PDUFA legislative proposals call for increased fees to help improve drug safety


Legislation to reauthorize the Prescription Drug User Fee Act (PDUFA) IV has been expanded, as expected, via a host of provisions designed to shape drug development and ensure the safe use of medications.

Key Points

Legislation to reauthorize the Prescription Drug User Fee Act (PDUFA) IV has been expanded, as expected, via a host of provisions designed to shape drug development and ensure the safe use of medications. The proposed revisions include the authorization of more tools and legal authority for FDA to monitor and mitigate drug risks and new manufacturer requirements for assessing, preventing, and correcting drug safety problems.

This broad bill implements an FDA-industry user fee agreement issued in January 2007 and a similar user fee plan for medical devices. The legislation, if approved, would provide a vehicle for Congress to retain incentives for manufacturers studying pediatric uses of drugs and devices, which were scheduled to expire. If the legislation is passed, FDA would have the authority to require postapproval clinical trials and to revise product labels within a set time frame. Manufacturers would have to disclose more information about ongoing clinical trials and study results and develop a range of pharmacovigilance activities to ensure appropriate use of medications that pose a high risk of adverse events. The bill allows more funding for FDA oversight of postmarket drug use and the expansion of the agency's information systems to track adverse events and detect emerging safety problems.


Some of the fee increases included in the revised PDUFA bill would be used to expand drug safety oversight and assessment throughout a product's life cycle, not just during the first 2 or 3 years after product approval, as is current policy. The payments would support additional staff members in FDA's Office of Surveillance and Epidemiology (OSE) in the Center for Drug Evaluation and Research (CDER) and would enhance the OSE's role in evaluating postapproval risk information and labeling changes. The goal of 1 specific project is to help reduce medication errors due to look-alike and sound-alike drug names; this project involves improving FDA's system for assessing proposed names.


One of the central provisions of the legislation would give FDA the authority to require that companies develop a Risk Evaluation and Mitigation Strategy (REMS) to ensure safe use of particularly high-risk drugs. Initially, the legislators wanted to require REMSs for all new drugs, but they agreed with the manufacturers' assertion that such a broad mandate could waste time and resources if it were applied to relatively safe products.

If passed, the legislation would allow manufacturers to submit a REMS plan in a new or supplemental application, and FDA also could require such a process based on new safety signals for marketed products. A REMS would evaluate the need to:


This legislation would also give FDA authority to expand safety requirements for all drugs.

Trial registration. The proposed changes to PDUFA IV would require more information about active clinical trials. To better inform patients of opportunities to participate in clinical trials, sponsors would have to submit more information about ongoing clinical trials to the ClinicalTrials.gov/ website (http:// http://www.clinicaltrials.gov/). The legislation would extend the registration requirement to all regulated drugs and would broaden registration listings to include a long list of specific trial information, including whether there is an expanded access program for a not-yet-approved treatment. Congress emphasized that the registration system should allow patients to easily search for trials based on disease or condition, trial location, and other factors, and that listings should be frequently updated.

Results. A key goal of the legislation attached to PDUFA is to link clinical trial registration to results information. Many pharmaceutical companies already offer this information voluntarily, but the legislators favor a more comprehensive approach. Although the details are unclear, policymakers expect that results listings would include published studies and all available FDA information about the drug (except proprietary trade secrets), such as the approved product label, review package, and related safety information.

One issue raised by manufacturers is whether sponsors can comply with registration and results disclosure policies without drawing charges of illegal promotion. Manufacturers fear that posting information about the indication and study design of a test product could be viewed as promoting unapproved uses. Similarly, requiring sponsors to provide summaries of a study in lay language could be regarded as making false claims. Pharmaceutical companies say that such summaries are of limited value and that clinical trial results should be written primarily for a medical and scientific audience.

Labeling changes. Under current policy, discussions between sponsors and FDA about label revisions may take months, or even years. The proposed legislation sets time frames for negotiating such changes, including the need for boxed warnings and additional information on contraindications, precautions, or adverse reactions. The system would provide a process for sponsors to question a requested change and for resolving disputes. But if FDA requires new labeling language, the agency will have greater power to compel compliance.

Curbs on conflicts-of-interest. The proposed legislation reflects congressional concerns that too many members of FDA advisory committees have financial links to industry. Although policymakers recognize that these panels can benefit from input from well-known experts, the legislation aims to increase the objectivity of advisory committees for safety issues by limiting the use of waivers to permit such testimony. Currently there are no limits on the number of waivers that can be issued. Congress also wants FDA to more actively solicit scientists and medical experts without financial ties to pharmaceutical companies to improve the advisory process.


An important step in reducing drug safety problems is to modernize FDA's electronic information system. User fees have supported improvements in the agency's information technology (IT) infrastructure for new drug review and oversight; the proposed changes would provide added resources to establish an all-electronic regulatory submission and review environment over the next 5 years. The system would allow manufacturers to electronically submit applications and would provide automated cross-links to previously submitted data, allowing FDA reviewers to retrieve all relevant submissions.

According to legislators, an updated IT system also would improve FDA's current adverse event reporting system (AERS) for collecting and analyzing AERs from manufacturers, health professionals, and patients. Congress furthermore supports FDA's efforts to build a more robust, active surveillance system instead of relying on spontaneous reports to signal problems. Additional resources would permit FDA to contract with government health programs and private health plans to access population-based epidemiologic data on millions of patients, which could enhance postmarketing drug surveillance. Expanded collaboration with payors, academia, and the Centers for Education and Research on Therapeutics (CERTS) would enable FDA to learn more about how a drug works in real-world postmarket circumstances, including the extent and outcomes of off-label drug uses.

Ms Wechsler is a Washington-based reporter specializing in federal and state healthcare issues.

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