GRAS Guidance

Originally Published NO March 2010

The functional-ingredients market is experiencing explosive growth worldwide. Consumer demand for health-promoting dietary supplements and functional foods is at an all-time high-inspiring traditional food manufacturers to invest heavily in the research and development of the next hottest functional food.

All food ingredients or additives in the United States must be considered generally recognized as safe (GRAS). As functional ingredients are increasingly used in foods, more companies are seeking GRAS status for their ingredients.

GRAS status implies that experts qualified by training and experience to evaluate the safety of food ingredients would concur that consumption of the ingredient by a population-including the elderly, pregnant women, children, and the diseased or immune-compromised-is safe.

The process of getting an ingredient GRAS affirmed can be challenging-and ultimately more rigorous than submitting premarket notification for a new dietary ingredient (NDI), which is required for dietary supplement ingredients not sold prior to 1994.

The preparation of a quality NDI notification is an arduous process, and fewer than 20% of applicants receive a prized "no objection" letter from FDA. However, the burden of proof for an NDI is that a product is "reasonably expected to be safe" when used according to the conditions of use stated on the label.

While this is certainly a high burden of safety, it is ultimately lower than the "general recognition" of safety required for GRAS ingredients. Thus, if a product or ingredient has achieved GRAS status, it's assumed to have met this burden with little doubt.

Evidence of Safety

In 1997, FDA issued a proposed rule changing its GRAS petition/affirmation procedure to a voluntary notification process. By that time, the number of petitions had become overwhelming, and the rate at which FDA processed these petitions had become very slow. Under this new proposed rule, which has yet to be finalized, an individual or company may or may not choose to notify FDA that it has "self-affirmed" a particular substance as GRAS. In either case, the expected evidence of safety must be met.

As stated in the proposed GRAS rule, safety is defined as "reasonable certainty that the substance is not harmful under the intended conditions of use." Scientific information supporting the safety of a substance may include analytical, in vitro, animal, and human studies. Whether or not a company chooses to notify FDA of the self-affirmation, industry experts advise that a safety assessment should be published in a peer-reviewed scientific journal. Prior to FDA notification, the article should probably be in circulation for at least six months.

GRAS rules acknowledge that various approaches may be taken to make a GRAS determination. Currently, most companies pursue GRAS determination by convening a panel of experts who are qualified by training and experience to evaluate the safety of food ingredients. This panel conducts a review of the GRAS dossier for a particular ingredient. The expert panel includes food-safety scientists and toxicologists with experience and expertise in the food industry. The expert panel is often the make-or-break component that determines whether or not FDA will take issue with a GRAS determination.

Experienced Help

Given the complexities and potential pitfalls of the GRAS self-affirmation process, companies seeking to self-affirm an ingredient as GRAS need to rely on experienced, independent, third-party organizations for guidance-and for very good reasons.

Choosing a firm that has practical experience from the preparation of numerous GRAS self-affirmation evaluations, and that has a team of highly qualified experts in the fields of toxicology, medicine, and food safety, along with the requisite knowledge and background in natural-products research and FDA regulations, is especially critical in ensuring your ingredient meets the high level of safety associated with GRAS status.

Only experts qualified by training and experience can accurately interpret results of toxicology studies and tease out the nuances from the results of the data to judge whether a product or ingredient has the proper foundational basis to achieve a certainty of safety at a particular level of consumption. FDA expects no less. This route provides significant protection for your company from liability and litigation.

First and foremost, companies need to understand that the marketer or manufacturer of a novel food ingredient is ultimately responsible for ensuring its safety. From a product liability and financial risk perspective, the dangers inherent in putting a substance into foods or beverages on the basis of a weak and insufficient GRAS determination are obvious. When it comes to GRAS, being confident in the determination is critical.

Furthermore, allowing an independent panel of experts qualified by training and expertise in the field to make the determination lends your ingredient a high level of credibility in the marketplace. Food companies considering the use of your ingredient in their products will have a much greater degree of confidence about an affirmation of safety that has been established through a highly qualified panel of experts. A sound GRAS determination increases your company's prospects for financial gain, reduces potential risk and future liability, and enhances the likelihood of producing a successful ingredient.

Irfan Qureshi, ND, is vice president for technical and regulatory affairs for AIBMR Life Sciences (Puyallup, WA). John R. Endres, ND, is chief scientific officer. The company guides global nutraceutical firms through the process of GRAS self-affirmation and FDA notification, and also provides a complete range of natural-products consulting services.