Agency Response Letter GRAS Notice No. GRN 000367 - Additional Correspondence
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See also Generally Recognized as Safe (GRAS).
CFSAN/Office of Food Additive Safety
December 7, 2016
Katrina V. Emmel, Ph.D.
GRAS Associates, LLC
27499 Riverview Center Blvd., Suite 212
Bonita Springs, FL 34134
Re: GRAS Notice No. GRN 000367
Dear Dr. Emmel:
The Food and Drug Administration (FDA, we) completed our evaluation of the supplement to GRN 000367 that you submitted on behalf of Sinochem Qingdao Co., Ltd. (Sinochem). We received the supplement on August 16, 2016. The supplement addresses modification of the identity and composition of purified steviol glycosides (SGs) to include additional SGs. Sinochem submitted clarifying information on September 8, 2016.
We previously responded to GRN 000367 on July 8, 2011. We stated that we had no questions at that time regarding Sinochem’s conclusion that purified (> 95%) SGs with rebaudioside A and stevioside as the principal components is GRAS 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.
FDA published the GRAS final rule on August 17, 2016 (81 FR 54960), with an effective date of October 17, 2016. As the supplement, dated August 8, 2016, was pending on the effective date of the GRAS final rule, we requested some additional information consistent with the format and requirements of the final rule. We received an amendment responding to this request on October 20, 2016.
In the supplement dated August 8, 2016, Sinochem informs us of its view that purified SGs (≥ 95%) with rebaudioside A and stevioside as well as rebaudioside B, rebaudioside C, rebaudioside D, rebaudioside M, and steviolbioside as the principal components 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.
Our use of “steviol glycosides,” or “SGs” 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 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 and Food Labeling in the Center for Food Safety and Applied Nutrition.
In the supplement, Sinochem provides a description of the method of manufacture for SGs and states that the manufacturing method is similar to the method described in GRN 000367 with three minor modifications. The method of manufacture described in the supplement includes: 1) a countercurrent extraction step in water, whereas the method described in GRN 000367 is described only as an extraction in water, 2) a crystallization step using food grade ethanol that is not included in GRN 000367, and 3) the use of centrifugation, oven drying, milling, and sieving to obtain the final powdered product, whereas in GRN 000367 the final product is obtained by spray drying.
Sinochem states that the specifications are essentially unchanged from those presented in GRN 000367, except for three items: 1) a specification for total SGs includes rebaudioside B, rebaudioside C, rebaudioside D, rebaudioside M, and steviolbioside, in addition to rebaudioside A and stevioside; 2) a specified limit for total heavy metals as lead; and 3) a specified limit for Pseudonomas aeurigonosa. In addition, Sinochem provides the results of five, non-consecutive batch analyses to demonstrate compliance with specifications.
In GRN 000367, Sinochem provides a review of published data including studies conducted in animals and humans. In the supplement, Sinochem also discusses an updated literature review of studies published through October 2016 and found that the results of in vitro bioassays, continue to show normal metabolic activity hydrolyzing relevant rebaudiosides to steviol. In addition, a scientific review article of all in vitro and in vivo genotoxicity studies confirmed the robust nature of the genotoxicity data available. The updated literature review did not reveal data that would contradict their previous safety conclusion.
Sinochem includes a report of a panel of individuals (Sinochem’s GRAS panel). Based on its review of the data and information in the supplement, Sinochem’s GRAS panel concluded that SGs is safe under the conditions of its intended use.
Based on all the available scientific information, Sinochem concludes that SGs with rebaudioside A and stevioside as well as rebaudioside B, rebaudioside C, rebaudioside D, rebaudioside M, and steviolbioside as the principal components is GRAS for its intended use in foods.
Standards of Identity
In the supplement, Sinochem states its intention to use SGs 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)
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 our evaluation of Sinochem’s supplement concluding that SGs is GRAS under its intended conditions of use, we did not consider whether section 301(ll) or any of its exemptions apply to foods containing SGs. Accordingly, our response should not be construed to be a statement that foods containing SGs, if introduced or delivered for introduction into interstate commerce, would not violate section 301(ll).
Based on the information that Sinochem provided, as well as other information available to FDA, we have no questions at this time regarding Sinochem’s conclusion that SGs with rebaudioside A and stevioside as well as rebaudioside B, rebaudioside C, rebaudioside D, rebaudioside M, and steviolbioside as the principal components is GRAS under its intended conditions of use. This letter is not an affirmation that SGs is GRAS under 21 CFR 170.35. Unless noted above, our review did not address other provisions of the FD&C Act. Food ingredient manufacturers and food producers are responsible for ensuring marketed products are safe and compliant with all applicable legal and regulatory requirements.
In accordance with 21 CFR 170.275(b)(2), the text of this letter responding to the supplement to GRN 000367 is accessible to the public at www.fda.gov/grasnoticeinventory.
Antonia Mattia, Ph.D.
Division of Biotechnology and GRAS Notice Review
Office of Food Additive Safety
Center for Food Safety and Applied Nutrition