December 29, 1999

Bruce K. Bernard, Ph.D.
SRA International, Inc.
1850 M Street, N.W.
Suite 290
Washington, DC 20036

Re: GRAS Notice No. GRN 000029

Dear Dr. Bernard:

The Food and Drug Administration (FDA) is responding to the notice, dated July 26, 1999, 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)). FDA received this notice on July 28, 1999 and designated it as GRAS Notice No. GRN 000029.

The subject of the notice is transglutaminase enzyme preparation (TGP) derived from a nontoxigenic and nonpathogenic strain of Streptoverticillium mobaraense. The notice informs FDA of the view of Ajinomoto that TGP is GRAS, through scientific procedures, for use as a protein cross-linking agent in the following foods: processed cheeses at a level of 250 parts per million (ppm); natural hard cheeses (domestic) at a level of 100 ppm; cream cheese at a level of 70 ppm; refrigerated yogurt at a level of 30 ppm; frozen desserts at a level of 20 ppm; vegetable protein dishes/vegeburgers/meat substitutes at a level of 25 ppm.

In this notice, Ajinomoto incorporated by reference its previous GRAS notice (GRN 000004) regarding the use of TGP in processed seafood at a level of 65 ppm. In GRN 000004, Ajinomoto incorporated by reference Food Master File 000612 (FMF 000612), which is FDA's record of Ajinomoto's submission to the Food Safety and Inspection Service 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 at levels of 65 ppm. In letters dated November 9, 1999 and December 15, 1999, SRA International, Inc., in behalf of Ajinomoto, corrected errors in the dietary exposure calculations submitted in GRN 000029 and provided additional information on the calculation of dietary exposure.

In the previous submissions that Ajinomoto incorporated into GRN 000029, Ajinomoto described (1) published information about the identity and function of transglutaminase enzymes from a variety of sources; (2) published information about the source of TGP (S. mobaraense); (3) published information about the identity and function of TGP derived from S. mobaraense; (4) information about the method of manufacture, which is based on standard procedures for fermentation-derived enzyme preparations; (5) unpublished toxicity studies conducted with TGP; (6) the basis for its conclusion that certain biologically active substances, which could be present in TGP, are either absent or are unlikely to be biologically active under the proposed conditions of use; and (7) the results of quality control tests that were conducted on five representative lots of TGP. Ajinomoto has stated that TGP meets the specifications in the Food Chemicals Codex (4th edition) and guidelines issued by the Joint Expert Committee on Food Additives (JECFA; a joint committee of the Food and Agriculture Organization/World Health Organization), and all substances used in the manufacture of TGP are food grade. In GRN 000029, Ajinomoto estimates that the cumulative dietary exposure (90th percentile, eaters only) to TGP would be 12 milligrams per person per day from the consumption of meats, seafood, dairy products, and meat substitutes.

Based on the information provided by Ajinomoto, as well as the information in FMF 000612 and GRN 000004 and other information available to FDA, the agency has no questions at this time regarding Ajinomoto's conclusion that TGP derived from a nontoxigenic and nonpathogenic strain of Streptoverticillium mobaraense 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 TGP. 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 Office of Premarket Approval's homepage on the World Wide Web.

Content last updated by pmg on 1999-DEC-30
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