As expected, must-pass legislation to reauthorize the Prescription Drug User Fee Act (PDUFA IV) has provided a vehicle to
renew numerous programs and to establish new policies to ensure the safe use of medications. The measure implements a user-fee
agreement issued in January 2007 as well as a similar user-fee plan for medical devices. It also continues incentives for
sponsors to study pediatric uses of drugs and devices and gives FDA authority to require postapproval studies. Manufacturers
will have to disclose more information about ongoing clinical trials and research results and must revise product labels within
a set time frame. There is more funding for FDA oversight of postmarket drug use and for agency information systems. And manufacturers
of more risky medications will have to adopt a range of pharmacovigilance activities to ensure appropriate product use.
More Fees for Services
In adopting PDUFA IV, Congress boosts the annual fees paid by pharma to adjust for inflation and the increased cost of overseeing
the drug-development-and-review process in an efficient and timely fashion. FDA and industry initially agreed on a fee program
that would collect nearly $400 million in 2008, with steady increases over the program's five-year period.
A new fee program also bolsters FDA review of direct-to-consumer (DTC) broadcast drug advertising, as discussed in Leading Indicators, April 2007. Some members of Congress sought to ban consumer advertising of new drugs for some months or years after coming
to market, noting that even a more efficient and comprehensive review of DTC ads would remain voluntary. Instead, the legislators
agreed to authorize stiffer fines and penalties for companies that fail to ensure the accuracy and fair balance of drug ads.
All parties will be watching closely to see if misleading commercials aggravate drug safety concerns.
Some of the PDUFA increases will be used to expand drug safety oversight and assessment throughout a product's life cycle—and
not just during the first two or three years after product approval, as currently allowed. The payments will support additional
staffers in FDA's Office of Surveillance and Epidemiology in the Center for Drug Evaluation and Research and enhance the safety
office's role in evaluating postapproval risk information and labeling changes. One specific project is to improve FDA's system
for assessing proposed product names, which aims to reduce medication errors from look-alike and sound-alike names.
Congress is raising the fees even more to support these and other initiatives. And FDA will need all the added fee revenues
the legislators provide because its appropriated funding is barely keeping up with inflation (see "Push for More Appropriations").
Push for More Appropriations
One of the legislators' pet provisions permits FDA to require companies to develop a Risk Evaluation and Mitigation Strategy
(REMS) to ensure safe use of particularly high-risk drugs. Initially, the legislators wanted to require a REMS for all new
drugs but agreed with manufacturers that such a broad mandate could waste time and resources if applied to relatively safe
Manufacturers may submit a REMS plan in a new or supplemental application, or FDA may require such a process based on new
safety signals for marketed products. A REMS would evaluate the need to:
•conduct additional postapproval studies and clinical trials
•require labeling changes to disclose new safety concerns
•prepare and distribute a Medication Guide or patient package insert
•develop a communication plan for disseminating additional information to healthcare professionals
•seek FDA prereview of advertising and marketing materials to ensure that ads describe serious risks appropriately and
•limit drug prescribing and distribution. FDA may determine that certain treatments should be prescribed only by specially
trained health professionals and only to certain patients. Distribution similarly may be limited to select wholesalers and
pharmacists. Additional laboratory testing, patient monitoring, and/or patient enrollment in a registry may be required.