FDA’s Center for Veterinary Medicine’s (CVM) oversight of Intentional Genomic Alterations (IGAs) in animals includes a risk-based evaluation with a particular focus on safety. What this means in practice is that, while IGA developers are generally required to have an approved application for IGAs in animals prior to marketing, as described below, for those alterations that are low risk, the Agency may not expect developers to seek approval of these IGAs.

For IGAs in animals that are in non-food producing species and that are either under other government oversight or are raised in contained and controlled laboratory conditions for research (e.g. mice), CVM has said that it will exercise enforcement discretion without a prior review of data. For other IGAs in animals, CVM has said that it may exercise enforcement discretion on a case-by-case basis if, after a risk-based review, it determines that the product or category of products is low risk to humans, animals and the environment.

Below is a list of those IGAs in animals that, following a risk-based review, FDA has determined are low risk and for which the agency does not expect submission of an application for approval. This is not a determination of “safety” under the Federal Food, Drug, and Cosmetic Act but is instead a determination that a product is low risk enough that it is not an FDA enforcement priority. If FDA becomes aware of new information about risk, it may revisit these decisions.

To increase transparency, FDA, with permission from the developer, intends to publish a summary of the types of data and information it evaluated and its conclusions for low-risk products that are for food use or first of their kind on the market.

IGAs in Animals Intended for Food Use

Acceligen Inc (a Recombinetics Company), PRLR-SLICK cattle, SLICK alteration disrupting Bos taurus g.(NC_037347.1) fs(39099129-39099368) in exon 9 of PRLR gene in Bos taurus (Risk Assessment Summary)

IGAs in aquarium fish, intended to cause the fish to fluoresce

GloFish Red Danio RZF2005 RDNA construct in Danio rerio
GloFish Purple Danio PZF2010 RDNA construct in Danio rerio
GloFish Blue Danio BZF2010 RDNA construct in Danio rerio
GloFish Orange Danio YZF2010 RDNA construct in Danio rerio
GloFish Green Danio GD2006 RDNA construct in Danio rerio

GloFish Orange Tetra YT2012 RDNA construct in Gymnocorymbus ternetzi
GloFish Green Tetra GT2011 RDNA construct in Gymnocorymbus ternetzi
GloFish Pink Tetra RT2012A RDNA construct in Gymnocorymbus ternetzi
GloFish Red Tetra RT2013 RDNA construct in Gymnocorymbus ternetzi
GloFish Purple Tetra PT2013 RDNA construct in Gymnocorymbus ternetzi
GloFish Blue Tetra BT2014 RDNA construct in Gymnocorymbus ternetzi

GloFish Green Barb GB2011 RDNA construct in Puntius tetrazona
GloFish Red Barb RB2015 RDNA construct in Puntius tetrazona
GloFish Purple Barb PB2019 RDNA construct in Puntius tetrazona
GloFish Orange Barb OB2019 RDNA construct in Puntius tetrazona

GloFish Orange Shark OS2016 RDNA construct in Epalzeorhynchos frenatus
GloFish Purple Shark PS2016 RDNA construct in Epalzeorhynchos frenatus
GloFish Blue Shark BS2017 RDNA construct in Epalzeorhynchos frenatus
GloFish Green Shark GS2017 RDNA construct in Epalzeorhynchos frenatus

GloFish Green Betta GBS2019 RDNA construct in Betta splendens
GloFish Orange Betta OBS2019 rDNA construct in Betta splendens
GloFish Pink Betta PiBS2019 rDNA construct in Betta splendens
GloFish Purple Betta PBS2021 rDNA construct in Betta splendens

GloFish Orange Catfish OCA2020 rDNA construct in Corydoras aeneus
GloFish Pink Catfish PiCA2020 rDNA construct in Corydoras aeneus
GloFish Green Catfish GCA2021 rDNA construct in Corydoras aeneus

GloFish Orange Pristella OPM2021 rDNA construct in Pristella maxillaris
GloFish Green Pristella GPM2021 rDNA construct in Pristella maxillaris
GloFish Purple Pristella PPM2021 rDNA construct in Pristella maxillaris

IGAs in animals of food-producing species intended for use as models of disease

Exemplar Genetics, LLC (dba Precigen Exemplar), ExeGen ATM miniswine ATM-NEO RDNA construct in Yucatan Miniature Swine
Exemplar Genetics, LLC (dba Precigen Exemplar), ExeGen LDLR miniswine LDLR-NEO RDNA construct in Yucatan Miniature Swine
Exemplar Genetics, LLC (dba Precigen Exemplar), ExeGen SCN5A miniswine SCN5A-NEO RDNA construct in Yucatan Miniature Swine
Exemplar Genetics, LLC (dba Precigen Exemplar), ExeGen NF1 miniswine NF1 RDNA construct in Yucatan Miniature Swine
Exemplar Genetics, LLC (dba Precigen Exemplar), ExeGen PKD1 miniswine PKD1 +/R3278C-BLAST RDNA construct at exon 29 in Yucatan miniature swine
Exemplar Genetics, LLC (dba Precigen Exemplar), ExeGen CLN3 miniswine CLN3 RDNA construct disrupting exon 7 and 8 of CLN3 gene in Yucatan miniature swine
Exemplar Genetics, LLC (dba Precigen Exemplar), ExeGen MYH7 miniswine MYH7 RDNA construct in Yucatan Miniature Swine
Exemplar Genetics, LLC (dba Precigen Exemplar), ExeGen CLN2 miniswine CLN2 RDNA construct in Yucatan Miniature Swine

Recombinetics, OssaPig-FH-PCSK9 Miniature Swine PCSK9-D374Y RDNA construct in Ossabaw Miniature Swine
Recombinetics, OssaPig-NF-NF1(FS41) Miniature Swine (Sus scrofa (g.(NC_010454.4)43530892C>T + 43530890_43530889insAGCTT in Ossabaw Miniature Swine)
Recombinetics, YorkaPig-HF-RBM20 (Sus scrofa g.(NC_010456.5)121244982C>A + 121244988-121244989CG>TC + 121244991-121244992AG>TC in Yorkshire Breed Large White Swine)
Recombinetics, OssaPig-LD-NASH Miniature Swine (Sus scrofa g.(NC_010447.5) 5087853-5087855GAC>CTG + 5087858G>C + 5087861T>C + 5087864C>G + 5087871-5087873CTC>GAA in Ossabaw Miniature Swine)
Recombinetics, OssaPig-NF-NF1(NS) Miniature Swine (g.(NC_010454.4)43530860G>T + 43530872C>T + 43530892C>T + 43530899T>C) in Ossabaw Miniature Swine

Sus Clinicals, Oncopig Cancer Model, Cre-inducible Neo-KRASG12D-TP53R167H rDNA construct in the ITPRID1 gene in cross-bred swine