Agency Response Letter GRAS Notice No. GRN 000343
CFSAN/Office of Food Additive Safety
November 22, 2010
Edward A. Steele
EAS Consulting Group, LLC
1940 Duke Street, Suite 200
Alexandria, VA 22314
Re: GRAS Notice No. GRN 000343
Dear Mr. Steele:
The Food and Drug Administration (FDA) is responding to the notice, dated May 21, 2010, that you submitted on behalf of Fugeia NV 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 May 26, 2010, filed it on May 28, 2010, and designated it as GRAS Notice No. GRN 000343.
The subject of the notice is wheat bran extract composed primarily of xylo- and arabinoxylo-oligosaccharides (wheat bran extract). The notice informs FDA of the view of Fugeia NV that wheat bran extract is GRAS, through scientific procedures, for use as an ingredient in baked goods and baking mixes, beverages and beverage bases, breakfast cereals, frozen dairy desserts, gelatin and puddings, grain products and pastas, jams and jellies, milk products, processed fruits and fruit juices, processed vegetables and vegetable juices, and snack foods at concentrations ranging from 2.4 to 3.2 grams of wheat bran extract per serving.
As part of its notice, Fugeia NV includes the report of a panel of individuals (Fugeia NV’s GRAS panel) who evaluated the data and information that are the basis for Fugeia NV’s GRAS determination. Fugeia NV considers the members of its GRAS panel to be qualified by scientific training and experience to evaluate the safety of substances added to food. Fugeia NV’s GRAS panel reviewed published safety and clinical studies and other relevant corroborating information relating to the safety of wheat bran extract. Based on this review, Fugeia NV’s GRAS panel concluded that wheat bran extract, meeting the specifications cited in the notice and manufactured according to current good manufacturing practice, is GRAS under the intended conditions of use.
Fugeia NV describes the identity and composition of wheat bran extract. Wheat bran extract is an off-white crystalline powder that is obtained from the arabinoxylan component of wheat bran. Wheat bran extract is composed primarily of xylo- and arabinoxylo-oligosaccharides, other poly- and oligosaccharides, and ferulic acid and glucuronic acid that are bound to the xylo- and arabinoxylo-oligosaccharides. The degree of polymerization (DP) of the main xylo- and arabinoxylo-oligosaccharide fraction varies between 2 and 15; the range of the average DP is 3 to 8. The range of the DP of the main xylo- and arabinoxylo-oligosaccharide fraction results in a molecular weight which varies between 282 and 1998.
Fugeia NV describes the method of manufacture of wheat bran extract as a partial enzymatic depolymerization of the water-insoluble arabinoxylan component of wheat bran. Wheat bran is first suspended in water with alpha-amylase to cleave the bran-contained starch. The destarched, water-insoluble bran is then (1) separated from the soluble bran and solubilized starch derivatives; (2) washed; and (3) resuspended in water in the presence of a hemicellulase enzyme preparation. The hemicellulase enzyme preparation solubilizes the xylo- and arabinoxylo-oligosaccharides, which are filtered and purified by ion exchange resin treatment, concentrated, and spray-dried.
Fugeia NV states that all equipment and materials used in the manufacturing process have a history of use in food processing and that wheat bran extract is manufactured in accordance with current good manufacturing practice. The alpha-amylase enzyme preparation is a commercially available, alpha-endo-amylase derived from Bacillus licheniformis; the hemicellulase enzyme preparation is a commercially available xylanase derived from a strain of Trichoderma longibrachiatum deposited in a recognized culture repository. Fugeia NV states that B. licheniformis and T. longibrachiatum are non-pathogenic and non-toxigenic. Fugeia NV states that the enzyme preparations comply with the recommended purity specifications for food grade enzymes as described in the 6th Edition of the Food Chemicals Codex. Fugeia NV further states that the enzymes are inactivated during the manufacturing process.
The notifier provides specifications for wheat bran extract. Fugeia NV reports physical specifications for appearance and taste and chemical specifications for xylo- and arabinoxylo-oligosaccharide content (at a minimum 70 percent of dry matter (DM)), the range of the average DP of xylo- and arabinoxylo-oligosaccharides (3 to 8), ferulic acid content (1 to 3 percent of DM), total poly- and oligosaccharides (at a minimum 90 percent of DM), protein (at a maximum 2 percent of DM), ash (at a maximum 2 percent of DM), total dry matter (at a minimum 94 percent), and beta-glucan (at a minimum 7 percent of DM). Specifications also include limitations on heavy metals (lead, arsenic, cadmium, and mercury) and microorganisms (mesophilic bacteria – total count, yeasts, fungi, Salmonella, Bacillus cereus, and Clostridium perfringens).
The notifier calculates estimated daily intakes for wheat bran extract based on the intended individual food uses and use levels in conjunction with food consumption data included in the National Center for Health Statistics 2003-2004 National Health and Nutrition Examination Surveys. On an all-user basis, the mean and 90th percentile intakes of wheat bran extract are 5.0 grams per person per day (g/p/d) and 10.1 g/p/d, respectively.
Fugeia NV discusses the safety of wheat bran extract as an ingredient in food. Fugeia NV notes that the Institute of Medicine of the National Academies established recommended intake levels for dietary fiber for men (38 g/p/d) and women (25 g/p/d) in 2001. Fugeia NV summarizes the history of consumption of cereals, which contain about 5 to 10 percent arabinoxylan, from which xylo- and arabinoxylo-oligosaccharides are derived. Fugeia NV discusses publicly available information about the absorption, digestion, metabolism, and excretion of arabinoxylan oligosaccharides and beta-glucans. These are not digested in the stomach or small intestine, but rather they are fermented by colonic microbiota producing short chain fatty acids (SCFA) as well as gases (i.e., hydrogen and carbon dioxide). The SCFA can then be absorbed and utilized for energy or further metabolized to gases. Fugeia NV tabulates and discusses published animal studies with diets containing as much as 5.5 percent of wheat bran extract, wheat bran or other fibers; published genotoxicity studies (Ames assay and chromosome aberration assay) of wheat bran extract, and published clinical studies of wheat bran extract and similar products (dietary exposures up to 15 g/p/d). Fugeia NV concludes based on the totality of evidence that wheat bran extract is GRAS under the intended conditions of use.
Fugeia NV discusses the prevalence of wheat allergenicity as well as the mechanism of action of allergic reactions. In addition, Fugeia NV compares and contrasts wheat allergenicity to wheat (gluten) intolerance in persons with celiac disease. Fugeia NV states that wheat bran extract typically contains less than 1 percent protein, whereas wheat and wheat bran typically contain 10-15 percent and 14-28 percent protein, respectively. Fugeia NV states that food products containing wheat bran extract will be labeled in accordance with the Food Allergen Labeling and Consumer Protection Act (FALCPA) of 2004.
Standards of Identity
In the notice, Fugeia NV states its intention to use wheat bran extract 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 fiber content of wheat bran extract and in describing clinical study information that Fugeia NV relies on to conclude that wheat bran extract is GRAS under the intended conditions of use, Fugeia NV raises a potential issue under the labeling provisions of the Federal Food, Drug, and Cosmetic Act (FFDCA). Under section 403(a) of the 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 wheat bran extract 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 wheat bran extract on the label or in labeling.
FALCPA amends the FFDCA to require that the label of a food that is or contains an ingredient that bears or contains a “major food allergen” declare the presence of the allergen (section 403(w)). FALCPA defines a “major food allergen” as one of eight foods or food groups (i.e., milk, eggs, fish, Crustacean shellfish, tree nuts, peanuts, wheat, and soybeans) or a food ingredient that contains protein derived from one of those foods. Issues associated with labeling food are the responsibility of ONLDS.
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 Fugeia NV’s notice that wheat bran extract is GRAS under the intended conditions of use, FDA did not consider whether section 301(ll) or any of its exemptions apply to foods containing wheat bran extract. Accordingly, this response should not be construed to be a statement that foods that contain wheat bran extract, if introduced or delivered for introduction into interstate commerce, would not violate section 301(ll).
Based on the information provided by Fugeia NV, as well as other information available to FDA, the agency has no questions at this time regarding Fugeia NV’s conclusion that wheat bran extract 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 wheat bran extract. As always, it is the continuing responsibility of Fugeia NV 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 000343, 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