Agency Response Letter GRAS Notice No. GRN 000325
CFSAN/Office of Food Additive Safety
August 30, 2010
Mr. Robert Enouen
The Procter & Gamble Company
11530 Reed Hartman Hwy.
Cincinnati, OH 45241
Re: GRAS Notice No. GRN 000325
Dear Mr. Enouen:
The Food and Drug Administration (FDA) is responding to the notice, dated January 20, 2010, 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 January 28, 2010, filed it on February 25, 2010, and designated it as GRAS Notice No. GRN 000325.
The subject of the notice is olestra. The notice informs FDA of the view of The Procter & Gamble Company (P&G) that olestra is GRAS, through scientific procedures, for use as a replacement for fats and oils in the following:
- pre-packaged ready-to-eat (RTE) and ready-to-heat (RTH) baked goods and baking mixes (bagels, biscuits, English muffins, bread, bread sticks (hard and soft), cakes, cookies, corn bread, corn muffins, tortillas and taco shells (hard and soft) croissants, crackers (not snack type), doughnuts, muffins, pancakes, crepes, French toast, sweet pastries and pies (dough portion), meat and vegetable pies and pastries (pastry portion), rolls, sweet rolls and quick breads, waffles, and pizza crust);
- the cheese portion of pre-packaged RTE and RTH prepared foods;
- pre-packaged RTE frostings and icings;
- pre-packaged RTE mayonnaise;
- pre-packaged RTE ice cream and frozen yogurt;
- pre-packaged RTE breakfast/granola/nutrition bars;
- pre-packaged RTE chocolate confections (chocolate portion).
The maximum use levels of olestra for the intended uses range from 67 to 100% replacement of added fats and oils. P&G’s intended uses do not include foods specifically marketed as infant or toddler products.
Olestra is currently used as a replacement for fats and oils in savory snacks and RTH popcorn (21 CFR 172.867; 61 FR 3118, January 30, 1996 and 69 FR 29428, May 24, 2004), and in pre-packaged RTE cookies (GRN 000227). Olestra is not considered a source of fat or calories for the purposes of nutrition labeling or for any nutrient content claims.
As part of its notice, P&G includes the report of a panel of individuals (P&G’s GRAS panel) who evaluated the data and information that are the basis for P&G’s GRAS determination. P&G considers the members of its GRAS panel to be qualified by scientific training and experience to evaluate the safety of substances added to food. P&G’s GRAS panel cites the report from P&G’s GRAS panel submitted in GRN 000227 that discusses method of manufacture and product specifications, analytical data, intended use levels, consumption estimates, multiple safety studies (including in vitro and in vivo genotoxicity studies, metabolic studies, chronic and 2-generation feeding studies in animals), and potential nutritional issues. In the report submitted in GRN 000325, P&G’s GRAS panel discusses publicly available scientific information and data pertaining to:
- the intended use levels in specified food products;
- consumption estimates for all current and intended uses;
- toxicology and nutrition; and
- the roles of carotenoids in the maintenance of health and the prevention of disease.
Based on this review, P&G’s GRAS panel concluded that food grade olestra that is manufactured in accordance with current good manufacturing practices, provided that vitamins A, D, E, and K are added to the olestra-containing foods at concentrations that meet the conditions specified in 21 CFR §172.867(d), is GRAS under the conditions of its intended use.
P&G describes a typical preparation of olestra as being composed of approximately 77% octa-, 23% hepta-, and 1% hexa-esters of sucrose with medium- and long-chain fatty acids. The chemical name for olestra is sucrose polyester. Specifications for olestra are published in the Food Chemicals Codex (6th Ed.).
P&G estimated the intake of olestra based on the level of fat replaced by olestra in current and intended food uses in the United States, in conjunction with food consumption data included in the United States Department of Agriculture’s (USDA) 1994-1996 Continuing Survey of Food Intakes by Individuals (CFSII 1994-1996) and the 1998 Supplemental Children’s Survey (CFSII 1998) (USDA 2000). P&G calculated the combined all-users intake from both current and intended uses as 4.6 and 10.6 grams per day (g/day) at the mean and 90th percentile, respectively. By comparison, P&G calculated corresponding all-users intake from current uses alone as 3.1 and 7.7 g/day.
P&G incorporates by reference the safety information from GRN 000227. This information includes absorption, distribution, metabolism and excretion (ADME) studies; animal studies; post-market studies examining gastrointestinal effects; and discussions surrounding fat-soluble vitamins and carotenoids. In GRN 000325, P&G includes an evaluation of published literature about carotenoids, including lutein and zeaxanthin. P&G notes that olestra is resistant to digestion by gastric and pancreatic lipases and therefore passes unabsorbed and unchanged through the digestive tract. P&G cites several studies that were performed to address the effects of olestra on gastrointestinal symptoms and reports that, like other indigestible compounds, olestra has nominal and clinically insignificant effects on the incidence of abdominal cramping and loose stools.
P&G states that although baseline serum carotenoid levels decrease with olestra exposure, there is no clear consequence to this effect and that no conclusive evidence links lowered carotenoid levels with increased cancer or cardiovascular disease risks. In P&G's view, the primary significance of carotenoids relates to their provitamin A activity, which can reduce the risk of vitamin A deficiency. However, sufficient levels of pre-formed vitamin A will be added to olestra-containing foods, consistent with 21 CFR 172.867(d), to off-set any potential effects of olestra on vitamin A levels.
P&G discusses lutein and zeaxanthin in relation to olestra consumption and eye health; specifically age-related cataract, age-related macular disease, and outcomes related to visual performance. P&G cites estimates that serum levels of lutein and zeaxanthin would be reduced by 15 percent at the 90th percentile intake level. P&G summarized observations intended to support their assertion that reductions in circulating levels of lutein and zeaxanthin are not expected to be clinically meaningful. P&G’s observations included:
- strong conservation of lutein and zeaxanthin in the macula (a published one year human intervention study with exposures of 17 g/day showed no reductions in macular levels);
- reduced lipophilicity of lutein and zeaxanthin relative to other carotenoids, implying reduced absorption into the olestra bolus as it passes through the body;
- expected increases in lutein and zeaxanthin intake in the United States.
In addition, P&G states that several conservative assumptions were made in the derivation of the estimated intakes for olestra and that actual intakes are likely to be much lower.
Standards of Identity
In the notice, P&G states its intention to use olestra in several food categories, including foods for which standards of identity exist, located in Title 21 of the Code of Federal Regulations. We note that an ingredient that is lawfully added to food products may be used in a standardized food only if it is permitted by the applicable standard of identity.
Potential Labeling Issues
In describing the intended use of olestra and in describing the information that P&G relies on to conclude that olestra is GRAS under the conditions of its intended use, including information about the caloric content of foods-containing olestra, P&G raises a potential labeling issue. Under section 403(a) of the Federal Food, Drug, and Cosmetic Act (FFDCA), a food is misbranded if its labeling is false or misleading in any particular. Section 403(r) of the FFDCA lays out the statutory framework for the use of labeling claims that characterize the level of a nutrient in a food or that characterize the relationship of a nutrient to a disease or health-related condition. If products that contain olestra bear any claims on the label or in labeling, such claims are the purview of the Office of Nutrition, Labeling, and Dietary Supplements (ONLDS) in the Center for Food Safety and Applied Nutrition. The Office of Food Additive Safety neither consulted with ONLDS on this labeling issue nor evaluated the information in your notice to determine whether it would support any claims made about olestra on the label or in labeling.
Use in Products Under USDA Jurisdiction
During its evaluation of GRN 000325, FDA consulted with the Risk and Innovations Management Division of the Food Safety and Inspection Service (FSIS) of USDA. Under the Federal Meat Inspection Act, Poultry Products Inspection Act, and the Egg Products Inspection Act, FSIS is responsible for determining the efficacy and suitability of food ingredients in meat, poultry and egg products as well as prescribing safe conditions of use. Suitability relates to the effectiveness of the ingredient in performing the intended purpose of use and the assurance that the conditions of use will not result in an adulterated product, or one that misleads consumers. FSIS considers that because olestra is incorporated into the pastry portion and not the meat portion of meat pies, it does not have jurisdiction over the evaluation of the use.
Section 301(ll) of the FFDCA
The Food and Drug Administration Amendments Act of 2007, which was signed into law on September 27, 2007, amends the FFDCA to, among other things, add section 301(ll). Section 301(ll) of the FFDCA prohibits the introduction or delivery for introduction into interstate commerce of any food that contains a drug approved under section 505 of the FFDCA, a biological product licensed under section 351 of the Public Health Service Act, or a drug or a biological product for which substantial clinical investigations have been instituted and their existence made public, unless one of the exemptions in section 301(ll)(1)-(4) applies. In its review of P&G’s notice that olestra is GRAS for the intended uses listed above, FDA did not consider whether section 301(ll) or any of its exemptions apply to foods containing olestra. Accordingly, this response should not be construed to be a statement that foods that contain olestra, if introduced or delivered for introduction into interstate commerce, would not violate section 301(ll).
Based on the information provided by P&G, as well as other information available to FDA, the agency has no questions at this time regarding P&G’s conclusion that olestra is GRAS under its intended conditions of use provided that olestra conforms to the conditions listed in 21 CFR 172.867(a), (b), (d), and (e). The agency has not, however, made its own determination regarding the GRAS status of the subject use of olestra. As always, it is the continuing responsibility of P&G 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 000325, as well as a copy of the information in this notice that conforms to the information in the GRAS exemption claim (proposed 21 CFR 170.36(c)(1)), is available for public review and copying via the FDA home page at http://www.fda.gov. To view or obtain an electronic copy of the text of the letter, follow the hyperlinks from the “Food” topic to the “Food Ingredients and Packaging” section to the “Generally Recognized as Safe (GRAS)” page where the GRAS Inventory is listed.
Mitchell A. Cheeseman, Ph.D.
Office of Food Additive Safety
Center for Food Safety and Applied Nutrition
cc: Valeria Jefferson, MPA
Risk and Innovations Management Division
Office of Policy and Program Development
Food Safety and Inspection Service
U. S. Department of Agriculture
George Washington Carver Center (GWCC)
5601 Sunnyside Avenue, Mail STOP 5271
Beltsville, MD 20705-5271
cc: Donald L. Wilke, Ph.D.
Principal Scientist, Product Safety & Regulatory Affairs
The Procter & Gamble Company