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U.S. Department of Health and Human Services

Food

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Agency Response Letter GRAS Notice No. GRN 000210

CFSAN/Office of Food Additive Safety
February 8, 2007

Dr. Stephen J. Franklin
Provexis plc
10 Williams House
Manchester Science Park
Lloyd Street North
Manchester
M15 6SE
UNITED KINGDOM

Re: GRAS Notice No. GRN 000210

Dear Dr. Franklin:

The Food and Drug Administration (FDA) is responding to the notice, dated August 9, 2006, 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 August 14, 2006, filed it on August 15, 2006, and designated it as GRAS Notice No. GRN 000210.

The subject of the notice is water soluble tomato concentrate (WSTC). The notice informs FDA of the view of Provexis plc (Provexis) that WSTC is GRAS, through scientific procedures, for use as an ingredient in yogurt drinks, fruit juices, and fruit flavored drinks at levels up to 3 grams (g) per serving.

As part of its notice, Provexis includes the report of a panel of individuals (Provexis' GRAS panel) who evaluated the data and information that are the basis for Provexis' GRAS determination. Provexis considers the members of its GRAS panel to be qualified by scientific training and experience to evaluate the safety of substances added to food. Provexis' GRAS panel discusses WSTC's composition, method of manufacture, specifications, and proposed estimated dietary intake. Provexis' GRAS panel also discusses published and unpublished studies conducted with WSTC and its individual components. Based on this review, Provexis' GRAS panel concluded that WSTC is GRAS when used as an ingredient in yogurt drinks, fruit juices, and fruit flavored drinks at levels up to 3 g per serving.

Provexis describes the method of manufacture and composition of WSTC. Provexis describes WSTC as an aqueous concentrate of tomato paste that consists of solids concentrated from a commercially available tomato puree, noting that it may range in color from deep yellow to golden to brown. WSTC is manufactured by adding water to tomato paste, then concentrating the water-soluble tomato compounds of interest through centrifugation and membrane filtration. The pH of the resulting aqueous concentrate is adjusted and it is concentrated further by evaporation at low temperature. Provexis states that all raw materials used in the production of WSTC meet food grade specifications. WSTC is composed of carbohydrate (~80%), protein (~6%), free amino acids (~3%), flavonoids, simple phenolics and low molecular weight organic acids and their derivatives (~0.9%), and other constituents (~8.2%). All constituents occur naturally in tomatoes. Provexis provides specifications for WSTC in its notice.

The notifier estimates the intake of WSTC for the intended uses. Provexis estimates that, depending on the serving sizes, the intake of WSTC would range from 3.9 grams/person/day (g/p/d) to 4.4 g/p/d at the mean and from 7.8 to 9.1 g/p/d at the 90th percentile level.

Provexis performed and describes comparative analysis of WSTC to tomatoes and other commercially-available tomato products. Based on this analysis, Provexis concludes that WSTC is similar in composition to tomatoes and other commercially available tomato products. Provexis notes that the components (mainly carbohydrates, with minor amounts of protein and free amino acids, and lesser amounts of flavonoids, phenolics, and organic acids) are all normally present in the diet and are expected to be metabolized by common metabolic pathways.

In addition to the comparative analysis, Provexis describes published toxicity studies in rodents fed tomatoes reporting no significant effects and unpublished human studies conducted with WSTC. Although these human studies were not formally designed to investigate the safety of WSTC, Provexis concludes that these studies showed that consumption of WSTC is well-tolerated and without adverse effects.

Potential Requirement for a Color Additive Petition

FDA notes that WSTC has the potential to impart color in food products that contain it. As such, the use of WSTC in food products may constitute the use of a color additive under section 201(t)(1) of the Federal Food, Drug and Cosmetic Act (FFDCA) and FDA's implementing regulations in 21 CFR Part 70. Under section 201(t)(1) and 21 CFR 70.3(f), the term color additive means a material that is a dye, pigment, or other substance made by a process of synthesis or similar artifice, or extracted, isolated, or otherwise derived from a vegetable, animal, mineral, or other source, and that is capable (alone or through reaction with another substance) of imparting color when added or applied to a food; except that such term does not include any material which the Secretary,(1) by regulation, determines is used (or intended to be used) solely for a purpose or purposes other than coloring. Under 21 CFR 70.3(g), a material that otherwise meets the definition of color additive can be exempt from that definition on the basis that it is used or intended to be used solely for a purpose or purposes other than coloring, as long as the material is used in a way that any color imparted is clearly unimportant insofar as the appearance, value, marketability, or consumer acceptability is concerned. Given the construct of section 201(t)(1) of the FFDCA and 21 CFR 70.3(f) and (g), the use of a substance that is capable of imparting color may constitute use as a color additive in addition to use as a food additive or GRAS substance. For example, beta-carotene is both approved for use as a color additive (21 CFR 73.95) and affirmed as GRAS for use as a nutrient supplement (21 CFR 184.1245); in some food products, beta-carotene is used for both purposes. Importantly, if the use of WSTC constitutes use as a color additive within the meaning of section 201(t)(1) of the FFDCA and FDA's implementing regulations in 21 CFR 70.3(f) and (g), section 721(a) of the FFDCA requires premarket review and approval of that use by FDA. Under section 402(c) of the FFDCA, a food product that contains an unapproved color additive would be deemed adulterated.(2)

Potential Labeling Issues

Under section 403(a) of the 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 WSTC and in describing the information that Provexis relies on to conclude that WSTC is GRAS under the conditions of its intended use, Provexis raises a potential issue under these labeling provisions of the FFDCA. This issue consists of physiological effects that Provexis views as beneficial. If products that contain WSTC bear any claims on the label or in labeling, such claims are the purview of the Office of Nutritional Products, Labeling, and Dietary Supplements (ONPLDS) in the Center for Food Safety and Applied Nutrition (CFSAN). The Office of Food Additive Safety neither consulted with ONPLDS on this labeling issue nor evaluated the information in your notice to determine whether it would support any claims made about WSTC on the label or in labeling.

Standards of Identity

In the notice, Provexis states its intention to use WSTC 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 Provexis, as well as other information available to FDA, the agency has no questions at this time regarding Provexis' conclusion that WSTC 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 WSTC. As always, it is the continuing responsibility of Provexis 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 000210, 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).

Sincerely,
Laura M. Tarantino, Ph.D.
Director
Office of Food Additive Safety
Center for Food Safety and Applied Nutrition



 


(1)The Secretary of the Department of Health and Human Services.

(2)We note that section 721(b)(4) of the FFDCA provides that a color additive shall be deemed to be safe and suitable for the purpose of listing under section 721(b) of the FFDCA while there is in effect a published finding of the Secretary declaring that the substance is exempt from the definition of "food additive" because of its being generally recognized by qualified experts as safe for its intended use as provided in section 201(s) of the FFDCA. Importantly, FDA's response to GRN 000210 does not constitute a "finding of the Secretary" within the meaning of section 721(b)(4) of the FFDCA.