The US applies a regulation under existing laws to all biotechnology products, providing a network of agency jurisdictions. In 2015, however, a modernisation of the regulatory system for biotechnology products was initiated, whose main goal was to ‘[e]nsure public confidence in the regulatory system and improve transparency, predictability, coordination, and efficiency of the regulatory system’. The review resulted in two key documents:

1. 2017 Update to the Coordinated Framework (OSTP, 2017), and
2. 2016 National Strategy for Modernizing the Regulatory System for Biotechnology Products (OECD, 2016).

In 2017, the US Administration initiated a review ’[t]o identify legislative, regulatory, and policy changes to promote agriculture, economic development, job growth, infrastructure improvements, technological innovation, energy security, and quality of life in rural America.’ The resulting report by the Interagency Task Force on Agriculture and Rural Prosperity noted that ‘[a]dvancements in genome editing and genomic selection have produced favorable crop and livestock traits, including resistance to drought, disease, and heat; enhancements to nutritional value; and increased resource efficiency. Those technologies, combined with public and private research and development investments, have enabled U.S. farmers to increase the supply and quality of crop and livestock commodities using fewer resources and at lower costs of production.’ (USDA, 2017).

The responsibility for the implementation of the regulation is spread over three separate agencies (Friedrichs, et al.):

• US Department of Agriculture (USDA) Animal and Plant Health Inspection Service (APHIS):
  • Protection of Plant Health, and
  • Safety of Veterinary Biologics.
• US Environmental Protection Agency (EPA):
  • Regulation of Plant Incorporated Protectants (PIPs) and bio-pesticides,
  • Safe use of New Pesticides, and
  • Safe use of Chemicals.
• US Food and Drug Administration (FDA):
  • Safety of Food, Food Additives and Feed, and
  • Safety of Veterinary and Human Drugs, and Human Biologics.

USDA APHIS

USDA Animal and Plant Health Inspection Service (APHIS) regulates biotechnology products through the control of movement (i.e. permits for, or notifications of, import, interstate movement, and environmental release) of regulated articles (living organisms that had been genetically engineered and involving a plant pest as a donor, recipient or vector). Under the “Am I regulated” (AIR) process, APHIS encourages developers to submit letters of inquiry, if they are not sure that their product falls under the relevant regulation; submissions to the process are considered on a case-by-case basis and answered (Friedrichs, et al.).^[1]

In May 2020, the USDA published a new rule on the ‘Movement of Certain Genetically Engineered Organisms’ (USDA, 2020), clarifying its oversight of plants produced through innovative new breeding techniques, such as genome editing. This USDA’s so-called ‘SECURE (Sustainable, Ecological, Consistent, Uniform, Responsible, Efficient) Rule’ codifies new exemptions for genetic modifications in plants, if:

• ‘The genetic modification is solely a deletion of any size; or
• The genetic modification is a single base pair substitution; or
• The genetic modification is solely introducing nucleic acid sequences from within the plant’s natural gene pool or from editing nucleic acid sequences in a plant to correspond to a sequence known to occur in that plant’s natural gene pool; or
• The plant is an offspring of a GE plant and does not retain the genetic modification in the GE plant parent.’

These exemptions are based on the following principles:

• ‘Plants created through conventional breeding have a history of safe use related to plant pest risk;
• The types of plants that qualify for these exemptions can also be created through conventional breeding; and
• There is no evidence that use of recombinant deoxyribonucleic acid (DNA) or genome editing techniques necessarily and in and of itself introduces plant pest risk, irrespective of the technique employed.

When a plant meets one of the above listed exemptions, therefore, it is not expected to pose plant pest risks greater than the plant pest risks posed by plants modified by conventional breeding […].’

The rule explains that it exempts ‘plants generated using plant breeding technologies that have non-templated insertions and deletions and that have a single base pair substitution, because they could otherwise be created by conventional breeding and pose no increased plant pest risk relative to their conventionally bred counterparts’, and that ‘APHIS does not believe it is necessary to regulate off-target effects of genome editing in plants because (1) the off-target mutation rate from genome editing is low relative to the background mutation rate that occurs in conventional breeding, and (2) whatever changes do occur are likely to be segregated away from the target mutation during the breeding process.’

The rule emphasises, however, that ‘APHIS has not, in this rulemaking […], taken the position that genome editing does not constitute genetic engineering. Taking such a position would be inconsistent with the generally accepted scientific characterization of genome editing technology […].’ The rule also outlines the revised detailed information requirements of APHIS.

US EPA

Since 2001, the US EPA exempts plant- incorporated protectants (PIPs) from sexually compatible plants that occurred naturally in the plant or that were moved through conventional plant breeding (40 CFR 174.25) from the United States Federal Insecticide, Fungicide, and Rodenticide (FIFRA) requirements (for example, for product registration/licensing and field testing) (Friedrichs, et al.; EPA, 2015). It furthermore exempts residues of PIPs from sexually compatible plants that occurred naturally in the plant or that were moved through conventional plant breeding (40 CFR 174.508) from the United States Federal Food, Drug and Cosmetic Act (FFDCA) tolerance requirements (for example, for pesticide residues in food or feed, provided the residues are not present in food at levels that are injurious or deleterious to human health) (Friedrichs, et al.; EPA, 2010).

During a meeting at the Organisation for Economic Cooperation and Development (OECD) in June 2018, a US EPA representative noted that the Agency was evaluating the extent to which the current exemptions covered genome edited PIPs and considering approaches to clarify the regulatory status of these materials (Friedrichs, et al.).

US FDA

Plants

The regulatory status of a food (and feed) in the US is ‘dependent upon the objective characteristics of that food, independent of the methods used to develop the food,’ based on an underlying policy outlined in 1992 (Friedrichs, et al.):^[2]

‘Section 409 – Food Additives:

• New components of food will be regulated as additives if they are not generally recognized as safe (GRAS), subject to certain exceptions.
• Food additives require premarket review and approval before they can be lawfully marketed. The safety standard for use of a food additive is reasonable certainty of no harm under the conditions of intended use in food.
• In order for use of a substance to be GRAS:

– there must be reasonable certainty of no harm under the conditions of intended use and general recognition of that fact.’

Animals

The regulation of genetically engineered animals is subject to the following rules (Friedrichs, et al.):

• Federal Food, Drug, and Cosmetic Act (FD&C Act), new animal drug provisions;
• National Environmental Policy Act (NEPA); and
• 2009 FDA Guidance for Industry (GFI) #187 (revised in 2017 to cover genome edited animals – DRAFT): genome edited animals are evaluated as new animal drugs for the safety and effectiveness of the application.^[3]

In 2017, the FDA launched two public consultations on (a) its regulatory approach to genome-edited plant-derived foods, and (b) application of genome editing to animals, but has not yet followed up with an official reaction to these consultations.

[1] Website: USDA APHIS “Am I regulated” (AIR) process (accessed: 10^th March 2023)

[2] Website: Determining the Regulatory Status of a Food Ingredient (accessed: 29^th April 2023)

[3] Website: Q&A on FDA Regulation of Intentional Genomic Alterations in Animals (accessed: 29^th April 2023)