Agency Response Letter GRAS Notice No. GRN 000437
CFSAN/Office of Food Additive Safety
January 27, 2013
Robert S. McQuate, Ph.D.
GRAS Associates, LLC
20482 Jacklight Lane
Bend, OR 97702-3074
Re: GRAS Notice No. GRN 000437
Dear Dr. McQuate:
The Food and Drug Administration (FDA) is responding to the notice, dated July 19, 2012, that you submitted on behalf of Garuda International, Inc. (Garuda) 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 July 24, 2012, filed it on July 31, 2012, and designated it as GRAS Notice No. GRN 000437.
The subjects of the notice are β-glucans from oat bran (oat bran β-glucans). Garuda describes two preparations (≥ 70 percent and ≥ 55 percent β-glucans). The notice informs FDA of the view of Garuda that oat bran β-glucans are GRAS, through scientific procedures, as a source of fiber in a variety of foods at levels resulting in 0.75 to 3.0 grams (g) of β-glucans per serving. Garuda intends oat bran β-glucans for use in bars; beverages; whole grain and specialty breads; breakfast cereals; lite cookies; reduced fat crackers; lite gravies and sauces; instant rice; macaroni products; reduced fat muffins; lite salad dressing; reduced fat snack chips; soups; tomato-based sauces; tortillas and taco shells; vegetarian patties and crumbles; reduced fat yogurt; and medical foods. Oat bran β-glucans are not intended for use in foods for infants and toddlers or in meat and poultry products.
Our use of "oat bran β-glucans" 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 substances in the ingredient statement of foods that contain these ingredients. Title 21 CFR 101.4 states that each ingredient must be declared by its 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 (ONLDS) in the Center for Food Safety and Applied Nutrition.
As part of its notice, Garuda includes the report of a panel of individuals (Garuda's GRAS panel) that evaluated the data and information that are the basis for Garuda's GRAS determination. Garuda considers the members of its GRAS panel to be qualified by scientific training and experience to evaluate the safety of substances added to food. Garuda's GRAS panel summarized its findings, which are based on the identity and source of oat bran β-glucans, the similarities of oat bran β-glucans to those from other edible cereals and fungi, the absence of adverse effects in published safety studies conducted on oat-derived β-glucans, and the history and current regulatory status of β-glucans in food. Based on this review, Garuda's GRAS Panel concluded that oat bran β-glucans are GRAS under the conditions of their intended use.
Garuda describes the identity and method of manufacture of oat bran β-glucans, and provides information on the composition of the two preparations. β-glucans are polysaccharides of unbranched, linear, mixed-linkage glucans. Garuda states that oat bran β-glucans, like those from barley, contain approximately 70 percent (1-4) linkages and 30 percent (1-3) linkages. Oat bran β-glucans are purified from oat bran using (1) water extraction and addition of alpha-amylase to hydrolyze starch and (2) filtration, ethanol-precipitation, and centrifugation to separate the soluble β-glucans from insoluble oat bran components. Garuda explains that the ethanol concentration determines which of the two preparations is produced. The concentrated β-glucans are dried under heat and vacuum to remove residual solvent, deactivate the alpha-amylase, and sterilize the β-glucan concentrate. The dried concentrate is screened to meet particle size specifications and packaged. Garuda states that the finished products are beige to light grey/brown powders. According to Garuda, the enzymes and processing aids used in the manufacture of oat bran β-glucans comply with Food Chemicals Codex specifications.
Garuda provides specifications and compositional information for the ≥ 70 percent and ≥ 55 percent oat bran β-glucan preparations. Specifications for the ≥ 70 percent preparation include β-(1-3, 1-4) glucan content (≥ 70 percent), particle size (< 60 mesh size), moisture (< 7 percent), lead (≤ 1.0 milligrams per kilogram (mg/kg)), mercury (≤ 1.0 mg/kg), arsenic (≤ 0.5 mg/kg), and cadmium (≤ 1.0 mg/kg), as well as limits on microbial contaminants. Analytical data provided by Garuda indicate that the ≥ 70 percent preparation contains approximately 88 percent total carbohydrates, 5 percent moisture, 2 percent protein, and 4 percent ash. Garuda provides batch analysis reports for the ≥ 70 percent preparation to demonstrate compliance with specifications.
Specifications for the ≥ 55 percent preparation include β-(1-3, 1-4) glucan content (≥ 55 percent), particle size (< 60 mesh size), moisture (≤ 5 percent), lead (≤ 1.0 mg/kg), mercury (≤ 1.0 mg/kg), arsenic (≤ 0.5 mg/kg), and cadmium (≤ 1.0 mg/kg), as well as limits on microbial contaminants. Analytical data provided by Garuda indicate that the ≥ 55 percent preparation contains approximately 84 percent total carbohydrates, 5 percent moisture, 5 percent protein, and 6 percent ash. Garuda provides batch analysis reports for the ≥ 55 percent preparation to demonstrate compliance with specifications.
In estimating the dietary exposure of oat bran β-glucans from the intended uses, Garuda explains that the intended uses of oat bran β-glucans are the same as the intended uses for barley β-glucans described in GRNs 000207 and 000344, with the exception of use in meat and poultry products. Given that the uses of oat bran and barley β-glucans are substitutive and given that Garuda does not intend the use of oat bran β-glucans in meat and poultry products, the notifier concludes that the estimated dietary exposure of oat bran β-glucans would likely be less than the 8.7 g and 16.5 g of β-glucans per person per day for the mean and 90th percentile, respectively, as calculated for barley β-glucans. In an amendment dated October 11, 2012, Garuda notes that the mean and 90th percentile estimated dietary exposures from GRN 000344 are equivalent to 0.17 and 0.36 g of β-glucans per kilogram body weight per day (per kg bw/d), respectively.1 Garuda intends to use oat bran β-glucans in medical foods at levels not to exceed 3.0 g β-glucans/person/day.
Garuda discusses its safety assessment of oat bran β-glucans, based on the history of oat consumption as well as on the similarity of β-glucans from oat bran to those from barley and yeast. Garuda explains that because the chemical structures and physiological properties of β-glucans from barley, yeast, and oat are similar, and because they are consequently handled similarly by the gastrointestinal tract, safety studies conducted with barley and yeast β-glucans can be used to corroborate the safety of oat bran β-glucans. Garuda discusses the results of published studies conducted using barley and yeast (Saccharomyces cerevisiae) β-glucans. Published studies on barley β-glucans included 28-day toxicity studies in mice and in rats; the published yeast β-glucans study was a 90-day toxicity study conducted in rats. The authors of the barley β-glucans studies determined that no adverse effects were observed at levels of 14.7 g barley β-glucans per kg bw/d and 5.6 g barley β-glucans per kg bw/d. These doses correspond to the highest level of intake consumed by mice and rats, respectively. Similarly, the authors of the yeast β-glucans study also determined that no adverse effects were observed at the highest level of intake (0.1 g yeast β-glucans per kg bw/d) administered by gavage to the rats. Garuda agrees with the conclusions described in these publications and concludes that the available studies on barley and yeast β-glucans support the safety of oat bran β-glucans for the intended use.
Standards of Identity
In the notice, Garuda states its intention to use oat bran β-glucans 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 discussing regulatory agency reviews relevant to oat bran β-glucans, Garuda references 21 CFR 101.81, which authorizes a health claim on the relationship between soluble dietary fiber from whole oat and barley sources and reduced risk of coronary heart disease. Under section 403(a) of the Federal Food, Drug, and Cosmetic Act (FD&C Act), a food is misbranded if its labeling is false or misleading in any particular. Section 403(r) of the FD&C Act 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 oat bran β-glucans bear any claims on the label or in labeling, such claims are the purview of ONLDS. 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 oat bran β-glucans on the label or in labeling.
In its notice, Garuda informs FDA that one intended use of oat bran β-glucans is use in medical foods. Section 5(b) of the Orphan Drug Act (ODA) defines a medical food as a food that is formulated to be consumed or administered enterally under the supervision of a physician and that is intended for the specific dietary management of a disease or condition for which distinctive nutritional requirements, based on recognized scientific principles, are established by medical evaluation. Section 403(q) of the FD&C Act lays out the statutory framework for nutrition labeling of food products. Section 403(r) of the FD&C Act lays out the statutory framework for health claims and nutrient content claims. Under section 403(q)(5)(A)(iv) of the FD&C Act and FDA's implementing regulations in 21 CFR 101.9(j)(8), the requirements for nutrition labeling do not apply to medical foods as defined in section 5(b) of the ODA. Under section 403(r)(5)(A) of the FD&C Act and FDA's implementing regulations in 21 CFR 101.13(q)(4)(ii) and 21 CFR 101.14(f)(2), the requirements for nutrient content claims and health claims, respectively, do not apply to medical foods as defined in section 5(b) of the ODA. For your information, FDA's response to Garuda's notice that oat bran β-glucans are GRAS for use in medical foods does not address the question of whether any particular food product that contains oat bran β-glucans as an ingredient would be a medical food within the meaning of section 5(b) of the ODA and, thus, would be exempt from the requirements for nutrition labeling, nutrient content claims, and health claims.
Section 301(ll) of the FD&C Act
The Food and Drug Administration Amendments Act of 2007, which was signed into law on September 27, 2007, amends the FD&C Act to, among other things, add section 301(ll). Section 301(ll) of the FD&C Act prohibits the introduction or delivery for introduction into interstate commerce of any food that contains a drug approved under section 505 of the FD&C Act, 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 Garuda’s notice that oat bran β-glucans are GRAS for the intended uses, FDA did not consider whether section 301(ll) or any of its exemptions apply to foods containing oat bran β-glucans. Accordingly, this response should not be construed to be a statement that foods that contain oat bran β-glucans, if introduced or delivered for introduction into interstate commerce, would not violate section 301(ll).
Based on the information provided by Garuda, as well as other information available to FDA, the agency has no questions at this time regarding Garuda’s conclusion that oat bran β-glucans are 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 oat bran β-glucans. As always, it is the continuing responsibility of Garuda 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 000437, 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 at www.fda.gov/grasnoticeinventory.
Dennis M. Keefe, Ph.D.
Office of Food Additive Safety
Center for Food Safety and Applied Nutrition
1Calculations are based on actual body weights of participants (ages 2 years and older) in the U.S. Department of Agriculture, 1994-96, 1998 Continuing Survey of Food Intakes by Individuals.