For each distinct area of safety assessment (i.e., preclinical, clinical, and in-market monitoring) the committee designed algorithms or stepwise decision trees to be applied to new ingredients for infant formulas. The committee’s approach was based on the uniqueness of the infant population. Therefore each step in the process requires empirical evidence from many disciplines and the application of the highest standards, whether using methods of bioassay, nutritional analysis, or basic chemistry. This approach could be applied to new ingredients to be added to infant formula regardless of the regulatory process used.
The committee structured this report so that the first three chapters provide the background information and rationale for the report. Chapter 2 reviews the parameters considered by the committee when defining “safety” and how to approach it from a practical, theoretical, and statistical point of view. Chapter 3 compares the biological and behavioral advantages of human milk with infant formulas and reviews how infant formulas were developed to meet the biological advantages of human milk.
The remainder of the report reviews the current regulatory processes involved in evaluating the safety of ingredients new to infant formulas and provides recommendations for the overall process (Chapter 4), preclinical studies (Chapter 5), clinical studies (Chapter 6), and finally, in-market surveillance (Chapter 7). In Appendix D the committee provides two case studies that have recently utilized the current regulatory process by submitting a GRAS Notification. The addition of LC-PUFAs and probiotics to infant formulas are used as examples of how the recommendations of the committee could be utilized for new ingredients in infant formula. LC-PUFAs may affect diverse functions within the brain and therefore demonstration of safety is critical; probiotics is presented because it is a complex ingredient that could potentially impact diverse organ systems and could potentially raise allergenicity concerns. The purpose of this exercise was not to make conclusions about the completeness of the information or the safety of the new ingredients, but to point out important assessments or steps that could be considered. In doing so, the committee emphasizes the importance of including some steps, such as follow-up surveillance and level 2 assessments, in future assessments of the safety of the addition of new ingredients to infant formulas.
The Committee on the Evaluation of the Addition of Ingredients New to Infant Formula provides FDA, Health Canada, and other regulatory bodies worldwide with a thorough discussion of the challenging issues surrounding the determination of the safety of new ingredients to be added to infant formulas. The committee encourages dialogue among members of government agencies, the public, industry, and academia to act on the recommendations set forth by this report in the best interest of our most vulnerable members of society—our infants.
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