Jill Wechsler
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Legislation to reauthorize the Prescription Drug User Fee Act (PDUFA IV) includes a host of provisions designed to enhance
FDA policies for ensuring the safe use of medications. These initiatives should provide more timely information on emerging
concerns about certain medicines, but also could drive up the cost of new drug development and delay access to new treatments.
The new measure will implement an FDA–industry user fee agreement issued last January (2007), as well as a similar user fee
plan for medical devices. Because these fees have to be renewed by September 30, 2007, the legislation provides a vehicle
for Congress also to renew incentives for manufacturers to study pediatric uses of drugs and devices, while further strengthening
drug safety policies. The bill gives FDA authority to require postapproval clinical trials and to revise product labels within
a set time frame. There is more funding to expand the agency's information systems for tracking adverse events and for detecting
emerging safety problems. And manufacturers of more risky medications will have to spell out a range of pharmacovigilance
activities to inform patients and prescribers of possible dangers and to ensure appropriate product use.
More fees for services
In adopting PDUFA IV, Congress will boost the annual fees paid by pharmaceutical and biotech companies 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 new user fee program that would collect nearly $400 million a year in 2008, with steady increases over
the program's five-year period. An additional fee program bolsters FDA review of drug TV advertising. However, the legislators are boosting drug user fees even more to broaden the range of activities that fall under postmarket
safety review. The increased payments will support additional staffers in FDA's Office of Surveillance and Epidemiology (OSE)
in the Center for Drug Evaluation and Research (CDER) and enhance the safety office's role in evaluating postapproval risk
information and labeling changes. An important change in the PDUFA program, moreover, permits the use of fee revenues to support
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.
Although some parties feel that FDA already is overly dependent on user fees, the agency will need all the added fee revenues
the legislators provide because FDA's appropriated funding is barely keeping up with inflation.
Managing risks
An important drug safety measure in the legislation gives FDA added authority to require a Risk Evaluation and Mitigation
Strategy (REMS) from sponsors when such an approach is needed to manage particularly risky products. 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 equally to well-understood, low-risk products.
For those drugs that raise increased safety concerns, manufacturers may submit a REMS plan in a new or supplemental application,
or FDA may require this process based on new safety signals or information that raises concerns about the safety of a drug
already on the market. A REMS would evaluate the need to:
- conduct additional postapproval studies and clinical trials to assess a specific safety signal.
- 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 health care information to health care professionals.
- seek FDA prereview of advertising and marketing materials to ensure that ads describe serious risks appropriately and fairly.
- limit drug prescribing and distribution. FDA may determine that certain treatments should be prescribed only by health professionals
that have special training or expertise and only for certain patients. Distribution similarly may be limited to select wholesalers
and pharmacists. Such limited access programs also may require additional laboratory testing, patient monitoring and/or patient
enrollment in a registry.
