December 29, 1999

Mr. John Carroll
Novo Nordisk BioChem North America, Inc.
77 Perry Chapel Church Road
Box 576
Franklinton, NC 27525

Re: GRAS Notice No. GRN 000022

Dear Mr. Carroll:

The Food and Drug Administration (FDA) is responding to the notice, dated May 14, 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 May 24, 1999 and designated it as GRAS Notice No. GRN 000022.

The subject of your notice is alpha-amylase enzyme preparation derived from a genetically modified strain of B. licheniformis (which contains a recombinant gene derived from B. licheniformis and B. amyloliquefaciens encoding alpha-amylase). 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).

Your notice describes (1) published information about the host microorganism; (2) published information about microbially derived alpha-amylases, and their use in food processing; (3) unpublished studies describing the technical effect of the subject alpha-amylase enzyme preparation; (4) published information about the safety of enzymes used in food processing including enzymes derived from genetically modified microorganisms; (5) published information that discusses the safety of the genetically modified strain of B. licheniformis, including the host organism and the components of the genetic material that is introduced into the host organism; (6) information to support your conclusion that the presence of the kanamycin antibiotic resistance gene is not a concern; (7) published information about the manufacturing process, which includes methods for the fermentation, processing, and formulation of the enzyme preparation; and (8) unpublished studies to support the safety of the subject alpha-amylase enzyme preparation. In addition, your notice includes an estimate of dietary exposure to the enzyme preparation. According to your notice, the enzyme preparation meets the specifications for enzyme preparations provided in the Food Chemicals Codex (4th ed., 1996) and the specifications for enzyme preparations provided by the Joint FAO/WHO Expert Committee on Food Additives.

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 derived from this genetically modified strain of B. licheniformis 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 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.

Content last updated by pmg on 1999-DEC-30
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