Are You Ready for Mandatory GRAS Notifications?

/in ,

The second Trump administration’s first Unified Regulatory Agenda of Federal Regulatory and Deregulatory Actions, published September 4, 2025, indicates that FDA is close to initiating a rulemaking to overhaul the generally recognized as safe (GRAS) regulations—a change that could significantly raise regulatory expectations for food manufacturers and ingredient suppliers.

What Does the Unified Agenda Say?

According to the unified agenda listing, “the proposed rule, if finalized, would amend the [GRAS] regulations…to require the mandatory submission of GRAS notices for the use of human and animal food substances that are purported to be GRAS.”  Substances that are listed as GRAS for the intended use by regulation, or have been granted a “no questions” letter by FDA, would be exempted.

The listing further notes that the rulemaking would clarify that FDA maintain and regularly update a public-facing GRAS notice inventory for all substances subject to the mandatory GRAS notice requirement for their intended uses.  It would also clarify the process by which FDA would determine that a substance is not GRAS.

The agenda indicates that a proposed rule is expected to be published in October 2025.

Putting It in Context

Under current regulations, companies can self-affirm that a substance—which includes ingredients as well as substances added indirectly (such as from food packaging)—is GRAS based on scientific evidence.  FDA’s GRAS notification program is voluntary; companies may notify FDA but are not required to.

The proposed rule would shift the system so that formal submission (notice) to the FDA becomes mandatory for most substances purported to be GRAS, except those already regulated or with prior FDA “no questions” letters.

The agenda listing follows Health and Human Services Secretary Robert F. Kennedy, Jr.’s March 2025 directive to FDA to explore revising the GRAS final rule and related guidance to eliminate the self-affirmation pathway.  “Eliminating this loophole will provide transparency to consumers, help get our nation’s food supply back on track by ensuring that ingredients being introduced into foods are safe, and ultimately Make America Healthy Again,” Secretary Kennedy said.

EPA Releases Strategic Plan for Endocrine Disruptor Screening Program

/in , , ,

EPA has released a notice requesting comment on its strategic plan to meet its obligations under the Federal Food, Drug, and Cosmetic Act (FFDCA) to screen for and protect against endocrine-disrupting effects in humans. Endocrine disruptors are chemicals that mimic, block, or disrupt the normal function of endocrine system hormones and can negatively impact biological processes within the endocrine, immune, and nervous systems. Under the new program, the Agency will assess pesticides more quickly and effectively to evaluate their potential to cause endocrine effects in humans. These assessments will be incorporated into pesticide review efforts made under the Federal Insecticide, Fungicide, and Rodenticide Act (“FIFRA”).

In the Agency’s press release regarding the program, the Deputy Administrator for Pesticide Programs in the Office of Chemical Safety and Pollution, Jake Li, noted that the program is a major milestone. He also stated that “starting with our highest priority chemicals, EPA will communicate more transparently our endocrine findings for humans.”

EPA review of preliminary data has identified 30 high-priority pesticides that these chemicals affect the endocrine system. The Agency requests additional endocrine data for human health for these chemicals in its request for comment. The Agency intends to fill any remaining data gaps by issuing FIFRA human health data requests for these chemicals in early 2024. These chemicals are identified in EPA’s List of Conventional Registration Review Chemicals, for Which an FFDCA Section 408(p)(6) Determination is Needed, which is available in docket EPA–HQ–OPP–2023–0474 on regulations.gov. FFDCA section 408(p)(6) requires EPA to ‘‘as appropriate, take action under such statutory authority as is available to the Administrator, including consideration under other sections of this chapter, as is necessary to ensure the protection of public health’’ for ‘‘any substance that is found, as a result of testing and evaluation under this section, to have an endocrine effect on humans.’’ In addition, in the Federal Register notice, EPA requested that stakeholders submit data on the endocrine effects of these pesticides. Data are requested during the notice’s 60-day comment period. After the assessment of the high-priority pesticides is completed, the Agency will request data on a second group of 126 pesticides.

In the strategic plan, EPA explains that the program will pull from existing data when possible.   and request new data if needed. Existing data has been collected under FIFRA and the FFDCA. EPA has chosen 400 conventional pesticide active ingredients that are being registered for the first time or are undergoing registration review for which, through the implementation of its Strategic Plan, the Agency will assess for endocrine effects and determine if additional protections are needed.

The comment period for this notice began on October 27, 2023, and has been extended to February 26, 2024.

Eight Circuit Vacates Chlorpyrifos Ban

/in , , ,

EPA’s ban on the pesticide chlorpyrifos was arbitrary and capricious because the Agency failed to adequately consider other options, the Eighth Circuit Court of Appeals ruled on November 2, 2023, in the case Red River Valley Sugarbeet Growers Ass’n v. Regan.

EPA’s 2021 revocation of all chlorpyrifos tolerances was the result of a Ninth Circuit decision ordering EPA to either modify chlorpyrifos tolerances to ensure they are safe for children or revoke them entirely.  EPA had previously determined that 11 “high-benefit” uses were likely to be safe if other uses were revoked.  But with only 60 days to make a decision and under a court directive not to “engage in additional fact-finding,” EPA opted to revoke all tolerances, effectively banning use of chlorpyrifos on all food and animal feed.

The Eighth Circuit characterized EPA’s decision to revoke all tolerances, despite evidence that some uses could be considered safe, as “g[iving] up” in the face of a “tight deadline.”  “EPA should not have reflexively rejected an approach it had the power to adopt, even if it would have required more work,” the court said.

Under the Federal Food, Drug, and Cosmetic Act, EPA can only leave in place tolerances that the Agency has determined to be safe after consideration of aggregate exposure, “including all anticipated dietary exposures.”  In a 2022 order denying objections to the 2021 revocation, EPA argued that it would not be reasonable to consider exposures solely from the 11 high-benefit uses as “anticipated” because EPA did not have reason to believe they would reflect real-world exposures.  EPA is required to determine whether tolerances are safe, not whether they will be safe “at some unspecified future time,” the Agency said.

The court rejected this interpretation of the statute, which was central to EPA’s decision not to implement a partial ban.  The Agency has an “obligation to ‘anticipate[]’ the effects of its own actions,” Chief Judge Lavenski Smith wrote for the three-judge panel.  If EPA proposed to “keep a set of high-benefit uses in place,” it could certainly “anticipate what would happen under its own proposal.”

The court vacated both the 2021 revocation and the 2022 denial order, remanding to EPA.  The Agency will have 45 days from the date of the ruling to petition for rehearing or rehearing en banc.

More information on the legal battles over chlorpyrifos tolerances can be found in a previous Verdant Law blog post.

FDA Issues Draft Guidance for MoCRA Facility Registration and Product Listing

/in , ,

The U.S. Food and Drug Administration (FDA) has released draft guidance, Draft Guidance for Industry: Registration and Listing of Product Facilities and Products, on the new regulatory requirements established in the Modernization of Cosmetics Regulation Act (MoCRA).  Among other provisions, MoCRA added section 607 to the Federal Food, Drug, and Cosmetics Act (FFDCA), requiring cosmetic product facility registration and cosmetic product listing.  The draft document details key registration and product listing requirements, including who must submit, what information is required, when registration and listings must be submitted, and how the FDA intends to accept registration and listing information.

All persons who own or operate a facility engaged in the manufacture or processing of a cosmetic product for distribution in the U.S. must register their facility.  Under MoCRA, a cosmetic product “means a preparation of cosmetic ingredients with a qualitatively and quantitatively set composition for use in a finished product.”  FFDCA section 607(a)(1) provides two exceptions regarding who must register.  The first exception is for small businesses that have average gross annual sales of less than $1 million in the previous three years, unless they manufacture or process cosmetics that regularly come in contact with the mucus membrane of the eye, are injected, are intended for internal use, or are intended to alter appearance for more than 24 hours (and are not meant to be removed by the customer).  The second exemption is for facilities subject to the drugs and devices requirements under chapter V of the FFDCA, unless they also manufacture cosmetics that are not subject to the drug and device requirements.  The same exemptions apply for submission of product listing information.

Facility registration requirements are outlined in sections 607(a) and (b) of the FFDCA.  The requirements for facility registration include all brand names under which the cosmetic products manufactured or processed in the facility are sold and the product categories for each cosmetic product manufactured or processed in the facility.  Registrations must be submitted by December 29, 2023, for facilities that were manufacturing or processing cosmetic products on December 29, 2022.  Facilities that began manufacturing or processing after December 29, 2022, must register within 60 days of first engaging in that activity or by February 27, 2024, whichever date is later.  Registrations must be updated within 60 days of any changes to the registration information and must be renewed biennially.

Product listing requirements are outlined in FFDCA section 607(c) and include the facility registration number for each facility where the cosmetic product is manufactured or processed, its applicable cosmetic category or categories, and a list of product ingredients (including fragrances, flavors, or colors).  Listings must be submitted by December 29, 2023, for products that were marketed on December 29, 2022.  Products that were first marketed after December 29, 2022, must be listed within 120 days of marketing the product, or within 120 days of December 29, 2023, whichever date is later.  Any updates to the listing must be made annually.

Importantly, FDA clarified that any prior registrations through the Agency’s voluntary cosmetics registration programs will not be transferred to the new system; submitters will have to re-submit this information.

According to FDA, an electronic submission portal should be open for submissions beginning in October 2023, although a paper submission form is also available.

EPA Exempts Categories of Genetically Engineered Plant-Incorporated Protectants from Regulatory Requirements

/in , , ,

On May 31, 2023, EPA published a final rule exempting two categories of plant-incorporated protectants (PIPs) created using genetic engineering from certain Federal Insecticide, Fungicide, and Rodenticide Act (FIFRA) registration requirements and from food or feed residue tolerance requirements under the Federal Food, Drug, and Cosmetic Act (FFDCA).  In addition to reducing regulatory burden, EPA stated in a press release that the final rule may result in increased research and development in this sector and provide more pest control options for farmers, ultimately reducing the use of conventional pesticides.

PIPs are defined (in part) at 40 CFR 174.3 as “pesticidal substance[s] that [are] intended to be produced and used in a living plant, or in the produce thereof, and the genetic material necessary for production of such a pesticidal substance.”  In 2001, EPA exempted PIPs derived through conventional plant breeding from FIFRA registration and FFDCA food tolerance requirements, but did not exempt PIPs created using biotechnology.  Because of recent scientific advances, however, EPA writes that PIPs “can now be created through genetic engineering that are virtually indistinguishable from those created through conventional breeding.”  The final rule adds exemptions for the following two categories of genetically engineered PIPs, which EPA states pose no greater risk than PIPs created through conventional breeding:

  1. PIPs in which genetic engineering has been used to insert a gene from a sexually compatible plant or to modify a gene to match a gene found in a sexually compatible plant. This category of PIPs requires EPA confirmation of eligibility for the exemption.
  2. Loss-of-function PIPs, in which a gene is modified through genetic engineering to reduce or eliminate the activity of that gene. The loss of the activity of that gene then results in the pesticidal effect.  For this category of PIP, biotechnology developers can either make a self-determination that their PIP meets the exemption criteria, which requires notification but no EPA review, or request EPA confirmation of eligibility for the exemption.

Exempted PIPs are still subject to the adverse effects reporting requirements at 40 CFR 174.71 and recordkeeping requirements.

In the preamble to the final rule, EPA established that the Agency is open to considering additional PIP category exemptions and expanding the categories of PIPs that are allowed to self-determine without EPA confirmation of their eligibility exemption.

EPA Requests Comments on New Approach Methodologies (NAMs) White Paper

/in , ,

EPA published a draft white paper, New Approach Methodologies (NAMs) in the Endocrine Disruptor Screening Program (EDSP) and is requesting public comment. The white paper was developed pursuant to the Federal Food, Drug, and Cosmetics Act (“FFDCA”), which requires EPA to develop a screening program to determine whether certain substances may have effects in humans that is similar to an effect produced by naturally occurring estrogen or other endocrine effects. The white paper states that some NAMs are acceptable alternatives for certain EDSP Tier 1 assays. Other NAMs may be useful for prioritization purposes and weight of evidence evaluations. The EPA press release discussing the draft white paper states that it will “reinvigorate [EPA’s] efforts to meet its requirement for EDSP screening of chemicals and continue to provide transparency of EDSP Tier 1 testing, which is the step in the EDSP that determines the potential for endocrine-disrupting effects and whether there is a need to obtain more data by requiring additional Tier 2 tests.” Tier 1 screenings are used to identify substances that have the potential to interact with the endocrine system, while Tier 2 screenings are used to identify adverse endocrine-related effects caused by a substance.

Currently, each chemical undergoing ESDP Tier 1 methods can take up to six years, and the cost to the industry of each chemical review is roughly $1 million, due significantly to vertebrate testing. Certain validated NAMs included in the white paper will allow EPA to use alternatives to vertebrate animal testing and other in vitro assays, ultimately allowing the Agency to review chemicals faster, more efficiently, and at a lower cost to the Agency.