Regulatory Guidelines for Clinical Studies

There are no expHcit requirements for clinical testing of infant formulas specified under Section 409 of the Food, Drug and Cosmetic (FD8cC) Act. Section 409 stipulates that a petition to establish safety of a food additive shall contain all relevant data bearing on the physical or other technical effect such additive is intended to produce. . ., but it does not dictate a specific type of clinical study. 

FDA does not require petitioners to conduct human clinical studies to support the safety of food additives or color additives used in food, but, if deemed necessary, it recommends that the studies conform to guidelines presented in section VI.A. of the Redbook (OFAS, 2001, 2003). These guidelines are comprehensive and relevant for the clinical testing of ingredients new to infant formulas. 

General guidance is provided to identify the scientific and ethical principles for clinical studies, including the need for presentation of a defensible rationale for human studies. The Redbook states that this rationale should be based on  

The Redbook suggests the sequence of and subjects for clinical studies. Early clinical studies are to determine the metabolism and level of the food or food additive that gives an adverse or toxic response in man (specifically physiological studies of the additive s disposition, its potential to induce enzyme levels or increase activity, and its interactions with other nutrients) (OFAS, 2001, P. 183). In general children are to be excluded from these early (typically acute or shorter duration) clinical studies. However tolerance studies, which are to be included among early studies, need to be conducted in infants because of the special nature of infant formulas. 

Infants are more likely to be included in what the Redbook describes as chronic intake studies, which are to be conducted once general safety in humans is established in the early adult studies. Here, the Redbook provides specific guidance on protocol design, study population, and statistical analyses, as well as on how reports of clinical studies should be presented. Box 6-1 lists questions that should be answered when conducting studies to determine the safety of a proposed additive. 

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