A federal court has upheld the legality of the US Food and Drug Administration's (FDA) approach to regulating substances that are Generally Recognized as Safe (GRAS).1 In a September 30, 2021 opinion, Judge Broderick of the Southern District of New York (SDNY) sent a strong message confirming that the GRAS regulatory framework is a lawful implementation of Federal Food, Drug, and Cosmetic Act (FD&C Act). Importantly, the ruling affirms that substances that are self-determined to be GRAS will not only continue to be exempt from premarket review by FDA, but also that the common list of complaints raised by the NGO community about the GRAS regulatory framework lack merit under the law.
Steptoe & Johnson LLP attorney Joe Dages served as counsel to amici curiae, the Safe Food Ingredient Council (SFIC), and was a principal author of their amicus brief, which was cited favorably multiple times in the opinion from Judge Broderick.
What are GRAS substances?
Congress amended Section 201(s) of the FD&C Act in 1958 to define a "food additive" as:
any substance the intended use of which results or may reasonably be expected to result, directly or indirectly, in its becoming a component or otherwise affecting the characteristics of any food…if such substance is not generally recognized, among experts qualified by scientific training and experience to evaluate its safety, as having been adequately shown through scientific procedures (or, in the case of a substance used in food prior to January 1, 1958, through either scientific procedures or experience based on common use in food) to be safe under the conditions of its intended use.2
At the same time, Congress also amended Section 409 of the FD&C Act to provide that substances qualifying as food additives must undergo premarket review. In so doing, Congress created a legal framework that exempted substances that are GRAS from premarket review. For over sixty years, FDA has interpreted the FD&C Act consistently—substances that are GRAS under their intended conditions of use are exempt from the premarket review processes that apply to food additives.
Why was a case about GRAS substances before a federal court?
Although FDA has always interpreted the FD&C Act to exempt GRAS substances from the need for premarket review, FDA has taken different approaches over the years for dealing with GRAS substances. Shortly after the 1958 amendment to the FD&C Act, FDA, on its own initiative, incorporated into its regulations a list of substances considered to be GRAS, but the agency acknowledged that this list was not comprehensive because it would be impracticable to list all substances that are GRAS for their intended use. Because many substances considered to be GRAS by the food industry were not included on the list, throughout the 1960’s many manufacturers requested FDA's opinion on whether their GRAS conclusions were justified, and received "opinion letters" from the agency. Then, in 1969, due to new information on some substances, President Nixon ordered a re-evaluation of GRAS substances and in 1972, the GRAS affirmation process began, which resulted in the promulgation of the GRAS affirmation regulations at 21 C.F.R. Part 184. A GRAS affirmation for a substance could be performed on FDA's own initiative, or it could be performed pursuant to a voluntary GRAS affirmation petition filed by an individual.
This affirmation process was resource intensive, however, because it involved rulemaking with the attendant notice and comment requirements. Beginning in 1997, therefore, FDA issued a proposed rule to replace the GRAS affirmation petition process with a voluntary GRAS notification (GRASN) program.3 Under the GRASN program, companies can voluntarily inform FDA of their conclusion that a substance is GRAS for its intended use. FDA then reviews the filing and, assuming it does not disagree with the findings, issue a so-called "no questions" letter. The GRASN program continued under the auspices of the proposed rule for 19 years, from 1997-2016, during which time FDA received hundreds of GRASNs, many of which appear today on the agency’s website.4
So, what’s the problem? The fact that GRAS substances are exempt from premarket review has drawn its fair share of criticism over the years. That criticism picked up volume following a 2010 report from the Government Accountability Office (GAO), concluding that FDA should, among other things: (1) strengthen its oversight over GRAS substances by finalizing the 1997 proposed rule; (2) minimize conflicts of interest in GRAS assessments performed by third parties; and (3) require any company that conducts a GRAS determination to provide FDA with basic information about this determination, such as the substance's identity and intended uses.5
This report drew the attention of FDA, industry, and the NGO community. Led initially by the PEW Charitable Trusts, and then later the Environmental Defense Fund, among others, a group of NGOs argued that allowing companies to make GRAS determinations "in secret" is dangerous because it means FDA cannot and does not know what substances are added to food. As a result, the NGOs argued that FDA could not fulfill its statutory obligations under the FD&C Act – such as assessing the true cumulative exposure to substances in the diet.
These criticisms, in turn, led to a 2014 lawsuit from the NGOs that resulted in a consent decree wherein FDA agreed to finalize its 1997 proposed rule by 2016.6 FDA complied, and published a final rule in 2016 that retained the voluntary GRASN program and confirmed FDA's long-standing interpretation that GRAS substances are exempt from premarket review under the FD&C Act.7
A group of NGOs then proceeded to sue FDA and the Department of Health and Human Services (HHS) once again in 2017, this time arguing that FDA’s 2016 final rule was unlawful.8 Four years later, Judge Broderick has now issued his opinion, ruling on competing motions for summary judgment filed by both the NGOs and the government.
What issues were before the court?
The NGOs' cause of action was premised on three alleged violations of federal law. First, that the 2016 final GRAS rule violates the US Constitution and the Administrative Procedures Act (APA) because it unlawfully subdelegates FDA’s duty to regulate the safety of the food supply to the private sector. Second, that the 2016 final rule is not only arbitrary and capricious under the APA, but that FDA also exceeded its own authority in issuing it, again in violation of the APA.9 Third, that the 2016 final rule is in conflict with the plain language of the FD&C Act because, among other things, it does not adequately address potential conflicts of interest in GRAS determinations, it discusses relying on unpublished data in a GRAS determination, and it fails to clarify that a GRAS substance can never be a carcinogen.
What did the court decide?
The court granted the government’s motion for summary judgment, effectively closing the case, finding that all of the NGOs causes of action lack merit under the applicable law.
Specifically, the court held that there was no subdelegation of FDA’s authority under the GRAS program, because the FD&C Act does not require the private sector to get premarket approval from FDA for a GRAS substance; importantly, and under the 2016 final rule, FDA still retains the authority to take enforcement action against substances on the market that are not GRAS. In this regard, the court noted that even if the 2016 final rule was never promulgated, the private sector would have the same options they have now (i.e., fail to appropriately notify FDA of a GRAS determination and risk enforcement action by the agency if FDA were to disagree with that determination).
With respect to the other alleged violations of the APA, the court performed the well-established two-step legal analysis under Chevron, U.S.A., Inc. v. Natural Res. Def. Council, Inc. to determine if FDA’s interpretation of the FD&C Act provisions for GRAS substances is acceptable.10 Under this analysis, a court first asks whether Congress has spoken directly to the issue (i.e., has Congress clearly instructed FDA to exempt (or not exempt) GRAS substances from premarket review?). If the answer is no, a court proceeds to step two, under which a court asks if the agency’s interpretation is reasonable (i.e., did FDA act reasonably in exempting GRAS substances from mandatory premarket review and in creating the voluntary GRASN program?).
Here, the court pointed out that the language the NGOs argued constitutes clear instruction by Congress to subject GRAS substances to premarket review—like the language in Section 409 of the FD&C Act requiring FDA to consider the "cumulative effects" of exposure to food additives that are subject to premarket review—is, at worst, ambiguous. Such language, the court concluded, could not have the meaning assigned to it by the NGOs because Congress "does not alter the fundamental details of a regulatory scheme in vague terms or ancillary provisions – it does not . . . hide elephants in mouseholes."11 That said, the court also noted an apparent lack of clarity in the statute because there is nothing in it expressly requiring FDA to not review all GRAS substance before they go on the market, so the court proceeded to "step two." In doing so, the court found that FDA's decision to exempt GRAS substances from premarket review was reasonable, because FDA carefully considered the merits of this approach and articulated its rationale, in detail, in the 2016 final rule. Specifically, the court noted that FDA has limited resources, that it still retains enforcement powers over GRAS substances on the market, and that the GRASN program works well to incentivize industry to notify the agency of proposed uses for GRAS substances.
Finally, the court concluded that the 2016 final rule is not in conflict with the FD&C Act, itself, for the reasons mentioned above. The court also determined that FDA has adequately addressed concerns about conflicts of interest by way of a 2017 draft guidance and through other ways, such as through provisions in the 2016 final GRAS rule requiring a GRASN to be certified as a "balanced" submission.12 While the court acknowledged that the 2016 final rule does discuss use of unpublished data, the court also noted that there is not blanket prohibition in the FD&C Act on considering such material, and that the final rule is reasonably clear in that the pivotal data used in reliance of a GRAS determination must be in the public domain. The court also quickly dismissed the NGOs concerns about the potential for a carcinogen to be considered a GRAS substance because the criteria for GRAS (i.e., general recognition that a reasonable certainty of no harm exists when the substance is used as intended) means that it is unlikely a carcinogen could be a GRAS substance. The court further noted that other courts and FDA have interpreted the FD&C Act's so-called Delaney Clause as not applying to GRAS substances because it technically prohibits FDA from finding a food additive to be safe if it causes cancer in man or animals.13
What are the immediate implications of the court’s ruling and what are some important takeaways from the opinion?
The NGOs have the right to appeal their case to the US Second Circuit Court of Appeals. Regardless of whether or not they choose to do so, the court’s ruling deals a strong blow to the NGOs attempts to remedy their complaints about the GRAS regulatory framework through our nation’s judicial system. The court was reasonably clear in that "[t]he remedy Plaintiffs seek lies with Congress, not [the judicial system]."14 One can probably expect that the NGOs will use this ruling as a basis to drum up additional support for a legislative amendment to the FD&C Act, and those efforts were already well underway even before the court’s ruling.15
Taking a step back, this decision leaves the GRAS regulatory framework unchanged, and the court's affirmation of the underlying legal basis and rationale for FDA's interpretation and implementation of that framework is stronger than it was before.
Notably, however, the court's Chevron analysis suggests that the FD&C Act is silent or unclear as to whether a GRAS substance must be the subject of a GRASN or some other form of premarket review. This determination suggests that, at least in this court’s view, the FD&C Act might give FDA the authority to require some form of premarket review for GRAS substances, should the agency later determine that is appropriate. Given the agency's limited resources and the long record of the existing GRASN program, however, the court’s conclusion provides ample support for FDA choosing to maintain the status quo.
The court's comments about relying on non-public data in a GRAS determination also are notable because they give some additional support to the idea that, while the pivotal data in a GRAS determination must be in the public domain, unpublished data can be helpful in corroborating that determination. And, while the court did not explicitly state the Delaney Clause does or does not apply to GRAS substances, the overall tenor of that discussion lends support for a finding that it does not. That said, the requirements for GRAS substances effectively render it very difficult to make a finding that a carcinogen can be GRAS under its intended conditions of use.
Steptoe & Johnson LLP will continue to monitor this case and other developments regarding GRAS substances. Please contact us if you have any questions.
2 See FD&C Act § 201(s).
3 Substances Generally Recognized as Safe (GRAS), US Food and Drug Administration, 62 Fed. Reg. 18938 (April 17, 1997).
4 See GRAS Notice Inventory, US Food and Drug Administration, https://www.fda.gov/food/generally-recognized-safe-gras/gras-notice-inventory.
5 FDA Should Strengthen Its Oversight of Food Ingredients Determined to Be Generally Recognized as Safe (GRAS), US Government Accountability Office (Mar. 5, 2010), available at https://www.gao.gov/products/gao-10-246.
6 See Consent Decree (D.I. 14), Ctr. for Food Safety v. Sebelius, No. 1:14-CV-00267-RC (D.D.C. Feb. 20, 2014).
7 Substances Generally Recognized as Safe (GRAS), US Food and Drug Administration, 81 Fed. Reg. 54960 (Aug. 17, 2016).
8 Complaint (D.I. 1), Ctr. For Food Safety v. Price, No. 1:17-CV-03833-VSB (S.D.N.Y. May 22, 2017).
9 The NGOs point to language in the FD&C Act, including the language in Section 409 requiring FDA to consider the "cumulative effects" of exposure to food additives that are subject to premarket review, as a basis to argue FDA’s interpretation of the FD&C Act is not in accordance with the law.
10 Chevron, U.S.A., Inc. v. Natural Res. Def. Council, Inc., 467 U.S. 837 (1984).
11 Whitman v. American Trucking Ass’ns, Inc., 531 U.S. 457, 468 (2001).
12 Draft Guidance for Industry: Best Practices for Convening a GRAS Panel, US Food and Drug Administration (Nov. 2017), available at https://www.fda.gov/regulatory-information/search-fda-guidance-documents/draft-guidance-industry-best-practices-convening-gras-panel.
13 See FD&C Act, § 409(c)(3).
14 Opinion and Order (D.I. 100), Ctr. For Food Safety v. Price, No. 1:17-CV-03833-VSB (S.D.N.Y. Sept. 30, 2021), pg. 29.
15 See, e.g., Toxic Free Food Act, H. R. 3699, 117th Congress (2021).
Director, EHS Regulatory