By Lynn L. Bergeson and Carla N. Hutton
On August 29, 2023, the U.S. Department of Energy’s (DOE) Bioenergy Technologies Office (BETO) announced that through the funding opportunity entitled “Accelerating Innovations in Biomanufacturing Approaches through Collaboration Between [the U.S. National Science Foundation (NSF)] and the DOE BETO funded Agile BioFoundry (ABF),” researchers will collaborate with the ABF consortium’s synthetic and bioengineering research projects. BETO and NSF have selected the following projects:
- Enabling Scalable Redox Reactions in Biomanufacturing (University of California, Irvine, and University of California, Davis): This project will enhance the carbon and energy efficiency of a biomanufacturing process by upgrading carboxylic acids into precursors for biofuels and chemicals used in industry. The goal is to create a more efficient process for carboxylic acid reduction that does not release any carbon into the atmosphere. The team will work to identify the principles necessary to enhance efficiency in the enzymes used in the process. Through outreach efforts, the researchers will provide hands-on exposure to science, technology, engineering, and math (STEM) fields for largely Hispanic populations and women, both groups underrepresented in science and engineering.
- A Synthetic Biology Toolbox for Studying Bacterial Transporters (University of Wisconsin -- Madison): This project will develop and use tools to close knowledge gaps surrounding transporters in Gram negative bacteria to facilitate the development of superior biomanufacturing hosts. Specifically, they will work to identify proteins that enhance the uptake of nutrients into the cells of microbes and the removal of toxic products. The work will enable the development of superior biomanufacturing microbial hosts and support translational research. Activities that teach biomanufacturing concepts to K-8 students and recruitment of underrepresented researchers will broaden the impacts of the work.
- Leveraging the Unique Metabolism of Megasphaera elsdenii for Metabolic Engineering to Medium and Long Chain Organic Acids for Use in Jet Fuels and Biomaterials (University of Georgia): The project will work to increase understanding of the metabolic pathways that allow the microorganism Megasphaera elsdenii to produce hexanoic acid, that can be engineered to create sustainable aviation fuel among a host of other products. Understanding how octanoic acid is created in this organism will enable scientists better to convert plant sugars to longer chain molecules and will provide paths for alternative approaches to bioprocessing. The team will recruit students from underrepresented groups and create classroom resources for use in elementary schools.
By Lynn L. Bergeson and Carla N. Hutton
The U.S. Environmental Protection Agency announced on August 4, 2023, that it is providing resources to help biotechnology developers exercise the full benefits of the exemptions available under the Plant Incorporated Protectants (PIP) exemption rule. These resources are available on EPA’s public website and include the following:
The PIPs Exemption Final Rule went into effect on July 31, 2023. More information on the final rule is available in our June 2, 2023, memorandum.
On May 31, 2023, EPA released a final rule exempting two categories of PIPs created using genetic engineering from certain 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. EPA states that the rule ensures that human health and the environment are protected while reducing costs for the regulated community, consistent with the September 2022 Executive Order 14081 on Advancing Biotechnology. According to EPA, the rule may also result in increased research and development activities, commercialization of new pest control options for farmers, and reduced use of conventional pesticides.
EPA notes that the final rule reflects the biotechnological advances made since 2001, when it 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. Specifically, the final rule exempts PIPs derived through genetic engineering from FIFRA registration and FFDCA tolerance requirements in cases where the PIPs are essentially equivalent to those exempted by the 2001 rule.
The rule contains conditions for exempting:
- 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; and
- Loss-of-function (LoF) 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. EPA states that for this category of PIP, “biotechnology developers can 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.”
EPA notes that it indicated in the preamble to the final rule that it would consider exempting additional categories of PIPs from both FIFRA registration and FFDCA tolerance requirements and expanding the categories of PIPs that are allowed the option to self-determine and do not require EPA confirmation of eligibility for the exemption.
By Lynn L. Bergeson and Carla N. Hutton
The Congressional Research Service (CRS) published an updated report on August 4, 2023, on the U.S. Department of Agriculture’s (USDA) Sustainable, Ecological, Consistent, Uniform, Responsible, Efficient (SECURE) rule. The revisions note that USDA’s Animal and Plant Health Inspection Service’s (APHIS) five-year Strategic Plan for fiscal years (FY) 2023-2027 states that “one of its objectives is to ensure the safe development of agricultural biotechnology products using a science-based regulatory framework, including efficient permit review for [genetically engineered (GE)] organisms, clear communication of regulations to stakeholders, coordination with other agencies, and harmonization of regulatory oversight for biotechnology products.”
As reported in in our September 13, 2022, blog item, in 2022, the Biden Administration issued Executive Order (EO) 14081, “Advancing Biotechnology and Biomanufacturing Innovation for a Sustainable, Safe, and Secure American Bioeconomy,” ordering USDA, the U.S. Food and Drug Administration (FDA), and the U.S. Environmental Protection Agency (EPA) to improve further the clarity and efficiency of regulatory processes for biotechnology products and increase coordination and communication among federal regulatory agencies. The report states that FDA “encourages developers of all new plant varieties to request premarket food safety consultations with the agency, which involves a discussion of the safety protocols and regulatory issues before the food is distributed in the market.” The report notes that in response to EO 14081, in May 2023, EPA announced changes to its regulations concerning GE plant-incorporated protectants (PIP). According to the report, these changes exempt certain PIPs from registration and tolerance requirements while implementing a notification process for transparency. EPA “intends to consider additional exemptions and expand the list of categories not requiring EPA confirmation as biotechnology progresses.” EPA’s rule (88 Fed. Reg. 34756) went into effect in July 2023.
According to the updated report, Congress “may be interested in monitoring how USDA’s revised regulatory requirements have affected the development and commercialization of GE and genome-edited products.” The updated report suggests that beyond that, Congress may consider monitoring how USDA, FDA, and EPA are assessing the effectiveness of the revised regulations, “as underlined by the self-determination aspect of the exemption status of new GE and genome-edited products.” The updated report states that further, Congress may also oversee how well the three agencies are working together to harmonize the regulation of biotechnology products moving forward.
By Lynn L. Bergeson and Carla N. Hutton
On August 1, 2023, the U.S. Environmental Protection Agency (EPA) announced the first five product and service categories chosen for the expansion of its Recommendations of Specifications, Standards, and Ecolabels for Federal Purchasing (Recommendations). EPA notes that this action supports the broader effort announced last year to expand the Recommendations by assessing additional standards and ecolabels. EPA states that later in 2023, it anticipates announcing the standards and ecolabels that pass the assessment and will be included in the Recommendations. EPA plans to consider additional product and service categories as resources allow.
EPA states that its Environmentally Preferable Purchasing (EPP) program’s Recommendations help U.S. federal government purchasers identify private sector standards and ecolabels to meet sustainable acquisition goals and mandates. They currently include more than 40 private sector environmental performance standards and ecolabels in over 30 purchase categories. The five product and service categories are:
- Food Service Ware (e.g., containers, cutlery, and dishware);
- Professional Services; and
- Uniforms and Clothing.
According to EPA, the expansion of the Recommendations is a key step toward implementing President Biden’s Executive Order on Catalyzing Clean Energy Industries and Jobs Through Federal Sustainability, as well as the accompanying Federal Sustainability Plan. EPA notes that the plan set ambitious goals, such as achieving net-zero emissions from federal procurement by 2050, maximizing the procurement of sustainable products and services, including products made with safer chemical ingredients.
By Lynn L. Bergeson and Carla N. Hutton
On July 27, 2023, the Organization for Economic Cooperation and Development (OECD) published a new document in its Series on Harmonization of Regulatory Oversight in Biotechnology, Safety Assessment of Transgenic Organisms in the Environment, Volume 10: OECD Consensus Document on Environmental Considerations for the Release of Transgenic Plants. The document addresses environmental risk/safety assessment at a broader level than previous consensus and guidance documents from the Working Party on the Harmonization of Regulatory Oversight in Biotechnology (WP-HROB). The purpose of the document is to describe an approach and provide illustrative examples for planning and structuring risk/safety assessments for the release of transgenic plants into the environment. It provides general information on key concepts and important points on which risk/safety assessors should focus when planning such assessments. According to OECD, these key features include the comparative approach, the familiarity with the biology of the unmodified plant species, the general protection goals, the assessment endpoints, the potential adverse effects associated with the environmental release, the pathways to harm and corresponding risk hypotheses, relevant information elements, and the use of environmental considerations in planning such assessment.
Annexes A through G describe seven examples of environmental considerations routinely examined by assessors and taken from actual experience gained during risk/safety assessment of transgenic plants intended for environmental release. OECD states that these environmental considerations are:
- Invasiveness and weediness;
- Vertical gene flow;
- Organisms (animals);
- Soil functions;
- Plant health;
- Crop management practices; and
- Biodiversity (protected species and habitats/ecosystems).
According to OECD, the set of science-based information and data contained in the volume “constitutes a solid reference and a practical tool for use during the biosafety assessment planning process.” This publication should be of interest to regulators and assessors from national authorities in charge of evaluating the risk/safety of transgenic plants prior to environmental release, as well as to plant breeders and the wider scientific community. The consensus documents published in Volumes 1 to 10 of the Series are available individually free of charge on the OECD Bio Track website.
By Lynn L. Bergeson and Carla N. Hutton
The July 2023 issue of the Organization for Economic Cooperation and Development’s (OECD) Chemical Safety and Biosafety Progress Report includes a summary of the April 2023 meeting of the Party on the Harmonization of Regulatory Oversight in Biotechnology (WP-HROB). During the meeting, WP-HROB agreed on next steps for preparing several consensus documents: “Environmental Considerations for Risk/Safety Assessment for the Release of Transgenic Plants” (led by the WP-HROB Bureau); “Revised Biology of Wheat” (led by Australia and the United States), both expected for publication in 2023; “Biology of the Mosquito Anopheles gambiae” (led by Australia, the African Union Development Agency -- New Partnership for Africa’s Development (AUDA-NEPAD), and the Agriculture & Food Systems Institute (AFSI)); and “Photoautotrophic Micro-algae for Biomass Production” (led by Canada and the United States). In addition, WP-HROB agreed on two proposals for new projects on the biology of mosquitoes, Anopheles albimanus and Anopheles stephensi (led by the United Kingdom, Brazil, and AUDA-NEPAD).
Three projects jointly developed by WP-HROB and the Working Party for the Safety of Novel Foods and Feeds (WP-SNFF) were reviewed at a joint session in April 2023:
- Revision of the OECD Council Recommendation on the safety of recombinant DNA organisms (2006), for which a revised draft was provisionally agreed for most provisions. A progress report will be delivered at the Chemicals and Biotechnology Committee (CBC) meeting in July 2023;
- Enhanced information exchange on new breeding techniques, for which a first set of information has been collected from delegations through a questionnaire; and
- The proposal on the “Safer-Innovation-Approach” in biotechnology, which was formally approved by WP-HROB in follow-up to a two-year pilot project.
The OECD Product Database, containing information on genetically engineered plant varieties approved for cultivation or use in foods and feeds, continues to be updated. A total of 393 entries of 26 crops, flowers, and trees are now available in the system, keeping pace with new information provided by OECD member countries, as well as a number of non-members.
By Lynn L. Bergeson and Carla N. Hutton
On June 27, 2023, the Office of Science and Technology Policy (OSTP) announced the release of a new action plan intended to “rapidly and equitably expand biotechnology and biomanufacturing education and job training programs in the United States.” According to OSTP, biomanufacturing “is a critical aspect of advanced manufacturing that can drive new, sustainable alternatives across industries” and “can unlock new solutions in health, climate change, clean energy, food security, agriculture, supply chain resilience, and national and economic security.” OSTP states that the action plan will help propel continued investment in the bioeconomy and maintain America’s leadership in this sector by preparing more Americans for these jobs and build a diverse pipeline that includes women, people of color, people living in rural communities, and others underrepresented in emerging fields.
The action plan includes the following core recommendations, along with select new and ongoing actions that the Biden Administration is taking and will take -- in collaboration with employers, unions; state, local, and Tribal governments; high schools; institutions of higher education; industry associations; and other stakeholders:
- Expand and diversify the talent pool for biotechnology and biomanufacturing jobs and careers to promote innovation and advance equity;
- Strengthen worker-centered sector strategies and other partnerships between employers, labor organizations, community colleges, and other training providers to grow and diversify the bioworkforce;
- Develop and rigorously evaluate innovative approaches to education and training for biotechnology and biomanufacturing jobs and careers, scaling and promoting those found to be most effective;
- Partner with state, local, and Tribal governments, education and training providers, bioscience associations, unions and other worker-serving organizations, and other stakeholders to raise awareness about the promise and potential of careers in the bioworkforce; and
- Improve data and analytic capacity and cross-sector collaboration to advance equity and support effective workforce development -- including the development of industry-recognized credentials and competency models.
According to OSTP, the Biden Administration is already beginning to implement the action plan by taking the following actions:
- The National Science Foundation (NSF), the U.S. Department of Energy (DOE), and the U.S. Department of Agriculture (USDA) will take action to expand partnerships with Historically Black Colleges and Universities (HBCU), Tribal Colleges and Universities (TCU), and Minority Serving Institutions (MSI);
- The U.S. Department of Education will create cross-sector collaborations through the Unlocking Career Success Initiative and launch a professional learning series focused on bioworkforce needs and the role of K-12 schools and postsecondary institutions;
- The U.S. Department of Labor (DOL) is prioritizing advanced manufacturing, including biomanufacturing, in key grant programs, such as the State Apprenticeship Expansion Formula grant;
- The U.S. Department of Commerce (DOC) will support a National Institute for Innovation in Manufacturing Biopharmaceuticals pilot program designed to attract high school students into biopharmaceutical manufacturing career pathways; and
- NSF, in partnership with DOL, DOC, and other agencies, will convene a forum to build alignment on recognized competency models, development of new competency models where needed, and exploration of credentialing mechanisms for the bioworkforce.
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.
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.
By Lynn L. Bergeson and Carla N. Hutton
On May 26, 2023, the U.S. Environmental Protection Agency (EPA) proposed amendments to the new chemicals procedural regulations under the Toxic Substances Control Act (TSCA). 88 Fed. Reg. 34100. According to EPA, the amendments are “intended to align the regulatory text with the amendments to TSCA’s new chemicals review provisions contained in the  Frank R. Lautenberg Chemical Safety for the 21st Century Act” (Lautenberg Act), improve EPA’s efficiency in the review process, and “update the regulations based on existing policies and experience implementing the New Chemicals Program.” EPA states that the proposed rule includes amendments that would “reduce the need to redo all or part of the risk assessment by improving information initially submitted in new chemicals notices, which should also help reduce the length of time that new chemicals notices are under review.” EPA proposed several amendments to the regulations for low volume exemptions (LVE) and low release and exposure exemptions (LoREX), which include requiring EPA approval of an exemption notice prior to commencement of manufacture, making per- and polyfluoroalkyl substances (PFAS) categorically ineligible for these exemptions, and providing that certain persistent, bioaccumulative, and toxic (PBT) chemical substances are ineligible for these exemptions, consistent with EPA’s 1999 PBT policy. Comments are due July 25, 2023. More information on the proposed rule is available in our May 24, 2023, memorandum.
When EPA receives a premanufacture notice (PMN), significant new use notice (SNUN), or microbial commercial activity notice (MCAN), EPA states that it is required to assess the risk associated with the new chemical substance or significant new use that is the subject of the notice under the conditions of use and make a determination for the chemical substance pertaining to the likelihood of such risk. EPA notes that under TSCA, the term “chemical substance” includes microorganisms. To improve the effectiveness and efficiency of these reviews, EPA proposes to amend the procedural regulations at 40 C.F.R. Parts 720, 721, and 725 to align with the requirements in TSCA Section 5, as amended by the Lautenberg Act, and to make additional updates. In particular, EPA proposes to amend the regulations to specify that EPA must make a determination on each PMN, SNUN, and MCAN received before the submitter may commence manufacturing or processing of the chemical substance, and to list the five possible determinations and the actions required in association with those determinations. In addition, EPA proposes to clarify the level of detail expected for the information that a submitter is required to include in a PMN, SNUN, or exemption notice for the notice to be considered complete. EPA also proposes amendments to the procedures for reviewing PMNs and SNUNs; specifically, procedures for addressing PMNs and SNUNs that have errors or are incomplete or that are amended during the applicable review period. Additionally, EPA is proposing to make several amendments to the regulations at 40 C.F.R. Section 723.50 for LVEs and LoREXs. According to EPA, these amendments would require EPA approval of an exemption notice before the submitter may commence manufacture, allow EPA to inform an LVE or LoREX holder when the chemical substance that is the subject of the exemption becomes subject to a significant new use rule (SNUR) and the chemical identity is confidential, make PFAS categorically ineligible for these exemptions, and codify EPA’s use of the 1999 PBT policy for these exemptions by making certain PBTs ineligible for these exemptions. Finally, EPA proposes to amend the regulations pertaining to suspensions for all TSCA Section 5 notices to allow submitters to request suspensions for up to 30 days via oral or e-mail request.
By Lynn L. Bergeson and Carla N. Hutton
On April 25, 2023, the U.S. Department of Agriculture’s (USDA) Animal and Plant Health Inspection Service (APHIS) announced that it published a new five-year strategic plan. According to APHIS, it incorporates input it received from stakeholders on the strategic framework, a summarized version of the plan that it published in June 2022. The plan includes six strategic goals that focus on working to:
- Protect agriculture from plant and animal diseases and pests. Objective 5 is “Ensure the development of safe agricultural biotechnology products using a science-based regulatory framework.” This includes:
- Conducting efficient risk-based permit review and issuance for organisms developed using genetic engineering to ensure they are safely contained or confined during movement or release;
- Using plain language to communicate clearly APHIS regulations, expectations, and guidance to stakeholders, particularly those working with modified non-plant organisms potentially subject to APHIS regulations; helping stakeholders understand regulations through outreach, workshops, toolkits, and other means; and
- Working with the U.S. Environmental Protection Agency (EPA) and the U.S. Food and Drug Administration (FDA) to increase coordination and harmonization of regulatory oversight for biotechnology products within each agency’s existing statutory framework;
- Cultivate a talented, diverse, and public service-focused workforce where employees are supported, valued, and engaged;
- Reduce the impacts of zoonotic and emerging diseases and climate change. Objective 3 is “Mitigate and adapt to the effects of climate change.” This includes:
- Incorporating climate change scenarios when evaluating the plant pest risk associated with biotechnology products; and
- Working with federal partners to develop clear, efficient, predictable, and risk-based regulatory pathways for safely bringing microbial and other new products that help address climate change to market, and helping developers of such products navigate the regulatory system;
- Maintain and expand the safe trade of agricultural products nationally and internationally. Objective 2, “Maintain and expand the Agency’s leadership role through international standard setting and collaboration,” includes promoting engagement, collaboration, and harmonization of agricultural biotechnology regulation with trading partners, the Organization for Economic Cooperation and Development (OECD), and other international and regional organizations. Objective 3, “Create safe export opportunities,” includes:
- Communicating to international stakeholders about APHIS’ processes and share outcomes of biotechnology product evaluations;
- Working with trade agencies on technical aspects of trade in biotechnology products; and
- Working with the regulatory authorities of U.S. trading partners to harmonize further regulatory frameworks for biotechnology products;
- Manage wildlife damage and threats to agriculture, natural resources, property, and people; and
- Promote the welfare of animals.