FDA's Office of Generic Drugs is poised to enter a new era with new leadership, even as the agency is saying it will draw on the expertise of veteran officials for key initiatives.

Gary Buehler is moving out of his post as head of OGD, FDA said March 4. "Mr. Buehler has accepted a position in my immediate office as the acting deputy for operations," Office of Pharmaceutical Science Director Helen Winkle said in a statement? on the change. "In this capacity he will play a key role in the center's negotiations/activities on generic drug user fees, and in leading other critical programs in OPS, and spearheading our efforts to implement quality management systems for OPS business operations."

OPS Assistant Director Keith Webber, PhD, will take over as acting head of OGD while FDA conducts a search for a permanent director. The agency is expected to recruit for the permanent head from outside, though FDA candidates are also expected to be considered.

OGD has faced ongoing problems - a glut of applications and a shortage of reviewers - that have been well understood by industry and FDA for some time, but have had more of a public airing recently. Two weeks before the change in leadership at OGD, Commissioner Margaret Hamburg told the Generic Pharmaceutical Association that the pace of generic drug approvals is not acceptable.

"No one benefits from a pending-application queue that will soon hit the 2,000 mark," Hamburg said Feb. 18 during her address to GPhA's annual meeting in Naples, Fla. "This is simply unacceptable. Uncertainty and delays are costly to consumers, costly to you - and hurtful to the public. But the unprecedented spike in generics applications has simply outstripped our capacity to properly review, which must remain our foremost focus."

Hamburg made clear the agency hopes to revive the idea of solving the problem by negotiating a user fee program for generic drugs (see ¹ Also see "ANDA User Fees: Industry Takes Holistic Approach, Wants Whole New Office" - Pink Sheet, 8 March, 2010.).

Buehler has led the office since 2000, and the change in leadership at OGD may help the agency show industry it is serious about bringing "new energy" to working through the backlog, Alston & Bird attorney Marc Scheineson pointed out. However, he noted, past history would suggest that a transition atop OGD will slow down reviews in the short term, since the tendency is to "slam on the brakes" while new leadership gets up to speed.

Webber's background will make him an interesting caretaker for OGD at a time when the agency may be developing policy to implement a follow-on biologics regulatory pathway. He first joined FDA in the Center for Biologics Evaluation and Research, and has expertise in protein analysis. The agency has been anticipating that reviews of follow-on products would be handled by the relevant division in the Office of New Drugs (² Also see "FDA Review Of Follow-On Biologics Would Put Brands, Generics Under One Roof" - Pink Sheet, 2 July, 2007.).

Buehler ran FDA's ANDA shop during a period of significant change for the generic industry. The last decade saw many massive blockbusters go off patent, and generic erosion took place more rapidly than ever before. That meant 180-day exclusivity was an even more important prize, driving firms to file applications earlier and earlier. During that time, Congress passed legislation that altered when and how FDA could approve ANDAs with exclusivity.

At one point, Buehler could cite steadily declining review times, but a flood of applications - many from small, less experienced foreign companies that required additional review work - combined with FDA's general resource constraints to create an average review time for ³ ANDAs that is now over 26 months.

Buehler's efforts to improve review efficiency appear to have been generally well regarded by industry, and GPhA has successfully fought for appropriations earmarks for OGD over the past several years. Still, the slow pace of review seems to have produced some frustrations, even as it produced business opportunities for some firms as well.

In an interview at the GPhA annual meeting, Watson CEO Paul Bisaro, the incoming chairman of the association, offered some suggestions for how OGD could review applications faster.

"We need the agency to consider restructuring itself to become more efficient," Bisaro said. "There are, I think, some pretty easy things they can do. ... They have to have the right personnel in the Office of Generic Drugs, toxicologists, medical doctors; if they need more lawyers to answer more citizen petitions, they need that."

The review backlog is "pretty daunting and we can't expect that overnight they're going to be able to reduce those things," Bisaro said. "But, what we need to be able to do is focus on those applications that make a difference," such as products that would be the first generic for a particular product. "They need to sort of rethink their strategy."

Watson has several high-profile potential first generics at the agency - including Concerta , Lovenox and Pulmicort - and so Bisaro may be acutely aware of how quickly the agency is untangling various regulatory and legal knots.

But Bisaro also expressed concern that OGD has taken on too much of an advisory role for firms that are not experienced at filing ANDAs. "One of the things they complain about is some of these applications are really bad. Well, I could tell you it's not a Watson application, it's not a Teva application, it's not a Mylan application. There are some companies out there who don't know how to file applications. Well ... don't write them 15 pages of deficiency, send it back to them and say, 'Try again.'"

OGD could "create a threshold that says, if I get to three pages, I don't have to tell you more because there's a lot more in there, go deal with it," Bisaro said. "And that would speed up their [process]."

Bisaro has also been a long-time advocate for allowing firms to make more manufacturing changes without prior FDA approval, which he says would also free up review resources (⁴ Also see "For Watson CEO Bisaro, “Operational Efficiency” Is An Industry-Wide Calling" - Pink Sheet, 23 June, 2008.).

Buehler has worked to eliminate many of the operational strictures that have prevented generic reviewers from speaking as fluidly with drug sponsors as their brand counterparts could. He also led efforts to make product-specific bioequivalence guidances available online to reduce the amount of correspondence that OGD would have to handle from sponsors. But his office has also seen the quality of generic antidepressants and epilepsy drugs questioned in the national media.

Buehler's presentations have often been the highlight of industry conferences, and he let his personality shine on the podium. Once, he compared expressionist paintings to Edward Hopper's pieces to explain the kind of data he was looking for in applications. And for the past two Octobers, he wore Phillies regalia to GPhA's technical conference as his baseball team made a playoff run.

Last year, however, the Phillies came up short, losing in the World Series to the better-financed Yankees. A lack of resources may have cost them the title.

- Michael McCaughan and M. Nielsen Hobbs ( ⁵ n.hobbs@elsevier.com )

FDA's Generic Drugs Office Faces Transition As Director Buehler Departs

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