Unraveling EPA’s New Gene Edited Plant Rules – Effective July 31, 2023July 31, 2023

Today, the EPA’s new gene editing rules go into effect, with noteworthy implications for the use of biotechnology in agriculture. This finalizes draft rulemaking that was proposed back in 2020, and these new rules clarify the broad scope of the agency’s jurisdiction over gene-edited crops, specifically those defined as plant-incorporated protectants (PIPs) under 40 CFR § 174.3.

For those unfamiliar, a PIP is essentially a pesticidal substance produced in a living plant or its produce. It includes the genetic material necessary for the production of this pesticidal substance, including any genetic changes present in the plant to confirm the presence of the pesticidal substance, such as a herbicide resistance trait. The idea is that instead of spraying pesticides on crops, the crops are genetically modified to produce their own pesticides. It’s an application of biotechnology that has reduced the need for synthetic pesticides and thereby minimizes the environmental impact of traditional chemical pesticides.

Under the Federal Insecticide, Fungicide, and Rodenticide Act (FIFRA), the EPA has authority to regulate pesticides, which under FIFRA includes substances intended for preventing, destroying, repelling, or mitigating pests as well as plant regulators, defoliants, desiccants, and nitrogen stabilizers. Under section 408 of the Federal Food, Drug and Cosmetic Act (FFDCA), the EPA also sets limits on the amount of pesticide residues that can be present in food or feed. In the absence of a tolerance for a pesticide residue, a food containing such a residue is subject to seizure by the government.

The new rules confirm that the EPA’s authority for tolerances extends to gene-edited crops cultivated in the U.S., as well as for food produced outside of the U.S. but imported into the country. Thus, any gene-edited produce that includes a PIP and is imported into the U.S. will be subject to the EPA’s tolerance approval process to ensure that any “pesticide residues” present in the food are within safe limits.

What’s truly noteworthy about the new rules are the two possible exemption criteria provided for PIPs produced through gene editing. Importantly, these exemptions apply only if the developer complies with general recordkeeping requirements specified in § 174.73 per sections 8 and 9 of FIFRA, 7 U.S.C. 136f and 136g , and only after compliance with the new relevant eligibility determination procedures specified in 40 CFR § 174.90. Organizations working with PIPs produced through gene editing should ensure familiarity and compliance with these recordkeeping rules, and determine when any events they may be engaged will fall under the EPA’s oversight, to ensure review of the exemption criteria ahead of any regulated activities.

The EPA notes that these new rules only exempt qualifying PIPs from regulation under FIFRA and the need to establish a tolerance for residues of qualifying PIPs under section 408(e) of the FFDCA; other statutory or regulatory requirements with USDA, FDA, State, or other agencies may still apply.

Exemption 1:  PIP created through genetic engineering from a sexually compatible plant.

An exemption extends to a plant-incorporated protectant when (1) that plant-incorporated protectant is genetically engineered by the submitter into another variety of that same plant species, (2) the substance produced is identical to the substance produced in the original recipient plant, and (3) no new modifications were made to the regulatory regions.

40 CFR 174.26(a)(1) now requires that any regulatory regions inserted as part of the native gene be identical to the regulatory regions of the native gene identified in the source plant.

All “PIPs created through genetic engineering from a sexually compatible plant” are required to undergo an EPA confirmation process to confirm exemption, through submission of data via the EPA’s electronic portal. There is no self-determination option under this exemption category.

There are four main data set categories for this submission: (1) Biology of the plant; (2) Description of how the trait was engineered into the plant; (3) Molecular characterization of the PIP; and (4) Information on the history of safe use for those PIPs that are either known mammalian toxins or toxicants or that are from a source plant that is a wild relative of the recipient plant.

Exemption 2: Loss of Function Exemption.

An exemption extends to a PIP when (1) that plant-incorporated protectant is genetically engineered by the submitter into another variety of that same plant species, and (2) the same native gene is targeted to create the loss-of-function PIP.

“Loss-of-function PIPs” are characterized by a modification that leads to the reduction or elimination of the activity of that gene, which then results in a pesticidal trait. The active ingredient of a loss-of-function PIP is exempt if the genetic material of the native gene is modified using genetic engineering to results in a pesticidal effect through the reduction or elimination of the activity of that gene.

For example, the inactivation of a gene coding for a plant receptor, which confers disease resistance, could be a “loss-of-function PIP”. There must be a direct relationship between the loss of function of the native gene and the pesticidal effect, i.e., it is not a “loss-of-function PIP” if the loss of a native allele affects a second gene, which then produces a pesticidal substance.

Under this exemption criteria, a developer may submit a self-determination letter, and/or request EPA confirmation that their PIP meets the criteria for this exemption as with the conventional breeding exemption above.

Information to be submitted for this exemption category includes (1) the identity of the modified plant (i.e., genus and species), (2) a description of the pesticidal trait, (3) a description of how the trait was engineered, including a description of the steps that were taken to ensure that no engineering components (e.g., Cas proteins) are expected to remain in the plant and (4) measures taken to maximize the likelihood that the modification to the recipient plant is limited to the intended modification, including ensuring off-target mutations were minimized (e.g., through the use of in silico techniques in guide RNA development). The EPA asks for this information to ensure the criteria for exemption are met and that no non-exempt inert ingredients remain in the final plant.

What does this mean for scientists developing gene edited plants, which may be considered PIPs? It is crucial to understand the financial and timeline implications of these new rules, and to adjust research and development processes accordingly to meet exemption criteria if possible. Budgets and timelines should build in potential EPA engagement and regulatory data generation prior to communicating any estimated commercialization dates, particularly with investors.

These new rules help clarify the complexities of regulating gene-edited crops in an increasingly globalized agricultural system. This latest update, alongside USDA’s new gene edited framework, is a testament to the increasing recognition of the need for a science-based and risk-appropriate regulatory process as part of the coordinated framework across the EPA, FDA and USDA. I’m looking forward to helping companies navigate through this latest development in the regulatory framework for gene edited plants grown in as well as imported into the United States, to bring innovative, safe and sustainable products to market.

Cassie J. Edgar, Patent Attorney and Chair of the Regulatory Law practice group, advises clients in intellectual property, regulatory law, crisis management, compliance, stewardship, lobbying, and matters with USDA, FDA, EPA, and FTC. Cassie is also Co-Chair of the Data Privacy and Cybersecurity practice group. For additional information, please visit MVS or contact Cassie directly via email at cassie.edgar@ipmvs.com.