The U.S. Department of Health and Human Services (HHS) announced on March 10 that HHS Secretary Robert F. Kennedy, Jr. has directed the Food and Drug Administration (FDA) “to take steps to explore potential rulemaking to revise” the Substances Generally Recognized as Safe final rule (GRAS Final Rule) (81 Fed. Reg. 54960 (Aug. 17, 2016)) to make GRAS notifications mandatory.

The announcement also indicates that HHS “is committed to working with Congress to explore ways legislation can completely close the GRAS loophole.” While it is certain that industry may resist any effort to create a mandatory GRAS pathway through regulation, it is questionable that FDA can change the current voluntary GRAS notification process into a mandatory one absent Congress amending the Federal Food, Drug, and Cosmetics Act (FDCA).

A mandatory program may have economic consequences that should be considered. Moreover, industry may argue that FDA already has the tools at its disposal to safeguard the food supply through challenging the self-determined GRAS status of any ingredient that is currently being marketed without prior authorization or review by the agency. Of course, given its limited resources, this is more easily said than done.

Analysis

In 2016, the FDA published the GRAS Final Rule, which became effective Oct. 17, 2016, even though the process has been available and used since 1997. As discussed in the preamble of the GRAS Final Rule, over 600 GRAS notifications (now called “GRAS notices”) were reviewed by the FDA between 1997 and 2016. Thus, during this time, the FDA was quite successful in encouraging companies to utilize a similar voluntary process to ensure proper oversight of food ingredient safety. While not explicitly stated, it is likely the FDA understood that absent a change in the law, it did not have the regulatory authority to create an alternative, mandatory review path for GRAS ingredients. 

However, the food substances about which the secretary and Congress have expressed concerns have either gone through the food additive process, the GRAS affirmation process (which was in effect before FDA issued the proposed GRAS rule), or the GRAS notification process and, at that time, were generally found not to raise a safety concern by FDA. Hence, the “loophole” referenced in the announcement and which some members of Congress have railed against over the years is a bit of a misnomer, as it is those substances that FDA has reviewed that have recently raised safety concerns. 

Regardless, it appears that the secretary and some in Congress are open to amending the FDCA to address the so-called GRAS loophole. Specifically, Congress could create a more streamlined means to assess the safety of a particular substance through a statutorily required GRAS notification process for direct food additives that would mirror the statutory requirements for food contact substances that was passed by Congress in 1997.

This option is intriguing from both an FDA and congressional perspective. This is because FDA already has the regulatory framework in place to implement any amendment to the FDCA that would require the filing of GRAS notices for ingredients.

Indeed, the present regulatory framework establishing whether a substance is GRAS is set forth under 21 CFR §170.30. In brief, this section states that GRAS status for a particular use of a substance must be based on technical evidence of safety and a basis to conclude that this technical evidence of safety is common knowledge.

“Common knowledge” is defined by two things: “general availability” to the public of the data and information relied on to establish safety, and a consensus among qualified experts — with experience evaluating the safety of substances directly or indirectly added to food — about the safety of the substance at issue for its intended use.

Publication in a peer-reviewed scientific journal is the common mechanism to establish that scientific information is generally available. Examples of “qualified experts” include panels specifically chosen to review the substance in question. Note, however, the FDA has stated that in most cases, a well-supported GRAS conclusion does not necessarily require an analysis by a GRAS panel.

The evaluation of whether use of a substance in food is safe, and whether safety is generally recognized, is a case-by-case evaluation. The FDA has defined “safe” (21 CFR 170.3(i) and 21 CFR 570.3(i)) as “a reasonable certainty in the minds of competent scientists that the substance is not harmful under the conditions of its intended use.” With that said, the use of a well-respected panel of independent toxicologists certainly strengthens any GRAS determination made by the company. 

Impact on Functional Foods and Drinks

Creating a mandatory review of all ingredients, however, may very well have a devastating effect on the rise of functional foods, which are conventional foods that are intended to promote health and wellness. Indeed, one only needed to walk the floor at Natural Products Expo West in early March to have determined that the lines between conventional foods and dietary supplements are starting to collapse if they have not already. Beverages are being marketed with functional ingredients that, while appropriate for use in dietary supplements, have never been vetted for use in conventional foods. However, it is likely that these ingredients are not the ones that have caught the eye of the secretary and Congress.

This large and growing market would break down under a new mandatory regime as ingredient companies, absent a grandfather clause, would be required to pull these ingredients from the conventional food marketplace. Companies that have built their entire future on these functional products will crater, and investment will dry up as those products that contain ingredients that help maintain health are once again relegated to the dietary supplement category.

Thus, any proposed legislation must take this aspect into account and ensure these products may continue to be provided to a public that demands them. Indeed, if the real purpose of the secretary and Congress in closing the GRAS loophole is to get unsafe ingredients out of the marketplace, they should have the FDA focus on those already-reviewed ingredients whose safety has come into question for quite some time, rather than closing the loophole.

Finally, as it sits today, the FDA is not without authority to act against substances that it believes are not GRAS. The FDA could use its soft power by alerting companies through warning letters, public alerts, and similar means that they believe an ingredient is not GRAS. If companies fail to heed the FDA’s recommendation, the agency has the power to institute a seizure action of the food containing the alleged ingredient or sue the company. While enforcement activity can use up scarce resources, targeted enforcement actions to discourage exploitation of the loophole could be a worthwhile expenditure.

Action You Could Take Now

During this time, it may be useful to ensure that your GRAS conclusions can withstand potential agency scrutiny. We would be happy to explain the GRAS requirements in more detail or review your GRAS dossiers to help ensure that you will be ready to move forward, no matter what change is made to the GRAS framework.

Regardless, the secretary’s call to action should be heeded by companies, especially those marketing functional ingredients, to ensure that their ingredients meet the FDA-GRAS standards (i.e., they satisfy the requirements and recommendations set forth in the GRAS Final Rule).