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CFSAN/Office of Food Additive Safety
January 15, 2010
James T. Heimbach, Ph.D., F.A.C.N.
923 Water Street
P.O. Box 66
Port Royal, VA 22535
Re: GRAS Notice No. GRN 000301
Dear Dr. Heimbach:
The Food and Drug Administration (FDA) has received the notice, dated July 16, 2009, that you submitted on behalf of BioVittoria Ltd. (BioVittoria), 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)). FDA received this notice on July 22, 2009, filed it on July 23, 2009, and designated it as GRAS Notice No. GRN 000301.
The subject of the notice is Siraitia grosvenorii Swingle (Luo Han Guo) fruit extract (SGFE). The notice informs FDA of the view of BioVittoria that SGFE is GRAS, through scientific procedures, for use as a sweetener and flavor enhancer in foods, excluding meat and poultry products, at levels determined by current good manufacturing practices, as well as use as a table top sweetener.
Title 21 CFR 101.4 states that all ingredients 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. Our use of "Siraitia grosvenorii Swingle (Luo Han Guo) fruit extract" or "SGFE" in this letter should not be considered an endorsement or recommendation of any of these terms as an appropriate common or usual name for the purpose of declaring the substance in the ingredient statement of foods that contain that ingredient. 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, BioVittoria includes a summary of conclusions of a panel of individuals (BioVittoria's GRAS panel) who evaluated the data and information that are the basis for BioVittoria's GRAS determination. BioVittoria considers the members of its GRAS panel to be qualified by scientific training and experience to evaluate the safety of substances added to food. BioVittoria's GRAS panel evaluated the identity, method of manufacture, product specifications, and the potential exposure resulting from the intended uses of SGFE as well as published and unpublished studies on SGFE and related substances. Based on this review, BioVittoria's GRAS panel concluded that SGFE that meets its established food grade specifications is GRAS under the conditions of its intended use.
BioVittoria provides information about the identity and composition of SGFE. SGFE is obtained from the fruit of S. grosvenorii Swingle, a plant known by various common names, one of which is Luo Han Guo. BioVittoria describes SGFE as a liquid or powder product composed of a mixture of naturally occurring compounds found in the fruit of S. grosvenorii Swingle. The primary components are cucurbitane glycosides known as mogrosides, specifically mogrosides II, III, IV, V, and VI, along with flavonoids and melanoidins. Mogroside V (CAS Reg. No. 88901-36-4) is identified as the major component, constituting over 30% of the product, and is primarily responsible for the sweetness of the product.
BioVittoria provides information about the manufacturing process and specifications for SGFE. Fresh S. grosvenorii Swingle fruits are mechanically crushed or shredded, followed by extraction for 30-40 minutes at 80°C with de-ionized water. The supernatant is allowed to cool to 50°C and is then clarified by passing through an ultrafiltration membrane to remove pectin and large protein molecules. The supernatant is passed through an adsorption resin that removes organic substances, principally mogrosides, and allows unwanted compounds (e.g., reducing sugars and mineral salts) to pass through into the waste stream. The resin adhered material is released by elution with food-grade aqueous ethanol. The eluent is heated to approximately 60°C and placed under partial vacuum, allowing the ethanol and water vapor to be condensed and recycled. The mother liquor is then cooled to approximately ambient temperature and subjected to a decolorizing step. The decolorized mother liquor is then concentrated to approximately 40% soluble solids to yield the final SGFE product which may also be spray-dried at 120°C to obtain a powdered form of the product. BioVittoria reports that all materials and chemical reagents used in the manufacturing process are food grade. The notifier provides specifications for SGFE that include, in addition to various physical properties, limits on moisture (≤ 6.0 %), arsenic (≤ 0.05 milligrams per kilogram (mg/kg)), cadmium (≤ 1 mg/kg), lead (≤ 1 mg/kg), phosphate organics (≤ 1 mg/kg), pesticide residues (≤ 1 mg/kg), and microbial contaminants (within specified limits).
BioVittoria estimates the intake of SGFE resulting from its intended use in foods. BioVittoria used dietary exposure data for sweetener use from a published study conducted by Renwick which predicted dietary exposures for the intense sweetener rebaudioside A (Ref. 1). In this study, published data on intake of intense sweeteners were collected from a large number of countries and were converted to sucrose equivalents using estimates of sweetness relative to sucrose. Renwick provided estimates of both mean and 90th percentile intakes of intense sweeteners, in sucrose equivalents, for different subpopulations. Based on these data and assuming a relative sweetness for SGFE that is 100 times that of sucrose, BioVittoria estimates the daily intake of SGFE for the general population to be 2.6 milligrams per kilogram body weight per day (mg/kg bw/day) and 6.8 mg/kg bw/day at the mean and 90th percentile level of intake, respectively. BioVittoria states that the use of SGFE in food is self-limiting due to organoleptic factors.
BioVittoria discusses published and unpublished studies pertaining to the safety evaluation of SGFE. BioVittoria considers published and unpublished studies conducted with SGFE, including a published subacute feeding study in rats; a published subchronic feeding study in dogs; and two unpublished studies in healthy men and women to determine effects on liver enzymes and blood glucose levels. Additional studies conducted with SGFE that BioVittoria considered include unpublished in vitro genotoxicity studies. BioVittoria also describes numerous published studies conducted with various S. grosvenorii extracts other than SGFE. Based on its consideration of all these studies, BioVittoria concludes that SGFE is safe for its intended use in foods.
Standards of Identity
In the notice, BioVittoria states its intention to use SGFE 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 (FFDCA)
The Food and Drug Administration Amendments Act of 2007, that 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 BioVittoria's notice that SGFE is GRAS for use as a sweetener and flavor enhancer in foods, excluding meat and poultry products, and as a table top sweetener, FDA did not consider whether section 301(ll) or any of its exemptions apply to foods containing SGFE. Accordingly, this response should not be construed to be a statement that foods that contain SGFE, if introduced or delivered for introduction into interstate commerce, would not violate section 301(ll).
Based on the information provided by BioVittoria, as well as other information available to FDA, the agency has no questions at this time regarding BioVittoria's conclusion that SGFE 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 SGFE. As always, it is the continuing responsibility of BioVittoria 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 000301, 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
Office of Food Additive Safety
Center for Food Safety and Applied Nutrition
- Renwick, A.G. 2008. The use of a sweetener substitution method to predict dietary exposures for the intense sweetener rebaudioside A. Food and Chemical Toxicology 46:S61-S69.