By Lisa R. Burchi, James V. Aidala, and Heather F. Collins, M.S.

On May 31, 2023, the U.S. Environmental Protection Agency (EPA) released a final rule exempting a class of plant-incorporated protectants (PIP) created using genetic engineering, from registration requirements under the Federal Insecticide, Fungicide, and Rodenticide Act (FIFRA), and from the food or feed residue tolerance requirements under the Federal Food, Drug, and Cosmetic Act (FFDCA). 88 Fed. Reg. 34756. PIPs are pesticidal substances produced by plants and the genetic material necessary for the plant to produce the substance. According to EPA’s May 25, 2023, press release, this rule will reduce costs for the regulated community and result in increased research and development activities, consistent with Executive Order 14081 on advancing biotechnology. EPA states that the rule also may result in the commercialization of new pest control options and reduced use of conventional pesticides. The final rule will be effective on July 31, 2023.

EPA states the final rule will allow PIPs to be exempt from FIFRA registration and FFDCA tolerance requirements in cases where they both pose no greater risk than PIPs that EPA has already concluded meet safety requirements, and when they could have otherwise been created through conventional breeding. The final rule reflects the biotechnological advances made since 2001, when EPA first exempted PIPs derived through conventional breeding from FIFRA registration and FFDCA tolerance requirements but did not at that time exempt PIPs created through biotechnology.

In the rule, EPA provides criteria and definitions that identify two categories of PIPs that are exempted through this action from FIFRA registration and FFDCA tolerance requirements:

• “PIPs created through genetic engineering from a sexually compatible plant” in which genetic engineering has been used to insert or modify a gene to match a gene found in a sexually compatible plant (to be codified at 40 C.F.R. Section 174.26); and
• “Loss-of-function PIPs” in which the genetically engineered modification reduces or eliminates the activity of a gene, which then helps make the plant resistant to pests (to be codified at 40 C.F.R. Section 174.27).

For the first exempted category, EPA will require a notification process for EPA to confirm that the PIP is eligible for the exemption. For the second exempted category (loss-of-function PIPs), developers of PIPs can submit to EPA a self-determination letter that the exemption applies. EPA also is establishing recordkeeping requirements for these exempted PIPs, clarifying general qualifications for exemption at 40 C.F.R. Section 174.21; clarifying the relationship between the existing exemptions for PIPs from sexually compatible plants (40 C.F.R. Section 174.25) and the newly issued exemption for “PIPs created through genetic engineering from a sexually compatible plant” (40 C.F.R. Section 174.26); and allowing the existing inert ingredient exemption at 40 C.F.R. Section 174.705 to include genetic engineering.

EPA notes that in the future, as biotechnology advances further, it intends to consider exempting additional categories of PIPs from both FIFRA registration and FFDCA tolerance requirements as well as adding categories of exempted PIPs to the list of categories that do not require EPA confirmation of eligibility.

Additional information, including the response to comment document, is available in docket EPA-HQ-OPP-2019-0508.

Commentary

This final rule is the next step for EPA’s Office of Pesticide Programs (OPP) on the path of EPA’s regulation of biotechnology pesticide products. It sets forth how OPP will handle products created by “Clustered Regularly Interspaced Short Palindromic Repeats” (CRISPR). In more general terms, CRISPR refers to manipulating plant genes with a method that was not available at the time the first biotechnology regulations were developed by EPA in the mid-1990s. This is why EPA needs to “update” its regulations, which is the purpose of the final rule.

Proponents of biotechnology methods argue that CRISPR allows the genes of plants to be manipulated more precisely and can be used to “simply” drop out a gene or add one from the same -- sexually compatible -- genome of the target plant. It follows that this is much like “traditional plant breeding” only done more precisely and more rapidly. Critics will likely raise questions about whether any product using this method, and not using traditional methods, might have some kind of unexpected result or unintended eventual effect. One can expect some adverse comments regarding these products even though EPA (among many others) lays out a rationale that this is an extension of its current regulations exempting products of traditional plant breeding from regulation under FIFRA/FFDCA (and not exempting such products from other regulatory authorities).

There also were concerns raised in comments submitted in response to the October 9, 2020, proposed rule. In particular, some in industry remain concerned that the final rule creates differential treatment for products due solely to the methods of development (i.e., biotechnology vs. conventional), thus subjecting products created using biotechnology to additional regulatory and recordkeeping requirements, even in cases when those products could have been created using older research and development approaches.

EPA’s basic requirements for biotechnology products that regulate inter-species gene manipulation would not change. Also worth noting is that the rule also would allow a developer to submit the product for EPA review to affirm that it qualifies for the exemption (i.e., a M009 Pesticide Registration Improvement Act (PRIA) action, which can lead to EPA delays in processing). The EPA docket includes a slide deck with a helpful summary of the final rule and its rationale.

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By Lynn L. Bergeson and Carla N. Hutton
 
The U.S. Government Accountability Office (GAO) published a “Science & Tech Spotlight” on synthetic biology on April 17, 2023. GAO defines synthetic biology as “a multidisciplinary field of biotechnology that involves engineering the genetic material of organisms -- such as viruses, bacteria, yeast, plants, or animals -- to have new characteristics.” According to GAO, scientists are currently exploring the use of synthetic biology to address environmental challenges by engineering organisms to use carbon dioxide, produce biofuels for vehicles, and transform methane into biodegradable plastics. GAO notes that the synthetic biology market could grow from about $10 billion in 2021 to between $37 billion and $100 billion dollars by 2030. Opportunities include:

• Widely adaptable. Synthetic biology holds the potential to help diagnose and treat diseases, improve industrial processes, and address some environmental challenges;
• More equitable access to biotechnology. Some of the tools needed for synthetic biology are low-cost and widely available, which could make access to beneficial applications more equitable; and
• Conservation efforts. Synthetic biology could support endangered species conservation, for example, by altering the genes of endangered plants to make them resilient to diseases.

GAO notes the following challenges:

• Safety and security concerns. Synthetic biology could pose a significant threat to national security if it were used for nefarious purposes, such as developing new biological or chemical weapons. Additionally, the computational tools used for synthetic biology could be vulnerable to cyberthreats such as automation hacking. For example, a bad actor could manipulate or steal information and use it to create drugs, weapons, or other harmful products.
• Environmental effects. Organisms made using synthetic biology and released into the environment could have unknown, unintended, and potentially irreversible effects on ecosystems. Such effects could be widespread if, for example, these organisms negatively affected food or water systems.
• Public acceptance and access. The public may hesitate to accept certain applications of synthetic biology due to concerns about interfering with nature and about unintended effects. In addition, some medical applications could be inaccessible for some patients due to cost or location of treatment centers.

GAO concludes the “Science & Tech Spotlight” with the following policy context and questions:

• Do policymakers have adequate access to expertise and resources to evaluate the societal effects and public policy implications of synthetic biology research and development?
• How effective is the coordination among 1) domestic and 2) global stakeholders for monitoring and assessing the risks associated with advances in synthetic biology research and applications?
• Is the current regulatory framework sufficient to address ongoing and future applications and their effects without unnecessarily hindering U.S. competitiveness in synthetic biology?

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By Lynn L. Bergeson and Carla N. Hutton
 
The U.S. Department of Agriculture’s (USDA) Animal and Plant Health Inspection Service (APHIS) announced on April 10, 2023, that it is inviting public comment on a draft Environmental Assessment (EA) and draft Plant Pest Risk Assessment (PPRA). 88 Fed. Reg. 21602. APHIS states that it produced these documents in response to a petition from Pioneer Hi-Bred International, Inc. seeking deregulation of a corn variety developed using genetic engineering to resist corn rootworm and tolerate glufosinate herbicides. APHIS is seeking public comment on these documents for 30 days. APHIS will thoroughly review and consider all public input submitted during the comment period and will use this information to complete and publish final environmental documents and its regulatory determination. Comments are due May 11, 2023. APHIS has posted the following documents:

• Petition;
• Draft Environmental Assessment; and
• Draft Plant Pest Risk Assessment.

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By Lynn L. Bergeson and Carla N. Hutton
 
The U.S. Environmental Protection Agency (EPA) will hold training on May 23, 2023, on Generalized Read-Across (GenRA), a publicly available tool that uses an automated approach to make reproducible read-across predictions of toxicity. EPA states that read-across “is a commonly used data gap filling technique whereby endpoint information for one substance is used to predict the same endpoint for another substance, supported by structural or other feature similarities.” According to EPA, while read-across sometimes relies on subjective or expert judgement, use of the GenRA tool could provide more objective and reproducible read-across predictions. Specifically targeted for decision-makers, this training will provide:

• A presentation overview of GenRA’s purpose and scope;
• A demonstration of GenRA’s interface and navigation; and
• Opportunities for participatory learning and engagement.

The virtual training will feature EPA’s Dr. Grace Patlewicz. The training will include a plenary presentation, small group discussions, and a chance to try out GenRA. EPA has divided the training into two parts to accommodate a variety of interests and schedules. Registration for one or both sessions is free but required.

• Session 1 (Presentation and Questions and Answers (Q&A)) 11:00 a.m. - 12:30 p.m. (EDT)

This session will provide an overview of GenRA content and function with opportunities for participation and Q&A.

• Session 2 (Breakout Sessions) 12:30 - 1:30 p.m. (EDT)

This session will break participants into breakout rooms to work on exercises in small groups, aided by facilitators.

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By Lynn L. Bergeson and Carla N. Hutton
 
The U.S. Department of Agriculture’s (USDA) Animal and Plant Health Inspection Service (APHIS) announced on March 23, 2023, the availability of a draft guide detailing the information requirements and process for submitting permit applications for microorganisms developed using genetic engineering. The draft Guide for Submitting Permit Applications for Microorganisms Developed Using Genetic Engineering under 7 CFR Part 340 is intended to assist developers with preparing a permit application for movement activities with modified microorganisms under 7 C.F.R. Part 340 (Movement of Organisms Modified or Produced through Genetic Engineering). The draft guide states that genetic engineering is defined in 7 C.F.R. Section 340.3 as “techniques that use recombinant, synthesized, or amplified nucleic acids to modify or create a genome.” According to the draft guide, regulated microorganisms include plant pests and other modified microorganisms that could pose a plant pest risk. Developers require a permit for regulated activities involving any modified microorganism that:

• Meets the definition of a plant pest in Section 340.3; or
• Is not a plant but has received deoxyribonucleic acid (DNA) from a plant pest, as defined in Section 340.3, and the DNA from the donor organism is either capable of producing an infectious agent that causes plant disease or encodes a compound that is capable of causing plant disease; or
• Is a microorganism used to control plant pests and could pose a plant pest risk.

Comments on the draft guide are due May 22, 2023. APHIS states that it will consider all comments received by May 22, 2023, prior to issuing the final version of the guide.

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By Lynn L. Bergeson and Carla N. Hutton
 
The U.S. Department of Agriculture (USDA) Animal and Plant Health Inspection Service (APHIS) announced on December 22, 2022, that it posted its final Regulatory Status Review (RSR) guide. The RSR guide details the information requirements and process for submitting an RSR request under the revised biotechnology regulations at 7 C.F.R. Part 340. Under the revised regulations, developers may request a permit and/or an RSR of a plant developed using genetic engineering that APHIS has not previously reviewed. Developers may submit a request for an RSR when they believe a modified plant is not subject to regulation. APHIS will review the modified plant and consider whether it might pose an increased plant pest risk compared to a nonregulated plant. If its review finds a plant is unlikely to pose an increased plant pest risk relative to the comparator plant, APHIS will post the request, its response letter, the plant, trait, and a general description of the Mechanism of Action (MOA) on its website. The posting of plant, trait, and MOA combinations provides a growing range of modifications that are eligible for exemption from regulation. Alternatively, if APHIS is unable to make such a finding, the modified plant is subject to regulation.

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By Lynn L. Bergeson and Carla N. Hutton
 
The U.S. Department of Agriculture’s (USDA) Animal and Plant Health Inspection Service (APHIS) announced on October 21, 2022, that it recently reviewed a corn plant and a potato plant that were modified using genetic engineering to determine whether they present an increased pest risk as compared to unmodified plants. APHIS has posted its Regulatory Status Review (RSR) responses on its website, as required under 7 C.F.R. Part 340. According to APHIS, the corn plant, from Infinite Enzymes, Inc., was modified to produce the enzyme manganese peroxidase in corn seed and to make it resistant to the herbicide glufosinate. The potato plant, from J.R. Simplot Company, was modified to make it resistant to potato late blight and potato virus Y and to alter the potato tuber’s sugar profile and quality.
 
According to APHIS, in both cases, it “found these plants unlikely to pose an increased plant pest risk compared to other cultivated corn and potato plants.” As a result, they are not subject to regulation under 7 C.F.R. Part 340. From a plant pest risk perspective, these plants may be safely grown and used in breeding in the United States. APHIS notes that its responses are based on information from the developers and its own:

• Familiarity with plant varieties;
• Knowledge of the traits; and
• Understanding of the modifications.

Under 7 C.F.R. Part 340, developers may request an RSR when they believe a modified plant is not subject to regulation. APHIS reviews the modified plant and considers whether it might pose an increased plant pest risk compared to a nonregulated plant. If its review finds a plant is unlikely to pose an increased plant pest risk relative to the comparator plant, APHIS issues a response indicating the plant is not subject to the regulations.

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By Lynn L. Bergeson and Carla N. Hutton
 
On September 7, 2022, the U.S. Department of Agriculture’s (USDA) Animal and Plant Health Inspection Service (APHIS) announced that it reviewed a new tomato from Norfolk Plant Sciences. The tomato was modified to alter its color and enhance its nutritional quality. APHIS found the plant is unlikely to pose an increased plant pest risk compared to other cultivated tomatoes and is not subject to regulation under 7 C.F.R. Part 340. That means, from a plant pest risk perspective, the plant may be safely grown and used in breeding in the United States.
 
APHIS announced on September 30, 2022, that it reviewed a modified corn plant from Agrivida, Inc. The corn was modified using genetic engineering to alter animal feed quality for improved digestion. APHIS also reviewed a modified potato from Toolgen, Inc. This potato was modified using genetic engineering to alter tuber quality by reducing browning. APHIS states that it found these plants are unlikely to pose an increased plant pest risk compared to other cultivated corn and potato and, thus, they are not subject to regulation under 7 C.F.R. Part 340.
 
APHIS’s Regulatory Status Review (RSR) responses under the revised biotechnology regulations at 7 C.F.R. Part 340 are available online. In each case, APHIS based its responses on information from the developers and its:

• Familiarity with plant varieties;
• Knowledge of the traits; and
• Understanding of the modifications.

Under 7 C.F.R. Part 340, developers may submit a request to APHIS for an RSR when they believe a modified plant is not subject to regulation. APHIS reviews the modified plant and considers whether it might pose an increased plant pest risk compared to a nonregulated plant. If APHIS’s review finds a plant is unlikely to pose an increased plant pest risk relative to the comparator plant, it will issue a response indicating the plant is not subject to the regulations.

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By Lynn L. Bergeson and Carla N. Hutton
 
On September 1, 2022, the U.S. Department of Agriculture’s (USDA) Animal and Plant Health Inspection Service (APHIS) announced the availability of two new resources to answer stakeholder questions regarding the revised biotechnology regulations under 7 C.F.R. Part 340:

• “Questions & Answers -- Working with Microorganisms Developed Using Genetic Engineering Under 7 CFR part 340”: The questions and answers (Q&A) cover topics such as what microorganisms are regulated, permit requirements, permit exemptions, and how to contact APHIS and what information to provide; and
   
• Updated Confirmation Request Guidance: The updated guidance provides clarification on preparing and submitting requests to APHIS to confirm a modified plant qualifies for an exemption and is not subject to the regulations in 7 C.F.R. Part 340, including information on how APHIS treats off-target modifications when considering confirmation requests.

These resources, along with other information on the revised biotechnology regulations, are available on the APHIS website. For additional questions regarding the regulation of modified microorganisms, contact APHIS at .(JavaScript must be enabled to view this email address). For questions regarding confirmation requests, contact APHIS at .(JavaScript must be enabled to view this email address).

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By  Lynn L. Bergeson and Ligia Duarte Botelho, M.A.

On May 27, 2022, EPA announced that it is seeking nominations for technical experts to serve as Special Government Employees (SGE) to participate in the review of the New Chemicals Collaborative Research Program with the Board of Scientific Counselors (BOSC), a federal advisory committee to the Office of Research and Development (ORD). EPA will consider nominees from industry, business, public and private research institutes or organizations, academia, government (federal, state, local, and Tribal), non-governmental organizations, and other relevant interest areas. EPA notes that it values and welcomes diversity. EPA encourages all qualified candidates to apply regardless of gender, race, disability, or ethnicity. The deadline to submit nominations is June 30, 2022, and submissions should be made via the BOSC website. More information on EPA’s Draft Document on “Modernizing the Process and Bringing Innovative Science to Evaluate New Chemicals Under TSCA” is available in Bergeson & Campbell, P.C.’s (B&C^®) March 14, 2022, memorandum.

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