Agency Response Letter GRAS Notice No. GRN 000436
CFSAN/Office of Food Additive Safety
January 18, 2013
Keller and Heckman, LLP
1001 G Street NW
Washington, DC 20001
Re: GRAS Notice No. GRN 000436
Dear Mr. Drozen:
The Food and Drug Administration (FDA) is responding to the notice, dated July 9, 2012, that you submitted on behalf of Roquette Freres (Roquette) 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 July 10, 2012, filed it on July 23, 2012, and designated it as GRAS Notice No. GRN 000436.
The subjects of the notice are two enzyme-modified dextrins, which differ by molecular weight (MW) distribution and average degree of polymerization. The notice informs FDA of the view of Roquette that enzyme-modified dextrins are GRAS, through scientific procedures, for use as bulking agents or as sources of fiber in baked goods, beverages (liquid non-dairy), cereals and granola bars, condiments and dressings, confections, dairy beverages, dairy (non-beverages), frozen desserts, gravies and sauces, meal replacements, pasta and grain products, prepared meals and soups (excluding meat and poultry products), processed fruits, shelf-stable desserts, snacks and crackers, and dry beverage powders, at levels of 3 to 9 grams per serving.
Our use of “enzyme-modified dextrins” 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. We note that the substances referenced in the notice are also called “resistant dextrins.” 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, Labeling, and Dietary Supplements (ONLDS) in the Center for Food Safety and Applied Nutrition.
As part of its notice, Roquette includes the report of a panel of individuals (Roquette’s GRAS panel) who evaluated the data and information that are the basis for Roquette’s GRAS determination. Roquette considers the members of its GRAS panel to be qualified by scientific training and experience to evaluate the safety of substances added to food. Roquette’s GRAS panel evaluated the information contained in the GRAS Notice including estimates of dietary exposure, method of production, product specifications, and published studies. Based on this review, Roquette’s GRAS panel concluded that enzyme-modified dextrins meeting established food grade specifications are GRAS under the conditions of their intended use.
Roquette describes the identity, composition, and method of manufacture of two enzyme-modified dextrins. Roquette states that these two products are derived from yellow dextrin. Yellow dextrin with a MW of 3000-10,000 daltons is formed by heating corn or wheat starch in the presence of small amounts of food-grade acid. The yellow dextrin is partially hydrolyzed using food-grade alpha-amylase, to depolymerize readily digestible polysaccharides. To obtain the first product, the hydrolysate is treated with activated carbon for decolorization and cationic and anionic resins (regulated by FDA for such uses, 21 CFR 173.25) to remove impurities, and then spray dried. To obtain the second product, the purified hydrolysate is subjected to chromatographic separation to remove low molecular weight sugars and then spray dried. Roquette describes the average degree of polymerization of enzyme-modified dextrin as approximately 4-10 for the first product and 12-25 for the second product. Roquette provides specifications for the products including loss on drying (≤ 5%), monosaccharides plus disaccharides (≤ 15% and ≤ 0.5% for the first and second products, respectively), ash (≤ 0.5%), protein content (≤ 0.3%), total fiber (65-75% for the first product and 82-88% for the second product), lead (≤ 1 milligram per kilogram (mg/kg)), as well as limits for microbial contamination. Roquette states that enzyme-modified dextrins do not fully conform to Food Chemicals Codex specifications for dextrin, specifically with regard to the iodine based identification test.
Roquette provides an estimate of dietary exposure for enzyme-modified dextrins based on the intended use in sixteen food categories and using food consumption data from the National Health and Nutrition Examination Surveys conducted in 2003-2004 and 2005-2006. Based on the data, Roquette calculated a mean exposure of 17.4 grams/day (g/d) (0.3 g/kg body weight (bw)/d) and a 90th percentile of 32.6 g/d (0.6 g/kg bw/d). Roquette states that the use of enzyme-modified dextrins is limited by quality considerations and consumer acceptability.
Roquette notes that the toxicological and human studies on enzyme-modified dextrin were performed using the product containing the higher fiber level. Roquette cites a published study that reported the results of an Ames assay, mouse lymphoma assay, and 90 day Sprague-Dawley rat feeding study. The results from Ames and mouse lymphoma assays showed that enzyme-modified dextrin has no mutagenic activity. The no observed adverse effect level from the 90 day rat study was the highest dose tested, which was 4.36 g/kg bw/d for the males and 6.50 g/kg bw/d for the females. Roquette cites published gastrointestinal tolerance studies in humans that showed that 45 g/d was well-tolerated in male volunteers. Roquette also cites a published human study which examined mineral absorption and retention (magnesium, calcium, and zinc). There were no adverse effects on mineral absorption and retention in male volunteers who consumed from 20 g/d up to 100 g/d over 31 days. Roquette states that the two products are chemically similar to each other with the exception that the product tested has a lower level of mono- and disaccharide sugars and higher levels of fiber and therefore the cited studies are relevant for both products.
Standards of Identity
In the notice, Roquette states its intention to use enzyme-modified dextrins 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.
The Food Allergen Labeling and Consumer Protection Act of 2004 (FALCPA) amends the Federal Food, Drug, and Cosmetic Act (FD&C Act) to require that the label of a food that is or contains an ingredient that bears or contains a “major food allergen” declare the presence of the allergen (section 403(w)). FALCPA defines a “major food allergen” as one of eight foods or food groups (i.e., milk, eggs, fish, Crustacean shellfish, tree nuts, peanuts, wheat, and soybeans) or a food ingredient that contains protein derived from one of those foods. Enzyme-modified dextrins derived from wheat may require labeling under FALCPA, because they may contain protein derived from wheat. Although issues associated with labeling food are the responsibility of ONLDS, issues associated with FALCPA exemptions are the responsibility of the Food Allergen Coordinator in the Office of Food Additive Safety (OFAS).
Potential Labeling Issues
In describing the intended use of enzyme-modified dextrins as sources of fiber, Roquette raises a potential issue under the labeling provisions of the 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 enzyme-modified dextrins bear any claims on the label or in labeling, such claims are the purview of the ONLDS. OFAS neither consulted with ONLDS on this labeling issue nor evaluated the information in your notice to determine whether it would support any claims made about enzyme-modified dextrins on the label or in labeling.
Section 301(ll) of the 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 Roquette’s notice that enzyme-modified dextrins are GRAS for the intended uses, FDA did not consider whether section 301(ll) or any of its exemptions apply to foods containing enzyme-modified dextrins. Accordingly, this response should not be construed to be a statement that foods that contain enzyme-modified dextrins, if introduced or delivered for introduction into interstate commerce, would not violate section 301(ll).
Based on the information provided by Roquette, and other information available to FDA, the agency has no questions at this time regarding Roquette’s conclusion that the two enzyme-modified dextrins are 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 enzyme-modified dextrins. As always, it is the continuing responsibility of Roquette 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 000436, 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