Infant Formula: Evaluating the Safety of New Ingredients

219 Pages·2004·4.34 MB·English

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

INFANT
FORMULA
EVALUATING THE SAFETY OF NEW INGREDIENTS
Committee on the Evaluation of the Addition of Ingredients
New to Infant Formula
Food and Nutrition Board
INSTITUTE OF MEDICINE
OF THE NATIONAL ACADEMIES
THE NATIoNAl ACADEmIES PrESS
Washington, D.C.
THE NATIONAL ACADEMIES PRESS • 500 Fifth Street, N.W. • Washington, DC 20001
NOTICE: The project that is the subject of this report was approved by the Governing Board of the
National Research Council, whose members are drawn from the councils of the National Academy of
Sciences, the National Academy of Engineering, and the Institute of Medicine. The members of the
committee responsible for the report were chosen for their special competences and with regard for
appropriate balance.
This study was supported by Contract No. 223-01-2460, TO4, and Contract No. 4500033271 be-
tween the National Academy of Sciences and the Food and Drug Administration, U.S. Department of
Health and Human Services, and Health Canada. Any opinions, findings, conclusions, or recommen-
dations expressed in this publication are those of the author(s) and do not necessarily reflect the view
of the organizations or agencies that provided support for this project.
Library of Congress Cataloging-in-Publication Data
Institute of Medicine (U.S.). Committee on the Evaluation of the Addition of Ingredients New to Infant
Formula.
Infant formula : evaluating the safety of new ingredients / Committee on the Evaluation of the
Addition of Ingredients New to Infant Formula, Food and Nutrition Board.
p. ; cm.
Includes bibliographical references.
ISBN 0-309-09150-0 (pbk.)
1. Infant formulas—Standards—United States. 2. Infant formulas—Law and legislation—United
States.
[DNLM: 1. Infant Formula—standards. 2. Evaluation Studies. 3. Food Analysis—methods. 4.
Food Contamination—prevention & control. 5. Infant Formula—legislation & jurisprudence. 6.
Infant Nutrition. WS 120 I59 2004] I. Title.
RJ216.I538 2004
613.2′083′2—dc22
2004008412
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Copyright 2004 by the National Academy of Sciences. All rights reserved.
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religions since the beginning of recorded history. The serpent adopted as a logotype by the Institute of
Medicine is a relief carving from ancient Greece, now held by the Staatliche Museen in Berlin.
COMMITTEE ON THE EVALUATION OF THE ADDITION OF INGREDIENTS
NEW TO INFANT FORMULA
RICHARD J. DECKELBAUM (Chair), Institute of Human Nutrition and Pediatric
Gastroenterology and Nutrition, Columbia University, New York, New York
LINDA ADAIR, Department of Nutrition, Schools of Public Health and Medicine,
University of North Carolina at Chapel Hill
MARK APPELBAUM, Department of Psychology, University of California, San Diego
GEORGE L. BAKER, Snowmass Village, Colorado
SUSAN S. BAKER, Department of Pediatrics, State University of New York at Buffalo
CHESTON M. BERLIN, Department of Pediatrics, Pennsylvania State University,
Hershey
WILLIAM C. FRANKE, Center for Advanced Food Technology, Rutgers, State
University of New Jersey, New Brunswick
MICHAEL K. GEORGIEFF, Department of Pediatrics, University of Minnesota,
Minneapolis
JAMES M. NTAMBI, Department of Biochemistry, University of Wisconsin, Madison
THEODORE D. WACHS, Department of Psychological Science, Purdue University,
West Lafayette, Indiana
Consultants
CARMI ZVI MARGOLIS, University Center for Health Sciences, Ben-Gurion
University of the Negev, Israel
PEARAY OGRA, State University of New York at Buffalo
ODED SUSSKIND, Brookline, Massachusetts
Editor
SARAH CARROLL, Minnetonka, Minnesota
Staff
MARIA ORIA, Study Director (from June 2003)
PAULA TRUMBO, Study Director (September 2002–June 2003)
SANDRA SCHLICKER, Study Director (until September 2002)
LESLIE J. VOGELSANG, Research Assistant
SANDRA AMAMOO-KAKRA, Senior Project Assistant (from September 2002)
HARLEEN K. SETHI, Senior Project Assistant (until September 2002)
v
FOOD AND NUTRITION BOARD
CATHERINE E. WOTEKI (Chair), College of Agriculture, Iowa State University, Ames
ROBERT M. RUSSELL (Vice Chair), Jean Mayer U.S. Department of Agriculture Human
Nutrition Research Center on Aging, Tufts University, Boston, Massachusetts
LARRY R. BEUCHAT, Center for Food Safety, University of Georgia, Griffin
SUSAN A. FERENC, SAF*RISK, LC, Madison, Wisconsin
NANCY F. KREBS, Department of Pediatrics, University of Colorado Health Sciences
Center, Denver
SHIRIKI KUMANYIKA, Center for Clinical Epidemiology and Biostatistics, University of
Pennsylvania School of Medicine, Philadelphia
REYNALDO MARTORELL, Department of International Health, Emory University,
Atlanta, Georgia
LYNN PARKER, Child Nutrition Programs and Nutrition Policy, Food Research and
Action Center, Washington, D.C.
BARBARA O. SCHNEEMAN, Department of Nutrition, University of California, Davis
NICHOLAS J. SCHORK, Polymorphism Research Laboratory, University of California,
San Diego
JOHN W. SUTTIE, Department of Biochemistry, University of Wisconsin, Madison
STEVE L. TAYLOR, Department of Food Science and Technology and Food Processing
Center, University of Nebraska, Lincoln
BARRY L. ZOUMAS, Department of Agricultural Economics and Rural Sociology,
Pennsylvania State University, University Park
Staff
LINDA D. MEYERS, Director
GAIL E. SPEARS, Staff Editor
GERALDINE KENNEDO, Administrative Assistant
ELISABETH RIMAUD, Financial Associate
vi
Reviewers
This report has been reviewed in draft form by individuals chosen for their diverse
perspectives and technical expertise, in accordance with procedures approved by the NRC’s
Report Review Committee. The purpose of this independent review is 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 for 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 wish to thank the follow-
ing individuals for their review of this report:
M. Tom Clandinin, MTI MetaTech, Inc.; Susan Ferenc, SAF*RISK, LC; Kenneth Fisher,
KD Consultants; Cutberto Garza, Cornell University; William C. Heird, Baylor College of
Medicine; Charlie Homer, National Initiative for Children’s Healthcare Quality; Nancy F.
Krebs, University of Colorado Health Sciences Center; Mary F. Locniskar, Hill’s Pet Nutri-
tion, Inc.; Michael Posner, University of Oregon; Catharine Ross, Pennsylvania State Uni-
versity; Steve L. Taylor, University of Nebraska, Lincoln; John E. Vanderveen, San Antonio,
Texas.
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 this report was
overseen by Dennis M. Bier, USDA/ARS Children’s Nutrition Research Center at Baylor
College of Medicine. Appointed by the Institute of Medicine, he was responsible for
making certain that an independent examination of this report was carried out in accor-
dance with institutional procedures and that all review comments were carefully consid-
ered. Responsibility for the final content of this report rests entirely with the authoring
committees and the institution.
vii
Preface
Infant formulas are unique because they are the only source of nutrition for many
infants during the first 4 to 6 months of life. They are critical to infant health because they
must safely support growth and development during a period when the consequences of
inadequate nutrition are most severe. The safety standard for an ingredient added to infant
formula is defined as a “reasonable certainty of no harm.” In recent years infant formula
manufacturers have proposed ingredients (e.g., long-chain polyunsaturated fatty acids [LC-
PUFAs], probiotics) that have created new scientific challenges that existing regulations may
not address. Meanwhile the Food and Drug Administration (FDA) has been working to
revise several aspects of its infant formula regulations, including requirements for quality
factors and current good manufacturing practices.
In 2002 FDA and Health Canada asked the Institute of Medicine’s Food and Nutrition
Board (FNB) to formulate an expert committee to review and identify gaps in methods
currently used to assess the safety of ingredients new to infant formulas. The committee
was asked to identify tools to evaluate the safety of these ingredients under intended
conditions of use in term infants. This charge included determining the data needed to
demonstrate the safety of a component already present in human milk, that is, the effect of
the matrix, and the utilization of preclinical and clinical studies and postmarket monitoring
in the safety assessment process. FDA also asked the committee to apply its recommenda-
tions to the recent addition of LC-PUFAs as new ingredients in infant formulas, and others
as appropriate.
A 10-member committee was appointed with expertise in the areas of pediatric nutri-
tion, pediatric gastroenterology, epidemiology and public health, statistics, food technology,
food regulatory processes, pediatric neurology, biochemistry, and infant formula manufac-
turing. Members brought a diversity of experience from research laboratories, industry, and
hospital and clinic settings. Many of the committee members had never met, yet the group
developed a cohesion that allowed them to work through and agree upon several difficult
issues over the 18-month project.
The committee sought additional expertise and background from several consultants.
ix
x PREFACE
Two medical education consultants worked with the committee to develop several decision-
making tools (algorithms) that emerged as important components of the committee’s recom-
mendations. An editorial consultant helped the committee bridge the gap from rough draft
to final report to ensure uniformity of style and maximum readability for all possible users.
Another consultant provided targeted guidance in the areas of immunology and endocrinol-
ogy. In addition, the committee held two open sessions to learn more about updated systems
and information that was relevant to its charge. In one open session, the committee reviewed
differences that might apply to safety of foods as compared with drugs. In the other open
session, one specialist discussed the use of growth charts and another from FDA’s Center for
Food Safety and Applied Nutrition discussed the Adverse Event Reporting System.
The committee held six meetings and utilized frequent conference calls to develop this
report. The committee decided at an early stage that as a general approach, it would first
review current (and past) approaches to establishing the safety of ingredients new to infant
formulas. Next, gaps or limits of the current systems were to be identified, and then recom-
mendations were to be proposed to improve current approaches. Realizing that detailed
recommendations for every possible new ingredient would be impossible to achieve within
the framework of the committee’s work, generic templates were designed to be utilized (and
modified) to fit a large range of potentially new ingredients with varying characteristics and
different levels of safety concern.
The committee proposes the use of a hierarchical approach to assess the safety of
ingredients new to infant formulas. These hierarchies, which often utilize algorithms, assist
decision-making through a step-by-step process that places priority on commonly used
assessments (e.g., screening) and progresses to more specific assessments (e.g., neuroimaging)
when early indicators suggest safety concerns. The primary benefit of using algorithms is
that they provide an appropriate balance of information and flexibility to navigate through
a decision-making process without being prescriptive. This is especially useful given the wide
diversity in possible new ingredients.
On behalf of the committee, I am grateful to FNB’s staff for their support and contribu-
tions. This report was guided by three study directors: Sandra Schlicker laid the initial
foundation for the committee’s work, Paula Trumbo provided input through the middle
stages of deliberation, and Maria Oria assisted the committee in bringing the report to its
conclusion. The committee is grateful to Leslie Vogelsang, research assistant, and Sandra
Amamoo-Kakra, senior project assistant, for their support and dedication. The committee
would also like to thank Linda Meyers, director of FNB, for her objective insights and
invaluable expertise that informed committee deliberations and conclusions and Allison
Yates for her leadership during the early stages of the project. This report would not have
been possible without the leadership and dedication of the FNB staff.
Finally, I wish to thank each member of the committee for his or her unique contribu-
tions and unfailing dedication to a report that has the potential to improve the safety of
infant formulas for a new generation.
Richard J. Deckelbaum, Chair
Committee on the Evaluation of the Addition of
Ingredients New to Infant Formula
Contents
EXECUTIVE SUMMARY 1
1 INTRODUCTION AND BACKGROUND 17
Infant Formula Regulations and Guidelines, 18
Charge to the Committee, 20
The Committee’s Approach, 22
Organization of the Report, 27
Summary, 27
References, 27
2 DEFINING SAFETY FOR INFANTS 29
Abstract, 29
Introduction, 30
U.S. Regulatory Agencies, 30
Fundamental Concepts of Safety Regulations, 30
Statistical Considerations in Food Safety Determination, 31
Models of Safety Assessment, 33
Special Considerations for Infant Formulas, 36
Summary, 39
References, 40
3 COMPARING INFANT FORMULAS WITH HUMAN MILK 41
Abstract, 41
Background, 42
History of the Development of Infant Formulas, 42
Challenges of Matching Human-Milk Composition and
Breastfeeding Performance, 44
Performance Advantages of Breastfeeding, 46
Risks of Breastfeeding, 50
xi