Center for Drug Evaluation and Research] has been more involved with assessing post-marketing safety issues. Do you see it playing a bigger role in monitoring products once they are on the market?

Crawford: CDER is like the scientific reservoir that gives compliance policy guides to the field. Although Center personnel may go into the field from time to time, that's unusual. The arms and legs of enforcement are in the field. But what to do and how to do it have generally been directed by the Center.

We are building up the field force with more professional school graduates. Its new director is John Taylor, an attorney with a lot of training in biology and toxicology. He worked as senior advisor for regulatory affairs for then-acting commissioner, Michael Friedman, from late 1996 through 1999. If John ever retires, I wouldn't be surprised to see a medical doctor in charge of the field force.

PE: What effect will the shift to risk management have on drug approvals or the ability to prevent, or anticipate, withdrawals?