Agency Response Letter GRAS Notice No. GRN 000365
CFSAN/Office of Food Additive Safety
August 18, 2011
George A. Burdock, Ph.D.
Burdock Group Consultants
801 North Orange Avenue
Orlando, FL 32801
Re: GRAS Notice No. GRN 000365
Dear Dr. Burdock:
The Food and Drug Administration (FDA) is responding to the notice, dated December 21, 2010, that you submitted on behalf of BrazTek International Inc., d/b/a Rio Natural (BrazTek) 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 this notice on December 27, 2010, filed it on December 28, 2010, and designated it as GRN No. 000365.
The subject of the notice is rebaudioside A purified from the leaves of Stevia rebaudiana (Bertoni) Bertoni (rebaudioside A). The notice informs FDA of the view of BrazTek that rebaudioside A is GRAS, through scientific procedures, for use as a general-purpose sweetener in foods, excluding meat and poultry products and infant formulas, at levels determined by good manufacturing practices, as well as use as a table top sweetener. BrazTek notes that rebaudioside A has recently been the subject of other GRAS notices, including GRN 000253, and incorporates by reference the information contained in GRN 000253. BrazTek also notes that FDA responded to these GRAS notices informing the notifiers that, at the time of its response, the agency had no questions regarding their conclusions that the rebaudioside A that is the subject of their respective notices is GRAS for its intended use as a sweetener in food.
The rebaudioside A that is the subject of GRN 000365 is a highly purified component of the leaves of the stevia plant. As such, FDA notes that a GRAS notice for the use of a specific purified component of stevia, such as rebaudioside A, and FDA’s response do not necessarily apply to the uses of other stevia products.
Our use of “rebaudioside A” or “rebaudioside A purified from the leaves of Stevia rebaudiana (Bertoni) Bertoni” 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 each ingredient 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.
As part of its notice, BrazTek includes the report of a panel of individuals (BrazTek’s GRAS panel) who evaluated the data and information that are the basis for BrazTek’s GRAS determination. BrazTek considers the members of its GRAS panel to be qualified by scientific training and experience to evaluate the safety of substances added to food. BrazTek’s GRAS panel evaluated the identity, method of manufacture, product specifications, and the potential exposure resulting from the intended uses of rebaudioside A as well as published and unpublished studies related to the safety evaluation of rebaudioside A. Based on this review, BrazTek’s GRAS panel concluded that rebaudioside A, produced under good manufacturing practice is GRAS under the intended conditions of use.
BrazTek provides information about the identity, method of manufacture, and specifications for its rebaudioside A. Rebaudioside A (CAS Reg. No. 58543-16-1), a glycoside of steviol, is identified as 13-[(2-O-β-D-glucopyranosyl-3-O-β-D-glucopyranosyl-β-D-glucopyranosyl)oxy] kaur-16-en-18-oic acid β-D-glucopyranosyl ester. Rebaudioside A is one of a group of known steviol glycosides, which differ from each other by the number of glycoside moieties and bonding order. Rebaudioside A is obtained from the leaves of S. rebaudiana (Bertoni) Bertoni through extraction and multiple purification steps. The leaves are extracted 2-3 times with water at 50-60°C and the extract is passed through an ion exchange resin, concentrated, and spray-dried. The spray-dried preparation is then crystallized/re-crystallized three times with 100% methanol, concentrated, filtered, sterilized and spray-dried to yield the final rebaudioside A product. BrazTek provides specifications for rebaudioside A that include the content of rebaudioside (A ≥97% by weight (w/w)), total ash (≤1%), loss on drying (6%), lead (≤1 part per million (ppm)), arsenic (≤1 ppm), residual methanol (≤200 ppm), and microbial contaminants (within specified limits). BrazTek states that the rebaudioside A product meets the specifications for steviol glycosides established by the Joint FAO/WHO Expert Committee on Food Additives (JECFA) at its 68th meeting in June 2007.
Braztek considers that the safe use of its rebaudioside A is supported by the fact that it is substantially equivalent to rebaudioside A, notified as GRAS to FDA on May 20, 2008 (GRN 000253). Braztek incorporates by reference the data and information in GRN 00253 pertaining to safety and consumption estimates. Braztek states that it has conducted a comprehensive search of the literature published from the time of the GRN 000253 submission in 2008 to the time of the submission of GRN 000365, and has found no information that would alter the conclusion of safety.
Standards of Identity
In the notice, BrazTek states its intention to use rebaudioside A 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 (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 BrazTek’s notice that rebaudioside A is GRAS for the intended use, FDA did not consider whether section 301(ll) or any of its exemptions apply to foods containing rebaudioside A. Accordingly, this response should not be construed to be a statement that foods that contain rebaudioside A, if introduced or delivered for introduction into interstate commerce, would not violate section 301(ll).
Based on the information provided by BrazTek, as well as other information available to FDA, the agency has no questions at this time regarding BrazTek’s conclusion that rebaudioside A 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 rebaudioside A. As always, it is the continuing responsibility of BrazTek to ensure that food ingredients 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 000365, 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.
Mitchell A. Cheeseman, Ph.D.
Office of Food Additive Safety
Center for Food Safety and Applied Nutrition