May 15, 2000

Scott H. Shore, Ph.D.
Novo Nordisk BioChem North America, Inc.
77 Perry Chapel Church Road, Box 576
Franklinton, NC 27525

Re: GRAS Notice No. GRN 000024

Dear Dr. Shore:

The Food and Drug Administration (FDA) is responding to the notice, dated June 4, 1999, that you submitted 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 your notice on June 7, 1999 and designated it as GRAS Notice No. GRN 000024.

The subject of your notice is alpha-amylase enzyme preparation produced by submerged fermentation of Bacillus licheniformis expressing a gene encoding a modified alpha-amylase derived from Bacillus stearothermophilus. The notice informs FDA of the view of Novo Nordisk BioChem North America, Inc. (Novo Nordisk) that this alpha-amylase enzyme preparation is GRAS, through scientific procedures, for use as a processing aid in the starch industry (for the liquefaction of starch in the production of syrups) and in the alcohol industry (for the thinning of starch in distilling mashes) at minimum levels necessary to accomplish the intended technical effect in accordance with current good manufacturing practices.

Your notice describes (1) scientific publications about the safety of the host microorganism, B. licheniformis; (2) scientific publications and book chapters about the structure and function of microbial derived alpha-amylases, and their use in food processing; (3) unpublished studies describing the technical effect of the enzyme preparation; (4) scientific publications and recommendations issued by international organizations on the safety of enzymes used in food processing including enzymes derived from genetically modified microorganisms; (5) published scientific articles that discuss the safety of the various components of the production organism, including the host organism, and the components of the genetic material that is introduced into the host organism; (6) information to support the notifier's conclusion that the presence of the kanamycin antibiotic resistance gene is not a concern, including an FDA draft guidance document on the use of antibiotic markers in transgenic plants and a publication of the International Food Biotechnology Council; (7) chapters in several books that discuss the manufacturing process, which includes methods for the fermentation, processing, and formulation of the enzyme preparation.

Based on the information provided by Novo Nordisk, as well as other information available to FDA, the agency has no questions at this time regarding Novo Nordisk's conclusion that alpha-amylase enzyme preparation produced by submerged fermentation of Bacillus licheniformis expressing a gene encoding a modified alpha-amylase derived from Bacillus stearothermophilus 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 this alpha-amylase enzyme preparation. As always, it is your continuing responsibility to ensure that food ingredients that you market 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.

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