Agency Response Letter GRAS Notice No. GRN 000317
CFSAN/Office of Food Additive Safety
July 12, 2010
Robert G. Hibbert
K & L Gates LLP
1601 K Street NW
Washington, DC 20006
Re: GRAS Notice No. GRN 000317
Dear Mr. Hibbert:
The Food and Drug Administration (FDA) is responding to the notice, dated January 7, 2010, that you submitted on behalf of Dr. Ranzell 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 January 8, 2010, filed it on January 13, 2010, and designated it as GRAS Notice No. GRN 000317. In a letter dated June 22, 2010, you informed FDA that the notifying entity should be changed to Edge Food Products, LLC (Edge Food Products). Accordingly, FDA considers Edge Food Products to be the notifier for GRN 000317.
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 a component in a brine solution to be injected into whole muscle cuts of pork or poultry, or mixed with ground pork or poultry to make patties. The brine solution contains concentrations of L-arginine between 0.2 - 0.6 percent.
Edge Food Products 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 No. 74-79-3). Edge Food Products points out that L-arginine is approved by FDA as a food additive under the conditions of use defined in 21 CFR 172.320. L-arginine meets the specifications set forth in the Food Chemicals Codex (6th edition). Furthermore, Edge Food Products states that the brine solution injected into pork or poultry, or mixed with ground pork or poultry to make patties, is composed of L-arginine and other GRAS substances and that the solution is prepared under current good manufacturing practices.
Edge Food Products intends to use L-arginine as a component in a brine solution to be injected into whole muscle cuts of pork or poultry, or mixed with ground pork or poultry to make patties. Edge Food Products explains that L-arginine is added to a brine solution at a concentration of 0.2 - 0.6 percent weight per volume. Edge Food Products states that the solution is mechanically injected into pork or poultry at a 10 – 20 percent concentration based on the initial weight of the pork or poultry; the solution is mixed with ground pork or ground poultry at a 6 – 8 percent concentration to form patties. Edge Food Products submitted calculations of the estimated amounts of added L-arginine that would be present after injection into pork and poultry based on the assumption that all added L-arginine would be retained in the pork and poultry. Specifically, Edge Food Products 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 meat (20 percent) and calculated that the added L-arginine would be 0.12 percent of the initial weight of pork and poultry.
In the notice, Edge Food Products included published information that reports that 3 - 6 grams of L-arginine is consumed in the diet every day. The notifier further reports that the L-arginine used in the brine solution is indistinguishable from the naturally occurring L-arginine in pork and poultry. The notifier also indicated that the concentration of L-arginine naturally present in meat is approximately 1.5 percent of the weight of the meat. Thus, the notifier concludes that the amount of L-arginine that would be added to pork and poultry under the intended conditions of use 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 intended use.
Edge Food Products submitted a published review article that included an assessment of several animal and adult human safety studies using orally administered L-arginine. Edge Food Products notes that 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 of L-arginine per day as the observed safe level, a determination that 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, Edge Food Products concludes there are no safety concerns.
Use in Products under USDA Jurisdiction
During its evaluation of GRN 000317, FDA consulted with the Risk and Innovations Management Division (RIMD) of the Food Safety and Inspection Service (FSIS) of the United States Department of Agriculture (USDA). 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 L-arginine as a component of the brine solution for use in whole muscle cuts of pork or poultry and ground pork or poultry to make patties. FSIS has no objection to the intended use of L-arginine, at concentrations between 0.2 - 0.6 percent in this solution in whole cuts of pork or poultry.
In regards to ground pork and ground chicken, FSIS applies the ground beef standard Code of Federal Regulations (CFR), Title 9, Part 319, Definitions and Standards of Identity of Composition, 319.15(a). Thus, FSIS advises that the brine solution containing L-arginine would not be permitted for use in ground pork or ground poultry. FSIS further advises that the brine solution containing L-arginine could be used in ground pork products labeled as “pork patties” or ground chicken products labeled as “chicken patties” since the standard of identity for the 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 from FSIS, RIMD, about the use of L-arginine in meat and poultry products. Edge Food Products should direct such an inquiry to Dr. John M. Hicks, Jr., Research 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.
Section 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 the intended uses, 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).
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 a component in a brine solution to be injected into whole muscle cuts of pork or poultry, or mixed with ground pork or poultry to make patties, at concentrations of L-arginine between 0.2 - 0.6 percent in the brine solution. 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 000317, 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.
Mitchell A. Cheeseman, Ph.D.
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