Agency Response Letter GRAS Notice No. GRN 000214 - Additional Correspondence
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See also Generally Recognized as Safe (GRAS).
CFSAN/Office of Food Additive Safety
May 2, 2016
Mr. Gary Yingling
Morgan Lewis Bockius LLP
1111 Pennsylvania Ave. NW
Washington, DC 20004
Re: GRAS Notice No. GRN 000214
Dear Mr. Yingling:
The Food and Drug Administration (FDA) is responding to the supplement, dated September 24, 2015, that you submitted on behalf of DSM Food Specialties (DSM) regarding additional uses of asparaginase enzyme preparation from Aspergillus niger expressing a gene encoding asparaginase from A. niger (asparaginase enzyme preparation). This is the subject of GRN 000214. You submitted GRN 000214 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 notice informed FDA of the view of DSM that asparaginase enzyme preparation is GRAS, through scientific procedures, for use as an enzyme to lower free L-asparagine levels in breads, cereal-based products, potato-based products, and reaction flavors, at levels up to 562 milligrams total organic solids per kilogram of final food (mg TOS/kg). In a letter dated March 12, 2007, FDA informed DSM that the agency had no questions at that time regarding DSM’s conclusion that asparaginase enzyme preparation is GRAS under the intended conditions of use.
In a supplement dated September 24, 2015, DSM informed FDA of its view that asparaginase enzyme preparation is GRAS, through scientific procedures, for additional uses, namely, in the processing of coffee and chocolate products. The asparaginase enzyme preparation is intended to be used at 20 mg TOS/kg of raw material, to reduce acrylamide. 
As part of this supplement, DSM confirms that the manufacture of asparaginase enzyme preparation from A. niger has not changed from that described in GRN 000214, and meets the specifications established for enzyme preparations in the current Food Chemicals Codex (FCC) and the General Specifications and Considerations for Enzyme Preparations Used in Food Processing established by the FAO/WHO Joint Expert Committee on Food Additives (JECFA, 2006). DSM supports this statement by providing the specifications for a manufacturing batch of asparaginase enzyme preparation. DSM states that the additional uses of asparaginase enzyme preparation, in the processing of chocolate and coffee products, do not significantly affect the overall margin of safety calculated for the uses outlined in GRN 000214. FDA confirmed this by calculating an estimated dietary intake of asparaginase enzyme preparation from the additional uses proposed by DSM. 
DSM also confirms performing a review of current scientific literature regarding the asparaginase enzyme preparation that is the subject of GRN 000214 through March 9, 2016. DSM reported no new safety data. DSM also states that the safety data discussed in the original notice, GRN 000214, are still applicable to this intended additional use. DSM also states that no asparaginase activity is present in the finished product.
Based on the information provided by DSM in GRN 000214, the supplement dated September 24, 2015, as well as other information available to FDA, the agency has no questions at this time regarding DSM’s conclusion that asparaginase enzyme preparation from Aspergillus niger expressing a gene encoding asparaginase from A. niger 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 asparaginase enzyme preparation from A. niger expressing a gene encoding asparaginase from A. niger. As always, it is the continuing responsibility of DSM 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 000214, 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 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
 Acrylamide forms when foods containing asparagine and reducing sugars are baked or fried at temperatures above 120°C. DSM intends to use asparaginase enzyme preparation in the manufacture of the proposed additional foods, to reduce L-asparagine levels thereby reducing acrylamide levels in these foods. FDA has not evaluated the efficacy of the asparaginase enzyme preparation.
 FDA notes that the most current FCC is the 9th edition (FCC, 2014).
 FDA estimates the 90th percentile dietary intake of asparaginase enzyme preparation to be 0.3 mg TOS per kg body weight per day for the additional proposed uses in the production of coffee and chocolate products.