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U.S. Department of Health and Human Services

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Agency Response Letter GRAS Notice No. GRN 000305

CFSAN/Office of Food Additive Safety

April 19, 2010

George A. Burdock, Ph.D.
Burdock Group
801 N. Orange Avenue
Suite 710
Orlando, FL 32801

Re: GRAS Notice No. GRN 000305

Dear Dr. Burdock:

The Food and Drug Administration (FDA) is responding to the notice, dated August 21, 2009, that you submitted on behalf of Griffith Laboratories (Griffith) 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 September 17, 2009, filed it on October 15, 2009, and designated it as GRAS Notice No. GRN 000305.

The subject of the notice is Carnobacterium maltaromaticum strain CB1 (viable and heat-treated).1 The notice informs FDA of the view of Griffith that C. maltaromaticum strain CB1 (viable or heat-treated) is GRAS, through scientific procedures, for use as an inhibitor of Listeria monocytogenes in a variety of foods including meat and poultry as follows: (1) viable C. maltaromaticum CB1 in ready-to-eat meat products; meat, poultry, and fish products; frozen meals; processed fruit salads and vegetable salads; sauces; and, soft cheese and cheese spread-type products and (2) heat-treated C. maltaromaticum CB1 as an inhibitor of L. monocytogenes in ready-to-eat meat products, meat, poultry, fish, and mixtures; fruits and vegetables; soups and stews; sauces and dressings; and, cheese and cheese spread-type products.

21 CFR 101.4 states that all ingredients must be declared by their common or usual name. In addition, 21 CFR 102.5 outlines general principles to use when establishing common or usual names for nonstandardized foods. Our use of “C. maltaromaticum strain CB1 (viable or heat-treated)” in this letter should not be considered an endorsement or recommendation of that term as an appropriate common or usual name for the purpose of declaring the substance in the ingredient statement of foods that contain that ingredient. Issues associated with labeling and the appropriate common or usual name of a food are the responsibility of the Office of Nutrition, Labeling and Dietary Supplements (ONLDS) in the Center for Food Safety and Applied Nutrition.

As part of its notice, Griffith includes the report of a panel of individuals (Griffith’s GRAS panel) who evaluated the data and information that are the basis for Griffith’s GRAS determination. Griffith considers the members of its GRAS panel to be qualified by scientific training and experience to evaluate the safety of substances added to food. Griffith’s GRAS panel discusses the identity and characteristic properties of C. maltaromaticum, as well as antibiotic resistance profiles of C. maltaromaticum strain CB1; the method of manufacture, specifications, and stability of C. maltaromaticum strain CB1 (viable or heat-treated); the intended conditions of use for C. maltaromaticum strain CB1 (viable or heat-treated), including the estimated daily intake of the products containing C. maltaromaticum strain CB1; and the natural presence of Carnobacterium species in food, particularly in meat, poultry, fish, and cheese, and the available published and unpublished research on the safety of C. maltaromaticum in foods. Griffith’s GRAS panel concluded that C. maltaromaticum strain CB1 (viable or heat-treated) is GRAS under the conditions of its intended use.

Griffith provides information about the identity and characteristics of C. maltaromaticum. Specifically, Griffith states that C. maltaromaticum strain CB1 is a naturally-selected, non-genetically modified bacterium. Griffith provides a discussion of the published literature on the initial isolation, characterization, and taxonomic history of Lactobacillus piscicola, a prior designation for strains isolated from stressed rainbow trout and salmon that were later reclassified as C. maltaromaticum. Griffith also provides published information on growth characteristics of C. maltaromaticum. Griffith states that there is no published information indicating that C. maltaromaticum strain CB1 (and other C. maltaromaticum strains) is resistant to antibiotics or contains readily transferrable genes that encode antibiotic resistance.

Griffith describes the manufacturing procedures for C. maltaromaticum strain CB1 (viable or heat-treated) noting that each step in the production of C. maltaromaticum strain CB1 (viable or heat-treated) is performed in accordance with current good manufacturing practices. According to Griffith, the manufacturing procedures and specifications for viable C. maltaromaticum strain CB1 remain the same as described in GRN 000159; however, in the current notice, Griffith provides detailed manufacturing procedures and specifications for heat-treated C. maltaromaticum strain CB1. Additionally, Griffith states that C. maltaromaticum strain CB1 (viable and heat-treated) has a shelf-life of at least one year when stored at 22 degrees Celsius.

Griffith intends to use viable C. maltaromaticum CB1 as an inhibitor of L. monocytogenes in ready-to-eat meat products; meat, poultry, and fish products; frozen meals; processed fruit salads and vegetable salads; sauces; and, soft cheese and cheese spread-type products at a levels up to 1 x 109 colony forming units per gram (cfu/g). Griffith intends to use heat-treated C. maltaromaticum CB1 as an inhibitor of L. monocytogenes in ready-to-eat meat products, meat, poultry, fish, and mixtures; fruits and vegetables; soups and stews; sauces and dressings; and, cheese and cheese spread-type products at levels between 1000 – 5000 parts per million (ppm). Griffith reports a calculated mean estimated daily intake (EDI) of 3.4 x 1010 cfu/day of viable C. maltaromaticum strain CB1 and a mean EDI of 1.4 g/day of heat-treated C. maltaromaticum strain CB1 for eaters only.

Griffith discusses published information documenting the presence of Carnobacterium spp. in a variety of foods. In the current notice, Griffith includes the same published information that was presented in GRN 000159 and states that no additional safety information on the consumption of C. maltaromaticum has been published since FDA responded to GRN 000159. Specifically, Griffith discusses the safety of tyramine which is found in food inoculated with C. maltaromaticum. Griffith concludes that the concentration of tyramine in food inoculated with C. maltaromaticum, would not result in adverse health effects. Griffith summarizes published and unpublished studies relevant to inhibition of the growth of L. monocytogenes mediated by bacteriocins. Griffith notes that one means by which C. maltaromaticum inhibits the growth of L. monocytogenes is through the production of bacteriocins. Griffith states that both C. maltaromaticum and its bacteriocins have been consumed for centuries. Griffith states that there have been no reports of adverse events associated with the human oral consumption of C. maltaromaticum. Based on the information pertaining to the natural presence of C. maltaromaticum in food, as well as the available published and unpublished research on the safety of C. maltaromaticum in foods, Griffith concludes that there are no safety concerns regarding the intended uses of C. maltaromaticum strain CB1 (viable or heat-treated) in foods.

Standards of Identity

In the notice, Griffith states its intention to use C. maltaromaticum strain CB1 (viable or heat-treated) in several food categories, including foods for which standards of identity exist, located in Title 21 of the Code of Federal Regulations. We note that an ingredient that is lawfully added to food products may be used in a standardized food only if it is permitted by the applicable standard of identity.

Potential Labeling Issues

Under section 403(a) of the Federal Food, Drug, and Cosmetic Act (FFDCA), a food is misbranded if its labeling is false or misleading in any particular. Section 403(r) of the FFDCA lays out the statutory framework for the use of labeling claims that characterize the level of a nutrient in a food or that characterize the relationship of a nutrient to a disease or health-related condition. In describing the intended use of C. maltaromaticum strain CB1 (viable or heat-treated) and in describing the information that Griffith relies on to conclude that C. maltaromaticum strain CB1 (viable or heat-treated) is GRAS under the conditions of its intended use, Griffith raises a potential issue under these labeling provisions of the FFDCA. If products that contain C. maltaromaticum strain CB1 (viable or heat-treated) bear any claims on the label or in labeling, such claims are the purview of ONLDS. The Office of Food Additive Safety neither consulted with ONLDS on this labeling issue nor evaluated the information in your notice to determine whether it would support any claims made about C. maltaromaticum strain CB1 (viable or heat-treated) on the label or in labeling.

Use in Meat, Poultry and Egg Products

During its evaluation of GRN 000305, 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 does not object to the use of C. maltaromaticum strain CB1 (viable and heat-treated) under the intended conditions of use. C. maltaromaticum strain CB1 (viable or heat-treated) will require ingredient labeling when used to treat meat products under the jurisdiction of FSIS. FSIS requested that FDA advise Griffith to seek regulatory guidance from FSIS, RIMD, about the use of C. maltaromaticum strain CB1 (viable or heat-treated) in meat and poultry products. Griffith should direct such an inquiry to Dr. John M. Hicks, Jr., RIMD, Office of Policy and Program Development, FSIS, via email at john.hicks@fsis.usda.gov.

Section 301(ll) of the 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 Griffith’s notice that C. maltaromaticum strain CB1 (viable or heat-treated) is GRAS, through scientific procedures, for use as an inhibitor of L. monocytogenes in a variety of foods including meat and poultry, FDA did not consider whether section 301(ll) or any of its exemptions apply to foods containing C. maltaromaticum strain CB1 (viable or heat-treated). Accordingly, this response should not be construed to be a statement that foods containing C. maltaromaticum strain CB1 (viable or heat-treated), if introduced or delivered for introduction into interstate commerce, would not violate section 301(ll).

Conclusions

Based on the information provided by Griffith, as well as other information available to FDA, the agency has no questions at this time regarding Griffith’s conclusion that C. maltaromaticum strain CB1 (viable or heat-treated) is GRAS, through scientific procedures, for use as an inhibitor of L. monocytogenes in a variety of foods including meat and poultry. The agency has not, however, made its own determination regarding the GRAS status of the subject use of C. maltaromaticum strain CB1 (viable or heat-treated). As always, it is the continuing responsibility of Griffith 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 000305, 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: Dr. 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


 



 

1When appropriate, viable C. maltaromaticum strain CB1 and heat-treated C. maltaromaticum strain CB1 are specifically referred to in this letter. Also when appropriate, the organism itself is referred to as C. maltaromaticum strain CB1.