The U.S. Department of Agriculture’s (USDA) Animal and Plant Health Inspection Service (APHIS) issued a proposed rule on June 6, 2019, on the movement of certain genetically engineered (GE) organisms. 84 Fed. Reg. 26514. The proposed rule would revise the regulations regarding the movement, including the importation, interstate movement, and environmental release of certain GE organisms in response to advances in genetic engineering and APHIS’ understanding of the plant pest risk posed by them, “thereby reducing regulatory burden for developers of organisms that are unlikely to pose plant pest risks.” APHIS notes that the proposed rule “would mark the first comprehensive revision of the regulations since they were established in 1987.” It would provide “a clear, predictable, and efficient regulatory pathway for innovators, facilitating the development of new and novel [GE] organisms that are unlikely to pose plant pest risks.” Comments on the proposed rule are due by August 5, 2019.
Overview of the New APHIS Regulatory Framework
APHIS proposes to revise the regulations in accordance with a new regulatory framework that APHIS believes will provide a “clear, predictable, and efficient regulatory pathway for innovators while facilitating the development of new and novel GE plants that are unlikely to pose a plant pest risk.” Interestingly, the approach contemplated is guided by the “the principles: Sustainable, Ecological, Consistent, Uniform, Responsible, Efficient, or SECURE for short,” according to USDA Undersecretary for Marketing and Regulatory Programs Greg Ibach. As its name suggests, the goal is to modernize the regulations to ensure safety while promoting innovation. APHIS states that it anticipates that adopting the new framework will result in significant savings for developers of GE organisms.
The revised regulatory framework would reflect the Secretary of Agriculture’s March 28, 2018, statement that provided clarification on USDA’s oversight of plants produced through plant breeding innovations. According to APHIS, the proposed framework is also consistent with the UDSA Office of Inspector General’s (OIG) recommendations, the 2008 Farm Bill requirements, and with the guiding principle of the Coordinated Framework that “[i]n order to ensure that limited Federal oversight resources are applied where they will accomplish the greatest net beneficial protection of public health and the environment, oversight will be exercised only where the risk posed by the introduction is unreasonable.”
APHIS' new regulatory approach is intended to prepare it for future advances in the genetic modification of plants. APHIS notes that for convenience it sometimes refers to plant varieties produced with innovative techniques that could otherwise have been achieved using methods of traditional plant breeding as “plant breeding innovations.” Where genetic modifications are similar in kind to those modifications made through traditional breeding, APHIS states that the plant pest risks should also be similar. These types of plants are equivalent to those that have a well recognized history of safe use and would be exempted from the proposed regulation. On the other hand, genetic modifications made in the future may result in increasingly complex products that, in turn, may pose new types of risks with which APHIS has less familiarity. Based on this conceptual divide, the proposal establishes a bifurcated regulatory approach, imposing on more complex future genetic modifications the regulatory review contemplated under the proposed regulations. Once products are reviewed by APHIS and found unlikely to pose a plant pest risk, similar products would be exempt from further review.
APHIS states that its approach for GE organisms is consistent with the 2017 National Academy of Sciences (NAS) Preparing for Future Products of Biotechnology report, which stated that regulation should take into account familiarity. The report noted that unfamiliar products, and those that may be developed in the future, may have few or no comparators with existing products within the regulatory system. Such products, therefore, would require more regulatory oversight than familiar products until enough is known about the new products to enable APHIS to assess accurately the plant pest risks associated with them. By focusing regulatory resources and risk analyses on unfamiliar products, APHIS states that it will be able to avoid conducting repetitive analyses, use its staff time more efficiently, and provide better stewardship of taxpayer dollars.
Key Features of the Proposed Rule
APHIS notes that the approach it is proposing would differ from the current regulatory framework in that regulatory efforts would focus on the properties of the GE organism itself rather than on the method used to produce it. This approach is consistent with other agency approaches, including the U.S. Environmental Protection Agency’s (EPA) review of nanoscale materials. As EPA noted in its January 12, 2017, Section 8(a) Toxic Substances Control Act (TSCA) rule for certain nanoscale materials, EPA did not base the requirements of the rule on an assumption that nanoscale materials as a class are likely to cause harm. Rather, EPA bases its evaluation “on the specific nanoscale material's own properties and those of any structural analogs.” APHIS “believe[s] that this new approach, which reflects [its] current knowledge of the field of biotechnology, would enable [it] to evaluate GE organisms for plant pest risk with greater precision than the current approach allows.” GE organisms that are determined to pose a plant pest risk would fall within the scope of the proposed regulations and require permits for movement. APHIS would define plant pest risk as “[t]he possibility of harm resulting from introducing, disseminating, or exacerbating the impact of a plant pest.”
APHIS will continue to regulate GE organisms that are in and of themselves plant pests, as well as other GE non-plant organisms that pose plant pest risks. Such organisms would require permits for movement. Other GE non-plant organisms that do not pose a plant pest risk would not fall under the scope of the regulations and therefore would not require permits for movement.
Under the current system, when making decisions regarding regulatory oversight of GE plants, APHIS assesses each transformation event (also sometimes referred to as the individual transformed line, transgenic line, or GE line) separately, even though the inserted genetic material may be identical or very similar to transformation events already assessed. This has sometimes been referred to as an “event-by-event” approach.
Under the proposed rule, developers would have the option of requesting a permit or a regulatory status review of a GE plant that has not been previously reviewed and determined to be nonregulated. APHIS would base decisions on regulatory status on its assessment of plant pest risk. If movement of a GE plant, by which APHIS means its importation, interstate movement, or environmental release, is found to be unlikely to pose a plant pest risk, APHIS would not have authority under the Plant Protection Act (PPA) to regulate the plant in accordance with 7 C.F.R Part 340. If APHIS is unable to reach such a finding, it would regulate the subject plant, which would be allowed to move only under permit.
Under Section 340.1(b) of the proposed rule, certain categories of modified plants would be exempted from the regulations in Part 340 because they could be produced through traditional breeding techniques and thus are unlikely to pose a greater plant pest risk than traditionally bred crops, which APHIS has historically not regulated. APHIS states that these products of biotechnology are likely to pose no greater plant pest risk than their traditionally bred comparators. APHIS restricts these exemptions to plants “because the long history of plant breeding gives us extensive experience in safely managing associated plant pest risks.”
Proposed Section 340.1(c) would exempt GE plants with plant-trait-mechanism of action (MOA) combinations that APHIS has already evaluated by conducting a regulatory status review and found to be unlikely to pose a plant pest risk. MOA refers to the biochemical basis for the new trait. The results of all completed regulatory status reviews would be publicly accessible on the APHIS website.
Under the proposed new regulatory framework, a developer would have the option to make a self-determination as to whether his or her GE plant belongs to one of the categories listed under Section 340.1(b) or (c) and is therefore exempt from the regulations. A developer who determines that his or her GE plant belongs to an exempted category would have the option under proposed Section 340.1(d), to request written confirmation from APHIS that the self-determination is valid. According to APHIS, “[t]hese confirmation letters, which would provide a clear and succinct statement about the regulatory applicability of the GE plant and the nexus to plant health, may be useful to developers wishing to market their products domestically or overseas by allowing them to provide verification to an importing country or other party that APHIS concurs with their self-determinations.” APHIS states that it “anticipates a timely turnaround time” in preparing and providing these confirmation letters to developers. Allowing for self-determinations would provide developers with regulatory relief and open more efficient and predictable pathways for innovators to get new modified plants that are unlikely to pose a plant pest risk to market, in turn supporting further innovation. APHIS expects that benefits will accrue to developers of all sizes, including small- and mid-sized ones, as well as academic institutions. At the same time, according to APHIS, it would be able to allocate its resources more efficiently than under the current regulations. Because APHIS would no longer have to perform the redundant task of assessing GE plants with plant-trait-MOA combinations that it has already determined are not subject to these regulations, it would be able to devote more attention to assessing and regulating those GE organisms that are likely to be associated with potential plant pest risks.
APHIS notes that a developer making a self-determination that APHIS then determines not to be valid may be subject to remedial measures or penalties if the organism is moved without proper authorization under Part 340. In addition, APHIS may exercise penalties and remedial measures (including but not limited to, quarantine, seizure, and/or destruction) under the authority of the PPA.
Under Section 340.4 of the proposed rule, the process by which APHIS would evaluate GE plants for plant pest risk would be called a regulatory status review. When evaluating the plant pest risk posed by a newly developed GE plant, APHIS would consider three fundamental elements in combination and individually: (1) the basic biology of the plant prior to modification; (2) the trait that resulted from the genetic modification; and (3) the MOA. Since any one or any combination of these three elements may affect plant pest risk, APHIS would determine the need for regulatory oversight by appraising the risk posed by the plant’s unique combination of the three elements.
The proposed rule would define trait as an observable (able to be seen or otherwise identified) characteristic of an organism. MOA would be defined as the “biochemical process(es) through which genetic material determines a trait.” For example, a plant may be modified to confer the trait of male sterility by either of two MOAs in pollen: expression of a protein that is toxic to the pollen grain (barnase system); or expression of a protein that changes deoxyribonucleic acids (DNA) in pollen-producing tissues (DNA adenine methylase system) in a disruptive way that ultimately results in death of those tissues.
For reasons described in greater detail in the proposed rule, the regulatory status review process would apply only to plants and not to GE plant pests or other GE non-plant organisms that fall within the scope of the regulations. APHIS requests comments, however, on whether the scope of the regulatory status review should be expanded to include non-plant GE organisms as well as GE plants, whether some equivalent process for evaluating such organisms for regulatory status should be developed instead, and, if so, what factors APHIS should consider in its analyses.
Information pertaining to the results of all completed regulatory status reviews would be publicly accessible on the APHIS website. This information would include a comprehensive list of GE plant-trait-MOA combinations that APHIS has evaluated for plant pest risk via the regulatory status review process under proposed Section 340.4. The list would also include GE plants for which APHIS has made determinations of nonregulated status under the petition process. Developers could use the list to aid them in making their self-determinations. For example, if a developer were to find that his or her newly developed GE plant had the same plant-trait-MOA combination as a GE plant previously found by APHIS to be not subject to its regulations, the developer “would know immediately that the newly developed plant would not be subject to APHIS regulation.” APHIS “anticipate[s] that should this rule be implemented, this list would grow as new regulatory status reviews are completed.”
For GE plants that do not fall into one of the exempted categories and have not previously been assessed through the regulatory status review process, developers would have the option of either requesting an immediate regulatory status review or requesting a permit for the movement of their GE plant in lieu of a regulatory status review. A developer who initially requests a permit would also have the option of following up with a request for a regulatory status review. According to APHIS, providing these options would allow for maximum flexibility in the research and development of novel GE plants for all types of developers (multi-national companies, small companies, and public sector researchers). Developers of GE organisms that are plant pests would continue to need permits to move those organisms.
Regulation of Plants that Produce Plant-Made Industrials and Pharmaceuticals
APHIS states that it recognizes that certain plants are genetically engineered to produce pharmaceutical and industrial compounds, also known as plant-made industrials and pharmaceuticals (PMPI). According to APHIS, federal oversight of outdoor plantings of PMPI-producing plants could be necessary to prevent the unlawful introduction into the human or animal food supply of pharmaceutical or industrial PMPI products, even when the principal purpose of the plants is not for human or animal food use. In addition to potential adulteration issues posed by such plants should they enter the food supply, APHIS notes that a gap in federal oversight could generate concerns from the general public regarding the safety and wholesomeness of the human or animal food supply, adversely impacting agricultural interests. Establishing growing and handling conditions to confine such plants, and inspecting to ensure such conditions are followed, may enable corrective actions before material from the plants is inadvertently released and causes public health or economic impacts.
Under the current regulations, APHIS requires permits for the environmental release of all GE plants that meet the definition of a regulated article and produce PMPIs. APHIS exercises oversight of all outdoor plantings of these regulated PMPI-producing plants. This oversight includes establishing appropriate environmental release conditions, inspections, and monitoring. PMPI-producing plants and the products obtained from them may also be regulated by the U.S. Food and Drug Administration (FDA) (authority over food and drugs) or EPA (chemical substances as defined by TSCA), depending on their use or intended use. If a PMPI-producing plant or plant product were potentially to be used for human or animal food, food additive approval might be required under the Federal Food, Drug, and Cosmetic Act.
APHIS states that to date, PMPI-producing GE plants regulated by it have been genetically engineered using a plant pest as the donor, vector, or vector agent, and thus fall under the scope of “regulated article” in the current regulations. Under the provisions of the proposed rule, a GE plant that is developed using a plant pest as a vector, vector agent, or donor of genetic materials would not necessarily be regulated, however. Rather, the GE plant would be regulated only if it had a plant-trait-MOA combination that APHIS has not yet evaluated for plant pest risk or if it was evaluated and found to pose a potential plant pest risk. Additionally, APHIS’ evaluations of GE plants for plant pest risk would generally not require data from outdoor plantings. Even if the plant represents a new plant-trait-MOA combination not previously reviewed, there is a likelihood that most, if not all, GE PMPI-producing plants that are currently under APHIS permits could be determined to be not regulated under the provisions of the proposed regulations after a regulatory status review because they are unlikely to pose a plant pest risk. Thus, according to APHIS, such plants could be grown outdoors without the need for APHIS permits and without APHIS oversight.
APHIS states that one of the reasons its oversight of such crops has been an important part of the coordinated framework for oversight of GE plants is that companies are not necessarily required to notify FDA or EPA when the developer plants PMPI-producing plants. For example, for PMPI-producing plants whose products are subject to FDA oversight, FDA has no regulations governing planting of such crops. For crops genetically engineered to produce human drugs, companies only have to go to FDA when they have reached the point that they are ready to begin clinical trials with the pharmaceutical derived from the plant. According to APHIS, “[t]his could be years after they first started growing the pharmaceutical-producing plant in the field.”
Under TSCA, EPA has requirements for new chemical substances, including industrial compounds produced in GE plants. APHIS states that, given its existing oversight, EPA does not currently have an oversight program nor regulations for GE plants that produce industrial compounds, however.
APHIS identified two options that have the potential for adequate federal oversight of outdoor plantings of plants engineered to produce PMPIs. Under one option, APHIS would use other authorities (e.g., 7 C.F.R. Part 360) to regulate outdoor planting of plants engineered to produce PMPIs. Under a second option, a statute would be enacted, or existing statutory authority amended, to grant one or more federal agencies explicit authority to provide oversight of outdoor plantings of all GE PMPI-producing plants and to evaluate GE PMPI-producing plants for all possible risks, beyond plant pest and noxious weed risks. APHIS states that it does not prefer one of these options over the other, nor does it consider the two options necessarily to be exhaustive. Rather, APHIS put them forward to indicate that it is aware of the implications of the proposed rule with regard to PMPIs, and to request specific public comment regarding the best manner to address this issue.
Plant-Incorporated Protectant Small-Scale Field Testing
Certain plants are genetically engineered to produce plant-incorporated protectants (PIP), meaning that they produce pesticides. PIPs fall under the regulatory oversight of EPA. Currently, only APHIS exercises regulatory oversight of PIP plantings on ten acres or less of land. Under the current regulations, APHIS requires permits or notifications for the environmental release of all GE plants that meet the definition of a regulated article and produce PIPs. APHIS states that it exercises oversight of all outdoor plantings of these regulated PIP-producing plants. This oversight includes the establishment of appropriate environmental release conditions, inspections, and monitoring.
According to APHIS, to date, PIP-producing GE plants regulated by APHIS have been genetically engineered using a plant pest as the donor, vector, or vector agent, and thus fall under the scope of a regulated article in the current regulations in Part 340. Under the provisions of the proposed rule, a GE plant that is developed using a plant pest as a vector, vector agent, or donor of genetic materials would not necessarily be regulated. Instead, the GE plant would be regulated only if it had a plant-trait-MOA combination that APHIS has not yet evaluated for plant pest risk or if it was evaluated and found to pose a potential plant pest risk. Additionally, APHIS’ evaluations of GE plants for plant pest risk would generally not require data from outdoor plantings. Even if the plant represents a new plant-trait-MOA combination not previously reviewed, there is a likelihood that many GE PIP-producing plants that are currently regulated under APHIS permits or notifications could be determined not regulated under the provisions of the proposed regulations after a regulatory status review because they are unlikely to pose plant pest risks. Thus, such plants could be grown outdoors without the need for an APHIS permit and without undergoing APHIS oversight.
APHIS states that it understands that this proposal would shift federal oversight of small-scale (ten acres or less) outdoor plantings of some PIPs to EPA. According to APHIS, EPA may decide to require experimental use permits for all, some, or none of such PIPs, and may conduct inspections of all, some, or none of those PIPs under permit. APHIS “is fully committed to coordinating with EPA on these issues.”
APHIS states that it understands that a memorandum of understanding (MOU) and services agreement may be necessary to provide personnel and other resources to assist EPA during the interim period while EPA implements its own program for the oversight of outdoor planting of PIPs of ten acres or less.
APHIS notes that it recognizes that there are challenges associated with such a transition that would also require EPA to incur the costs associated with setting up a revised regulatory program. Further, such a transition would require policies, procedures, and guidance regarding APHIS’ interaction with EPA. APHIS does not consider the approach listed above necessarily to be exhaustive. Rather, APHIS puts it forward to indicate that it “is aware of the implications of this rule with regard to small-scale testing of PIPs and to request specific public comment regarding the best manner to address this issue.”
The proposed rule moves the needle significantly in updating and modernizing the federal government’s approach to evaluating and assessing risks posed by GE organisms. Under the current regulations, a GE organism is a regulated article if the donor organism, recipient organism, vector, or vector agent is a plant pest, or if APHIS has a reason to believe the GE organism is a plant pest. Based on its experience under current regulations, APHIS has compiled evidence that genetically engineering a plant with a plant pest as a vector, vector agent, or donor does not necessarily result in a GE plant that itself poses a plant risk. Additionally, APHIS recognizes that genetic engineering techniques have been developed that do not use plant pests and yet may result in GE organisms that pose a plant risk.
APHIS thus is proposing to revise its regulatory approach to align with current scientific knowledge and to base its decision to regulate on the plant-trait-MOA set of considerations. The focus on the inherent risks of a particular product, as opposed to the method by which the product was made, is correct and aligns with other federal agency approaches to assessing risks.
The proposal’s streamlining of the APHIS permitting process is commendable. Through transparent decision making and permitting developers to self-determine that their GE plants are exempt from regulation (with potential penalties to encourage careful self-determinations), APHIS eliminates a regulatory bottleneck that can stifle innovation and will be able to focus its resources on GE plants that are more likely to pose a risk. The approach set forth in the proposal is a step in the right direction to addressing some of the challenges innovators in this space have faced in commercializing new technologies, as discussed in our report from the Synthetic Biology Project, The DNA of the U.S. Regulatory System: Are We Getting It Right for Synthetic Biology? As discussed there, the pathway to market for new products utilizing evolving technologies can be difficult to navigate, posing a challenge for companies in their efforts to commercialize new ideas. Similarly, the novelty posed by some of these evolving products can make it difficult for regulatory agencies to evaluate risks. Comment is specifically requested on many aspects of the proposal. Stakeholders are urged to review the proposal and comment by August 5, 2019.
As reported in our July 24, 2018, memorandum, “APHIS/USDA Prepare to Revise Regulations Pertinent to Genetically Engineered Organisms,” APHIS signaled on June 29, 2018, its intent to prepare a “programmatic environmental impact statement (EIS) in connection with potential changes to the regulations regarding the importation, interstate movement, and environmental release of certain genetically engineered organisms.” The EIS will have a significant impact on how APHIS chooses to amend its regulation of GE organisms. APHIS requested comment on issues to be considered in preparing the EIS, as well as how to define the scope of the alternatives and environmental impacts. Comments were due July 30, 2018.
On January 4, 2017, the Obama White House announced the release of the 2017 Update to the Coordinated Framework for the Regulation of Biotechnology. The 2017 Update provides a comprehensive summary of the roles and responsibilities of EPA, FDA, and USDA with respect to regulating biotechnology products. Together with the National Strategy for Modernizing the Regulatory System for Biotechnology Products, published in September 2016, the 2017 Update offers a “complete picture of a robust and flexible regulatory structure that provides appropriate oversight for all products of modern biotechnology.” Within that regulatory structure, the federal agencies “maintain high standards that, based on the best available science, protect health and the environment, while also establishing transparent, coordinated, predictable and efficient regulatory practices.” More information is available in our January 9, 2017, memorandum, “White House Announces Release of Final Update to the Coordinated Framework for the Regulation of Biotechnology.”
On March 9, 2017, NAS published a report entitled Preparing for Future Products of Biotechnology, prepared by the Committee on Future Biotechnology Products and Opportunities to Enhance Capabilities of the Biotechnology Regulatory System. Lynn L. Bergeson, Managing Partner of Bergeson & Campbell, P.C. (B&C®), was an external contributor to the Committee’s deliberations and presented before the Committee on the subject of the biotechnology regulatory system. More information on the report is available in our March 13, 2017, memorandum, “National Academies Report Finds Future Biotechnology Products May Overwhelm Agencies.”