At the same time, FDA will expand OSE operations with the help of additional user-fee revenues earmarked for postmarket surveillance.
Under the PDUFA IV agreement, user-fee revenues may support the safety monitoring of any drug on the market—not just newly
approved drugs. OSE also gains $30 million from fee revenues to contract with data banks and health plans for access to information
on drug adverse events. The agency envisions a "transformation of the drug-safety program" by tapping into population-based
epidemiological and observational data banks to carry out targeted postmarketing surveillance, to look at class effects of
drugs, and to better detect safety signals. The final bill also boosts user fees by an additional $225 million over five years,
starting with $25 million more for fiscal year 2008. This funding will support the extra work involved in designing and overseeing
the REMS program, monitoring labeling changes, and establishing the enhanced clinical-trials registry and results database.
Closing the gap
By providing more resources for postmarket oversight, FDAAA may help elevate the status of OSE and epidemiologists. But it
remains to be seen how much the physicians and clinicians that review new drug applications pay attention to the safety assessors.
The still-wide gulf between the two operations was apparent at the joint meeting in July 2007 of FDA advisory committees for
Endocrinologic and Metabolic Drugs and for Drug Safety and Risk Management. The purpose was to evaluate concerns raised by
several postmarketing studies about the increased risk of heart attacks for patients taking GlaxoSmithKline's (GSK) diabetes
treatment "Avandia" (rosiglitazone).
At this high-visibility session, OND staffers disagreed with their counterparts at OSE about removing Avandia from the market.
The safety experts claimed that serious risk evidence for Avandia warranted a re-evaluation of the drug's health benefits.
OSE officials indicated that it would be better to pull a potentially safe drug from the market than to permit patient access
to an unsafe one, especially if alternative treatments are available. The advisory panels agreed that Avandia has serious
adverse event problems, but, in the end, voted to keep the drug on the market with added label warnings reflecting increased
cardiovascular concerns, as recommended by OND staffers and GSK. However, the contradictory messages from these FDA experts
added to the perception that the agency does not have a solid grasp on how to handle difficult drug-safety decisions.
The opinions expressed by OSE staffers also raise concerns among manufacturers that such views will encourage an even more
risk-averse approach at FDA in approving new drugs for market. Many drug manufacturers agree with Novartis CEO Dan Vasella
that FDA has become overly cautious in assessing new medicines in the wake of all the highly publicized safety controversies.
For example, the European Medicines Agency recently approved Novartis's diabetes drug "Galvus" (vildagliptin), while FDA has
requested additional clinical trials for the drug that will take several years to complete. The agency also has indicated
that it is unlikely to approve any new COX-2 inhibitors after denying applications for Merck's "Arcoxia" (etoricoxib) and
more recently for Novartis's "Prexige" (lumiracoxib). In addition to delaying approvals, FDA is investigating any signal of
unexpected adverse events and making some of this information public.
FDA has begun to publish an online drug-safety newsletter that highlights hot issues and adverse events for newly approved
products. The agency also issues MedWatch reports about safety issues almost daily.
While FDAAA is lengthy and complex, it won't be the last word from Congress on protecting the public from dangerous medicines.
The legislators are likely to renew efforts next year to establish a legal pathway for follow-on biologics. Such a measure
would provide a legislative vehicle for perhaps a full moratorium on TV commercials for prescription drugs and stiffer penalties
for violating new disclosure and registration requirements.
Jill Wechsler is Pharmaceutical Technology's Washington editor, 7715 Rocton Ave., Chevy Chase, MD 20815, tel. 301.656.4634, jwechsler@advanstar.com
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