Agency Response Letter
GRAS Notice No. GRN 000090

Gary Yingling
Enzyme Technical Association
1800 Massachusetrs Ave., N.W.
2^nd Floor
Washington, D.C. 20036-1800

Re: GRAS Notice No. GRN 000090

Dear Mr. Yingling:

The Enzyme Technical Association (ETA) submitted a notice dated November 8, 2001, 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 Food and Drug Administration (FDA) received the notice on November 16, 2001, filed it on November 16, 2001, and designated it as GRAS Notice No. GRN 000090. In a letter dated April 3, 2002, FDA responded to GRN 000090. The purpose of this current letter is to clarify information we provided to you in our April 3, 2002 response letter.

The subjects of the notice were carbohydrase and protease from Aspergillus oryzae, and carbohydrase from Rhizopus oryzae. The notice informed FDA of the view of the Enzyme Technical Association (ETA) that these enzyme preparations are GRAS, through common use in food, for use as enzymes in catalyzing specific reactions in the processing of food. Each of the enzyme preparations is used at levels not to exceed current good manufacturing practice.

Because the protease enzyme preparation from A. oryzae would be used to tenderize meat, FDA consulted with the Labeling and Consumer Protection Staff of the Food Safety and Inspection Service of the United States Department of Agriculture (FSIS) during its evaluation of GRN 000090. Under the Federal Meat Inspection Act and the Poultry Products Inspection Act, FSIS is responsible for determining the efficacy and suitability of food ingredients in meat and poultry products as well as prescribing safe conditions of use. Suitability relates to the effectiveness of the ingredient in performing the intended purpose of use and the assurance that the conditions of use will not result in an adulterated product, or one that misleads consumers.

In our April 4, 2002, letter, we informed you that the Food Safety and Inspection Service (FSIS) of the United States Department of Agriculture had concluded that ETA needed to provide data establishing that the protease enzyme preparation from A. oryzae was being used at the lowest level necessary to achieve the intended technical effect in the specific meat and poultry products to which application is desired, and that ETA should seek regulatory guidance from FSIS about the use of protease enzyme preparation from A. oryzae in meat and poultry products.

In a letter dated October 3, 2003, from ETA to FDA, you attached a copy of a letter dated November 26, 2002, from FSIS to ETA. In that letter, FSIS clarified its position regarding the use of proteolytic enzymes obtained from A. oryzae in meat and poultry products in light of a regulation that lists proteolytic enzymes as a class of substances that may be used as a tenderizing agent to treat certain raw meat and poultry products at a level not to exceed 3 percent of the weight of the untreated product.

Proteolytic enzymes are listed as a class of substances in Title 9 of the Code of Federal Regulations (CFR), Section 424.21(c) for use as a tenderizing agent to treat raw poultry muscle tissue of hen, cock, mature turkey, mature duck, mature goose, mature guinea, and raw meat cuts at a level not to exceed 3 percent of the weight of the untreated product. Although protease enzymes from A. oryzae are not specifically listed in 9 CFR 424.21(c), for the purpose of suitability determinations FSIS normally regulates the use of specific ingredients, such as proteolytic enzymes, not the source from which they are obtained. Therefore, FSIS has no objection to the use of the A. oryzae protease enzyme preparation to tenderize raw poultry muscle tissue of hen, cock, mature turkey, mature duck, mature goose, mature guinea, and raw meat cuts at a level not to exceed 3 percent of the weight of the untreated product. If ETA's proposed use deviates from these conditions specified in 9 CFR 424.21(c), FSIS would need suitability data on the proposed conditions of use to perform an acceptability determination.

In light of the specific circumstances described above, we are issuing this letter to clarify the position of FSIS regarding the use of protease enzyme preparation from A. oryzae in meat and poultry products.

Sincerely,    /s/ Laura M. Tarantino, Ph.D. Acting Director Office of Food Additive Safety Center for Food Safety      and Applied Nutrition

cc: Dr. Robert Post, Director
Labeling and Consumer Protection Staff
Office of Policy, Program Development and Evaluation
Food Safety and Inspection Service
1400 Independence Ave., SW, Suite 602, Annex
Washington, DC 20250-3700