Von Eschenbach closer to approval as FDA head; CMS Administrator McClellan departing

Although acting FDA Commissioner Andrew von Eschenbach, MD, has been on the job since September 2005, it was only last month that he received approval from the Senate's Health, Education, Labor and Pension (HELP) committee for his nomination as FDA commissioner to be considered by the full Senate. However, the step was an incremental one at best for Dr von Eschenbach and the agency, which has been without an officially appointed commissioner for all but 18 months over the past 5½ years.

"We need a strong leader at the FDA right now, one who has a mandate to act," said Sen Mike Enzi (R-Wyo), head of the HELP committee, after the committee's unanimous vote of approval. "There are many items before the FDA that require the immediate attention of an FDA commissioner vested with full authority. It is time for the Senate to move forward with this nomination."

Despite Sen Enzi's urging for a quick consideration of the nomination by the full Senate, a pair of Republican senators, David Vitter of Louisiana and Jim DeMint of South Carolina, have threatened to once again place a hold on Dr von Eschenbach's approval, this time over issues surrounding the importation of drugs from overseas and the safety of medical abortion with mifepristone and misoprostol (RU-486). These new concerns have made it less certain whether a vote on Dr von Eschenbach's nomination will occur before November's midterm elections.

FDA received reports in March of 2 deaths following medical abortions with mifepristone and misoprostol. One of those deaths was found by FDA to be unrelated to the use of mifepristone and misoprostol, while the other is still under investigation. A determination has not been made about whether the use of mifepristone and misoprostol for medical abortion played any role in causing the deaths of 4 women that were previously reported by FDA.

Politics already have played a role in the delay of Dr von Eschenbach's nomination while in the HELP committee, in part because Democratic senators criticized FDA's treatment of over-the-counter availability for Plan B. The Plan B controversy was said to have been a main catalyst for the departure of Dr von Eschenbach's predecessor, Lester Crawford, DVM, PhD, who served just 2 months as FDA's fully approved commissioner before stepping down.

Such political wrangling involved in approving a new FDA head has become more common and has interfered with the agency's mission and its ability to fulfill its functions as the nation's food and drug safety watchdog, according to Scheineson.

"There's a good argument for why an FDA commissioner shouldn't be a confirmed position anyway," Scheineson said. "The protection for any commissioner is to base decisions on sound science and try to keep politics on the sideline as long as possible."

The delays in his nomination's approval and the caveat of being an "acting" commissioner have not hindered some FDA efforts under Dr von Eschenbach, who was previously director of the National Cancer Institute. Beyond the agency's Plan B decision, FDA in the last year has refocused its enforcement efforts on unapproved medications, issued rules on revised labels, and taken steps to reform the drug approval process, particularly in the area of changing from a paper-based to an electronic system to handle new product submissions and to track postmarketing data.

"They've found an exceptional candidate in this case who has proven management and substantive experience. They couldn't find a better guy, so they want to keep him engaged and not frustrated," Scheineson said.

PONDERING PDUFA

Whether or not Dr von Eschenbach is able to clear the final hurdles to approval, important agency issues will still loom, one of which is the consideration of renewing the Prescription Drug User Fee Act (PDUFA). The act, which expires in October 2007, authorizes FDA to collect payments from drug manufacturers in exchange for timely product reviews-the PDUFA requires FDA to review and take action on 90% of standard and priority drugs within 10 months of their submission.

Critics of FDA have suggested that the PDUFA-imposed deadlines may need to be adjusted to prevent a perceived rush in FDA's decision process, which according to some studies has contributed to an increase in the addition of black box warnings and post-marketing withdrawals since the PDUFA's initiation in 1992.

"The debate has always been whether these additional resources and additional personnel and increasing percentages of resources supplied by industry was jeopardizing the public health in any way," Scheineson said. "Most statistics have shown that the hundreds of drugs that have been approved and the health benefits of those drugs in the marketplace have dramatically outweighed the relative handful of drugs that have had postmarketing issues."

A larger concern for the agency would be a loss in funding associated with a decline in applications, according to Scheineson.

"If anything, the biggest jeopardy to FDA is if the number of applications fall dramatically because those application fees are relied upon," he said. "That's a good incentive for the agency to interact with industry to make sure science is developing to the stage where lots of phase 3 research is being done and new therapeutic products are being developed."

MCCLELLAN STEPS DOWN

A new administrator for the Centers for Medicare and Medicare Services (CMS) will be guiding Medicare through the second year of offering its Part D prescription drug plan.

Mark McClellan, MD, PhD, who led CMS through its massive initiation of Medicare Rx Prescription Drug Coverage during his 2½-year tenure, announced that he would resign from the position early last month.

HHS Secretary Mike Leavitt appointed CMS Deputy Administrator Leslie Norwalk to serve as acting administrator of CMS effective October 15. Norwalk will oversee CMS as sign-ups for the new Part D enrollment period begin in November. However, challenges such as addressing the controversial "donut hole" coverage gap and further encouraging uninsured seniors to sign up for the plan will need to be among the priorities addressed.

In a statement responding to Dr McClellan's departure, President Bush said McClellan was "critical in the successful implementation of the Medicare prescription drug benefit-the most important healthcare reform in 40 years." President Bush also said McClellan, who served as FDA commissioner from 2002 to 2004 "has been a trusted advisor and he leaves behind a strong record of accomplishment."

Dr McClellan has not announced his future plans, but there has been speculation that the former Stanford University professor may be considering a return to academia .

SOURCES

Senate Health, Education, Labor and Pensions Committee. FDA nominee von Eschenbach approved; Enzi calls on Senate to move forward; provide agency confirmed head [press release]. Washington, DC: September 20, 2006. Available at: http://help.senate.gov/Maj_press/2006_09_20_d.pdf. Accessed September 24, 2006.

U.S. Food and Drug Administration. Mifeprex (mifepristone) information. Washington DC: April 21, 2006. Available at: http:// http://www.fda.gov/cder/drug/infopage/mifepristone/. Accessed September 27, 2006.

Bush GW. President's statement on Dr. Mark McClellan resignation as CMS administrator [press release]. Washington, DC: September 5, 2006. Available at http:// http://www.whitehouse.gov/news/releases/2006/09/20060905-8.html. Accessed September 24, 2006.