Agency Response Letter GRAS Notice No. GRN 000447
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CFSAN/Office of Food Additive Safety
July 3, 2013
Chief Technology Officer
Solanic B.V., an AVEBE Group Company
P.O. Box 15
9640 AA Veendam
Re: GRAS Notice No. GRN 000447
Dear Mr. Giuseppin:
This letter corrects our letter in response to GRAS Notice No. GRN 000447 dated May 24, 2013. The purpose of this revised letter is to correct the units used to express the intended dietary exposure values for potato protein isolates.
The Food and Drug Administration (FDA) is responding to the notice, dated August 10, 2012, 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 October 18, 2012, filed it on November 5, 2012, and designated it as GRAS Notice No. GRN 000447.
The subjects of the notice are fractionated potato protein isolate (>35 kilodalton (kDa)) and fractionated potato protein isolate (<35 kDa) (potato protein isolates). The notice informs FDA of the view of Solanic B.V., an AVEBE Group Company (Solanic) that potato protein isolates are GRAS, through scientific procedures, for various technical effects in comminuted meat products and comminuted poultry products at levels up to 3%; for various technical effects in alcoholic beverages, baked foods and baking mixes, cheeses, dairy product analogs, egg products (i.e., meringues), fats and oils, frozen dairy desserts and mixes, fruit and water ices, gelatins, puddings, and fillings, milk products, nuts and nut products, and plant protein products at levels ranging from 0.01 to 15%; for use as sources of protein in sports drinks and protein sports bars at levels ranging from 1 to 10% and during fermentation.
In its notice, Solanic includes a report from a panel of individuals (Solanic’s GRAS panel) that evaluated the data and information that are the basis for Solanic’s GRAS determination. Solanic considers the members of its GRAS panel to be qualified by scientific training and experience to evaluate the safety of substances added to food. Solanic’s GRAS panel evaluated the identity and composition, method of manufacture and specifications, intended dietary exposure, and published data and information supporting the safety of potato protein isolates. Based on this review, Solanic’s GRAS panel concluded that potato protein isolates produced in accordance with current good manufacturing practices (cGMP) and meeting established specifications are GRAS under the conditions of their intended use.
Solanic describes the identity and composition of potato protein isolates. Solanic notes that the structure and composition of potato protein isolates are comparable to proteins present in intact potatoes. Potato protein isolates comprise >90% of a homogenous, off-white, free-flowing powder that also contains <10% moisture. The powder has no objectionable flavor or odor.
Solanic describes the manufacturing process for potato protein isolates beginning with raw, commercially available potato cultivars. The potatoes are washed and rasped to yield a potato juice that is treated with sodium bisulfite to prevent browning. Solids, fibers, and undesirable particulates are removed from the potato juice by mechanical techniques. Potato protein isolates are fractionated from the juice by chromatography and eluted using citric acid and formic acid. The fractions are then regenerated, concentrated, thermally conditioned, and pH-adjusted. Excess triglycoalkaloids are removed using a polishing step and may be further removed by additional thermal processing and a secondary ion-exchange step conducted in accordance with 21 CFR §173.25. Potato protein isolates are then spray-dried, stored at >20% dry matter (DM), and treated with ultraviolet light to reduce microbial contamination. Solanic states that the source potatoes are quality-inspected and that potato protein isolates are manufactured in accordance with cGMP and Hazard Analysis Critical Control Point plans and using food grade raw materials.
Solanic provides food grade specifications for potato protein isolates including purity (>90% protein), solubility (5% solution, >80%), and ash (<100 grams per kilogram (g/kg) DM). Solanic provides limits for total glycoalkaloids (<312 milligrams per kg (mg/kg) protein), sulfites (<100 mg/kg), and heavy metals including lead (<0.1 mg/kg), mercury (<10 micrograms (μg) per kg), cadmium (<0.4 μg/kg), and arsenic (<50 μg/kg). Solanic also provides limits for microbial contaminants. Solanic provides analytical data for three non-consecutive lots of potato protein isolates to demonstrate the consistency of the manufacturing process and the established specifications. Solanic also demonstrates the stability of potato protein isolates.
Solanic combines data from the 2003-2004, 2005-2006, and 2007-2008 installments of the National Health and Nutrition Examination Survey to estimate the intended dietary exposure for potato protein isolates. Solanic estimates a daily dietary exposure for potato protein isolate (<35 kDa) of 0.038 g/kg body weight per day (g/kg bw/d) and 0.08 g/kg bw/d based on the mean and 90th percentile consumption of the intended foods, respectively. Solanic estimates a daily dietary exposure for potato protein isolate (>35 kDa) of 0.036 g/kg bw/d and 0.078 g/kg bw/d based on the mean and 90th percentile consumption of the intended foods, respectively.
Solanic states that potatoes and their constituents (including proteins) have a long history of consumption by humans. Given the similarities between potatoes and potato protein isolates, Solanic considers the nutritional and toxicological aspects of potatoes to be relevant to potato protein isolates, and thus exposure to glycoalkaloids and protease inhibitors (both substances naturally occur in potatoes) are key safety considerations for consumption of potato protein isolates. Solanic considers that published authoritative opinions and scientific studies support the safety of exposure to glycoalkaloids and protease inhibitors from the consumption of potato protein isolates.
Solanic discusses published animal studies supporting the safety of protease inhibitors. These studies show that the physiological effects of soybean trypsin inhibitors are similar to those of potato protease inhibitors. Solanic thus considers studies conducted for soybean trypsin inhibitors to be applicable to potato protease inhibitors. Solanic cites a published study conducted using pigs in which administration of soybean trypsin inhibitor at the highest dose tested (276 mg/kg bw/d) resulted in no adverse pancreatic effects. Solanic also cites published human studies in which no adverse gastrointestinal effects were observed following consumption of potato protease inhibitors.
Solanic discusses the results of published in vitro and in vivo studies supporting the safety of potato protein isolates. The results of reverse mutation assays conducted using bacterial cells show that potato protein isolates are not mutagenic. The authors of a 90-day study in which male and female Wistar Crl:(WI) BR rats (10/sex/group) were fed diets containing potato protein isolates observed no serious adverse effects or mortality at the highest dose tested (8.414 g/kg bw/d for males and 9.768 g/kg bw/d for females).
Solanic discusses published studies addressing the potential allergenicity of potato proteins. Solanic notes that the authors of these studies have observed cross-reactivity for various potato proteins in patients allergic to various foods (apple, pear, celery, carrot), pollen (birch, olive), or natural rubber. However, Solanic notes that the potato is not considered to be a major food allergen.(1) Furthermore, Solanic’s search of the publicly available literature shows that case reports of potato allergy are uncommon. Based on this information, Solanic concludes that the intended food uses of potato protein isolates will not present a greater allergic potential than that currently occurring from existing dietary uses of potatoes.
Standards of Identity
In the notice, Solanic states its intention to use potato protein isolates 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.
Labeling of Sulfite Content
Under 21 CFR 101.100(a)(4), which requires that any products containing sulfites at or above 10 parts per million declare the presence of sulfites on the label, potato protein isolates must declare the presence of sulfites on the label. If Solanic has any questions about the appropriate labeling of this food ingredient, Solanic should contact the staff in the Office of Nutrition, Labeling, and Dietary Supplements.
Use in Products under USDA Jurisdiction
During its evaluation of GRN 000447, FDA consulted with the Risk and Innovations Management Staff (RIMS) 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
Regarding suitability, FSIS has no objection to the use of potato protein isolates, either the >35 kDa or <35 kDa fraction, for use as a binder in comminuted meat products and comminuted poultry products where binders are permitted at levels up to 3%. If you would like FSIS to consider suitability for whole muscle meat products or whole muscle poultry products, egg products, or use of potato protein isolates at levels above 3%, FSIS advises that you will need to submit additional data to RIMS for review prior to implementation.
FSIS advises that the ingredient will need to be declared on the label of comminuted meat products and comminuted poultry products containing it as “potato protein isolates.” FSIS requested that FDA advise Solanic to direct any questions regarding product labeling to Ms. Rosalyn Murphy-Jenkins by telephone at (301) 504-0868 or via email at Rosalyn.firstname.lastname@example.org.
Any additional questions should be directed to Dr. William Shaw, RIMS, Office of Policy, Program, and Development, Food Safety and Inspection Service, via email at William.Shaw@fsis.usda.gov.
Section 301(ll) of the Federal Food, Drug, and Cosmetic Act (FD&C Act)
The Food and Drug Administration Amendments Act of 2007, which was signed into law on September 27, 2007, amends the FD&C Act to, among other things, add section 301(ll). Section 301(ll) of the FD&C Act prohibits the introduction or delivery for introduction into interstate commerce of any food that contains a drug approved under section 505 of the FD&C Act, 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 Solanic’s notice that potato protein isolates are GRAS for the intended uses, FDA did not consider whether section 301(ll) or any of its exemptions apply to foods containing potato protein isolates. Accordingly, this response should not be construed to be a statement that foods that contain potato protein isolates, if introduced or delivered for introduction into interstate commerce, would not violate section 301(ll).
Based on the information provided by Solanic, as well as other information available to FDA, the agency has no questions at this time regarding Solanic’s conclusion that potato protein isolates 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 potato protein isolates. As always, it is the continuing responsibility of Solanic 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 000447, 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 at www.fda.gov/grasnoticeinventory.
Dennis M. Keefe, Ph.D.
Office of Food Additive Safety
Center for Food Safety and Applied Nutrition
cc: William K. Shaw Jr., Ph.D.
Stop Code 3782, Patriots Plaza III, Cubicle 8-163A
1400 Independence Ave. SW
Washington, DC 20250-3700
(1)The Food Allergen Labeling and Consumer Protection Act of 2004 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.