The National Academies Press

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From page 1... ... Despite these recommendations, the vast majority of infants worldwide are fed infant formulas (e.g., liquid or reconstituted powders) at some point in their first year of life, whether as their sole source of nutrition or in combination with human milk, supplemental foods, or both. Read the entire page →
From page 2... ... The committee also reviewed the special needs of infants and their implications for evaluating the safety of infant formulas. The committee developed and used algorithms throughout the report to graphically depict the overall process and recommends the use of stepwise decision-tree approaches for the process and for preclinical studies, clinical studies, and in-market surveillance. Read the entire page →
From page 3... ... Act, associated regulations, and FDA's Toxicological Principles for the Safety Assessment of Direct Food Additives and Color Additives Used in Food, also known as the Redbook,1 provide guidelines that are used to assess the safety of food ingredients and infant formulas. The Canadian Food and Drugs Regulations, administered by Health Canada, include specific requirements for infant food, novel food, and food ingredients. Read the entire page →
From page 4... ... Use of a Hierarchical Approach Since infants have distinct needs and vulnerabilities, a set of guidelines should be developed to provide a hierarchy of decision-making steps for manufacturers seeking to add new ingredients to infant formulas. Because specific safety assessments will need to be targeted according to the nature of the ingredient, the set of guidelines should allow for flexibility in the approach, while being rigorous and scientifically based. Read the entire page →
From page 5... ... Additional Elements of a Safety Assessment Elements of the safety assessments of infant formulas need to be standardized (e.g., toxicity studies, risk assessment) Read the entire page →
From page 6... ... FIGURE ES-1 Proposed process for evaluating the safety of ingredients new to infant formulas algorithm. In-market assessment should be planned in conjunction with preclinical and clinical testing. Read the entire page →
From page 7... ... Also, guidelines should provide the most appropriate animal models at relevant developmental stages for testing infant formulas. For example, the most commonly used animal models for general toxicological studies are the rat and mouse, which are of limited use for developmental studies because of the difficulty of feeding formula to a preweanling rodent. Read the entire page →
From page 8... ... Organ level studies - Gastrointestinal tract No - Hepatic - Renal - Hematology - Immune - Endocrine - Neurologic 5 Any positive test for toxicity or concern for Yes safety? No 6 10 7 DISCONTINUE Neurological Safety Assessment DISCONTINUE PROCESS (See Figure ES-3) Read the entire page →
From page 9... ... No 4 Any evidence of adverse effect/event or concern Yes for safety? No 9 6 5 Continue to clinical Re-evaluate results before DISCONTINUE studies considering clinical trials PROCESS FIGURE ES-3 Proposed levels of assessment for preclinical studies algorithm. Read the entire page →
From page 10... ... Specifically, the committee recommends that any addition of an ingredient new to infant formulas should be judged against two controls: the previous iteration of the formula without the added ingredient and human milk. The proposed rule does not define "normal" growth, nor does it identify what represents a biologically meaningful difference among groups of infants consuming different formulas. Read the entire page →
From page 11... ... Sidebar B: Clinical Endpoints Assess symptoms and adverse laboratory indicators in the following: - Gastrointestinal tract - Kidney - Blood - Immunological system 4 - Endocrinological system Abnormal growth or Assess absorption, distribution, adverse effect/event on Yes metabolism, and excretion of specific organ, immune, or ingredient where appropriate endocrine systems Sidebar C: No Developmental-Behavioral Assessment 6 Assess: - Sensory and motor function Dev elopmental-Behav ioral Assessment - Cognitive development (See Sidebar C and Figure ES-6) - Temperament - Neurological function 7 5 Abnormal function in major DISCONTINUE Yes developmental areas PROCESS No 8 MANUFACTURER/REGULATORY AGENCY DETERMINES INGREDIENT IS SAFE FIGURE ES-4 Proposed clinical studies algorithm. Read the entire page →
From page 12... ... - Gastrointestinal tract - Liver - Kidney - Blood 8 - Immune Evidence of - Endocrine adverse Yes effect/event? 3 Lev el 2 Assessment (See Sidebar B) Read the entire page →
From page 13... ... In-Market Surveillance to Detect Adverse Effects Although satisfactory completion of the appropriate preclinical and clinical studies diminishes the likelihood of systematic adverse reactions, the risks for adverse reactions cannot be ignored. Adverse effects may not be detected in preclinical studies if the wrong animal model was chosen, if the assessment instrument chosen measured a function other than the one adversely affected by the new ingredient, or if a subpopulation of individuals who are highly sensitive to the new ingredient added to infant formulas was not sufficiently represented in clinical studies. Read the entire page →
From page 14... ... parent reports. No Sidebar C: Level 2 Assessment 12 Lev el 1 Assessment Detailed measures of function in major (See Sidebars A and B) Read the entire page →
From page 15... ... ? Sidebar B: Level 3 Assessment The fol owing issues should be considered in lev el 3 No assessment: - The domains to be inv estigated and the 9 Lev el 1 Assessment: instruments to be used wil l vary depending on the organ or functional systems that are most PASSIVE SURVEILLANCE like ly to be affected by the ingredient and 1-800 line or Internet web site result s from in-market, preclinical, or clinical studies. Read the entire page →
From page 16... ... � Infant formulas are consumed by the vast majority of infants and are the sole source of nutrition for a large segment of infants up to the first 6 months of life. � Manufacturers are increasingly interested in adding new ingredients to formulas in an attempt to mimic the perceived and potential benefits of human milk. Read the entire page →

From page 1...

... Despite these recommendations, the vast majority of infants worldwide are fed infant formulas (e.g., liquid or reconstituted powders) at some point in their first year of life, whether as their sole source of nutrition or in combination with human milk, supplemental foods, or both.