The number of companies pursuing self-recognized GRAS status for their ingredients is on the rise, new data shows.
Since the GRAS notification program was launched in 1997, the Food and Drug Agency (FDA) has received 356 GRAS notifications for a variety of substances, including carbohydrates, lipids, proteins and chemicals.
Of those, 45 were filed in the 10-month period of 2010, ending November 1, or 12.6 percent of the total. (A complete listing is viewable here).
Of course these figures do not take into account companies that self-determine GRAS status, but do not submit their notice to the federal agency – and that number is assuredly exponentially higher, said John Endres, chief scientific officer of AIBMR Life Sciences of Puyallup, Wash.
"It's actually a problem," said Endres, whose chief role is helping companies navigate the GRAS-affirmation process. "The FDA doesn't know how many self-affirmed ingredients are out there. When they look at a product with an unusual ingredient, they have to go to the company to see if they did self-affirmed GRAS or not. I suspect that in the future, the FDA will create some kind of registration process, whereby companies need to at least register their self-affirmation status."
The principle of 'generally recognized as safe' for food additives has been in existence since 1958. The rules of the game changed significantly in 1997, however, when the FDA launched the self-affirmation GRAS process, and the voluntary notification process.
Under the new procedure, a company can have a safety dossier prepared and have an independent panel of experts evaluate whether a given food additive is safe. But the company is not required to publish that information and submit it to the FDA to review. It is believed that only a small percentage of the total self-affirmed GRAS determinations are ever submitted to the FDA.
"One way of looking at it is, if a self-affirmed GRAS determination was properly performed, and the expert panel, qualified to evaluate the safety of the food ingredient, unanimously concluded its safety for its intended use, a company should have confidence that the FDA is most likely to agree with that determination," Endres said. "Going that extra step really can add that extra level of validity to the ingredient in the eyes of the industry. But not all companies in the industry are well-informed, and their data – or even how they present the determination – may not pass the FDA's muster."
How the GRAS review process works
If the FDA receives a GRAS submission, it has 180 days to complete its evaluation process, although it has often been taking closer to 220 days, Endres said. Upon review, the agency either contacts the company with additional questions, allowing them to withdraw their application, or issues the much sought after 'no objection letter,' which effectively allows the GRAS designation to stand.
"When the FDA has questions, they will kindly advise the company that they are about to receive a 'bad day letter,' giving the company the option to withdraw their submission," Endres said. "A company will then often pull the notification, maybe try to fix the problem, and can come back and try it again. If they don't pull it and the FDA officially issues a statement questioning their submission – that's a ding no company wants to have, because it's all published on the FDA's Web site."
Of the 19 GRAS notices that have thus far gone through the FDA review process in 2010, four have been withdrawn.
Who's pursuing GRAS?
As far as AIBMR Life Sciences is concerned, the consultancy has seen a definite increase in the number of companies contracting its GRAS-preparation services.
"I would say industry interest in GRAS has been steadily rising for the past three years, but even in the latter half of this year there has been another big increase," Endres said. "What I suspect is happening is that many of the really big food companies - the Coca-Colas, Nestles, Krafts and Cargills – are more interested in functional ingredients for food and beverage products. They are being contacted by ingredient manufacturers, but generally won't include them in their products until the manufacturer has a 'no-objection letter' from the FDA in hand."
"There are many ingredient companies who have had self-determined GRAS status for some years and are now preparing to submit their notifications for FDA review," he said.
For its part, the FDA is swamped, said Endres, who just returned from a meeting with agency officials in early November. “They are really overwhelmingly busy."
Recent GRAS notices
Here are just a few of the companies that have, in recent months, issued press releases announcing self-affirmed GRAS status for their food ingredients. While a few have submitted their dossiers to the FDA, most have not yet done so:
Ajinomoto AminoScience announced it has confirmed GRAS status of its AjiGRAS-Leucine ingredient. Amino acids, including leucine, have long been available to dietary and nutritional supplement manufacturers, but due to regulatory constraints, manufacturers have been limited to using amino acids only to enhance the quality of protein in foods. This FDA-acknowledged GRAS status marks the first time leucine can be added as an ingredient into conventional foods and beverages to support and enhance normal metabolic function.
The AlphaWave L-Theanine ingredient by Ethical Naturals has self-affirmed GRAS. The GRAS applies to beverages, hard candy, chewing gum and food bars. AlphaWave is manufactured in a proprietary process in which the L-Theanine is derived from another naturally occurring amino acid; it is equal to the most highly purified material available. Published data supports the following structure/function claims for AlphaWave: helps relax without drowsiness; promotes mental clarity and focus; and reduces nervous tension.
BioVin grape extract
California company Cyvex Nutrition has achieved self-affirmed GRAS for its BioVin Full Spectrum Grape Extract and BioVin 20 Grape Skin Extract. BioVin is a full spectrum grape extract manufactured from whole red wine grapes from the Rhone Valley in France. By using the grape in its entirety – including stems, seeds and skin – all the beneficial phytochemicals can be extracted including anthocyanidins, proanthocyanidins, trans-resveratrol and polyphenols. BioVin 20 contains no less than 20 percent polyphenols.
Black pepper extract
BioPerine, a patented black-pepper extract by Sabinsa Corp, has earned self-affirmed GRAS. The extract contains 98 percent piperine, which is said to bind to so-called Transient Receptor Potential Vanilloid receptors in the nervous system. This triggers metabolic processes favoring the flow of nutrients in the body. Sabinsa said BioPerinehas been studied for enhanced nutritional gut absorption in herbal extracts, water-soluble vitamins, fat-soluble vitamins, antioxidants, amino acids and minerals. According to the GRAS monograph, maximum use levels of BioPerine are 15ppm (15mg/kg) in specific foods, with the 90th percentile estimated intake of 13.32mg of BioPerine per person per day, as the safe level for food use and intake.
The patent-pending ingredient Clear Valley by Cargill has achieved self-affirmed GRAS. The new omega-3 is a canola/flaxseed blend containing up to 30 percent ALA, and it will be available in most food applications. Its taste neutrality, nine-month shelf life and formulation ease make it particularly well-suited for cookies, cereal bars, crackers, snacks and spreads.
geniVida, pure and soy-free genistein from DSM Nutritional Products, has earned self-affirmed GRAS. Research shows that geniVida genistein reduces menopausal symptoms, including the number and duration of hot flashes in menopausal and post-menopausal women. Genistein exerts estrogen-like regulation of bone metabolism and assists in the bone remodeling process; it is also associated with bone and prostate health benefits for mature men.
Montana-basedTSI Health Scienceshas become the first US supplier to offer GRAS-certified glucosamine derived from shellfish. Its PUREFLEX Glucosamine Salts have obtained self-affirmed GRAS status for use in conventional foods and beverages. The independent panel evaluated three ingredients: PUREFLEX Glucosamine Hydrochloride, PUREFLEX Glucosamine Sulfate Sodium and PUREFLEX Glucosamine Sulfate Potassium. All are made in a cGMP-certified facility.
Lutein and lutein esters
The Lutemax line of free lutein and lutein esters by OmniActive Health Technologies have achieved self-determined GRAS status. The ingredients can be added to products without affecting taste or aroma. They are manufactured in an integrated supply chain using marigolds planted by a dedicated group of farmers in India free if feed-grade additives, preservatives and pesticides. The company also secured GRAS for its newest ingredient offering, Lutemax 2020, for use in a range of food and beverage applications.
ORAC-15M grape extract
California ingredient company Ethical Naturals has completed self-affirmed GRAS for its ORAC-15M antioxidant ingredient. Life Science Research Organization convened the independent panel, the results of which may be submitted to the FDA in the future. The natural grape extract is standardized to contain 80 percent polyphenols and 15,000 ORAC units/gram. ORAC-15M is already used in supplements and by a number of beverage brands that use supplement labeling. It is made in a powder form, which is highly soluble with a low flavor/color profile.
Sodium lauryl sulfate
Tabletting agent Texapon K 12 P PH, a pharmaceutical grade sodium lauryl sulfate (SLS), has earned self-affirmed GRAS status by Cognis. Texapon can now be used in dietary supplements and foods at the quantity of 30mg twice a day. It is ideal for hard tablets or powders that require a surfactant for wetting or processing as it helps guarantee consistently high quality. Its small and consistent particle size is particularly efficient in tabletting processes.
A division of NOW Health Group, HealthCo, announced that it has achieved self-affirmed GRAS status for its ingredient Stevia FSE. The ingredient is sold in bulk powder, private label consumer sizes and food-service bulk packets. Stevia FSE is enzymatically treated to remove the bitter aftertaste; it uses the whole stevia leaf, not just an isolated fraction, and no masking agents are used because none are needed. The ingredient is also NOP-certified organic and kosher.
Minnesota company KIP Biotech has achieved self-affirmed GRAS for its water-soluble phytosterol. The company's technology allows the phytosterols to be added to a wide variety of products, including carbonated and noncarbondated beverages, energy drinks, coffee and soups – without impacting product taste, clarity or texture.
A technology to convert functional oils into water-soluble ingredients – including omega-3, resveratrol, co-Q10, vitamin D and vitamin E – has successfully achieved self-determined status. SoluBlend Technologies' exclusive water-soluble technology allows a wide range of popular fat-based nutraceuticals to be blended into a variety of functional beverages and foods for the first time in a tasteless, odorless lipid.