• Decrease font size
  • Return font size to normal
  • Increase font size
U.S. Department of Health and Human Services


  • Print
  • Share
  • E-mail

Conclusions and Recommendations

Table of Contents: Managing the Risks from Medical Product Use: Creating a Risk Management Framework

Previous Section : What Factors in the Development Process could affect Risk Identification?

The Task Force found that the data show no increase in the rate of drug withdrawals since PDUFA. There is also no evidence that drugs reviewed under PDUFA (the 1994-1997 cohort) have resulted in higher rates of serious adverse events identified postmarketing than have drugs reviewed before PDUFA. In fact, we found the rates of serious adverse events identified postmarketing were lower for drugs reviewed under PDUFA.

The Task Force also found that, overall, the key elements of FDA's quality control system are in place and are regularly followed. FDA's premarketing review and decision process are being managed to produce high-quality review decisions.

Despite these findings, the Task Force believes that the three Centers that conduct premarketing review of human medical products could enhance the application of FDA's quality control system in the following ways:


  1. Initiate steps to have each Center establish separate QA/QC units to support the QA/QC system as a normal part of all activities. Responsibilities should include the following:
    • Peer review a sample of product approval review administrative records for quality of the analysis and completeness of the documentation.
    • Establish procedures for continuation of review when there has been an administrative disruption of the process (e.g., loss of primary reviewer, change of division).
    • Prospectively track scientific disputes among reviewers and evaluate whether the disputed issue is predictive of problems after marketing.
  2. Ensure and document ongoing professional education and current core competency training for all reviewers.
  3. Complete the Good Review Practice (GRP) documents and keep them current.
  4. Systematically analyze significant postmarketing events and incorporate them into GRP as lessons learned.


Additional options

Options that could address, in part, the factors in medical product development that limit the identification of some risks include:

  1. Evaluate the practicality and value of expanding the use of large, community-based simple trials designed to identify serious adverse events in a larger and more representative patient population prior to approving the product for widespread use.
  2. Develop tools to concentrate early postapproval use in populations for whom an advantage of the new product over alternative products has been demonstrated.





1 Government Accounting Office, FDA Drug Review -- Postapproval Risks 1976-1985, GAO/PEMD-90-15, April 1990.

2 A Dear Healthcare Professional letter is usually sent by the manufacturer to inform healthcare professionals about important safety-related changes to product labeling.

3 A review of the rate of unanticipated adverse events leading to drug withdrawals is reported in detail in Friedman, M.A., J. Woodcock, M. Lumpkin, J. Shuren et al., "The Safety of Newly Approved Medicines: Do Recent Market Removals Mean There is a Problem?" JAMA, Vol. 281, No. 18, May 12, 1999.

4 FDA, Center for Drug Evaluation and Research, 1998 Report to the Nation, May 1999.

5 Redux, Pondimin, Seldane, Duract, and Posicor were withdrawn from the market in 1997 and 1998; Seldane and Pondimin were approved prior to PDUFA.

6 Patients with serious and life-threatening diseases who lack effective treatment have told the Agency that prompt access to new treatments is extremely important to them. These patients are willing to accept greater uncertainty about risks and benefits in exchange for earlier access.

7 21 Code of Federal Regulations 10.70.

8 21 Code of Federal Regulations 10.75.

9 See, for example, CDER's Manual of Policies & Procedures 4151.1 on "Resolution of Disputes: Roles of Reviewers, Supervisors and Management; Documenting Views and Findings and Resolving Differences."

10 The FDA is one of the six founding members of the International Conference on Harmonisation (ICH), which is a joint initiative involving both regulators and industry in scientific and technical discussions of the testing procedures that are required to ensure and assess the safety, quality and efficacy of medicines.

11 The background rate of an event in a given population is the rate at which events occur in people who are not exposed to the given product.

12 In cases where no alternative exists, a product would not be withdrawn, but relabeled to achieve more careful use.


Next Section : Part 3: How does FDA conduct Postmarketing Surveillance and Risk Assessment?