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CFSAN/Office of Food Additive Safety
October 27, 2010
Clyde Takeguchi, Ph.D.
Phoenix Regulatory Associates
21525 Ridgetop Circle, Suite 240
Sterling, VA 20166
Re: GRAS Notice No. GRN 000335
Dear Dr. Takeguchi:
The Food and Drug Administration (FDA) is responding to the notice, dated April 19, 2010, that you submitted on behalf of Arboris LLC (Arboris) 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 20, 2010, filed it on May 4, 2010, and designated it as GRAS Notice No. GRN 000335.
The subject of the notice is pine tree phytosterol esters (PTPE). The notice informs FDA of the view of Arboris that PTPE are GRAS, through scientific procedures, for use as an ingredient in multiple food categories including margarine and vegetable-based spreads, yogurt and yogurt-like products, milk-based juice beverages, ice cream and non-standardized ice cream products, cream cheese and cream cheese-like products, snack bars, salad dressing, standardized and non-standardized bread products, baked goods, beverages, dairy analogs, cheese and cream, breakfast cereal, mayonnaise, pasta and noodles, sauces, salty snacks, processed soups, puddings, confections, vegetarian meat analogs, fruit/vegetable juice, vegetable oils, egg products, including egg whites and substitute egg products.
Our use of “PTPE” 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. Title 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 principles to use when establishing common or usual names for nonstandardized foods. Issues associated with labeling and the appropriate common or usual name of a food are the responsibility of the Office of Nutrition, Labeling, and Dietary Supplements in the Center for Food Safety and Applied Nutrition.
Arboris incorporates by reference the GRAS notice for pine tree phytosterols previously submitted on behalf of Arboris on April 30, 2008 (GRN 000250). The intended conditions of use, including the food categories and use levels for the present GRN 000335 are the same as those described in GRN 000250.
Arboris states that PTPE are a creamy white semi-solid material containing 90 percent phytosterol esters and 6 percent free phytosterols. Arboris notes that this content complies with current Food Chemicals Codex (6th edition) specifications for the content of phytosterol esters in vegetable oil phytosterol esters. Arboris further characterizes the sterol content of PTPE, noting that it contains beta-sitosterol predominantly (not more than 80 percent) and describes its other significant sterols and stanols, notably campesterol (not more than 15 percent) and campestanol (not more than 5 percent). Arboris also provides other specifications including acid value (not more than 2 milligrams (mg) KOH per gram), moisture (not more than 0.1 percent) and heavy metals (less than 10 mg per kilogram (kg), and lead (less than 0.1 mg/kg).
Arboris describes the manufacturing process noting that PTPE are produced by esterification of pine tree-derived phytosterols with food grade fatty acids derived from vegetable oils. The pine tree-derived phytosterol starting material, derived from pine species Pinus elliottii and P. taeda, was the subject of GRN 000250 and the manufacturing process is described therein. Fatty acids intended to be esterifed to the pine tree phytosterols are first esterifed with alcohol, typically methanol, to form a fatty acid ester. These fatty acid esters are then combined with free phytosterols derived from pine and allowed to react with a catalyst under a vacuum at high temperatures. The resulting phytosterol esters are then separated and purified in a series of steps including, filtration, distillation or vacuum evaporation, bleaching, deodorization, and crystallization resulting in the final product to which food grade antioxidants are added.
Arboris notes that it intends for PTPE that are the subject of GRN 000335 to be used in accordance with conditions of use previously described in completed GRAS notices for uses of phytosterol esters and, as such, will substitute for other phytosterol ester ingredients without changing the cumulative exposure to phytosterol esters. Arboris estimates that the dietary exposure for all proposed uses of phytosterols and phytosterol esters, including GRN 000335 and others incorporated by reference, is 7.3 grams per person per day (g/p/d) at the mean and 12.9 g/p/d at the 90th percentile.
Arboris discusses the safety of PTPE by reviewing previous GRAS notices for phytosterols and phytosterol esters (GRNs 000039, 000048, 000053, 000061, 000112, 000176, 000177, 000181, 000206) as well as discussing approvals for phytosterol and phytosterol esters around the world. Arboris incorporated by reference GRN 000250, submitted April 30, 2008, which provided an updated discussion of the published scientific literature describing the metabolism and safety of phytosterol and phytosterol esters, in addition to discussing the similarity in safety and metabolism between vegetable or plant oil derived phytosterols and phytosterols derived from pine. Based on this review, Arboris concludes that the intended uses of PTPE described are safe.
Standards of Identity
In the notice, Arboris states its intention to use PTPE 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.
Section 301(ll) of the Federal Food, Drug, and Cosmetic Act (FFDCA)
The Food and Drug Administration Amendments Act of 2007, which was signed into law on September 27, 2007, amends the Federal Food Drug and Cosmetic Act (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 Arboris’ notice that PTPE is GRAS for the intended uses, FDA did not consider whether section 301(ll) or any of its exemptions apply to foods containing PTPE. Accordingly, this response should not be construed to be a statement that foods that contain PTPE, if introduced or delivered for introduction into interstate commerce, would not violate section 301(ll).
Based on the information provided by Arboris, as well as other information available to FDA, the agency has no questions at this time regarding Arboris’ conclusion that pine phytosterol esters 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 pine phytosterol esters. As always, it is the continuing responsibility of Arboris 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 000335, 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