Just before the Memorial Day recess, Congress approved legislation to enhance public health agencies' ability to respond to
bioterrorist threats. A key addition to the bill reauthorizes the Prescription Drug User Fee Act (PDUFA) for five years. The
revised program significantly increases companies' fees to support expanded FDA operations, gives the agency more flexibility
in using fee revenues, and backs new initiatives to streamline the drug development and approval process.
Defending Against Bioterrorism
Continuing SuccessCongress adopted the proposal-negotiated by FDA and industry-largely so it could renew the highly praised program before it
expires on September 30. Regulators and manufacturers applauded the program's success in accelerating FDA review of new drug
applications (NDAs) in return for hefty payments.
The industry anted up about $135 million for the fiscal year 2001 and is expected to pay $162 million this year. Adding that
to government appropriations, FDA will have $325 million in resources for drug review activities this year, compared with
$120 million in 1992. The extra resources have allowed FDA to increase its review staffs for drugs and biologics by more than
Under PDUFA III, user fees-for application, product review, and establishment- will increase noticeably, to a projected $223
million in fiscal year 2003 and rise to $260 million in 2007. The current fee for filing a full NDA is $313,000, but it could
soon top $500,000. Under the program, fees will be levied against more products, including pediatric supplements.
FDA officials lobbied heavily for increased resources to support an expanding work load for its Center for Drug Evaluation
and Research (CDER) and Center for Biologics Evaluation and Research (CBER). One problem for FDA is that fee revenues have
failed to meet projections in recent years because of a decline in submissions, so the agency sought to revise the system
for assessing fees and controlling their use. FDA garnered support for such changes from healthcare organizations and patient
advocates concerned about the agency's limited capability to monitor postapproval safety and marketing.
Some critics expressed fears that higher user fees would increase manufacturers' influence over the agency and urged Congress
to boost FDA's budget and eliminate user fees altogether. That idea never gained much support on Capitol Hill, where legislators
preferred to boost user fees and to allow FDA to use of some of the funds to expand postmarketing regulation.
PDUFA III tackles several thorny topics related to how FDA reviews applications, but it makes very few changes in review performance
goals. The agency will continue to review and act on 90 percent of standard applications for new drugs and biologics within
ten months, and priority applications within six months.
However, the bill does address FDA's tendency to issue "approvable" letters to meet user fee deadlines for taking "action"
on an application. That often leads to multiple review cycles which delay final approval. To prevent such problems, the agency
will now notify sponsors quickly of any "substantive deficiencies" found in the initial application review. The program also
replaces the "approvable" action letter with a "complete response" letter, which will inform sponsors in detail about any
deficiencies that remain and actions necessary for FDA approval.
To see if such changes improve the situation, FDA will use part of a $7 million, new-initiatives fund to assess first-cycle
reviews of all NDAs filed under PDUFA III. The agency will also conduct a broader analysis of CDER and CBER review processes
to identify any need for further system redesign.
Other measures aim to facilitate drug testing and development by expanding opportunities for sponsors to request FDA evaluation
of study protocols and issues related to clinical trial design. A new program will permit biotech manufacturers to request
FDA to have an independent consultant review a protocol. The legislation establishes procedures for resolving disputes over
review actions and scientific matters. It also authorizes two pilot tests of additional innovations that may accelerate development
of fast-track therapies.
Expanding SurveillanceOne major change allows FDA to use fee revenues to support review of risk management initiatives and to expand agency systems
for tracking and analyzing adverse drug events. That initiative will focus on product safety issues raised during the period
after a new medicine comes to market-two years for most products and up to three years for therapies that require a black
box or bold warning, a medication guide, or restricted distribution.
The legislation also specifies that FDA may list on its website sponsors who fail to meet Phase IV study commitments. The
agency may require sponsors to notify prescribers about the shortcoming and about unanswered product benefit and safety questions.
FDA also will gain resources to expand its access to outside health databases that can provide independent evaluations of
new product uses that raise important safety concerns.
Those measures aim to encourage companies to develop risk management strategies during drug development. The program urges
sponsors to discuss such plans with FDA before filing an NDA, including clinical trial limitations, disease epidemiology,
the need for additional Phase IV studies, and other risk management tools.
To ensure that FDA has the resources to carry out those initiatives, the legislation provides additional funding for CDER's
Office of Drug Safety (up to $5 million next year) and its Division of Drug Marketing, Advertising, and Communications. DDMAC
would receive an extra $2.5 million next year and $7.5 million more in 2007 to ensure that DTC advertising is not false or
misleading. The Office of Generic Drugs also benefits from added funding, but it will be up to Congressional appropriations
committees to allot those amounts each year.
Consumers Gain InputAlthough Congress accepted the joint FDA/industry PDUFA III agreement, legislators added a few provisions in response to interest-group
concerns. The bill requires FDA to include patient advocacy groups, healthcare professionals, and academics in the next round
of user fee negotiations, which will begin in about four years. The agency will publish the resulting proposal to avoid charges
that the plan was developed behind closed doors.