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 since they must safely support growth and development during a period when the consequences on inadequate nutrition are most severe. Existing guidelines and regulations for evaluating the safety of conventional food ingredients (e.g., vitamins and minerals) added to infant formulas have worked well in the past; however they are not sufficient to address the diversity of potential new ingredients proposed by manufacturers to develop formulas that mimic the perceived and potential benefits of human milk. This book, prepared at the request of the Food and Drug Administration (FDA) and Health Canada, addresses the regulatory and research issues that are critical in assessing the safety of the addition of new ingredients to infants.

Contents

• THE NATIONAL ACADEMIES
• COMMITTEE ON THE EVALUATION OF THE ADDITION OF INGREDIENTS NEW TO INFANT FORMULA
• FOOD AND NUTRITION BOARD
• Reviewers
• Preface
• Executive Summary
• 1. Introduction and Background
  • INFANT FORMULA REGULATIONS AND GUIDELINES
  • CHARGE TO THE COMMITTEE
  • THE COMMITTEE'S APPROACH
  • ORGANIZATION OF THE REPORT
  • SUMMARY
  • REFERENCES
• 2. Defining Safety for Infants
  • ABSTRACT
  • INTRODUCTION
  • U.S. REGULATORY AGENCIES
  • FUNDAMENTAL CONCEPTS OF SAFETY REGULATIONS
  • STATISTICAL CONSIDERATIONS IN FOOD SAFETY DETERMINATION
  • MODELS OF SAFETY ASSESSMENT
  • SPECIAL CONSIDERATIONS FOR INFANT FORMULAS
  • SUMMARY
  • REFERENCES
• 3. Comparing Infant Formulas with Human Milk
  • ABSTRACT
  • BACKGROUND
  • HISTORY OF THE DEVELOPMENT OF INFANT FORMULAS
  • CHALLENGES OF MATCHING HUMAN-MILK COMPOSITION AND BREASTFEEDING PERFORMANCE
  • PERFORMANCE ADVANTAGES OF BREASTFEEDING
  • RISKS OF BREASTFEEDING
  • SUMMARY
  • REFERENCES
• 4. Strengthening the Current Processes to Evaluate New Ingredients for Infant Formulas
  • ABSTRACT
  • INTRODUCTION
  • THE CURRENT U.S. REGULATORY SYSTEM
  • PROPOSED SAFETY ASSESSMENT PROCESS
  • SUMMARY
  • REFERENCES
• 5. Testing Ingredients with Preclinical Studies
  • ABSTRACT
  • INTRODUCTION
  • THE IMPORTANCE OF APPROPRIATE PRECLINICAL STUDIES
  • CURRENT REGULATORY GUIDELINES FOR PRECLINICAL STUDIES
  • OVERVIEW OF RECOMMENDED LEVELS OF ASSESSMENT
  • CONDUCTING PREANIMAL TESTS
  • CONDUCTING ANIMAL TOXICITY STUDIES
  • CONDUCTING NEUROLOGICAL TESTS
  • SUMMARY
  • REFERENCES
• 6. Going Beyond Current Clinical Studies
  • ABSTRACT
  • INTRODUCTION
  • THE IMPORTANCE OF CLINICAL STUDIES
  • CURRENT REGULATORY GUIDELINES FOR CLINICAL STUDIES
  • GENERAL APPROACH TO CONDUCTING CLINICAL STUDIES
  • OVERVIEW OF RECOMMENDED LEVELS OF ASSESSMENT
  • GROWTH
  • SPECIFIC ORGAN SYSTEMS
  • DEVELOPMENTAL-BEHAVIORAL OUTCOMES
  • SUMMARY
  • REFERENCES
• 7. Selecting an In-Market Surveillance Plan
  • ABSTRACT
  • BACKGROUND
  • OVERVIEW OF RECOMMENDED LEVELS OF ASSESSMENT
  • CRITERIA AND METHODS FOR IN-MARKET SURVEILLANCE
  • SUMMARY
  • REFERENCES
• A Acronyms and Glossary
• B Composition of Infant Formulas and Human Milk for Feeding Term Infants in the United States
• C Redbook Table of Contents
• D Applying the Recommended Approaches
• E Biographical Sketches of Committee Members

This study was supported by Contract No. 223-01-2460, TO4, and Contract No. 4500033271 between 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 recommendations 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.

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.