FDA Leglislation Tackles Safety Issues

Published on: 
BioPharm International, BioPharm International-09-01-2007, Volume 20, Issue 9
Pages: 40–45

The new legislation authorizes the use of fee revenues for drug safety oversight and assessment throughout a product's lifecycle.

Legislation to reauthorize the Prescription Drug User Fee Act (PDUFA IV) will provide more tools and legal authority for the US Food and Drug Administration to monitor and mitigate drug risks, while also boosting user fees and extending several FDA programs. The bill, which the Congress is expected to finalize by the end of this month, implements an FDA–industry user fee agreement issued in January, and a similar plan for medical devices. Additional provisions renew incentives for manufacturers to study pediatric uses of drugs and establishes such incentives for medical devices.

Jill Wechsler

To strengthen drug safety policies, the bill gives FDA authority to require postapproval clinical trials and to revise product labels within a set time-frame. Manufacturers will have to disclose more information about ongoing clinical trials and study results. There is more funding for FDA oversight of postmarket drug use and to expand the agency's information systems for tracking adverse events and for detecting emerging safety problems. Also, manufacturers of medications known to be risky will have to spell out a range of pharmacovigilance activities to inform patients and prescribers of possible dangers and to ensure appropriate product use. These initiatives should provide more timely information on emerging concerns about certain medicines, but also could drive up the cost of developing new therapies and delay access to new treatments.



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 maintaining an efficient and timely drug development and review process. FDA and industry initially agreed on a new user fee program that would collect nearly $400 million a year starting in 2008, with steady increases over the program's five-year period. An additional fee program bolsters FDA review of drug TV advertising further.

The legislators increased drug user fees even more to support a number of new safety initiatives. An important change is to authorize the use of fee revenues for drug safety oversight and assessment throughout a product's lifecycle—and not just during the first two or three years after product approval, as currently allowed. Moreover, the bill gives FDA authority to require a risk evaluation and mitigation strategy (REMS) from companies when the regulators decide that a formal approach is needed to manage particularly risky products. 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 healthcare information to healthcare professionals

  • seek FDA pre-review of advertising and marketing materials to ensure that ads describe serious risks appropriately and fairly

  • limit drug prescribing and distribution. FDA may determine that specific treatments should be prescribed only by specially trained health professionals and for certain patients. Distribution similarly may be limited to select wholesalers and pharmacists. Such limited access programs may require additional laboratory testing, patient monitoring, and patient enrollment in a registry.


In addition to establishing a REMS for certain products, the legislation enhances FDA authority to implement new oversight and disclosure policies for all drugs. These include:

  • Speedy labeling changes: Congress strengthens FDA authority to require manufacturers to make certain labeling changes to reflect new safety information. Instead of lengthy discussions between sponsors and FDA about the need to revise a product label, the legislation sets timeframes for negotiating such changes. The new system offers a process for sponsors to challenge a requested labeling change and for resolving disputes.

  • Timely completion of postapproval studies: FDA currently may request additional clinical trials and analyses following approval of a new therapy, but lacks authority to penalize companies that fail to complete these studies. The new policy calls for discussion of postapproval study options earlier in the approval process to ensure that agreements are realistic and address important issues. Manufacturers will have to propose timetables for completing these studies, report periodically on their progress, and explain why they cannot meet the set goals if problems arise.

  • More information on active clinical trials: To better inform patients of opportunities to participate in clinical trials, sponsors will have to submit information about more ongoing studies to the ClinicalTrials.gov website. The legislation expands listings to cover most regulated drugs and biotech therapies. It also beefs up registration listings to include a long list of specific information, including whether there is any expanded access program for a not-yet-approved test treatment.

  • Mandatory disclosure of research results: A key goal of the new policy is to link clinical trials registration to results information. Many manufacturers already post study results voluntarily, but the legislators seek a more comprehensive approach. Policymakers expect that such listings will include published studies and all FDA information on the drug (except proprietary trade secrets), such as the approved product label and relevant safety information.

  • Curbing conflicts-of-interest: The legislation reflects Congressional concerns that too many members of FDA advisory committees have financial links to the industry. Although policymakers recognize that these panels can benefit from input from experts who may have such conflicts, the legislation aims to make advisory committees more objective on safety issues by limiting waivers needed to permit such testimony.


A prime initiative for reducing drug safety problems is to modernize FDA's electronic information systems. User fees have supported improvements in the agency's IT infrastructure for new drug review and oversight; now PDUFA IV will provide added funds to establish an all-electronic regulatory submission and review environment over the next five years. The envisioned system will allow manufacturers to send in applications electronically with automated cross-links to previously submitted data, while FDA reviewers will be able to retrieve all relevant submissions and data and tools for searching and analyzing them. The goal is a system that can handle two-way transmission of regulatory correspondence.

A modern IT system also would improve FDA's current adverse event reporting system (AERS) for collecting and analyzing such reports from manufacturers, health professionals, and patients. In addition, Congress supports FDA efforts to build a more robust active surveillance system instead of relying on spontaneous adverse event reports to identify emerging safety problems. Additional resources will permit FDA to contract with government health programs and private health plans to access population-based epidemiological data on millions of patients to expand postmarketing drug surveillance. More collaboration with government and academic organizations and with the Centers for Education and Research on Therapeutics (CERTS) will enable FDA to learn more about how a treatment works in real-world postmarket circumstances, including the extent and outcomes of off-label drug uses.

PDUFA funds also will expand FDA staffing of epidemiologists, safety evaluators, and programmers who are able to use such IT resources. New research in this area should provide a better understanding of the role of epidemiologic analysis and use of databases in evaluating medical product safety.

Jill Wechsler is BioPharm International's Washington editor, Chevy Chase, MD, 301.656.4634, jwechsler@advanstar.com