Regulating Gene Editing in Livestock

At the beginning of this year, the FDA issued the final version of its Guidance for Industry (GFI) #187B, establishing how FDA will review and approve gene edits and modifications in livestock and other animals. The Breakthrough Institute previously praised the draft GFI, which was published last spring, as a step in the right direction and laid out several recommendations for improvement. We are pleased to see that FDA maintained all positive aspects of the draft guidance and incorporated several of our recommendations for improvement.

FDA initially published Draft GFI #187 in 2017, but reintroduced a significantly improved draft separated into two sections (A and B) in May 2024 after the USDA and FDA issued a memorandum of understanding clarifying that FDA would maintain jurisdiction over intentional genomic alterations (IGAs) in livestock. This ended more than two decades of uncertainty that had plagued companies working on livestock biotechnology. These include Aquabounty Technologies, which initially approached FDA about approval for its genetically engineered, faster-growing salmon in the 1990s and received final approval in 2015. Aquabounty announced in late 2024, after years of regulatory delays and court battles, that it is shutting down.

While not perfect, GFI #187B sets a reasonable standard and process for regulatory approval of food animals with IGAs such as gene edits.

The FDA made a series of improvements between the draft and final guidance, including:

• Draft GFI #187B repeatedly suggested that applicants contact CVM for guidance. The final GFI offers numerous examples better illustrating what to expect from the approval process. As our comment on the draft guidance notes, this is likely to make it easier for developers of IGAs in animals to develop a thorough business plan, which will in turn increase their chances of success and make it easier to attract investors.

• The final guidance requires a degree of evidence of product safety that is more directly related to the actual risk.

  • It clarifies that animals that are “highly mobile” (e.g.: insects, fish) face a greater standard for environmental assessment than animals that are less mobile, such as cows.

  • It explicitly states that applicants should provide information enabling FDA to determine whether the article contains potentially mobilizable DNA sequences or sequences that may encode pathogens, toxicants, or allergens. Articles that do not pose these risks are not subject to unnecessary additional screening for related concerns.

• The draft GFI made the important distinction that animals that are unlikely to contain engineered articles, such as dams carrying genetically engineered embryos, are not subject to special disposal requirements, and may be used for food purposes. The final GFI takes an important additional step by easing disposal requirements for animals that do contain genetically engineered material. First, it clarifies that cremation is not universally required, but composting or burial may be acceptable. Further, if developers receive investigational food use authorization, meat from animals with IGAs may enter the food stream with appropriate precautions. This is notable because companies developing animals with IGAs in the past have lamented the cost and waste associated with cremation of numerous food animals.

The final GFI still imposes several unreasonable standards. It states that researchers should provide evidence of durability from multiple non-contiguous generations. This requirement is onerous for species with long gestation periods such as swine and, especially, cattle. It may take four years or more to produce multiple generations of cattle with an IGA. In this time period, conventional livestock breeders will likely have improved commercial lineages, for example breeding cows with greater milk yields, effectively leaving animals with the IGA behind or even obsolete.

Nevertheless, we commend FDA on their revisions to this important guidance. Clear, risk-based, and efficient FDA review is critical to enable livestock biotechnology to flourish in the U.S. and to retain U.S. scientific leadership in the field. As more applications are submitted to FDA, we hope that FDA continues to learn and update the livestock IGA review process, including identifying common risks, offering companies a more clear expectation for the regulatory review process, speeding the rate of review, and decreasing the cost. Together, this will enable greater innovation to improve the environmental, economic, climate, and animal and human health outcomes of livestock production processes.

You can read our original comment on Draft GFI #187 below: