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Introduction and Background

RATIONALE FOR THE STUDY

Each year, millions of families in the United States purchase infant formula, as over two-thirds of U.S. infants receive some formula by 6 months of age (CDC, 2024). The Food, Drug, and Cosmetic Act (FD&C Act; 21 U.S.C. 321(z)) defines infant formula as “a food which purports to be or is represented for special dietary use solely as a food for infants by reason of its simulation of human milk or its suitability as a complete or partial substitute for human milk” (section 201(z) of the FD&C Act and U.S. Food and Drug Administration (FDA); “regulations define infants as persons not more than 12 months” of age (21 CFR § 105.3(e)).

Infant formula is often the sole source of nutrition for infants, a vulnerable population experiencing rapid and critical growth and development. While most food laws and regulations also apply to infant formula, additional requirements appear in section 412 of the FD&C Act and in FDA regulations at 21 CFR § Parts 106 and 107. For example, nutrient requirements can be found under section 412(i) of the FD&C Act and 21 CFR § 107.100, which specify levels of protein, fat, essential fatty acids, 15 vitamins, and 12 minerals. In addition, infant formula manufacturers must meet the rigorous requirements, as described in in 21 CFR § 106.96, to demonstrate that the formula meets the minimum requirements for quality factors (assessment of protein quality and demonstration that it supports normal infant physical growth).

A “new infant formula” is defined as

A “major change” of an infant formula is defined as

Ninety days before a new infant formula is introduced or delivered for introduction into interstate commerce, the manufacturer must submit a “new infant formula notification” to FDA as described in U.S.C. 350a(c)(1)(B) and FDA regulations (21 CFR § 106.120(a)). As part of such a notice, the manufacturer must provide assurance that the infant formula meets the requirements for the quality factors in 21 CFR § 106.121. FDA’s regulations specify the types of studies that must be conducted to demonstrate this, described in more detail in the sections that follow (21 CFR § 106.96(a)); additional information on the data and information that must be provided in the new infant formula submission (21 CFR § 106.121(a)); and provide exemptions from conducting these particular studies under certain conditions.

CONGRESSIONAL REQUEST

Congress included language in the 2023 Consolidated Appropriations Act (P.L. 117-328) directing FDA to seek to enter into an agreement with the National Academies of Sciences, Engineering, and Medicine (the National Academies) “to examine and report on challenges in supply, market competition, and regulation of infant formula in the United States.” The act also included other provisions¹ that encourage FDA to consider approaches to harmonizing regulatory requirements for infant formula. Two of the U.S. premarket regulatory requirements for infant formula involve specific quality factors: (1) the biological quality of protein in the infant formula

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¹ Congressional direction for actions in the Food and Drug Omnibus Reform Act of 2022; see Appendix C.

and (2) the ability of the infant formula to support normal physical growth. These quality factors are areas of potential harmonization. Therefore, FDA requested that the National Academies examine and report on the state of the science regarding methodologies for assessing biological quality of protein in an infant formula and the state of the science regarding methodologies for assessing the ability of an infant formula to support normal physical growth. Additionally, the evidence reviews considered study designs commonly used in other global regions (see Box 1-1).

THE COMMITTEE’S TASK AND APPROACH

The committee sought evidence from several sources that included conducting scoping reviews on topics relevant to the task, searching the unpublished literature and government documents for regulatory information in the United States and Europe and seeking input though an open session with the sponsor and an open session data-gathering workshop. Additional details about the committee’s methodology can be found in Chapter 2.

ORGANIZATION OF THE REPORT

This report is organized into five chapters. This chapter describes the study rationale and statement of task. Chapter 2 describes the study methodology, including the protocols for evidence scans of the published literature. Chapter 3 reviews current and alternative approaches to assessing protein quality in infant formula and provides relevant conclusions and recommendations. Chapter 4 reviews study designs and reports requirements for assessing infant growth and provides conclusions and recommendations for growth monitoring studies. Chapter 5 discusses areas where the committee feels that research is needed related to the quality factors.

REFERENCE