Agency Response Letter GRAS Notice No. GRN 000327
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CFSAN/Office of Food Additive Safety
August 23, 2010
Luis A. Mejia, Ph.D.
Archer Daniels Midland Company
4666 East Faries Parkway
Decatur, IL 62526
Re: GRAS Notice No. GRN 000327
Dear Dr. Mejia:
The Food and Drug Administration (FDA) is responding to the notice, dated February 26, 2010, that you submitted 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 March 1, 2010, filed it on March 9, 2010, and designated it as GRAS Notice No. GRN 000327. In a letter dated May 13, 2010, ADM limited the intended use of the ingredient to those foods described in the following paragraph.
The subject of the notice is cruciferin-rich canola/rapeseed protein isolate (CRCPI) and napin-rich canola/rapeseed protein isolate (NRCPI). The notice informs FDA of the view of Archer Daniels Midland Company (ADM) that CRCPI and NRCPI are GRAS, through scientific procedures, for use alone or together as an ingredient in dairy products, grain products, fruit and vegetable juices and beverages, salad dressings, meal replacements, and nutritional bars.
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 “CRCPI” and “NRCPI” 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, ADM includes the report of a panel of individuals (ADM’s GRAS panel) who evaluated the data and information that are the basis for ADM’s GRAS determination. ADM considers the members of its GRAS panel to be qualified by scientific training and experience to evaluate the safety of substances added to food. ADM’s GRAS panel evaluated estimates of dietary exposure, method of manufacture, and product specifications as well as published and unpublished studies. Based on this review, ADM’s GRAS panel concluded that CRCPI and NRCPI meeting ADM’s food grade specifications are GRAS under the conditions of intended use.
ADM describes the manufacturing process for CRCPI and NRCPI. The process begins with the production of defatted canola/rapeseed meal from varieties of canola/rapeseed low in glucosinolates and erucic acid, followed by isolation of the protein fractions from the meal. Canola/rapeseed is first heated, partially dehulled, pressed, extracted with hexane, and the hexane removed under vacuum. The proteins are then concentrated and extracted by ultrafiltration followed by separation through centrifugation. Cruciferin is precipitated out as micelles, resolubilized, spray-dried, and sieved to obtain CRCPI. The supernatant from the ultrafiltration step is further concentrated, spray-dried, and sieved to obtain NRCPI. ADM states that CRCPI and NRCPI are manufactured under good manufacturing practices and meet appropriate food grade specifications. ADM notes that CRCPI contains a minimum of 80 percent cruciferin, a globulin storage protein, and NRCPI contains a minimum of 80 percent napin, an albumin storage protein.
ADM provides specifications for CRCPI and NRCPI including protein content (greater than or equal to 90 percent), fat (less than or equal to 2 percent), moisture (less than or equal to 9 percent), ash (less than or equal to 6 percent), total glucosinolates (less than 30 micromoles per gram), erucic acid (less than 0.04 percent), lead (less than 0.5 milligrams/kilogram), and limits for microbiological plate counts.
ADM states that CRCPI and NRCPI, used alone or together, are intended for use as ingredients in various food categories at levels of 2 to 50 percent. ADM notes that the use levels of CRCPI and NRCPI are self-limiting. ADM estimates the range of mean and 90th percentile daily intakes of the combination of CRCPI and NRCPI for different age groups. The highest mean and 90th percentile estimated intake were in the age group 13 to 19 years at 31.9 grams/person/day (g/p/d), and 89.0 g/p/d, respectively.
ADM discusses the safety of CRCPI and NRCPI. ADM discusses two published 13-week rodent studies, one with CRCPI and one with NRCPI. ADM concludes that these studies showed no adverse effects at a level of 20 percent of CRCPI or NRCPI in the diet. ADM discusses other published toxicological studies on canola protein isolates in support of their safety determination. ADM also discusses unpublished genotoxicity studies on CRCPI and NRCPI and concludes that CRCPI and NRCPI are not mutagenic. ADM also considers the issue of allergenicity by reviewing both published and unpublished studies on canola proteins in support of their safety determination.
Standards of Identity
In the notice, ADM states its intention to use CRCPI and NRCPI 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
In describing the intended use of CRCPI and NRCPI, ADM lists meal replacements and nutritional bars, two food categories that often contain health or nutrient content claims. 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. If products that contain CRCPI and NRCPI 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 CRCPI and NRCPI on the label or in labeling.
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 ADM’s notice that CRCPI and NRCPI are GRAS for the intended uses, FDA did not consider whether section 301(ll) or any of its exemptions apply to foods containing CRCPI or NRCPI. Accordingly, this response should not be construed to be a statement that foods that contain CRCPI or NRCPI, if introduced or delivered for introduction into interstate commerce, would not violate section 301(ll).
Based on the information provided by ADM, as well as other information available to FDA, the agency has no questions at this time regarding ADM’s conclusion that CRCPI and NRCPI are 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 CRCPI and NRCPI. As always, it is the continuing responsibility of ADM 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 000327, 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