Advisers to the Nation on Science, Engineering, and Medicine

The National Academy of Sciences is a private, nonprofit, self-perpetuating society of distinguished scholars engaged in scientific and engineering research, dedicated to the furtherance of science and technology and to their use for the general welfare. Upon the authority of the charter granted to it by the Congress in 1863, the Academy has a mandate that requires it to advise the federal government on scientific and technical matters. Dr. Ralph J. Cicerone is president of the National Academy of Sciences.

The National Academy of Engineering was established in 1964, under the charter of the National Academy of Sciences, as a parallel organization of outstanding engineers. It is autonomous in its administration and in the selection of its members, sharing with the National Academy of Sciences the responsibility for advising the federal government. The National Academy of Engineering also sponsors engineering programs aimed at meeting national needs, encourages education and research, and recognizes the superior achievements of engineers. Dr. Charles M. Vest is president of the National Academy of Engineering.

The Institute of Medicine was established in 1970 by the National Academy of Sciences to secure the services of eminent members of appropriate professions in the examination of policy matters pertaining to the health of the public. The Institute acts under the responsibility given to the National Academy of Sciences by its congressional charter to be an adviser to the federal government and, upon its own initiative, to identify issues of medical care, research, and education. Dr. Harvey V. Fineberg is president of the Institute of Medicine.

The National Research Council was organized by the National Academy of Sciences in 1916 to associate the broad community of science and technology with the Academy’s purposes of furthering knowledge and advising the federal government. Functioning in accordance with general policies determined by the Academy, the Council has become the principal operating agency of both the National Academy of Sciences and the National Academy of Engineering in providing services to the government, the public, and the scientific and engineering communities. The Council is administered jointly by both Academies and the Institute of Medicine. Dr. Ralph J. Cicerone and Dr. Charles M. Vest are chair and vice chair, respectively, of the National Research Council.

www.national-academies.org

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Review of the Environmental Protection Agency’s Draft IRIS Assessment of Formaldehyde (2011)

The Use of Title 42 Authority at the U.S. Environmental Protection Agency (2010)

Review of the Environmental Protection Agency’s Draft IRIS Assessment of Tetrachloroethylene (2010)

Hidden Costs of Energy: Unpriced Consequences of Energy Production and Use (2009)

Contaminated Water Supplies at Camp Lejeune—Assessing Potential Health Effects (2009)

Review of the Federal Strategy for Nanotechnology-Related Environmental, Health, and Safety Research (2009)

Science and Decisions: Advancing Risk Assessment (2009)

Phthalates and Cumulative Risk Assessment: The Tasks Ahead (2008)

Estimating Mortality Risk Reduction and Economic Benefits from Controlling Ozone Air Pollution (2008)

Respiratory Diseases Research at NIOSH (2008)

Evaluating Research Efficiency in the U.S. Environmental Protection Agency (2008)

Hydrology, Ecology, and Fishes of the Klamath River Basin (2008)

Applications of Toxicogenomic Technologies to Predictive Toxicology and Risk Assessment (2007)

Models in Environmental Regulatory Decision Making (2007)

Toxicity Testing in the Twenty-first Century: A Vision and a Strategy (2007)

Sediment Dredging at Superfund Megasites: Assessing the Effectiveness (2007)

Environmental Impacts of Wind-Energy Projects (2007)

Scientific Review of the Proposed Risk Assessment Bulletin from the Office of Management and Budget (2007)

Assessing the Human Health Risks of Trichloroethylene: Key Scientific Issues (2006)

New Source Review for Stationary Sources of Air Pollution (2006)

Human Biomonitoring for Environmental Chemicals (2006)

Health Risks from Dioxin and Related Compounds: Evaluation of the EPA Reassessment (2006)

Fluoride in Drinking Water: A Scientific Review of EPA’s Standards (2006)

State and Federal Standards for Mobile-Source Emissions (2006)

Superfund and Mining Megasites—Lessons from the Coeur d’Alene River Basin (2005)

Health Implications of Perchlorate Ingestion (2005)

Air Quality Management in the United States (2004)

Endangered and Threatened Species of the Platte River (2004)

Atlantic Salmon in Maine (2004)

Endangered and Threatened Fishes in the Klamath River Basin (2004)

Cumulative Environmental Effects of Alaska North Slope Oil and Gas Development (2003)

Estimating the Public Health Benefits of Proposed Air Pollution Regulations (2002)

Biosolids Applied to Land: Advancing Standards and Practices (2002)

The Airliner Cabin Environment and Health of Passengers and Crew (2002)

Arsenic in Drinking Water: 2001 Update (2001)

Evaluating Vehicle Emissions Inspection and Maintenance Programs (2001)

Compensating for Wetland Losses Under the Clean Water Act (2001)

A Risk-Management Strategy for PCB-Contaminated Sediments (2001)

Acute Exposure Guideline Levels for Selected Airborne Chemicals (nine volumes, 2000-2010)

Toxicological Effects of Methylmercury (2000)

Strengthening Science at the U.S. Environmental Protection Agency (2000)

Scientific Frontiers in Developmental Toxicology and Risk Assessment (2000)

Ecological Indicators for the Nation (2000)

Waste Incineration and Public Health (2000)

Hormonally Active Agents in the Environment (1999)

Research Priorities for Airborne Particulate Matter (four volumes, 1998-2004)

The National Research Council’s Committee on Toxicology: The First 50 Years (1997)

Carcinogens and Anticarcinogens in the Human Diet (1996)

Upstream: Salmon and Society in the Pacific Northwest (1996)

Science and the Endangered Species Act (1995)

Wetlands: Characteristics and Boundaries (1995)

Biologic Markers (five volumes, 1989-1995)

Science and Judgment in Risk Assessment (1994)

Pesticides in the Diets of Infants and Children (1993)

Dolphins and the Tuna Industry (1992)

Science and the National Parks (1992)

Human Exposure Assessment for Airborne Pollutants (1991)

Rethinking the Ozone Problem in Urban and Regional Air Pollution (1991)

Decline of the Sea Turtles (1990)

Copies of these reports may be ordered from the National Academies Press

(800) 624-6242 or (202) 334-3313

www.nap.edu

The U.S. Food and Drug Administration (FDA) has regulatory responsibility for a vast number of products—foods, drugs, cosmetics, biologics, veterinary products, medical devices, tobacco, and products that emit radiation—and often faces difficult management decisions as to how to ensure the safety of the products that it regulates. FDA recognized that collecting and evaluating information on the risks posed by the regulated products in a systematic manner would aid in its decision-making process. Consequently, FDA and the Department of Health and Human Services (DHHS) asked the National Research Council (NRC) to develop a conceptual model that could evaluate products or product categories that FDA regulates and provide information on the potential health consequences associated with them. As a result of that request, NRC formed the Committee on Ranking FDA Product Categories Based on Health Consequences.

The project was to be conducted in two phases. For the first phase, the committee was to produce a brief letter report that described a conceptual model that could be used to rank product categories. For the second phase, the committee was to develop, refine, and apply the model to conduct a risk ranking of FDA product categories. The letter report was completed and provided to FDA in February 2009 and is provided in Appendix A. On receipt of the letter report, FDA and DHHS re-evaluated the project and determined that the original scope was too ambitious, that a ranking of products or product categories would be premature, and that the project should be revised to focus more on developing a framework that could be used to evaluate and characterize the public-health consequences associated with FDA-regulated products or product categories in the context of various decision scenarios. Furthermore, FDA and DHHS wanted a framework that would provide a common set of metrics that would enable each center to evaluate the public-health consequences using a common terminology and approach that would allow comparisons within and among disparate programs. The present report reflects the change in scope; it describes the risk-characterization framework proposed by the committee, illustrates the use of

that framework with several case studies, and provides the committee’s conclusions and recommendations.

This report has been reviewed in draft form by persons chosen for their diverse perspectives and technical expertise in accordance with procedures approved by the NRC’s Report Review Committee. The purposes of the independent review are to provide candid and critical comments that will assist the institution in making its published report as sound as possible and to ensure that the report meets institutional standards of objectivity, evidence, and responsiveness to the study charge. The review comments and draft manuscript remain confidential to protect the integrity of the deliberative process. We thank the following for their review of this report: Susan Alpert, Medtronic; Robert L. Buchanan, University of Maryland; Julie A. Caswell, University of Massachusetts; Louis Anthony Cox, Jr., Cox Associates; Robert L. Davis, Kaiser Permanente; James K. Hammitt, Harvard University and Toulouse School of Economics; Lee-Ann Jaykus, North Carolina State University; Gregory M. Paoli, Risk Sciences International, Inc.; Birgit Puschner, University of California, Davis; Jim E. Riviere, North Carolina State University; Joseph V. Rodricks, ENVIRON; and Hugh H. Tilson, University of North Carolina.

Although the reviewers listed above have provided many constructive comments and suggestions, they were not asked to endorse the conclusions or recommendations, nor did they see the final draft of the report before its release. The review of the report was overseen by the review coordinator, Lauren Zeise, California Environmental Protection Agency, and the review monitor, Chris G. Whipple, ENVIRON. Appointed by NRC, they were responsible for ensuring that an independent examination of the report was carried out in accordance with institutional procedures and that all review comments were carefully considered. Responsibility for the final content of the report rests entirely with the committee and the institution.

The committee gratefully acknowledges staff from several centers at FDA for attending the committee’s public session to discuss their current approaches for decision-making at the various centers.

The committee is also grateful for the assistance of the NRC staff in preparing this report. Staff members who contributed to the effort are Ellen Mantus, project director; James Reisa, director of the Board on Environmental Studies and Toxicology; Norman Grossblatt, senior editor; Heidi Murray-Smith, program officer; Mirsada Karalic-Loncarevic, manager of the Technical Information Center; Radiah Rose, manager of editorial projects; Keri Schaffer, research associate; and Panola Golson, program associate.

I would especially like to thank all the members of the committee for their efforts throughout the development of this report.