GRAS Notice Inventory > Agency Response Letter GRAS Notice No. GRN 000226
`
`Page 1 of 4
`
`Archived Content
`The content on this page is provided for reference purposes only. This content has not been
`altered or updated since it was archived.
`
`Agency Response Letter GRAS
`Notice No. GRN 000226
`
`Return to inventory listing: GRAS Notice Inventory (http://www.fda.gov/grasnoticeinventory)
`
`See also Generally Recognized as Safe (GRAS) (/Food/IngredientsPackagingLabel-
`ing/GRAS/default.htm) and about the GRAS Notice Inventory (/Food/IngredientsPackag-
`ingLabeling/GRAS/NoticeInventory/default.htm)
`
`CFSAN/Office of Food Additive Safety
`January 03, 2008
`
`Edward A. Steele
`EAS Consulting Group, LLC
`1940 Duke Street, Suite 200
`Alexandria, Virginia 22314
`
`Re: GRAS Notice No. GRN 000226
`
`Dear Mr. Steele:
`
`The Food and Drug Administration (FDA) is responding to the notice, dated May 26, 2007, that you
`submitted on behalf of Enzymotec, Ltd. (Enzymotec) 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 29, 2007, filed
`it on May 31, 2007, and designated it as GRAS Notice No. GRN 000226.
`
`The subject of this notice is lecithin derived from krill (krill-derived lecithin). The notice informs FDA
`of the view of Enzymotec that krill-derived lecithin is GRAS, through scientific procedures, for use
`in various products as described below (Table 1).
`
`Table 1
`Enzymotec's intended conditions of use
`
`RIMFROST EXHIBIT 1049 page 0001
`https://www.fda.gov/Food/IngredientsPackagingLabeling/GRAS/NoticeInventory/ucm153...
`5/16/2017
`
`

`

`GRAS Notice Inventory > Agency Response Letter GRAS Notice No. GRN 000226
`
`Page 2 of 4
`
`Food
`
`Breakfast bars
`
`Dairy product analogs (soy products)
`
`Fat spreads
`
`Milk-based beverages
`
`Yogurt
`
`Soft candy
`
` Level of Use
`
`3.8 percent
`
`0.6 percent
`
`10.0 percent
`
`0.6 percent
`
`0.7 percent
`
`3.3 percent
`
`Enzymotec's krill-derived lecithin is a complex mixture of primarily neutral and polar phospholipids,
`with phosphatidylcholine as the principle phospholipid present. Enzymotec defines
`phosphatidylcholine as 1,2-diacyl-sn-glycero-3-phosphocholine. Enzymotec notes that the fatty
`acid substituents of phosphatidylserine from plant and marine sources are different. In the case of
`krill-derived lecithin, Enzymotec notes that these fatty acids are primarily the long-chain
`polyunsaturated fatty acids docosahexaenoic acid (DHA) and eicosapentaenoic acid (EPA).
`Enzymotec notes that plant-derived lecithin is GRAS for use in foods generally, in accordance with
`good manufacturing practices (21 CFR 184.1400).
`
`Enzymotec describes the method of manufacture of its krill-derived lecithin. Krill are shrimp-like
`crustaceans of the family Euphausiidae. The starting material is a composite biomass of krill
`known as krill meal. The protein and sugar content of the krill meal is removed using a solvent
`extraction process, leaving the lecithin-containing lipid fraction. Enzymotec notes that the solvents
`used in this process are of food-grade quality and are used in accordance with the current good
`manufacturing practice.
`
`Enzymotec states that krill-derived lecithin is produced in two grades, A and B that differ in the
`purification level of phospholipids and the combined DHA and EPA content. For Grade A, total
`phospholipids are specified to be between 40 and 50% w/w, and for Grade B total phospholipids
`are to be between 70 and 95% w/w. The combined DHA and EPA content is approximately 14-
`18% for Grade A, and 20-25% for Grade B. Enzymotec provides batch analysis data indicating that
`phosphatidylcholine represents up to approximately 80% of the total phospholipids present in both
`Grade A and Grade B. Batch analysis data also indicate that Grade A contains approximately 50%
`neutral lipids (mono, di-, triglycerides and free fatty acids), whereas, in Grade B, these are not
`detected. Enzymotec provides additional specifications for both Grade A and Grade B krill-based
`lecithin, including peroxide value, moisture, lead, cadmium and mercury.
`
`Enzymotec states that phosphatidylcholine is a common constituent of plant and animal cells and,
`as such, is a normal constituent of the human diet. Enzymotec describes several commonly
`consumed phosphatidylcholine-rich foods, such as egg yolk, soybean oil, sunflower oil, rapeseed
`oil, various grains, wheat germ, fish, legumes, yeast, and peanuts.
`
`Enzymotec indicates that the metabolism of phosphatidylcholine is well described in the scientific
`literature and notes that there is no difference in the metabolism of phosphatidylcholine derived
`from plant or animal sources. Enzymotec reviews published information regarding the normal
`absorption, distribution, metabolism and excretion of phosphatidylcholine consumed in the diet
`indicating that phosphatidylcholine is metabolized through well-described processes to safe and
`endogenous products.
`
`RIMFROST EXHIBIT 1049 page 0002
`https://www.fda.gov/Food/IngredientsPackagingLabeling/GRAS/NoticeInventory/ucm153...
`5/16/2017
`
`

`

`GRAS Notice Inventory > Agency Response Letter GRAS Notice No. GRN 000226
`
`Page 3 of 4
`
`Enzymotec discusses FDA's recommendations regarding the levels of menhaden oil used in
`various foods that are consistent with safe levels of exposure to DHA and EPA. Enzymotec
`(1)
`emphasizes that in all applications where either krill-based lecithin or menhaden oil can be used,
`the levels of lecithin (hence the combined levels of DHA and EPA) from krill-based lecithin are
`lower than what is allowed from menhaden oil. The notifier also assures that krill-based lecithin will
`not be used in foods that contain other significant sources of DHA and EPA as ingredients. The
`notifier also states that the menhaden oil rule permits several additional applications where krill-
`based lecithin would not be used.
`
`With regard to potential environmental contaminants associated with krill that could pose a health
`risk, Enzymotec notes that krill are unlikely to bioaccumulate lipid-soluble environmental
`contaminants since they are very low in the marine food chain. Further, Enzymotec presents
`analytical data for both Grade A and Grade B lipid fractions for contaminants, such as PCBs,
`pesticides, dioxins, arsenic, lead, mercury and cadmium, and state that the levels are consistent
`with levels found in other food ingredients.
`
`Allergen Labeling
`The Food Allergen Labeling and Consumer Protection Act of 2004 (FALCPA) amends the Federal
`Food, Drug, and Cosmetic Act to require that the label of a food that is or contains an ingredient
`that bears or contains a "major food allergen" declare the presence of the allergen (section 403
`(w)). FALCPA defines a "major food allergen" as one of eight foods or food groups (i.e., milk, eggs,
`fish, Crustacean shellfish, tree nuts, peanuts, wheat, and soybeans) or a food ingredient that
`contains protein derived from one of those foods. Issues associated with labeling food are the
`responsibility of the Center for Food Safety and Applied Nutrition's Office of Nutritional Products,
`Labeling, and Dietary Supplements.
`
`Standards of Identity
`In the notice, Enzymotec states its intention to use krill-derived lecithin 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.
`
`Conclusion
`Based on the information provided by Enzymotec, as well as other information available to FDA,
`the agency has no questions at this time regarding Enzymotec's conclusion that krill-derived
`lecithin is 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 krill-derived lecithin. As always, it is
`the continuing responsibility of Enzymotec 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
`000226, as well as a copy of the information in this notice that conforms to the information in the
`proposed GRAS exemption claim (proposed 21 CFR 170.36(c)(1)), is available for public review
`and copying on the homepage of the Office of Food Additive Safety (on the Internet at
`http://www.cfsan.fda.gov/~lrd/foodadd.html).
`
`RIMFROST EXHIBIT 1049 page 0003
`https://www.fda.gov/Food/IngredientsPackagingLabeling/GRAS/NoticeInventory/ucm153...
`5/16/2017
`
`

`

`GRAS Notice Inventory > Agency Response Letter GRAS Notice No. GRN 000226
`
`Page 4 of 4
`
`Sincerely,
`
`Laura M. Tarantino, Ph.D.
`Director
`Office of Food Additive Safety
`Center for Food Safety and Applied Nutrition
`
`FDA has affirmed the GRAS status of menhaden oil for use as a direct food ingredient (21 CFR
`(1)
`184.1472) provided that the combined intake of EPA and DHA from consumption of menhaden oil
`does not exceed 3 grams per person per day (g/p/d). FDA had raised concerns about the
`consumption of high levels of EPA and DHA and possible adverse effects of consumption on
`bleeding time, glycemic control, and low-density lipoprotein cholesterol levels (62 FR 30751 at
`30757; June 5, 1997). FDA subsequently revised the menhaden oil rule to reallocate the uses of
`menhaden oil in conventional food, while maintaining the 3 g/p/d limit on EPA and DHA, and to
`require that menhaden oil not be used as an ingredient in foods in combination with another added
`oil that is a significant source of EPA and DHA (70 FR 14530; March 23, 2005).
`
`More in GRAS Notice Inventory
`(/Food/IngredientsPackagingLabeling/GRAS/NoticeInventory/default.htm)
`
`RIMFROST EXHIBIT 1049 page 0004
`https://www.fda.gov/Food/IngredientsPackagingLabeling/GRAS/NoticeInventory/ucm153...
`5/16/2017
`
`