Agency Response Letter
GRAS Notice No. GRN 000184

William A. Olson, Ph.D.
Center for Regulatory Services, Inc.
5200 Wolf Run Shoals Road
Woodbridge, VA 22192-5755

Re: GRAS Notice No. GRN 000184

Dear Dr. Olson:

The Food and Drug Administration (FDA) is responding to the notice, dated October 31, 2005, that you submitted on behalf of SÜDZUCKER AG Mannheim/Ochsenfurt (SÜDZUCKER) 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 1, 2005, filed it on November 4, 2005, and designated it as GRAS Notice No. GRN 000184.

The subject of the notice is isomaltulose. The notice informs FDA of the view of SÜDZUCKER that isomaltulose is GRAS, through scientific procedures, for use as a nutritive sweetener in a variety of foods as described in Table 1.

Table 1
Conditions of use proposed by SÜDZUCKER

Food Category	Use levels (percent)]
Baked goods and baking mixes (21 CFR 170.3(n)(1))	10-25
Beverages (21 CFR 170.3(n)(2), 21 CFR 170.3(n)(3))	1-10
Cereal-based products (21 CFR 170.3(n)(4))	cereals 20-35; bars 5-20
Confectionery and frostings (21 CFR 170.3(n)(9))	15-99
Chewing gum (21 CFR 170.3(n)(6))	5-35
Frozen dairy desserts and mixes (21 CFR 170.3(n)(20))	30
Fruit and water ices (21 CFR 170.3(n)(21))	15
Gelatins, desserts, puddings, etc. (21 CFR 170.3(n)(22))	15-30
Jams, jellies and spreads (21 CFR 170.3(n)(28))	25-40
Nuts and peanut spreads (21 CFR 170.3(n)(32))	45
Milk products (21 CFR 170.3(n)(31))	3-20
Processed fruit and fruit juices or vegetable juices (21 CFR 170.3(n)(35)), (21 CFR 170.3(n)(36))	1-10
Snack foods (21 CFR 170.3(n)(37))	10-25
Sugar substitutes (21 CFR 170.3(n)(42))	2 - >99
Sweet sauces, toppings, syrups (21 CFR 170.3(n)(43))	15-30
Other categories: nutritive formula energy-reduced foods meal replacements/slimming foods	5-20 5-40 5-20

The subject of GRN 000184 is 6-O-α-D-glucopyranosyl-D-fructofuranose, monohydrate (CAS Reg No. 13718-94-0; molecular formula C₁₂ H₂₂ O₁₁, referred to as isomaltulose. Isomaltulose is a reducing disaccharide consisting of one glucose and one fructose moiety linked by an α-1,6- glycosidic bond, and is a water soluble, white or colorless crystalline powder.

SÜDZUCKER describes the method of manufacture and provides product specifications for isomaltulose. Isomaltulose is manufactured from food-grade sucrose. An aqueous sucrose solution is applied to a column with an immobilized enzyme preparation consisting of non-viable cells of Protaminobacter rubrum (strain designated by the Dutch culture collection (Centraalbureau voor Schimmelcultures (CBS)) as CBS 574.77).⁽¹⁾ The enzyme sucrose-6-glucosylmutase (EC 5.4.99.11) converts the α-1,2 glycosidic bond of sucrose into the α-1,6 bond of isomaltulose. The resultant isomaltulose is crystallized, dried, then purified by filtration and ion exchange. Specifications include an assay content of at least 98 % 6-O-α-D-glucopyranosyl- D-fructofuranose and limits on lead (less than 0.1 milligrams per kilogram). SÜDZUCKER intends isomaltulose to be used as a nutritive sweetener that would totally or partially replace sucrose or other highly digestible carbohydrates. Isomaltulose provides a moderate sweetness, bulk, and texture to foods. SÜDZUCKER considers that the greater cost and lower solubility in water of isomaltulose compared with sucrose would limit those foods in which it would replace sucrose.

The notice includes a published review summarizing published in vivo and in vitro studies demonstrating that isomaltulose is completely hydrolyzed and absorbed in the small intestine as glucose and fructose. The notifer concludes that the safety of isomaltulose is, therefore, equivalent to that of sucrose, which, like isomaltulose, is a disaccharide composed of glucose and fructose. The review discusses biological data, toxicological studies, metabolic studies, and studies on gastrointestinal tolerance, and concludes that the use of isomaltulose would not be a health concern.

SÜDZUCKER used the reported per capita refined sugar consumption in the United States and assumed a five-to-ten percent market share replacement of isomaltulose for sucrose to estimate daily intake of isomaltulose at approximately 3 to 6 grams (g)/person per day. SÜDZUCKER notes that isomaltulose has been found at low concentrations in honey and cane sugar juice. Dietary intake of isomaltulose from consumption of honey would likely be less than one gram. SÜDZUCKER notes that isomaltulose has been in use as a food ingredient in Japan since 1985 and has recently been authorized as a novel food or food ingredient in Europe.⁽²⁾

Based on the information provided by SÜDZUCKER, as well as other information available to FDA, the agency has no questions at this time regarding SÜDZUCKER's conclusion that isomaltulose 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 isomaltulose. As always, it is the continuing responsibility of SÜDZUCKER 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, as well as a copy of the information in your notice that conforms to the information in proposed 21 CFR 170.36(c)(1), is available for public review and copying on the homepage of the Office of Food Additive Safety (on the Internet at http://www.cfsan.fda.gov/~lrd/foodadd.html).

Sincerely,

Laura M. Tarantino, Ph.D.
Director
Office of Food Additive Safety
Center for Food Safety and Applied Nutrition

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⁽¹⁾Non-viable cells of P. rubrum are immobilized by entrapment in beads of calcium alginate gel, formed from calcium chloride (21 CFR 184.1193) and sodium alginate (21 CFR 184.1724). SÜDZUCKER notes that the immobilization system is consistent with 21 CFR 173.357.

⁽²⁾(European Commission decision of 25 July 2005 authorizing the placing on the market of isomaltulose as a novel food or novel food ingredient under Regulation (EC) No 258/97 of the European Parliament and of the Council).