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June 30, 2023 - Agtech, United States, European Union, Regulatory

The EU’s New Proposal for Plants Developed Using New Genomic Techniques: How Does it Compare to U.S. Regulation?

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After much anticipation, the EU Commission’s proposal for a regulation on plants developed using New Genomic Techniques (NGTs) is now under consideration. For an overview of the EU proposal, please see MoFo’s recent post. Here, we provide a brief overview of U.S. regulation of plants produced through modern biotechnology and compare that regulatory regime to the EU’s proposed regulation.

Update: As of July 5th, the final proposal is publicly available on Eur-Lex.

Overview of U.S. Regulation of Plants Produced through Modern Biotechnology

The U.S. regulation of plants produced through modern biotechnology (including, e.g., gene-edited plants) is similar in many respects but also differs considerably from the EU Commission’s proposed risk-based regulatory approach. In general, both reflect the growing international trend towards loosening regulations for gene-edited plants that are closely related to conventional breeding. However, the way this is overseen in the United States does not exactly correspond with the new EU developments.

Federal regulation of plants produced through modern biotechnology in the United States is distributed across three federal agencies in an often overlapping manner, with each agency’s regulations reflecting implementations of different statutes, the various motivations and definitions of which do not always align.

The United States regulates plants produced through modern biotechnology with the Coordinated Framework for the Regulation of Biotechnology, which was established in 1986 as a collaborative approach across the following U.S. agencies: the Environmental Protection Agency (EPA), the Food and Drug Administration (FDA), and the Department of Agriculture (USDA).

The EPA regulates the sale, distribution, and use of pesticides, including Plant Incorporated Protectants (PIPs) that could not have been developed through conventional breeding. PIPs are plant-produced pesticidal substances, such as a plant protein that inhibits fungal growth, and the genetic material that can cause a plant to produce that substance. They may or may not be genetically edited.

The FDA, in parallel, regulates the safety of food, including animal feed and food additives — regardless of whether they have been genetically edited.

The USDA’s regulation includes mandatory labeling/disclosure administered by the Agricultural Marketing Service (USDA-AMS) and regulation of importation, transportation, and environmental release of plants and plant pests developed using genetic engineering that may pose a risk to plant health by the Animal and Plant Health Inspection Service (USDA-APHIS).

Of these U.S. regulations, the most comparable to the proposed EU NGT regulation is USDA-APHIS’s Revised Biotechnology Regulations (previously known as the SECURE rule), which were revised in May 2020. 

Key Differences in U.S. and Proposed EU Regulation

The SECURE rule contains several exemptions, which in many ways sound quite similar to the EU’s category 1 plants—though there are also key differences.

Notably, exemptions from USDA-APHIS’s Revised Biotechnology Regulations are self-determined, though developers may voluntarily reach out to USDA-APHIS for confirmation of an exemption.  Additionally, while the proposed EU regulations require all exempt plants to be listed in a single public database, engineered plants that are exempt from the USDA-APHIS requirements can be released or otherwise enter the U.S. market without explicit disclosure by USDA-APHIS. While USDA-APHIS maintains a publicly available database of voluntary requests for confirmation of exemption under the Revised Biotechnology Regulations, companies that self-determine if an exemption applies do not appear in any federal database. Thus, unlike in the proposed EU regulations, USDA-APHIS’s Revised Biotechnology Regulations do not require notification procedures or publication in a database if an exemption applies.

Both the proposed EU regulations and USDA-APHIS’s regulations are risk-based approaches.  Notably, however, USDA-APHIS’s analyses are driven wholly by plant pest risk.  In contrast, the EU’s risk assessment as currently written considers a broader array of types of potential risks, such as risks to human health.  In the United States, the FDA would consider human health risks for plants that are intended for human or animal consumption—but, as we have summarized separately, the FDA and USDA do not share implementing regulations, and the USDA-APHIS exemptions do not apply to FDA review.

Focusing just on comparing the discrete USDA-APHIS Revised Biotechnology Regulations exemptions themselves with the EU’s proposed category 1 criteria, the acceptable modifications in the EU’s category 1 plants sound much like the USDA-APHIS’s §§ 340.1(b)(1)-(3) exemptions on a technical level (e.g., substitutions, deletions, and changes corresponding to alleles present in a relevant gene pool). However, a major difference is that the §§ 340.1(b)(1)-(3) exemptions are currently limited to single modifications, while the EU criteria include up to 20 modifications (e.g., up to 20 nucleotide insertions, deletion of any number of nucleotides, some types of targeted insertions and substitutions; targeted inversions, etc.; see brief discussion below and our separate post for the full list of criteria). (USDA-APHIS’s Revised Biotechnology Regulations also have other specific exemptions for certain microbial pesticides and PIPs and various narrow situations not discussed here).

For example, a gene-edited plant that has a single, targeted modification may qualify for an exemption under § 340.1(b) if that same plant could have been created through conventional breeding — and it would seemingly also be considered a category 1 plant in the EU, assuming its sequence shares “similarity with the targeted site that can be predicted by bioinformatic tools,” which is not an explicit factor under USDA-APHIS’s Revised Biotechnology Regulations.  In contrast, a plant with multiple targeted edits that resulted in substitution of, say, 3 total bases could still seem to equally fall under the EU’s category 1, but would likely not qualify from a current exemption to USDA-APHIS’s Revised Biotechnology Regulations, as USDA-APHIS has clarified that “[i]n general, multiple modifications made simultaneously in the same plant developed using genetic engineering will not qualify for an exemption under § 340.1.”

Although the EU’s category 1 NGT plants in some respects encompass a wider baseline set of exemptions, USDA’s list of exempt genetically modified plants is designed to grow over time. For example, the EU’s category 1 exempts plants with up to 20 genetic modifications of the types referred to in Annex I, provided they meet the sequence similarity restrictions outlined in our EU proposal overview. In contrast, as noted above, in the United States, a plant with multiple targeted genetic changes (much less 20) would not immediately qualify for a § 340.1(b) exemption, unless the modifications were all present together in the gene pool. However, new plants that have the same plant-trait-mechanism-of-action (PTMOA) combination as a plant that USDA-APHIS has previously reviewed and deregulated do qualify for a permit exemption (and these can contain, theoretically, any number of changes), as well as plants that USDA-APHIS determined not to regulate prior to the implementation of its Revised Biotechnology Regulations. Further, plants that are produced by crossing exempt plants are also exempt from USDA-APHIS’s Revised Biotechnology Regulations, even if they wouldn’t meet an individual exemption if the modifications were produced as simultaneous edits. 

The EU Commission plans to produce a first monitoring report no sooner than three years after the first products have been notified and authorized. The criteria for category 1 NGT plants and their exemptions from Annex I of the proposal are not set in stone and could be changed, e.g., new exemptions could be added, so it is possible that the EU exemptions could, in practice, expand similarly to USDA-APHIS’s Revised Biotechnology Regulations exemptions.

The EU’s rules for category 2 plants also seem facially similar to USDA-APHIS’s Revised Biotechnology Regulations permitting and Regulatory Status Review (RSR) provisions for non-exempt plants, in that they have simplified requirements in comparison to the respective legacy approaches but still require a risk assessment and some level of monitoring. However, the RSR provisions in USDA-APHIS’s Revised Biotechnology Regulations directly broaden the pipeline of exemptions, while the EU categories do not seem as elastic. On the other hand, USDA-APHIS’s Revised Biotechnology Regulations provisions apply broadly to importation, interstate movement, and environmental release, while the EU’s category 2 provisions are mostly aimed at plants produced for food or feed.

More broadly, as the EU adopts a single risk-based regulatory approach to gene-edited plants, U.S. regulation remains fragmented across federal agencies. For example, even if a gene-edited, plant-based food falls under one of the USDA permit exemptions described above, that food must still undergo FDA’s Voluntary Plant Biotechnology Consultation Program, or else risk FDA enforcement action.[1]

Finally, consumer transparency surrounding gene-edited plants differs significantly between the United States and EU. Both EU and USDA regulations do not require labeling of food that could “occur naturally” (i.e., food that is “found in nature” in the United States) or be obtained through “conventional breeding.” However, because the USDA does not define these terms, the mandatory label disclosure for U.S. bioengineered food encompasses more food products than the EU’s labeling requirements, which limit labeling to gene-edited plants that do not meet the broad requirements for category 1 NGTs.

Overall, the new EU proposal would bring regulations to plants developed using NGTs that are much more in line with U.S. regulations, but exactly how the regulations would cover an individual NGT-produced plant may still differ. It will be interesting to see how the various regulations continue to morph and whether they become streamlined in practice.

Elena Klonoski, a summer associate in our Boston office, contributed to the drafting of this post.

[1] Edward L. Rubin & Joanna K. Sax, Administrative Guidance and Genetically Modified Food, 60 Ariz. L. Rev. 539, 561 (2018).