Push for Safety
One reason drug approvals may continue to slow down is because agency staffers are devoting considerable time and resources
to implementing new safety initiatives. A top priority for Woodcock is to convince critics on Capitol Hill and elsewhere that
FDA can and will do more to monitor drug safety and ensure appropriate medication use. A new five-year plan spells out how
FDA will spend the extra $30 million in user-fee revenues authorized by FDAAA to enhance drug safety capabilities.
To handle all these added tasks, Woodcock has expanded CDER's Office of Surveillance and Epidemiology (OSE) from three to
One new task is to develop summaries of adverse drug events to identify new and potential risks after a product is on the
market for a year or two. Another important assignment is to implement the Risk Evaluation and Mitigation Strategies (REMS)
In March, FDA published a list of 25 previously approved brand and generic drugs that already have some kind of restricted
distribution system. These manufacturers have to file a REMS with FDA by September 21, 2008, and FDA can require a REMS for
new drugs that similarly warrant special controls on drug dispensing and patient use. FDA expects to publish new guidance
on key elements of a REMS to assist companies developing new drugs that raise safety issues.
CDER's "Safety First" initiative is clarifying internal processes for managing these initiatives. The aim is to better integrate
pre- and post-approval safety assessment, thus avoiding future clashes between OND and OSE. Safety officials in every new
drug review office will oversee and coordinate assessment of safety issues, which will involve interdisciplinary teams of
experts from both offices.
Woodcock notes that OSE will have lead regulatory responsibility for observational epidemiologic studies and medication error
prevention, including review of proprietary names, packaging, and container labeling. But safety officers won't get a veto
over approvals, as recommended by critics both inside and outside the agency.
Safety experts also are involved in FDA's campaign to publicize information on medication safety signals as they emerge. The
same week that FDA published its REMS policy, it also issued several early communications on emerging safety concerns. One
involved new signals of heart attack risks involving two leading HIV/AIDS therapies, GlaxoSmithKline's Ziagen (abacavir) and
Bristol-Myers Squibb's Videx (didanosine). The agency also said it would conduct a safety review of Johnson & Johnson's Regranex
(becaplermin) skin gel for diabetics, in order to determine links to cancer and death. FDA also reported that it is investigating
a possible connection between suicide and Merck's popular asthma treatment Singulair (montelukast).
Such announcements aim to provide information on possible medication problems so that medical professionals can alert patients
appropriately. The danger is that these warnings can trigger overreactions that lead to noncompliance. Equally troubling is
the prospect that a proliferation of FDA warnings may prompt patients and providers to ignore the alerts. FDA has issued more
public health advisories in recent months than in most preceding years.
Show Me the Funding
By demonstrating renewed commitment to post-market surveillance, FDA officials hope to regain public trust in its operations.
At the annual meeting of the Food and Drug Law Institute (FDLI) in March, former CDER director Carl Peck described FDA as
operating in a "guerrilla environment" created by "ambitious politicians, media competing for headlines, and opportunistic
academics." A case in point, he noted, was a widely cited study in the New England Journal of Medicine indicating that new drugs approved close to user-fee deadlines turn out to be less safe than those approved without any pressure
to meet review time frames.
Not so, according to CDER deputy director Douglas Throckmorton, who pointed out that agency approval and withdrawal data is
"considerably different" from what the analysts reported. FDA plans to submit its own findings to NEJM, but that's unlikely to make headlines.
The good news is that there seems to be a growing consensus that FDA needs a major boost in resources to regain its stature
as an effective, science-based regulatory agency. Senator Edward Kennedy (D-MA), chairman of the Senate Health Committee,
added an amendment to the Senate budget resolution for 2009 that would boost FDA's budget by a total of $375 million in the
coming year, without increasing reliance on user fees.
In recent statements, FDA Commissioner Andrew von Eschenbach has become more open about FDA's funding shortfall. In a speech
at the March FDLI meeting, he described FDA as a "patient in peril." Von Eschenbach noted that increased FDA reliance on user
fees limits the agency's flexibility, and urged full backing for the Reagan-Udall Foundation. But at a Senate appropriations
hearing last month, he said that FDA might have the trouble absorbing a $375 million boost in one year. At the same time,
von Eschenbach acknowledged that the slim increase in the Administration's budget plan is too little; $200 million would be
just right, he said.
Jill Wechsler is Pharmaceutical Executive's Washington correspondent. She can be reached at email@example.com