Food

Agency Response Letter GRAS Notice No. GRN 000290

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CFSAN/Office of Food Additive Safety

November 2, 2009

Robert G. Hibbert
Kirkpatrick & Lockhart Preston Gates Ellis LLP
1601 K Street, NW
Washington, DC 20006-1600

Re: GRAS Notice No. GRN 000290

Dear Mr. Hibbert:

The Food and Drug Administration (FDA) is responding to the notice, dated May 4, 2009, that you submitted on behalf of Dr. Ranzel Nickelson, 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). FDA received the notice on May 5, 2009, filed it on May 6, 2009, and designated it as GRAS Notice No. GRN 000290. In a letter, dated October 2, 2009, you informed FDA that the notifying entity changed to Edge Food Products, LLC (Edge Food Products). Accordingly, FDA considers Edge Food Products to be the notifier for GRN 000290. In telephone conversation on October 29, 2009, a representative for Edge Food Products limited the intended use to those foods described in the following paragraph.

The subject of the notice is L-arginine. The notice informs FDA of the view of Edge Food Products that L-arginine is GRAS, through scientific procedures, for use as an ingredient in a brine solution to be injected into beef subprimals, or mixed with ground beef to make beef patties. The brine solution contains levels of L-arginine between 0.2 - 0.6 percent.

The notifier provides information about the chemical identity of, and specifications for, L-arginine. L-arginine is one of the 20 amino acids commonly found in proteins (Chemical Abstract Service Registry number is CAS Reg. No. 74-79-3). The notifier points out that L-arginine is approved by FDA as a food additive for use as an ingredient (21 CFR 172.320). L-arginine meets the specifications set forth in the Food Chemicals Codex (6th edition). Furthermore, the notifier states that the brine solution injected into beef subprimals, or mixed with ground beef to make beef patties, is composed of L-arginine and other GRAS substances and that the solution is prepared under current good manufacturing practices.

The notifier intends to use L-arginine as an ingredient in a brine solution to be injected into beef subprimals or mixed with ground beef to make beef patties.The notifier explains that L-arginine is added to a brine solution at a level of 0.2 - 0.6 percent weight per volume. The notifier states that the solution is mechanically injected into whole cuts of beef at a 10 – 20 percent level based on the initial weight of beef; the solution is mixed with ground beef at a 6 – 8 percent level to form beef patties.

The notifier included in the notice published information which reports that 3 - 6 grams of L-arginine are consumed in the diet every day.The notifier also indicated that the level of L-arginine naturally present in meat is approximately 1.5 percent of the weight of the meat. The notifier further reports that the L-arginine used in the brine solution is indistinguishable from the naturally occurring L-arginine in beef. Additionally, the notifier submitted calculations of the estimated amounts of added L-arginine that would be present after injection into beef based on the assumption that all added L-arginine would be retained in the beef. Specifically, the notifier used the values for the maximum amount of L-arginine that may be added to brine (0.6 percent) and the maximum amount of brine that may be added to beef (20 percent) and calculated that the added L-arginine would be 0.12 percent of the initial weight of beef.Thus, the notifier concludes that the amount of L-arginine that would be added to beef would not significantly increase the amount of L-arginine that is already naturally present in meat and would only become a part of what is already consumed on a daily basis. For this reason, the notifier did not calculate an estimated daily intake for L-arginine based upon the proposed use.

The notifier submitted a published review article which included an assessment of several animal and adult human safety studies using orally administered L-arginine.The overall assessment of the review article was that orally administered L-arginine caused no adverse effects in humans. Specifically, the researchers identified 20 grams per day as the observed safe level, a determination which was corroborated by animal data. Therefore, based on this safety data, generally known information about the metabolism of L-arginine in humans, and the fact that the amount of L-arginine added to meat from the intended use is less than what is naturally present in the meat, the notifier concludes there are no safety concerns.

Use in Meat, Poultry, and Egg Products

During its evaluation of GRN 000290, FDA consulted with the Risk and Innovations Management Division, Office of Policy and Program Development, of the Food Safety and Inspection Service (FSIS) of the United States Department of Agriculture.Under the Federal Meat Inspection Act, Poultry Products Inspection Act, and the Egg Products Inspection Act, FSIS is responsible for determining the efficacy and suitability of food ingredients in meat, poultry and egg 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.

FSIS reviewed the L-arginine as an ingredient in a brine solution for use in beef subprimals and ground beef used to make beef patties. FSIS has no objection to the intended use of L-arginine, at levels between 0.2 - 0.6 percent in this solution in beef subprimals.

FSIS advises that the brine solution containing L-arginine would not be permitted for use in ground beef since ground beef has a standard of identity per the Code of Federal Regulations (CFR), Title 9, Part 319, Definitions and Standards of Identity of Composition, 319.15(a). FSIS further advises that the brine solution containing L-arginine could be used in products labeled as "beef patties" since the standard of identity for this beef product allows for the addition of added water, as per 9 CFR 319.15(c).

FSIS requested that FDA advise Edge Food Products to seek regulatory guidance regarding labeling requirements for components of their solution from FSIS, Labeling and Program Delivery Division. Edge Food Products should direct such an inquiry to Dr. John M. Hicks, Jr., Risk and Innovations Management Division, Office of Policy and Program Development, Food Safety and Inspection Service, United States Department of Agriculture, George Washington Carver Center (GWCC), 5601 Sunnyside Ave., Mailstop 5271, Beltsville, MD 20705-5271. The telephone number for that office is (301) 504-0884 and the telefax number is (301) 504-0876.

301(ll) of the Federal Food, Drug, and Cosmetic Act (FFDCA)

The Food and Drug Administration Amendments Act of 2007, which was signed into law on September 27, 2007, amends the FFDCA to, among other things, add section 301(ll). Section 301(ll) of the FFDCA prohibits the introduction or delivery for introduction into interstate commerce of any food that contains a drug approved under section 505 of the FFDCA, a biological product licensed under section 351 of the Public Health Service Act, or a drug or a biological product for which substantial clinical investigations have been instituted and their existence made public, unless one of the exemptions in section 301(ll)(1)-(4) applies.In its review of Edge Food Products' notice that L-arginine is GRAS, through scientific procedures, for use as an ingredient in a brine solution to be injected into beef subprimals, or mixed with ground beef to make beef patties, at levels of L-arginine between 0.2 - 0.6 percent, FDA did not consider whether section 301(ll) or any of its exemptions apply to foods containing L-arginine.Accordingly, this response should not be construed to be a statement that foods containing L-arginine, if introduced or delivered for introduction into interstate commerce, would not violate section 301(ll).

Conclusions

Based on the information provided by Edge Food Products as well as other information available to FDA, the agency has no questions at this time regarding Edge Food Products' conclusion that L-arginine is GRAS for use as an ingredient in a brine solution to be injected into beef subprimals, or mixed with ground beef to make beef patties, at levels of L-arginine between 0.2 - 0.6 percent. The agency has not, however, made its own determination regarding the GRAS status of the subject use of L-arginine. As always, it is the continuing responsibility of Edge Food Products 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 GRN 000290, 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 via the FDA home page at http://www.fda.gov.To view or obtain an electronic copy of the text of the letter, follow the hyperlinks from the "Food" topic to the "Food Ingredients and Packaging" section to the "Generally Recognized as Safe (GRAS)" page where the GRAS Inventory is listed.

Sincerely,

Mitchell A. Cheeseman, Ph.D.
Acting Director
Office of Food Additive Safety
Center for Food Safety and Applied Nutrition

cc: John M. Hicks, Jr. DVM, MPH
Risk and Innovations Management Division
Office of Policy and Program Development
Food Safety and Inspection Service
United States Department of Agriculture
George Washington Carver Center (GWCC)
5601 Sunnyside Ave., Mailstop 5271
Beltsville, MD 20705-5271

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