Q: What is an intentional genomic alteration in an animal?

A: Intentional genomic alterations (IGAs) in animals are alterations made using modern molecular technologies, which may include random or targeted DNA sequence changes, including nucleotide insertions, substitutions, or deletions, or other technologies that introduce specific changes to the genome of the animal. Some of the more commonly used terms for types of modern molecular technology are “genetic engineering” and “genome editing” but there may be other technologies developed over time that can make IGAs.

Q: How are IGAs in animals being used?

A: IGAs in animals are in development for many potential uses.

  • Biopharm: IGAs in animals that are intended to cause the animal to produce particular substances, such as human insulin, for pharmaceutical use.
  • Research: IGAs in animals that are intended to make the animals more susceptible to particular diseases, such as cancer, in order to gain a better basic understanding of the disease for the development of new therapies or in order to evaluate new medical therapies.
  • Xenotransplantation: IGAs in animals that are intended to make better and safer sources for cells, tissues, or organs that can be used for transplantation into humans.
  • Therapies in companion animals (e.g., pets): IGAs in animals intended to enrich or enhance the animals’ interaction with humans (i.e., hypoallergenic pets) or make them resistant to a disease or condition.
  • Disease resistance: IGAs in animals that make the animals resistant to one or more diseases. The animals may be used for food, biomedical applications, or as companion animals.
  • Food:  IGAs in animals to produce healthier meat (e.g., with a healthier fat composition) or to grow more efficiently.

Q: How are IGAs in animals regulated?

A: FDA approval of IGAs in animals ensures that they are safe for the animal, safe for anyone that consumes food from the animal, and that they are effective. FDA’s regulatory system is science and risk-based. For certain products with risks that are understood and mitigated, FDA may not expect submission of an approval application. For those products that go through the approval process, data requirements are proportionate to the risks of the product, for example an IGA in a non-food animal will not require food safety data. For those IGAs that are seeking an approval from FDA, the agency also assesses potential risks from approval of the IGA to the environment under the National Environmental Policy Act (NEPA).

Q: What’s the difference between animal clones and IGAs in animals?

A: The animal clones that were the subject of FDA’s risk assessment on animal cloning (released in January of 2008) are “just clones”—that is, they are copies of individual conventionally-bred animals, and do not contain any IGAs. What can be confusing is that an animal clone can be genetically altered (i.e., be genetically engineered or genome edited), and an animal with an IGA can be reproduced by cloning. Our regulatory process covers IGAs in animals, irrespective of whether they were reproduced by cloning. It does not cover animal clones that do not contain an IGA (“just clones”).

Q: Will IGAs in animals be regulated the same if they’re used for food or if they’re intended to produce pharmaceuticals for people?

A: IGAs in animals are subject to premarket oversight whether they are intended to be used for food or to produce pharmaceuticals or other useful products. There may be some differences in what the actual oversight process entails depending on the kinds of risk(s) the products may pose, and the kinds of uses for which they are intended. In addition, the pharmaceuticals produced from animals with IGAs must be approved through the same process as applies to other pharmaceuticals.

Q: Will FDA be looking at effects of the IGA on the health of animals?

A: FDA’s review process looks at the effect on the health of the animal.

Q: Can any food from animals with IGAs enter the food supply?

A: On November 19, 2015, FDA approved an application related to AquAdvantage Salmon, a genetically engineered (GE) Atlantic salmon. For details on the kinds of studies that were conducted to assess food safety, please see the Freedom of Information Summary, Section IX. In addition, on December 14, 2020, the FDA approved an application for an intentional genomic alteration in a line of domestic pigs, referred to as GalSafe pigs. The meat and tissues from GalSafe Pigs are approved for human food use. On March 7, 2022, FDA completed a risk assessment for genome-edited beef cattle and their offspring and determined that it would exercise enforcement discretion and did not expect submission of an approval application. This is the FDA’s first such risk determination for enforcement discretion for an IGA in an animal for food use. 

Q: How will food from animals with IGAs be labeled?

A: The United States Department of Agriculture’s Agricultural Marketing Service (USDA AMS) regulates labeling statements concerning bioengineered content in certain human food, including AquAdvantage Salmon, under the National Bioengineered Food Disclosure Standard. USDA also regulates the labeling of most meat not covered by the National Bioengineered Food Disclosure Standard, such as meat from the GalSafe pigs. 

Q: What about environmental effects?

A: Environmental review is part of FDA’s review process. We expect that the environmental risks that IGAs in animals may pose will differ on a case-by-case basis. For example, the concerns raised by a highly contained biomedical animal will be very different from the concerns raised by an animal intended for release in the environment. We will work closely with individual developers of IGAs in animals to make sure that their environmental submission addresses all of the potential risks these animals may pose.

Q: Are there any IGAs in animals on the market now?

A: In 2003, FDA chose to exercise enforcement discretion and did not expect an approval application for an IGA in an aquarium fish that fluoresces in the dark. FDA made this decision in part because the fish (Zebra danio) is not a species used for food, and in part because the agency was able to determine that it did not pose any additional environmental risks compared with conventional Zebra danios. (Zebra danios are unable to survive outside the very warm waters of the tropics, which effectively limits the ability of an escaped or released fish to affect the U.S. environment.)

Additionally, there are many different kinds of IGAs in rats and mice used in laboratory research throughout the world.

In addition, as described below, FDA has approved five applications for IGAs in animals. The first was in 2009, when FDA’s Center for Veterinary Medicine (CVM) approved an IGA in a GE goat that produces a human biologic in its milk. The Center for Biologics Evaluation and Research approved the human biologic, ATryn. In November 2015, FDA approved an application related to AquAdvantage Salmon, a GE Atlantic salmon. In December 2015, FDA’s CVM approved an IGA in a GE chicken that produces a human biologic in its eggs. The Center for Drug Evaluation and Research approved the human biologic, Kanuma (sebelipase alfa). In 2019, FDA’s CVM approved a recombinant DNA (rDNA) construct in GE rabbits that produces an active ingredient of a human biologic in the rabbits’ mammary gland and that is secreted into the rabbits’ milk. The Center for Biologics Evaluation and Research later approved the human biologic, Sevenfact. In December 2020, CVM approved an IGA in a line of GE pigs intended for human food use and as a potential source of biomedical uses.  

Q: Does introducing an IGA into an animal cause it to look different from other animals without IGAs?

A: Despite some of the doctored photographs that you may have seen circulating on the internet, making an intentional genomic alteration to an animal does not result in outlandish physical combinations, such as a bird with the head of a rabbit.

Almost all animals with IGAs will look the same as their conventional counterparts, although there are some IGAs that are intended to make the animal look slightly different (such as the GloFish).

Q: Do the offspring of an animal with an IGA also contain that same IGA?

A: In general, most IGAs that are being developed at this time are introduced into animals in a way that results in the IGAs being passed on to their offspring (also referred to as “heritable”). The initial animal and all of its descendants inherit the trait. Other IGAs are not designed to be passed on to any offspring (also referred to as “non-heritable”), meaning that none of the offspring will have the trait.

Q: What does the review process for approval of an IGA in an animal entail?

A: FDA’s guidance on regulation of IGAs in animals recommends a review process that includes seven categories:

  • Product definition: a broad statement characterizing the IGA in the animal and the claim being made for it;
  • Molecular characterization of the IGA: a description of the IGA and how it was produced;
  • Molecular characterization of the animal lineage: a description of the method by which the genomic alteration was introduced into the animal and how it is passed on to any offspring;
  • Phenotypic characterization of the animal: comprehensive data on the characteristics of the animal and its health;
  • Durability plan: the sponsor’s plan to demonstrate that the alteration will remain the same over time, and continue to have the same effect;
  • Environmental impact and food safety: the assessment of any environmental impacts and, for animals of food species, an assessment of the safety of food derived from those animals with IGAs showing it is safe to eat for humans and animals;
  • Claim validation: a demonstration that the IGA achieves its intended effect.

Q: How will FDA inform the public about new IGAs in animals, its decisions on them, and the science behind those decisions?

A: FDA’s approvals, including for IGAs in animals, are published in the Federal Register, codified in the Code of Federal Regulations, and posted on its website here. Following approvals, FDA will also provide electronic access to a summary of all information (other than confidential business or trade secret information) used in FDA’s decisions as part of the freedom of information summary routinely published upon approval. A list of IGAs in animals that, following a risk-based review, FDA has determined we do not expect submission of an application for approval is here.