U. S. Food and Drug Administration
Center for Food Safety and Applied Nutrition
Office of Food Additive Safety
July 3, 2002

Dr. Bruce Bernard
SRA International, Inc
1920 L Street, N.W.
Suite 420
Washington, D.C. 22036

Re: GRAS Notice No. GRN 000095

Dear Dr. Bernard:

The Food and Drug Administration (FDA) is responding to the notice, dated December 21, 2001, that you submitted on behalf of Ajinomoto, USA (Ajinomoto) 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 December 26, 2001, filed it on January 3, 2002, and designated it as GRAS Notice No. GRN 000095.

The subjects of the notice are transglutaminase enzyme preparation (TGP) and stabilized transglutaminase preparation (STGP). Both enzyme preparations are derived from a nontoxigenic and nonpathogenic strain of Streptoverticillium mobaraense. The notice informs FDA of the view of Ajinomoto that TGP and STGP are GRAS, through scientific procedures, for use as a cross-linking agent in food in general at the lowest levels necessary to achieve the desired technical effect

Ajinomoto incorporates by reference three previous GRAS notices (GRN 000004, GRN 000029, and GRN 000055) for various food uses of TGP. Ajinomoto also incorporates by reference Food Master File 000612 (FMF 000612), which is FDA's record of Ajinomoto's submission to the Food Safety and Inspection Service (FSIS) of the U.S. Department of Agriculture regarding the use of TGP as a protein cross-linking agent in processed low fat/low salt meat food products and poultry food products. In its present and previous submissions, Ajinomoto notes that it consulted with a panel of individuals (Ajinomoto's GRAS panel) who evaluated the data and information that are the bases for Ajinomoto's GRAS determination. Ajinomoto considers the members of its GRAS panel to be qualified by scientific training and experience to evaluate the safety of substances added to food.

In its present notice for the use of TGP and STGP in food in general, Ajinomoto describes STGP as TGP that contains hydrolyzed wheat protein, which is manufactured by the enzymatic and acid hydrolysis of wheat protein.⁽¹⁾ The addition of hydrolyzed wheat protein makes STGP more stable than TGP upon exposure to air. Ajinomoto states that hydrolyzed wheat protein complies with the specifications for partially hydrolyzed proteins in the Foods Chemicals Codex, 4th Edition (1996) and acid hydrolysates of proteins in the First Supplement to the 4^th Edition of the Food Chemicals Codex (1997).

Ajinomoto recognizes that hydrolyzed wheat protein present in STGP may cause allergic reactions in individuals allergic to wheat. Ajinomoto consulted with its GRAS panel on this issue and concluded that STGP should be distinguished from TGP and that the ingredient section on the label of the STGP that it supplies to the food industry must inform its customers that STGP contains hydrolyzed wheat protein. Ajinomoto also concluded that it must make its customers aware that a condition of safe use of STGP is the declaration, in the ingredient statement on the label of food products that contain STGP, of the presence of hydrolyzed wheat protein.⁽²⁾

Ajinomoto estimates that the mean daily intake of the concentrated TG, present in TGP and STGP at approximately 10 percent, from the intended use would be 6.5 milligrams per person per day and the 90th percentile intake would be 14.2 milligrams per person per day. Ajinomoto presents experimental data on the levels of use of TGP that are required to achieve the intended technical effects for several representative foods (sausage, pork loin ham, restructured steak, yogurt, tofu, and bread). Based on these data, Ajinomoto concludes that there are optimum levels of use of TGP in these foods. Because the important food characteristics decline when these optimum levels of use are exceeded, Ajinomoto concludes that the use of TGP and STGP is self-limiting.

Based on the information provided by Ajinomoto in this notice and in FMF 000612, GRN 000004, GRN 000029, GRN 000055, as well as other information available to FDA, the agency has no questions at this time regarding Ajinomoto's conclusion that TGP and STGP are GRAS under the intended conditions of use, provided that the ingredient statement of foods products that contain STGP include the source of the stabilizing protein hydrolysate - i.e., hydrolyzed wheat protein. The agency has not, however, made its own determination regarding the GRAS status of the subject use of TGP and STGP. As always, it is the continuing responsibility of Ajinomoto 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).

⁽¹⁾Because peptide-bound glutamine accounts for more than 25 percent of the hydrolysate, the supplier of hydrolyzed wheat protein refers to it as "glutamine peptide ."

⁽²⁾Ajinomoto's present notice for the use of TGP and STGP in food in general supersedes its previous submissions regarding the use of TGP in selected food categories, including meat food products and poultry food products. FDA will send you a separate letter that describes our understanding that Ajinomoto's conclusion that the declaration of the presence of wheat-derived protein in the ingredient statement of foods that contain STGP is also a condition of safe use for the food products covered under GRN 000004, GRN 000029, and GRN 000055. Under proposed 21 CFR 170.36 (f), we will make that letter 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). We also will send a copy of that letter to FSIS.