When it comes to reform of the U. S. Food and Drug Administration, you won’t get the right answers if you don’t ask the right questions.

It’s been widely reported this week that the FDA approved more “first-of-a-kind” drugs in 2008 (21) than it did in 2007 (18). During that same period fewer “black box” warnings (both new and updated) were awarded in 2008 (46) than in 2007 (62). What do these numbers mean?

To some they signal an agency that isn’t as concerned with safety as it was only 12 months earlier. More drugs approved? Fewer black boxes? And why, these same FDA watchers wonder, isn’t the FDA’s Division of Drug Marketing, Advertising, and Communications sending out more warnings and untitled letters to curb the abuses of pharmaceutical marketing?

These are the wrong questions to be asking now. The real questions that need to be asked include why did the FDA miss review deadlines for at least 15 drugs? Why are a growing number of complete response letters, which are issued when the complete review indicates that there are deficiencies remaining that preclude the approval of the application, sounding more and more like the old-style not-approvable variety? And why are more and more complete response letters requesting information that was never discussed during the review process or at advisory committee meetings?

But the big question is why is ambiguity trumping predictability in the regulatory process? This is the key issue that must be addressed by the new FDA Commissioner. That’s the question. If the FDA adopts the position of doing nothing until it knows everything, that will send a chilling message to the pharmaceutical industry to dial back R&D unless the program looks like a sure thing.

And there are no “sure things” in pharmaceutical discovery and development.

Industry seeks clarity. They want bright lines. They want to know the rules. They want predictability. This may sound simple and fair, but inside the FDA it has proven to be a fractious bureaucratic kulturkampf. “Change is not required,” as management guru W. Edwards Deming once said. “Survival is not mandatory.” And that doesn’t mean change for show, for politics—it means thoughtful, timely, strategic change that enhances the public health. And that kind of change requires not walking on egg shells, but breaking them. Outgoing FDA Commissioner Andrew von Eschenbach learned that the hard way.

Changing the minds of regulators to embrace bright lines rather than broad definitions is a challenging proposition because changed minds must begin with change agents. The new commissioner must seek out and work with those career officials within the FDA who are smart, confident, and gutsy enough to embrace new ways of doing business, who support bright lines over draft guidances, and embrace pragmatism over dogmatic doctrine. And those people are there and they are excited about the possibilities of an FDA that will lead rather than an agency that buffets from side-to-side based on gusting political winds.

FDA’s Critical Path initiative, its effort to foster a national effort to modernize the sciences through which agency-regulated products are developed, evaluated, and manufactured, is a promising example of the agency’s desire to embrace change. Going forward, the agency’s stakeholders will be looking for other “surrogate markers” to gauge FDA’s willingness to continue the aggressive determination to both protect and advance the public health seen under commissioner Mark McClellan.

Despite new draft guidances that attempt to draw bright lines, what is and is not “in compliance” remains more art than science. Industry is confused, and the public health is not served. Predictability is power in pursuit of the public health. Predictability is the result of creative, forward-thinking leadership that rises above bureaucratic ambiguity. Driving this philosophy won’t be easy for the new commissioner—because swimming against the tide of an entrenched bureaucracy never is. But if the commissioner communicates this philosophy, leads by doing, and empowers change agents within the FDA career staff, the tide will turn.


Peter J. Pitts is President of the Center for Medicine in the Public Interest and a former FDA Associate Commissioner.