Agency Response Letter GRAS Notice No. GRN 000609
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See also Generally Recognized as Safe (GRAS).
CFSAN/Office of Food Additive Safety
June 6, 2016
Madhu Soni, Ph.D.
Soni & Associates, Inc.
749 46th Square
Vero Beach, FL 32968
Re: GRAS Notice No. GRN 000609
Dear Dr. Soni:
The Food and Drug Administration (FDA) is responding to the notice, dated November 11, 2015, that you submitted on behalf of Axiom Foods and SPRIM Strategy & Intelligent Innovation (Axiom) 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 November 16, 2015, filed it on December 9, 2015, and designated it as GRAS Notice No. GRN 000609. Axiom provided additional information in an amendment on February 19, 2016.
The subject of the notice is rice protein containing 80% and 90% protein. The notice informs FDA of the view of Axiom that rice protein is GRAS, through scientific procedures, for use as an ingredient, formulation aid, and texturizer in baked goods and baking mixes, beverages and beverage bases, breakfast cereals, dairy product analogs, fats and oils, grain products and pastas, milk products, plant protein products, processed fruits and fruit juices, processed vegetables and vegetable juices, and soups and soup mixes at levels ranging from 0.96% to 34.3%.,
As part of its notice, Axiom includes the statement of a panel of individuals (Axiom’s GRAS panel) that evaluated the data and information that are the basis for Axiom’ GRAS determination. Axiom considers the members of its GRAS panel to be qualified by scientific training and experience to evaluate the safety of substances added to food. Axiom’s GRAS panel evaluated information describing the identity and composition, manufacturing process and specifications, and estimated dietary exposure to rice protein, as well as published and unpublished studies supporting the safety of rice protein. Based on this review, Axiom’s GRAS panel concludes that rice protein produced in accordance with good manufacturing practices is GRAS under the conditions of its intended use.
Axiom describes the method of manufacture for rice protein that begins with whole grain brown rice (Oryza sativa). A slurry of milled rice is hydrolyzed using amylase in water. Once the hydrolysis is complete, approximately 80% of the liquid is removed. The remaining crude protein is washed, separated from the liquid, dried at >80°C, and milled. Axiom states that all materials used in the manufacturing process are suitable food grade materials.
Axiom provides specifications for the two rice protein products. These include specifications for protein (≥80% and ≥90%), fat (≤5% and ≤2.5%), total carbohydrate (≤18% and ≤10%), and limits for microbial contaminants. Axiom also provides specifications for heavy metals for both rice protein products, including total arsenic (≤0.2 milligrams per kilogram (mg/kg)), cadmium (≤0.3 mg/kg), lead (<0.25 mg/kg), and mercury (<0.045 mg/kg). The value for inorganic arsenic is below the level recommended by the Codex Alimentarius Commission (Codex). Axiom analyzed five consecutive lots of each product for all specifications. In addition, Axiom analyzed five nonconsecutive lots of each product for arsenic. Axiom obtained a mean value of 0.04 mg/kg for total arsenic, whereas inorganic arsenic was present at a level below the limit of quantitation (LoQ, <0.05 mg/kg). All lots meet the proposed specifications.
Axiom calculates the dietary exposure to rice protein based on the intended food uses and use levels in conjunction with food consumption data included in the National Health and Nutrition Examination Survey (NHANES, 2011-2012). The estimated user-only exposures to rice protein are 10.3 grams/person/day (g/p/d) (181 mg/kg body weight (bw)/d) and 17.3 g/p/d (388 mg/kg bw/d) at the mean and the 90th percentile, respectively.
Axiom discusses data and information supporting the safety of rice protein. Axiom concludes from the nutritional and compositional comparisons between their rice protein products and other protein extract formulations, including whey and soy, that rice protein has similar profiles to other commercially available protein extracts generally considered safe. Axiom discusses a study showing that Chinese wild brown rice was not mutagenic as assayed by bone marrow micronucleus, sperm abnormality, and a reverse mutation assay using Salmonella typhimurium. Axiom also discusses several safety and tolerance studies in rats and humans that reported no adverse effects. Axiom further discusses studies on digestibility and allergenicity of rice and rice products and concludes that it is unlikely that exposure to rice protein at the intended use level is of safety concern.
Because inorganic arsenic exposure estimation using the LoQ value was still below safe levels proposed by either the Agency for Toxic Substances and Disease Registry or the European Food Safety Authority, Axiom concludes that there is no safety concern with their intended use of rice protein.
Based on the totality of evidence, including the history of safe consumption of rice products, Axiom concludes that the intended use of rice protein is GRAS.
Standards of Identity
In the notice, Axiom states its intention to use rice protein 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 content of rice protein and discussing the human studies that Axiom relies on to conclude that rice protein is GRAS under the intended conditions of use, Axiom raises a potential issue under the labeling provisions of the Federal Food, Drug, and Cosmetic Act (FD&C Act). Under section 403(a) of the 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 rice protein bear any claims on the label or in labeling, such claims are the purview of the Office of Nutrition and Food Labeling (ONFL) in the Center for Food Safety and Applied Nutrition. The Office of Food Additive Safety neither consulted with ONFL on this labeling issue nor evaluated the information in your notice to determine whether it would support any claims made about rice protein on the label or in labeling.
Section 301(ll) of the FD&C Act
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 Axiom’s notice that rice protein is GRAS for the intended uses, FDA did not consider whether section 301(ll) or any of its exemptions apply to foods containing rice protein. Accordingly, this response should not be construed to be a statement that foods that contain rice protein if introduced or delivered for introduction into interstate commerce, would not violate section 301(ll).
Based on the information provided by Axiom, as well as other information available to FDA, the agency has no questions at this time regarding Axiom’s conclusion that rice protein 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 rice protein. As always, it is the continuing responsibility of Axiom 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 000609, 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
 Axiom states that it does not intend to add rice protein to products under USDA’s jurisdiction. Additionally, rice protein will not be added to infant formulas.
 The use levels are based on purity criteria of 80% protein; for 90% protein the use levels will be adjusted accordingly.
 Axiom also provides information on how the 80% and 90% rice protein products are made. The whole grain brown rice is tested to determine protein content. The higher protein is tagged for the product containing 90% protein.
 When two values are given, the first corresponds to the product containing 80% protein and the second to the product containing 90% protein.
 In 2014 Codex proposed a maximum level for inorganic arsenic in polished rice of 0.200 mg/kg in the report, Joint FAO/WHO Food Standards Programme Codex Alimentarius Commission, 37th Session, Geneva, Switzerland, 14-18 July 2014.