FDA Releases Guidance for Industry on Foods Derived from Plants Produced Using Genome Editing

On February 22, 2024, the U.S. Food and Drug Administration (FDA) issued a long-awaited guidance document titled, Guidance for Industry: Foods Derived From Plants Produced Using Genome Editing (Final Guidance). The Final Guidance clarifies FDA’s regulatory approach for assessing the safety of foods intended for human or animal consumption derived from genome-edited plants. In addition, FDA describes two processes through which developers of such foods may voluntarily engage with the agency pre-market depending upon the food’s risk-based characteristics.

Regulatory History: FDA Oversight of Foods Derived From New Plant Varieties

Six years after its initial publication of the Coordinated Framework for the Regulation of Biotechnology (the Coordinated Framework) in 1986, the Office of Science and Technology Policy (OSTP) within the Executive Office of the President (EOP) issued a 1992 update to further outline a risk-based and comprehensive federal regulatory policy for oversight of biotechnology under FDA, U.S. Environmental Protection Agency (EPA), and U.S. Department of Agriculture (USDA) statutes.[1]

That same year, FDA published a Statement of Policy clarifying its oversight of foods derived from new plant varieties under the Federal Food, Drug, and Cosmetic Act (FDCA).[2] The Policy (NPV Policy) explained that use of genetic modification techniques to develop new plant varieties is part of a continuum that includes traditional breeding methods and newer methods like recombinant DNA techniques. FDA clarified that foods derived from genetically engineered plants generally are subject to the same FDCA requirements as other foods, and FDA would regulate such foods using “an approach identical in principle to that applied to foods developed by traditional plant breeding.” FDA explained that the main factors in assessing safety “should be the characteristics of the food product, rather than the fact that the new methods are used.” FDA noted that unintended occurrences of unsafe levels of toxicants in such foods could render the food injurious to health and thus adulterated under section 402(a)(1) of the FDCA, but clarified that FDA normally considers transferred genetic material to be generally recognized as safe (GRAS) within the meaning of section 201(s) of the FDCA given that “[n]ucleic acids are present in the cells of every living organism, including every plant and animal used for food for humans or animals.” With respect to intended expression product(s) present in such foods, such as nutrients, if the substance “is already present at generally comparable or greater levels in currently consumed foods, there is unlikely to be a safety question sufficient to call into question the presumed GRAS status of such naturally occurring substances and thus warrant formal premarket review and approval by FDA.” Likewise, minor variations in molecular structure that do not affect safety would not ordinarily affect the substance’s GRAS status. In contrast, if the intended expression product differs significantly in structure, function, or composition from substances found currently in food, such substance might not be GRAS and thus may be regulated as a food additive. FDA outlined principles for assessing the safety of foods derived from genetically engineered plants and encouraged developers to consult with the agency on safety assessments and the regulatory status of such foods.

In 1996, FDA issued Guidance for Industry on Consultation Procedures under FDA’s 1992 Statement of Policy for Food Derived from New Plant Varieties. The 1996 Guidance outlined an approach through which developers could consult with FDA on safety assessments for foods derived from genetically engineered plants as well as the procedures that FDA would use to conduct such consultations.

Based in large part on advances in science and technology that significantly altered the biotechnology landscape, particularly the development of genome editing techniques, in 2015, the EOP issued a memorandum directing FDA, EPA, and USDA to update the Coordinated Framework and develop a long-term strategy to strengthen the federal regulatory system while supporting innovation. The EOP also established a Biotechnology Working Group, with representatives from the EOP, FDA, EPA, and USDA and, in 2016, the Working Group issued a National Strategy for Modernizing the Regulatory System for Biotechnology Products, which laid out various goals and objectives to strengthen the federal regulatory system while facilitating innovation.

In January 2017, FDA established a docket to receive public comments on the use of genome editing techniques to produce new plant varieties for human or animal food, and invited comment on questions relating to potential food safety risks (2017 Request for Comment).[3] In June 2017, OSTP updated the Coordinated Framework to clarify which biotechnology products are within the authority and responsibility of each agency, the roles of each agency, processes for coordination, and review timelines.

Final Guidance: Application of NPV Policy to Foods from Genome-Edited Plants

In the Final Guidance, FDA explains that based upon the more than 580 comments it received in response to its 2017 Request for Comment and its evaluation of more than 200 new plant varieties since the NPV Policy was issued, it has determined that the NPV Policy’s principles are applicable to foods produced from genome-edited plant varieties. FDA will therefore generally apply the NVP Policy to assess the safety of such foods.

With respect to food for animals, the Final Guidance emphasizes that because an animal food derived from a single plant variety may constitute a significant portion of an animal diet, a change in nutrient or toxicant composition that might be considered insignificant for human consumption may constitute a very significant change for an animal. Therefore, nutrient composition and availability in animal food are especially important safety considerations for animal health.

Regarding potential allergenicity of human food, FDA explains that the potential that a known food allergen could be transferred from one food source to another continues to be a concern. FDA recommends that developers consult with the agency before: (1) transferring genetic material from an organism known to produce food allergens into a different food source; (2) modifying an organism’s genetic material to produce proteins similar or identical to those from an organism known to produce food allergens; (3) attempting to modify the levels of specific allergens in food crops subject to labeling under section 403(w) of the FDCA; or (4) adding to food a new protein whose potential allergenicity is not known.

The Final Guidance clarifies that, like foods from genetically engineered plants, foods from genome-edited plants are subject to the same FDCA requirements as other foods, and FDA’s interpretation of the FDCA as explained in the NPV Policy applies to foods from genome-edited plants. Since FDA issued the NPV Policy, Congress added section 403(w) to the FDCA, which requires the label of a human food containing an ingredient that is, or contains protein from, a “major food allergen” to declare the presence of the allergen, and such requirement also applies to foods from genetically engineered/genome-edited plants.

Voluntary Premarket Pathways for Foods Derived from Genome-Edited Plants

FDA reiterates that food manufacturers must ensure that the products they offer for sale are safe and lawful and, historically, developers of foods from new plant varieties have voluntarily consulted with the agency before marketing such foods. Firms may voluntarily inform FDA of the steps they have taken to ensure the safety of foods from genome-edited plant varieties. For foods from genome-edited plants that have one or more of the specific characteristics identified in the Final Guidance (and thus may be more likely to raise food safety questions or regulatory considerations), FDA recommends that firms use the agency's current voluntary premarket consultation process. For foods with none of the characteristics identified in the Final Guidance, FDA recommends a new premarket pathway – a voluntary premarket meeting.

• Voluntary Premarket Consultation Process: FDA strongly recommends that developers of genome-edited plants with any of the following modifications engage with FDA through its voluntary premarket consultation process:
  • Modifications to endogenous genes that create significant homology to a known allergen relevant to human health or a toxin relevant to human or animal health;
  • Modifications that cause a non-negligible increase in levels of potentially harmful components, including toxicants, allergens, anti-nutrients, and other components that can exhibit non-nutritive physiological effects on humans or animals;
  • Modifications that cause a non-negligible change in the nutritional value of the food;
  • Modifications that change how the plant or food from the plant is used;
  • Modifications that introduce (a) new genes and/or genetic elements that do not naturally occur in that species or (b) additional copies of endogenous genes that are retained in the genome once genome editing is complete.

  The Final Guidance provides examples of modifications that would fall within each of these categories.

• Voluntary Premarket Meetings: For all other modifications, FDA recommends that developers schedule a voluntary premarket meeting to provide FDA with information about the food and its food safety characteristics. FDA intends to summarize each voluntary premarket meeting in a memorandum of meeting and to maintain a list of such meetings on its website. FDA expects this premarket pathway to take less time than a premarket consultation.

FDA expects these processes to improve the efficiency of regulatory processes for biotechnology products, in line with Executive Order 14081, Advancing Biomanufacturing and Biotechnology Innovation for a Sustainable, Safe, and Secure Bioeconomy and ease the pathway to market for foods from genome-edited plants, while keeping FDA safeguards in place.

While the guidance is final, public comments may be submitted at any time at https://www.regulations.gov/ using Docket ID FDA-2019-D-4658.

If you have any questions concerning the material discussed in this client alert, please contact the members of our Food, Drugs, and Devices practice.