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CFSAN/Office of Food Additive Safety
April 10, 2013
Nancy L. Schnell
U.S. Deputy General Counsel - Marketing and Regulatory
800 Sylvan Avenue
Englewood Cliffs, NJ 07632
Re: GRAS Notice No. GRN 000117
Dear Ms. Schnell:
The Food and Drug Administration (FDA) is responding to your supplement, dated December 22, 2010, that you sent regarding an additional use for the subject of GRN 000117. Good Humor-Breyers, a Unilever Company (Unilever) initially submitted GRN 000117 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). The subject of GRN 000117 is ice structuring protein (ISP) preparation from Saccharomyces cerevisiae carrying a gene encoding a protein with the amino acid sequence of an ISP from ocean pout (ISP preparation). The notice informed FDA of the view of Unilever that ISP preparation is GRAS, through scientific procedures, for use as a texturizer in frozen novelty desserts to provide ISP at a level of 0.01 percent (100 milligrams ISP per kilogram (mg ISP/kg)) in the finished product. In a letter dated April 17, 2003, FDA informed Unilever that the agency had no questions at that time regarding Unilever’s conclusion that ISP preparation is GRAS under the intended conditions of use.
In the supplement dated December 22, 2010, Unilever informed FDA of Unilever’s conclusion that ISP preparation is GRAS for use in frozen sauces of frozen meals, at a maximum level of 50 mg ISP/kg of frozen sauces. The frozen meals include FDA-regulated products (e.g., containing seafood ingredients) and USDA-regulated products (e.g., containing meat or poultry products). ISP preparation alters the structure of ice crystals, resulting in firmer frozen sauces. Unilever estimates that the additional use of ISP preparation results in a cumulative dietary exposure of 0.15 mg ISP/kg body weight per day (mg ISP/kg bw/d) per user at the 90th percentile.
Unilever based its GRAS conclusion on information submitted in GRN 000117 as well as a review of the scientific literature and exposure information submitted in the supplement. Unilever notes that no new safety data for ISP preparation have been published since GRN 000117 was submitted (October 2002). As part of the December 22, 2010, supplement, Unilever includes the report of a panel of individuals (Unilever’s GRAS panel) who evaluated the data and information that are the basis for Unilever’s GRAS conclusion. Unilever considers the members of its GRAS panel to be qualified by scientific training and experience to evaluate the safety of substances added to food. Unilever’s GRAS panel considers that the additional use of ISP preparation would not significantly increase the dietary exposure to the ingredient, nor would it present allergenicity concerns, which Unilever considers to be the main potential safety issue. Unilever’s GRAS panel concludes that ISP preparation is GRAS as currently used in frozen novelty desserts (described in GRN 000117) and for the intended use in frozen sauces of frozen meals.
Use in Products under USDA Jurisdiction
During its evaluation of the supplement dated December 22, 2010, FDA consulted with the Risk and Innovations Management Division of the Food Safety and Inspection Service (FSIS) of the United States Department of Agriculture (USDA). Under the Federal Meat Inspection Act, Poultry Products Inspection Act, and the Egg Products Inspection Act, FSIS is responsible for determining the efficacy and suitability of food ingredients in meat, poultry, and egg products as well as prescribing safe conditions of use. Suitability relates to the effectiveness of the ingredient in performing the intended purpose of use and the assurance that the conditions of use will not result in an adulterated product, or one that misleads consumers.
FSIS understands that ISP preparation is present in the final food and has a technical effect until the final food is heated. As a result, FSIS would not consider ISP preparation to be a processing aid. Therefore, FSIS advises that the ingredient will need to be declared on the label of meat and poultry products containing it as “ice structuring protein.”
FSIS requested that FDA advise Unilever to seek regulatory guidance from FSIS, Labeling and Program Delivery Division, about the use of ISP preparation in meat and poultry products. Unilever should direct such an inquiry to Dr. William Shaw, Risk and Innovations Management Division, Office of Policy, Program, and Development, Food Safety and Inspection Service, via email at William.Shaw@fsis.usda.gov.
Labeling of ISP Preparation
While FDA notes that FSIS has concluded that uses of ISP preparation in USDA-regulated products must be labeled, FDA has not determined whether the new uses of ISP preparation in FDA-regulated products would meet the criteria for exemption from ingredient labeling described in 21 CFR 101.100 (a)(3)(ii). Issues with labeling are the purview of the Office of Nutrition, Labeling, and Dietary Supplements (ONLDS) in the Center for Food Safety and Applied Nutrition. The Office of Food Additive Safety (OFAS) neither consulted with ONLDS regarding labeling of ISP preparation nor evaluated the information in your supplement to determine whether ISP preparation should be labeled.
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. ISP preparation may require labeling under FALCPA, because the notified ISP is identical to ISP found in the serum of ocean pout (a fish).
FALCPA provides two mechanisms by which a manufacturer may request that a food ingredient covered by FALCPA be exempted from FALCPA's labeling requirements. An ingredient derived from a major food allergen is eligible for an exemption if it does not cause an allergic response that poses a risk to human health or if it does not contain allergenic protein.
In GRN 000117, Unilever states that ISP preparation does not pose a risk for fish allergic consumers. Unilever provided scientific evidence supporting this conclusion in a FALCPA exemption notification to OFAS. OFAS received this notification on January 7, 2013, and is evaluating the scientific data in the notification to determine whether ISP preparation is eligible for exemption from FALCPA’s labeling requirements. Questions about OFAS’ review of Unilever’s FALCPA exemption notification should be directed to the Food Allergen Coordinator in OFAS.
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 Unilever’s supplement concluding that ISP preparation is GRAS for the intended uses, FDA did not consider whether section 301(ll) or any of its exemptions apply to foods containing ISP preparation. Accordingly, this response should not be construed to be a statement that foods that contain ISP preparation, if introduced or delivered for introduction into interstate commerce, would not violate section 301(ll).
Based on the information provided by Unilever in GRN 000117, the supplement dated December 22, 2010, as well as other information available to FDA, the agency has no questions at this time regarding Unilever’s conclusion that ISP preparation 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 ISP preparation. As always, it is the continuing responsibility of Unilever 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 the supplement to GRN 000117, 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 http://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
cc: William K. Shaw Jr., Ph.D.
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