Congress Renews User Fees, Boosts Bioterror Provisions

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 Success

Congress 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 900 employees.

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 Surveillance

One 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 Input

Although 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.