U.S. flag An official website of the United States government

On Oct. 1, 2024, the FDA began implementing a reorganization impacting many parts of the agency. We are in the process of updating FDA.gov content to reflect these changes.

U.S. Food and Drug Administration
  1. Home
  2. Animal & Veterinary
  3. Development & Approval Process
  4. Biotechnology Products at CVM: Animals and Animal Food
  5. Intentional Genomic Alterations (IGAs) in Animals
  6. Q&A on FDA Regulation of Intentional Genomic Alterations in Animals
  1. Intentional Genomic Alterations (IGAs) in Animals

Q&A on FDA Regulation of Intentional Genomic Alterations in Animals

Q: What is the FDA doing to regulate intentional genomic alterations in animals?

A: On May 2, 2024, the FDA released Guidance for Industry (GFI) #187A “Heritable Intentional Genomic Alterations in Animals: Risk Based Approach” and draft GFI #187B “Heritable Intentional Genomic Alterations in Animals: The Approval Process.” GFI #187A describes FDA’s risk-based regulatory approach to the oversight of heritable intentional genomic alterations (IGAs) in animals and draft GFI #187B describes how the approval process applies to heritable IGAs in animals. This guidance includes in its scope animals with IGAs developed through use of genome editing technologies, as well as techniques such as the introduction of rDNA constructs through genetic engineering.

Q: What is genome editing?

A: “Genome editing” is a term used to describe a relatively new set of technologies that enable one to make precise changes in the DNA of a plant, animal or other living organism. For example, such technologies can be used to introduce, remove, or substitute one or more specific nucleotides (letters in the DNA code) at a specific site in the organism’s genome. Genome editing is being performed using, for example, clustered regulatory interspersed short palindromic repeat associated nucleases (CRISPR), zinc-finger nucleases (ZFNs), transcription activator-like effector nucleases (TALENs), and oligonucleotide-directed mutagenesis (ODM).

Q: What is the difference between genome editing and genetic engineering?

A: Genome editing is a much more precise method of making changes to the genome of a plant, animal, or other living organism than methods used previously to make such changes. It also allows for the intentional addition, substitution, or deletion of specific nucleotides (letters in the DNA code) in an organism’s genome. Genetic engineering generally allows for the introduction of new DNA (referred to as a recombinant DNA or rDNA construct) into an organism to alter that organism’s genome, but generally without control of the location in the genome in which the insertion of that rDNA construct would occur. With genome editing, researchers and developers of products can direct the changes they wish to make to specific locations.

Q: When did the FDA first issue guidance on the regulation of genetically engineered animals?

A: The FDA first issued draft guidance on the regulation of genetically engineered (GE) animals and their products in 2008. (FDA used the term “GE” to describe the animals within the scope of that guidance to reflect the technology in use at the time. Because IGAs now can also be produced through newer technologies, we are using the more inclusive term, IGA.) After a public comment period, the agency issued final guidance #187 in 2009 to help industry understand the existing statutory and regulatory requirements as they apply to GE animals and to inform the public about the process FDA is using to regulate them. In 2017 FDA issued draft revised GFI #187, which clarified that the scope of the GFI includes IGAs in animals developed with modern molecular technologies including genetic engineering and genome editing. On May 2, 2024, FDA issued GFI #187 as two companion documents, GFI #187A and draft GFI #187B.

Q: How does the agency regulate IGAs in animals?

A: FDA uses a risk-based approach to regulation of IGAs in animals that ranges from; Category 1 products for which we do not expect developers to consult with us prior to marketing an animal containing an IGA; to Category 2 products for which we may not expect developers to submit an application for approval of the IGA if, after looking at data submitted about that product’s risk, we find that we understand the product’s risks for the specified intended use, any identified risks are appropriately mitigated, and we have no further questions for which we would need to see additional data to address; to Category 3 products for which FDA will review and, where the data supports it, approve a product using data requirements that are proportionate to the risk associated with the particular product. FDA’s approval of IGAs in animals ensures that the IGA is safe for the animal, safe for anyone that may consume food from the animal, and that it is effective, i.e. it does what the developer claims it will do. For IGAs that we approve, we also assess the environmental impacts of approving the application and determine if any potential impacts are significant.

Q: When should developers of IGAs in animals first come to FDA?

A: Because the science around IGAs is rapidly developing, the FDA welcomes potential developers to consult with us about appropriate regulation of products. We encourage developers to contact us if they have any questions regarding whether the agency believes the IGAs in animals that they are developing would be appropriate for consideration as Category 2 IGAs for which we would not expect submission of an approval application or, if we do expect submission of an application, what type of data we expect in support of the application. For these reasons, we recommend that developers first come to the agency early in the development process; we can then work closely with them during the investigational phase of the development to ensure that animals do not inadvertently enter the food supply, and that data sets to address safety requirements are developed efficiently and appropriately.

Q: What are the elements of the approval process for IGAs in animals as described in GFI 187?

A: GFI #187B recommends the following with respect to approval applications for IGAs in animals:

  • Product definition: a broad statement characterizing the animal, and the claim being made for the animal;
  • 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 resulting animal and its health;
  • Durability assessment and plan: the developer’s demonstration that the alteration is stable, and that it will remain the same over the lifetime of the product, while continuing to have the same effect.
  • Environmental impact and food safety: the assessment of any environmental impacts, and for food-producing animals whose genomes have been intentionally altered, an assessment of the safety of food derived from those animals for humans and animals;
  • Claim validation: a demonstration that the IGA achieves its intended effect.

Q: Is food from animals with IGAs being held to a different standard than food from plants produced from the same technologies?

A: Under the FD&C Act, food must be safe for consumption regardless of whether it is derived from plants or animals, or whether the genome of the plant or animal it is derived from has been intentionally altered. Although the regulatory process for food from animals with IGAs is different from that for food from plants with such altered DNA, as dictated by different statutory requirements, ultimately, they both must be safe to be marketed legally in the United States.

Q: What is the role of the various components of FDA with respect to IGAs in animals?

A: The FDA’s Center for Veterinary Medicine (CVM) regulates the IGA in the animal, including the effects of the IGA on the safety (i.e. health) of the resulting animal, as well as on the safety of foods from these animals, where relevant. In addition, CVM evaluates whether the IGA results in the effects that have been claimed (e.g., that the animal has a particular, different fatty acid profile or that a biopharm animal produces the pharmaceutical it is supposed to produce).

For animals producing substances to be used in or as drugs, biologics, or devices for use in humans, the Center for Drug Evaluation and Research (CDER), the Center for Biologics Evaluation and Research (CBER), or the Center for Devices and Radiological Health (CDRH), respectively, review such products. For animals producing substances to be used in or as veterinary biologics, USDA/APHIS regulates the veterinary biologic. In addition, CVM will consult with the Center for Food Safety and Applied Nutrition (CFSAN) on food safety issues during its review if a particular question arises for which CFSAN has expertise.

Q: Is FDA working with USDA on the regulation of IGAs in animals?

A: FDA works closely with USDA on various issues related to the regulation of IGAs in animals. FDA and USDA entered into a Memorandum of Understanding that allows the agency to share information about submissions concerning IGAs in animals and describes how the agencies cooperate during the regulatory process.

Q: How are animals with IGAs different from their conventional counterparts?

A: From a scientific perspective, the only intrinsic difference is that these animals contain an intentional alteration of the genome achieved using modern molecular technologies that gives them a new trait or characteristic, such as producing a pharmaceutical, being resistant to a disease, or growing faster. The degree of difference between these animals and their counterparts that do not have intentional genomic alterations will depend on the nature of new trait that the resulting animal possesses.

Q: Will these animals pass their new traits on to their offspring?

A: It depends. IGAs in animals that are developed to be passed on to their offspring are referred to as “heritable.” In general, IGAs are introduced at the early embryo stage or in cells that go on to make embryos that develop into the altered animal. The altered genome is heritable because it will be in every cell of the resulting animal, including those that are responsible for making sperm and egg for the next generation.

In other cases, IGAs are not intended to be inherited—for example, IGAs used for gene therapy in animals. These genomic alterations are not found in the germ cells of those animals, and their offspring will not contain the genomic alteration.

Q: How does FDA address potential environmental risks associated with IGAs in animals? Are concerns different for different kinds of animals?

A: Any potential environmental issues would be a function of the traits introduced into those animals and the conditions under which those animals would be raised. For example, a biopharm animal intended to be kept in a contained environment poses a different set of risks from an animal with an IGA that is intended to be released into the environment. FDA will consider potential environmental effects on a case-by-case basis as required by the National Environmental Policy Act. In general, we recommend that early in development developers consult FDA about potential environmental issues and that they consult with FDA prior to developing their approaches to environmental assessments so that we can agree on the risk questions to be addressed and the resulting scope of the environmental review.

Back to Top