The Self-Affirmed GRAS Pathway

At present, companies can determine that a substance is GRAS without notifying FDA if there is consensus among experts qualified by scientific training (Editor's note: on August 10, 2026, FDA proposed a rule which, if finalized, would make notification of GRAS determination mandatory in most cases). This pathway has served the industry well in providing flexibility and supporting innovation by providing companies with an incentive to invest in research and development of new substances. This pathway allows the companies to go to market quickly and have an opportunity to recover their investment before their competitors can enter the market; therefore, it does encourage competition.

The self-affirmed GRAS pathway is based upon scientific procedures and requires the same quantity and quality of scientific evidence as is mandated to obtain approval of a food additive. However, it offers more flexibility, is faster than the food additive process, and allows companies to protect their intellectual property (IP).

On March 10, 2025, Department of Health and Human Services (HHS) Secretary Robert F. Kennedy Jr. instructed FDA to explore rulemaking to eliminate the self-affirmed GRAS pathway (resulting in the August 10 proposed rule). This action may have the unintended consequence of discouraging companies from investing in research and development (R&D) of new substances because of the time and cost required to follow a food additive petition route. 

A good example of the use of the self-affirmed GRAS pathway is from 2001, when beverage companies were competing to be the first to introduce stevia, a natural nonnutritive sweetener, to the market. Companies used peer-reviewed, published, scientific papers on the safety of stevia in their self-affirmed GRAS determinations, which was the fastest route to go to market ahead of competitors.

Criticisms of the Self-GRAS Pathway

There are several criticisms of the self-affirmed GRAS pathway. Critics argue that it creates the impression of a lack of transparency and can lead to a potential conflict of interest and inconsistent practices. Some also say that it can raise consumer concerns regarding the safety of the substances evaluated through this pathway because the data is not available publicly.

Companies can independently reach the conclusion that a substance is GRAS without notifying FDA if there is consensus among qualified experts with scientific training. This sometimes creates the impression of a lack of transparency to the consumer and the FDA, but is allowed in law. Safety determinations and supporting data may never become public and are the IP of the company. If a reason arises for FDA to question the safety conclusion, then the agency can request confidential access to the data.

The Pew Charitable Trusts' Food Additives Project (2010–2013)³ conducted an influential, multi‑year investigation into the lack of transparency and oversight in FDA's GRAS process. Their findings are widely cited in scientific, regulatory, and policy discussions because they document systemic weaknesses in how food chemicals enter the U.S. food supply.

Another criticism of the self-affirmed GRAS pathway is that manufacturers may choose to rely only on hand-picked experts, some of whom are paid and may be influenced to agree with the manufacturer's conclusion, which can raise questions about the independence of a GRAS panel's conclusion.

Since FDA notification is voluntary, FDA may not be made aware of every substance entering the market through a self-affirmed GRAS determination. This is allowed by law and protects company IP. However, the science used to determine safety must already be published in the public domain.

Other concerns deal with the quality of dossiers, expert review, and panel procedures, which can vary across companies. Organizations are at liberty to choose which experts serve on their GRAS panels. These decisions are made independently by each company, and the quality of the dossiers depends on individual company practices. One way to address potential discrepancies in this area is for industry to establish a code on how companies should conduct these assessments, which would help standardize the quality of dossiers.

Even in instances when the science is robust, the confidential nature of self-affirmed GRAS determinations can undermine trust in the process from a consumer perspective. Safety data from the determinations are not required to be made publicly available, unless the company chooses to notify FDA.

Color Additives and GRAS Misconceptions

In separate public statements, Secretary Kennedy has called for eliminating the self-affirmed GRAS pathway and has also expressed concerns about synthetic food dyes such as Red No. 40, Yellow No. 5, and Yellow No. 6. However, certified color additives are not evaluated through the GRAS pathway. Instead, they are regulated under FDA's color additive petition process in 21 CFR § 71 and, if approved, are listed in 21 CFR § 73 when exempt from certification, or in 21 CFR § 74 when subject to certification.

The current concern is how color additives are regulated and perceived. Certain synthetic certified colors, including Red No. 40, Yellow No. 5, Yellow No. 6, Blue No. 1, Blue No. 2, Green No. 3, and Red No. 3, have been criticized because of public concerns about possible behavioral effects in children associated with consumption of food items containing these dyes. 

Manufacturers are increasingly interested in replacing some synthetic colors with natural color additives exempt from certification, such as Galdieria extract blue (listed in 21 CFR § 73.167) and butterfly pea flower extract (listed in 21 CFR 7 § 3.69). These recently approved natural color additives are authorized for specified uses at levels consistent with good manufacturing practices (GMP), but in many cases, they have a shorter history of commercial use than the long-established certified colors. As a result, simply replacing a certified synthetic color with a newer natural color additive does not automatically increase consumer confidence, and any such transition should be evaluated carefully based on the specific safety data available for each substance.

How Companies Can Prepare for Challenges to GRAS Self-Determination

In this current environment, what actions can companies take while preparing for potential legal and regulatory challenges to the self-GRAS affirmed pathway?

First, ensure that the scientific data supporting each self-affirmed GRAS substance is comprehensive, up to date, and available in scientific peer-reviewed journals. It is also important to ensure that the data is robust enough to withstand legal and regulatory challenges, as well as the scrutiny of other independent scientists and scientific organizations. 

Be prepared to conduct additional safety studies to address emerging safety concerns or evolving public health debates. For example, the replacement of synthetic dyes with natural color alternatives may require additional safety evaluations. Because many of these natural colorants have not been used as extensively or for as long as their synthetic counterparts, robust safety data will be needed to support their use.

Companies should also monitor and prepare for regulatory and legal changes. They should regularly review internal processes to ensure compliance with existing regulations, and proactively prepare for potential future changes to regulations to avoid disruptions and maintain customer confidence in their products.

An Example of GRAS Regulatory Change by FDA

In 2015, FDA took the significant step of determining that partially hydrogenated oils (PHOs), then the major source of artificial trans fat in the food supply, were no longer GRAS. The date after which manufacturers could not add PHOs to foods, with few exceptions, was June 18, 2018. However, to allow for an orderly transition in the marketplace, FDA allowed more time for products to work their way through distribution by extending the final compliance date to January 1, 2021. 

In the past, most of the trans fat in foods came from PHOs, formed through a manufacturing process that converts vegetable oil into a solid fat at room temperature. Trans fat also occurs naturally in food products from ruminant animals (e.g., milk, butter, cheese, meat products). FDA's actions have not affected these natural sources of trans fat.

Eating trans fats raises the level of low-density lipoprotein (LDL) cholesterol in the blood. An elevated LDL cholesterol level increases the risk of developing heart disease. The removal of PHOs from processed foods is estimated to prevent thousands of heart attacks and deaths each year. Due to the health concerns associated with trans fat, FDA now requires it to be declared on the Nutrition Facts label.

The self-affirmed GRAS pathway also comes with cost implications. Assembling a good panel of experts can cost more than $500,000. These costs can eventually be transferred to consumers.

Opportunities for Improving GRAS Self-Determination

To promote a diverse and innovative food industry, there is a need to encourage companies to continue investing in R&D and to bring new substances to market that meet customer needs. The self-affirmed GRAS determination offers companies a pathway that is well-tested and uses sufficient scientific rigor to bring new and innovative products to market, ahead of competitors. 

However, there are opportunities for improvement in self-affirmed GRAS assessments. One way is to add discipline and consistency in how self-affirmed GRAS assessments are conducted across industry. Establishing a code of practice—i.e., a standardized way to conduct self-affirmed GRAS determinations—could realize significant improvements over the current system. FDA still maintains the right to question the data if there is a safety issue, and there still is sufficient regulatory oversight to guarantee safety. 

Ultimately, this discussion is about food safety and protecting public health. Food safety expert Larry Keener has defined food safety as, "The chemical, physical, or biological status of a food or food ingredient that will allow its consumption without incurring an excessive risk of injury, morbidity, or mortality." 

The burden of proof for safety remains on industry. Those seeking GRAS affirmation for their products or ingredients must provide proof that the risk of consumption is less than or equivalent to similar substances already on the market. They are also required to prove that consumption of their products will not cause harm when used in a manner consistent with the guidelines established in the GRAS petition. 

The future of the self-affirmed GRAS pathway will ultimately depend on balancing transparency, scientific rigor, and regulatory oversight without discouraging innovation. Companies that invest in robust safety data, standardized evaluation practices, and proactive regulatory preparedness will be best positioned to maintain consumer confidence and adapt to an evolving food safety landscape.

References:

1.  U.S. Food and Drug Administration (FDA). "Eligibility for Classification as Generally Recognized as Safe (GRAS)." 21 CFR § 170.30. Code of Federal Regulations. https://www.ecfr.gov/current/title-21/chapter-I/subchapter-B/part-170/subpart-B/section-170.30.
2. FDA. "Guidance for Industry: Frequently Asked Questions About GRAS for Substances Intended for Use in Human or Animal Food." October 2016. https://www.fda.gov/regulatory-information/search-fda-guidance-documents/guidance-industry-frequently-asked-questions-about-gras-substances-intended-use-human-or-animal-food.
3. The Pew Charitable Trusts. "Fixing the Oversight of Chemicals Added to Our Food: Findings and Recommendations of Pew's Assessment of the U.S. Food Additives Program." November 2013. https://www.pew.org/-/media/legacy/uploadedfiles/phg/content_level_pages/reports/foodadditivescapstonereportpdf.pdf.