FDA’s Regulation of 

Intentional Genomic Alterations in

Animals Using Genome Editing

Stella S. Lee, Ph.D.

Animal Bioengineering and Cellular Therapies Team

Office of New Animal Drug Evaluation

Center for Veterinary Medicine

Food and Drug Administration
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Potential Uses of Genome Editing 

in Animals

• To enhance production/food quality traits 

• To improve animal health (e.g., disease resistance)

• To produce products intended for human therapeutic 

use (referred to as “Biopharm animals”) 

– Animals for pharmaceutical production

– Animals for production of tissues for xenotransplantation

• To develop animal models of human disease

• To control human disease transmission 

• To enrich/enhance the animals’ interactions with 

humans (e.g., allergenicity)
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New Animal Drug (NAD)

• Federal Food, Drug, & Cosmetic Act (New Animal Drug 

Provisions) 

– Definition of “drug”: article (other than food) intended to 

affect the structure or any function of the body of man or 

other animals

– Definition of “new animal drug”: any drug intended for use 

for animals other than man

• For approval, NAD application should demonstrate:

– Safety, target animal and food safety (if applicable)

– Effectiveness (ensure the article meets the claim)

• An NAD is considered adulterated if it is marketed 

without FDA approval
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Guidance for Industry 187

• Original Guidance issued in 2009: “Regulation of 

Genetically Engineered Animals Containing Heritable 

Recombinant DNA Constructs”

• Definition of “article”

– Recombinant DNA construct intended to affect the structure 

or function of an animal = new animal drug 

• Intentional genomic alterations may be heritable or 

non-heritable (e.g., gene therapy) 

• For heritable alterations, regulation applies to the 

intentionally altered genomic DNA in both the founder 

animal and the subsequent lineage of animals
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Draft Revised Guidance for Industry 187

• Issued in January 2017 for public comment: 

“Regulation of Intentionally Altered Genomic DNA in 

Animals”

• Scope expanded to animals whose genomes have been 

intentionally altered = “IGA animals”

– random (i.e., using recombinant DNA technology) or targeted 

DNA sequence changes 

– specific changes (i.e., using genome editing or other 

technologies)

• For detailed description:

https://www.fda.gov/downloads/AnimalVeterinary/GuidanceComplianceEnf

orcement/GuidanceforIndustry/UCM113903.pdf
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Regulation of Intentional Genomic 

Alterations to Animals

• Currently 3 NAD applications approved

– Genetically engineered animals containing heritable 

recombinant DNA, including those intended to produce 

human therapeutics

– e.g., Biopharm goat (2009), Biopharm chicken (2015)

• Flexible, risk-based regulatory framework based on 

science 
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New Animal Drug Review Process

• Product definition

• Product characterization

– Molecular characterization of the alteration

– Molecular characterization of the animal lineage

• Phenotypic characterization 

• Genotypic/phenotypic durability assessment and plan

• Environment safety

• Human food safety/feed safety

• Claim validation/effectiveness
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Product Lifecycle Review

Pre-INAD INAD NADA

First 

Contact

Discovery/ Information 

of Proof of Concept Product Development Approval and Marketing

• Jurisdiction Determination

• Regulatory Pathway 

Determination

• Presubmission

Conferences

• Requirement for 

Technical Sections

• Post-Approval 

Reporting 

Requirements

Other FDA Centers*

*For “Biopharm animals”, NADA approval is generally required prior to the 

human product approval as the animal is part of the “manufacturing process” 

for the human product.
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Safety Concerns for IGA Animals

• Off-target genome editing

– Off-targets may vary in different animals, cell types, etc. 

– Multiple off-target prediction/detection methods

– Challenges for thorough evaluation of potential off-targets 

and data analysis

• Unintended consequences of on-target editing

– e.g., animal safety issues with myostatin-edited animals

• Germline alteration: unknown long term effects 

• Other safety concerns
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Considerations for IGA Animals

• Product Definition/Characterization

– What is the intended use? Used for food production?

– What is the intended genomic alteration?

– How is the alteration made? Methods to introduce the 

intended alteration, including the materials used?

– How is the alteration evaluated? 

– How are the potential off-targets evaluated? 

• Animal Safety

– Adverse events due to unintended off-target(s)? 

– Unintended biological consequences of on-target 

alteration(s)?

– Immunogenicity?
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Considerations for IGA Animals

• Environmental/Food Safety

– Level of animal containment?

– Impact on the environment? 

– What are the risks/consequences for interaction with wild 

populations?

– Toxicity?

– Allergenicity?

– Is there an analytical method(s) in place to detect IGA 

animals from non-edited animals if needed?

• Genotypic/Phenotypic Durability

– Durability plan to demonstrate the alteration is stable over 

time
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CVM Contact Information

When?

• Early in development/proof 

of concept studies

• General discussion

• Jurisdiction determination

• Make a recommendation as 

to whether/when the 

sponsor should open an 

INAD or submit to a 

Veterinary Master File 

• Walk you through general 

regulatory obligations and 

responsibilities

Who?

• AskCVM@fda.hhs.gov

• Animal Bioengineering & 

Cellular Therapies

– Project Manager: Sarah 

Bembe 

(sarah.bembe@fda.hhs.gov)

– Leader: Heather Lombardi 

(heather.lombardi@fda.hhs.

gov)
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Concluding Remarks

• Animals whose genomes have been intentionally 

altered, including heritable alterations, are regulated 

using a flexible, risk-based regulatory approach to 

ensure safety to human and animal health

• Recommend early communication with CVM

• Collaborative evaluation within FDA centers and 

government agencies