Agency Response Letter GRAS Notice No. GRN 000221
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CFSAN/Office of Food Additive Safety
October 23, 2007
Vice President, Regulatory Affairs
Kemin Health, L.C.
600 E. Court Avenue, Suite A
Des Moines, IA 50309-2021
Re: GRAS Notice No. GRN 000221
Dear Ms. Trinker:
The Food and Drug Administration (FDA) is responding to the notice, dated April 4, 2007, that you submitted in accordance with the agency's proposed regulation, proposed 21 CFR 170.36 (62 FR 18938; April 17, 1997; Substances Generally Recognized as Safe (GRAS); the GRAS proposal). FDA received the notice on April 9, 2007, filed it on April 11, 2007, and designated it as GRAS Notice No. GRN 000221.
The subject of the notice is suspended lutein. The notice informs FDA of the view of Kemin Health L.C. (Kemin) that suspended lutein is GRAS, through scientific procedures, for use as an ingredient in term infant formula at a maximum level of 250 micrograms per liter (μg/l). In this letter the term "suspended lutein" denotes the mixture of the carotenoids lutein and zeaxanthin (crystalline lutein) that are suspended in safflower oil.
21 CFR 101.4 states that all ingredients must be declared by their common or usual name. In addition, 21 CFR 102.5 outlines general principals to use when establishing common or usual names for nonstandarized foods. Our use of "suspended lutein" in this letter should not be considered an endorsement or recommendation of that term as an appropriate common or usual name for the purpose of declaring the substance in the ingredient statement of foods that contain that ingredient. Issues associated with labeling and the appropriate common or usual name of a food are the responsibility of the Office of Nutritional Products, Labeling, and Dietary Supplements in the Center for Food Safety and Applied Nutrition.
As part of GRN 000221, Kemin includes the report of a panel of individuals (Kemin's GRAS panel) who evaluated the data and information that are the basis for Kemin's GRAS determination. Kemin considers the members of its GRAS panel to be qualified by scientific training and experience to evaluate the safety of substances added to food. Kemin's GRAS panel evaluated estimates of dietary exposure, method of production, and product specifications as well as published and unpublished studies. Based on this review, Kemin's GRAS panel concluded that suspended lutein that meets appropriate food grade specifications and is manufactured in accordance with current good manufacturing practices is GRAS under the conditions of its intended use.
Crystalline lutein was the subject of GRN 000140 and is incorporated by reference into GRN 000221. The notified substance in GRN 000221 is a safflower oil suspension of crystalline lutein. GRN 000140 includes the identity and composition of, as well as, the method of manufacture of crystalline lutein. GRN 000221 discusses the identity, composition, and method of manufacture of suspended lutein. Kemin reports that the main components of suspended lutein are at least 21 percent lutein by weight and at least 0.8 per cent zeaxanthin by weight and provides specifications for this ingredient.
In GRN 000221, Kemin describes the use of suspended lutein in term infant formula at levels not to exceed 250 μg/l, which Kemin notes is equivalent to 37 micrograms per 100 kilocalories. Kemin estimates the mean and 90th percentile intake of dietary carotenoids for children from 2 through 6 months to be 200 and 820 micrograms per day (μg/d) respectively, and for children between 7 months to 11 months of age to be 460 and 1,100 μg/d, respectively. For the use in term infant formula, as described in GRN 000221, Kemin estimates a daily intake of 195 μg/d of suspended lutein.
GRN 000221 discusses published and unpublished studies in GRN 000140, as well as several published animal studies that became available after the agency review of GRN 000140, and two unpublished growth studies conducted in healthy term infants. Kemin concludes that the growth studies provide corroborative evidence for the safety of suspended lutein.
In GRN 000221, Kemin describes the crystalline lutein that it uses to prepare its suspended lutein. As such, the use of suspended lutein in food products may constitute the use of a color additive under section 201(t)(1) of the Federal Food, Drug and Cosmetic Act (FFDCA) and FDA's implementing regulations in 21 CFR Part 70. During the review of GRN 000221, FDA requested that Kemin present its view on whether the intended use of suspended lutein would be exempt from the definition of color additive. In an amendment to GRN 000221, dated September 4, 2007, Kemin presented its reasons for concluding that the intended use of suspended lutein would be exempt from the definition of color additive under section 201(t) of the FFDCA and FDA's implementing regulations in 21 CFR 70.3(f) and (g). Importantly, if the use of suspended lutein constitutes use as a color additive within the meaning of section 201(t)(1) of the FFDCA and FDA's implementing regulations in 21 CFR 70.3(f) and (g), section 721(a) of the FFDCA requires premarket review and approval of that use by FDA.
Under section 412 of the FFDCA, a manufacturer of a new infant formula must make a submission to FDA, providing required assurances about the formula, at least 90 days before the formula is marketed. Kemin should be aware that FDA's response to Kemin's GRAS notice does not alleviate the responsibility of any infant formula manufacturer who intends to market an infant formula that contains suspended lutein to make the submission required by section 412.
Based on the information provided by Kemin, as well as other information available to FDA, the agency has no questions at this time regarding Kemin's conclusion that suspended lutein is GRAS under the intended conditions of use. The agency has not, however, made its own determination regarding the GRAS status of the subject use of suspended lutein. As always, it is the continuing responsibility of Kemin to ensure that food ingredients that the firm markets are safe, and are otherwise in compliance with all applicable legal and regulatory requirements.
In accordance with proposed 21 CFR 170.36(f), a copy of the text of this letter responding to GRN 000221, as well as a copy of the information in this notice that conforms to the information in the proposed GRAS exemption claim (proposed 21 CFR 170.36(c)(1)), is available for public review and copying on the homepage of the Office of Food Additive Safety (on the Internet at http://www.cfsan.fda.gov/~lrd/foodadd.html).
Laura M. Tarantino, Ph.D.
Office of Food Additive Safety
Center for Food Safety and Applied Nutrition