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Date: March 1, 2004
Contacts: Christine Stencel, Media Relations Officer
Chris Dobbins, Media Relations Assistant
Office of News and Public Information
202-334-2138; e-mail <>


Report Recommends More Explicit Guidelines
For Assessing Safety of New Ingredients Added to Infant Formula

WASHINGTON -- Although the federal regulatory processes for evaluating the safety of food ingredients have worked well for conventional substances, they were not designed to address the unique needs and vulnerabilities of infants and are insufficient to ensure the safety of new types of ingredients proposed for infant formula, says a new report from the Institute of Medicine of the National Academies. The committee that wrote the report laid out guidelines that clarify the types and extent of safety testing necessary for new formula ingredients, particularly unconventional substances derived from novel sources or technologies. It also called for outside experts to take a more proactive role in determining how and when such tests should be done.

"The current regulatory processes do not fully address the unique role of formula as a food source," explained committee chair Richard J. Deckelbaum, professor of nutrition and pediatrics and director, Institute of Human Nutrition, Columbia University, New York City. "Formula is infants' only food if they are not being breast-fed. The processes used to regulate the safety of any new additions to formula should be tailored to these products' distinct role and the special needs and susceptibilities of infants. Our report offers a set of guidelines and steps to accomplish this goal."

A key limitation of the current approach is the lack of explicit guidelines to help formula manufacturers and their outside expert reviewers determine what safety data are needed on a proposed ingredient and how they should be gathered. To help fill this gap, the report offers a set of "decision trees" -- hierarchical series of questions leading to specific action steps -- to guide manufacturers and reviewers in determining the level and extent of safety testing needed at various stages.

The decision trees encapsulate and simplify the various regulations governing infant formula, which originate from different legislative acts and frequently are unclear to manufacturers or the experts charged with reviewing safety data. The Food and Drug Administration's "Generally Recognized As Safe" (GRAS) notification process is the most common approach used when new substances are added to foods, including formula. While manufacturers typically generate or obtain safety data through preclinical toxicity studies and clinical data, GRAS notification does not provide guidelines for tests specifically designed to address ingredients for infant formula, leaving it up to manufacturers and their expert reviewers to determine what data are needed. Formula manufacturers also must abide by the Infant Formula Act, which mandates the basic nutrients their products should include, but likewise does not specify needed safety tests.

Clarification of the decision-making process is crucial given the increasing number of potential ingredients -- such as bioactive peptides and enzymes -- that are either generated from unconventional sources or produced through new technologies. Although the current regulatory approaches have worked well for ascertaining the safety of conventional substances such as vitamins and minerals, they are not as well-suited to evaluating these new types of ingredients, the report says.

To demonstrate how the decision trees would work, the committee applied them to two novel ingredients recently added to formula: long-chain polyunsaturated fatty acids and beneficial microorganisms called probiotics. These examples illustrate only how the decision-making models work; the committee was not asked to judge the safety of these substances.

The committee also recommended strengthening the current regulatory approach by ensuring balanced composition of the expert panels that often are used to evaluate the safety of new ingredients proposed for formula. As part of GRAS notification, a manufacturer must show that qualified experts -- usually brought together as a panel -- agree that a proposed ingredient is safe for its intended purpose. If the experts concur, the manufacturer notifies FDA that the substance is "generally recognized as safe," which the agency may either question or accept by raising no objections. The committee urged regular use of panels and strongly recommended that a physician – preferably a pediatrician – be included among the experts reviewing formula ingredients.

FDA also should develop specific guidelines for how manufacturers should choose reviewers. The selection of experts is critical because these individuals should be responsible for deciding the level of testing needed to ensure a proposed ingredient's safety, the report says. Furthermore, they should determine the extent of follow-up surveillance that is needed once the new ingredient has reached the market.

FDA is proposing new regulations implementing the Infant Formula Act that would require formulas with new ingredients to be evaluated for their ability to contribute to normal infant growth and development through studies that follow participants for 120 days -- a process that some manufacturers already voluntarily undertake. Growth studies should be the centerpiece of clinical evaluations of formula, the report says, but it notes that because formula is many babies' sole source of nutrition for up to six months, growth studies should last 180 days as well. This time frame also increases the chances that any longer-term effects of the new ingredient would be recognized. The report also recommends that proposed ingredients be judged by their tendency to cause allergic reactions; infants' tolerance of them; their impact on normal stomach and intestinal microbes; whether they interfere with infants' ability to get the benefits of other nutrients; and whether nutritional imbalances might occur if, for example, the particular ingredient's effects require the presence of another substance.

In several previous reports, the Institute of Medicine has documented the health and social benefits of breast-feeding and recommended that infants be breast-fed. However, the vast majority of American babies age six months and older are fed at least some infant formula. Since the inception of large-scale production of formula in the 1920s, manufacturers have sought ways to better simulate breast milk and impart health benefits. For example, they added iron in 1959 to reduce the risk of iron-deficiency, and in 1984 they introduced the amino acid taurine, which may aid growth and development.

The study was sponsored by the U.S. Food and Drug Administration and by Health Canada. The Institute of Medicine is a private, nonprofit institution that provides health policy advice under a congressional charter granted to the National Academy of Sciences. A committee roster follows.

Infant Formula: Evaluating the Safety of New Ingredients will be available later this summer from the National Academies Press; tel. 202-334-3313 or 1-800-624-6242 or on the Internet at Reporters may obtain a pre-publication copy from the Office of News and Public Information (contacts listed above).

[ This news release and report are available at ]

Food and Nutrition Board

Committee on the Evaluation of the Addition of Ingredients New to Infant Formula

Richard J. Deckelbaum, M.D. (chair)
Robert R. Williams Professor of Nutrition and Pediatrics, and
Institute of Human Nutrition
College of Physicians and Surgeons
Columbia University
New York City

Linda Adair, Ph.D.
Associate Professor
Department of Nutrition
Schools of Public Health and Medicine
University of North Carolina
Chapel Hill

Mark Appelbaum, Ph.D.
Associate Vice Chancellor, and Professor
Department of Psychology
University of California
San Diego

George L. Baker, M.D.
Medical Director and Vice President
Mead Johnson Nutritionals (retired)
Snowmass Village, Colo.

Susan S. Baker, M.D., Ph.D.
Professor of Pediatrics, and
Pediatric Gastroenterology, Nutrition, and Hepatology
Children's Hospital of Buffalo
State University of New York

Cheston M. Berlin Jr., M.D.
Professor of Pediatrics and Pharmacology
Milton S. Hershey Medical Center
Pennsylvania State University

William C. Franke, Ph.D.
Associate Director
Center for Advanced Food Technology
Rutgers University
New Brunswick, N.J.

Michael K. Georgieff, M.D.
Professor and Co-director
Center for Neurobehavioral Development
University of Minnesota

James M. Ntambi, Ph.D.
Associate Professor
Department of Biochemistry and Nutritional Sciences
University of Wisconsin

Theodore D. Wachs, Ph.D.
Professor of Psychological Sciences
Purdue University
West Lafayette, Ind.


Maria Oria, Ph.D.
Study Director