Q: What is a genetically engineered animal?
A: A genetically engineered (GE) animal is one that contains an intentional genomic alteration (IGA) made by inserting additional or altered genetic material (e.g., recombinant DNA (rDNA)) through use of modern biotechnology tools. The IGA is intended to give the animal a new trait or characteristic. Examples of the kind of GE animals that are being developed are provided below.
Q: What kinds of GE animals are being developed?
A: Many kinds of GE animals are in development.
- Biopharm animals are those that have undergone genetic engineering to produce particular substances, such as human insulin, for pharmaceutical use.
- Research animals may be engineered to make them 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.
- Xenotransplant animals are being engineered so they can be used as sources for cells, tissues or organs that can be used for transplantation into humans.
- Companion animals that are modified to enrich or enhance their interaction with humans (i.e., hypoallergenic pets).
- Disease resistant animals may be used either for food use or biopharm applications. These animals have received modifications that make them resistant to common diseases, such as mastitis (a very painful infection of the udder) in dairy cows, or particularly deadly diseases, such as bovine spongiform encephalopathy (BSE).
- Food use animals have been engineered to provide healthier meat, such as pigs that contain healthy omega-3 fatty acids at levels comparable to those in fish.
Q: How are GE animals regulated?
A: FDA regulates the IGA in GE animals under the “new animal drug”1 provisions of the Federal Food, Drug, and Cosmetic Act (FD&C Act) and FDA’s implementing regulations for new animal drugs. CVM's Guidance for Industry #187 is intended to help industry understand the requirements that are established by statute and regulations as they apply to IGAs in these animals, including those of the National Environmental Policy Act (NEPA), and to inform the public about the process FDA is using to regulate IGAs in GE animals. The guidance does not create any new obligations. It clarifies how the regulations apply to IGAs in GE animals.
Q: What’s the difference between animal clones and GE 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 rDNA constructs. What can be confusing is that an animal clone can be genetically engineered (i.e., have an rDNA construct introduced into it), and a GE animal can be reproduced by cloning. Our regulatory process covers GE animals, irrespective of whether they were reproduced by cloning. It does not cover animal clones that do not contain an IGA/rDNA construct (“just clones”).
Q: Will GE animals be regulated the same if they’re used for food or if they’re intended to produce pharmaceuticals for people?
A: IGAs in GE 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 GE animals must be approved through the same process as applies to other pharmaceuticals.
Q: Will FDA be looking at effects on the health of animals?
A: Before FDA can approve a new animal drug, it must determine that the drug is safe for the animal receiving it. Therefore, before we can approve an IGA in a GE animal, we must determine that the IGA is safe for the animal containing it. To do that, we look at the health of the animal.
Q: Is food from GE animals in the food supply?
A: On November 19, 2015, FDA approved an application related to AquAdvantage Salmon, a GE Atlantic salmon, and on March 8, 2019, deactivated an import alert pertaining to GE salmon. AquaBounty may now import eggs from the salmon to be raised at its secure land-based aquaculture facility in Indiana. For details on the kinds of studies that were conducted to assess food safety, please see the Freedom of Information Summary, Section IX.
We will not approve any application for an IGA in a GE animal for food use unless we find that the food from those GE animals is safe.
Q: Will food from GE animals be labeled?
A: The United States Department of Agriculture’s Agricultural Marketing Service (USDA AMS) regulates labeling statements concerning bioengineered content for human food such as GE salmon, 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.
Q: What about environmental effects?
A: Environmental evaluation that meets the requirements of NEPA is required prior to any approval. We expect that the environmental risks that GE animals may pose will differ on a case-by-case basis. For example, the concerns raised by a GE cow that is resistant to mastitis will be very different from the concerns raised by a GE fresh-water fish that is engineered to grow more rapidly. We will work closely with individual sponsors of applications for IGAs in animals to make sure that their environmental assessments address all of the potential risks these animals may pose.
Q: Are there any GE animals on the market now?
A: In 2003, FDA chose to exercise enforcement discretion for a GE 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 GE rats and mice used in laboratory research throughout the world.
In addition, as described below, FDA has approved four GE animal-related applications. 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, for the treatment and control of bleeding episodes occurring in adults and adolescents 12 years of age and older with hemophilia A or B with inhibitors.
Q: Do GE animals look different from other animals?
A: Despite some of the doctored photographs that you may have seen circulating on the internet, adding a new gene to an animal does not result in outlandish physical combinations, such as a bird with the head of a rabbit. Genetic engineering simply doesn’t work that way.
Almost all GE animals 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: Are the offspring of a GE animal also considered GE?
A: In general, most GE animals that are being developed at this time are intended to pass their new GE traits on to their offspring. Such traits are called heritable. The initial GE animal and all of its descendants inherit the GE trait. Other GE animals have “non-heritable” traits, meaning that none of the offspring will have the trait.
Q: What exactly does the review process of a GE animal entail?
A: FDA's guidance on regulation of GE animals recommends a review process that includes seven categories:
- Product definition: a broad statement characterizing the IGA in the GE animal and the claim being made for it;
- Molecular characterization of the construct (the IGA): a description of the rDNA construct or other genomic alteration and how it is produced;
- Molecular characterization of the GE animal lineage: a description of the method by which the rDNA construct or other genomic alteration was introduced into the animal and whether it is stably maintained over time;
- Phenotypic characterization of the GE animal: comprehensive data on the characteristics of the GE 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/feed safety: the assessment of any environmental impacts and, for GE animals of food species, an assessment of the safety of food derived from those GE animals showing it is safe to eat for humans and/or animals;
- Claim validation: a demonstration that the animal containing the rDNA construct/IGA has the characteristics that the developer says it has.
Q. How will FDA inform the public about new GE animals, its decisions on them, and the science behind those decisions?
A. FDA’s new animal drug approvals (including for IGAs in animals) are published in the Federal Register, codified in the Code of Federal Regulations, and posted on its website at Animal Drugs @ FDA. 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.
1The new animal drug approval requirements are described in the Code of Federal Regulations under 21 CFR 514.