Eric Schulze, PhDAnimal Biotechnology Interdisciplinary Group

Center for Veterinary MedicineU.S. Food and Drug Administration

Regulation of Animal Biotechnology at FDA: An Overview

1. Overview of Animal Biotechnology

2. Regulatory Process

CVM-ABIG Presentations

1. Overview of Animal Biotechnology• Introduction - Animal Biotechnology• Animal Cloning• Genetically Engineered (GE) Animals

• Food (Milk, Meat, Eggs, Blood, Rennet)• Locomotion/Mechanical Power• Companionship/Rodent Control/• Protection/Herding• Fiber (Feathers, Wool, Hides)• Fuel (Dung, Bones)• Shelter (Hides, Bones)• Medicines (Insulin, Heparin)

Human and Animal Interactions

• Improvements in isolating/characterizing naturally occurring desirable traits by chromosomal mapping, other technologies

• Accelerated introduction of naturally occurring desirable traits by assisted reproductive technologies

• Introduction of new traits by using tools of modern biotechnology genetic engineering

What’s Different Now?

Natural Breeding

Selective Breeding

AI ± Frozen Semen

In Vitro Fertilization

Embryo Split

Animal Cloning

Likelihood of Desired Genetic Outcome for Naturally Occurring Traits

Assisted Reproductive Technologies (ARTS)

Genetic Engineering

Animals With Non-Heritable

Constructs

Animals With Heritable

Constructs

Natural Breeding

Selective Breeding

AI ± Frozen Semen

In Vitro Fertilization

Embryo Split

Animal Cloning

Likelihood of Desired Genetic Outcome

((( (((

Genetic Engineering Is a Tool Separate From ARTS

Introduces Specific, Desirable Traits That May Or May Not Be Naturally

Occurring

Introduces Specific, Desirable Traits That May Or May Not Be Naturally

Occurring

Genetic EngineeringGenetic Engineering

Accelerates the Introduction of Naturally Occurring Desirable Traits into

Herds

Accelerates the Introduction of Naturally Occurring Desirable Traits into

Herds

Assisted Reproductive Technologies

Assisted Reproductive Technologies

The Methods Are Different

Genetic Engineering

GE Animals withHeritable Constructs

Animals with Non-Heritable

Constructs

CloningNatural

BreedingAI ± Frozen

SemenEmbryo

Splitin vitro

FertilizationSelective Breeding

Genetic Engineering

GE Animals withHeritable Constructs

Animals with Non-Heritable

Constructs

Cloning

Genetic engineering is different; occupies different risk space

Animal cloning is on a continuum with other ARTs

Animal Biotechnology (from the Regulator’s Perspective)

1. Overview of Animal Biotechnology• Introduction - Animal Biotechnology• Animal Cloning• Genetically Engineered (GE) Animals

GE animals can be produced via NT, but for regulatory purposes, are considered as "GE" not

"clones“.

≠

GE animals have altered or additional genetic material.

Clones may be thought of as “Twins separated in time”.

Clones v GE Animals

• Food safety• Animal health• Weight of evidence evaluation

Animal Cloning- FDA Risk Assessment

• Most adverse outcomes early in life

• No unique risks; Increased frequency

• LOS seen in cattle and sheep– Surrogate dams– Clones

• No apparent health risks after juvenile period.

Animal Cloning - RA Conclusions:Risks to Animals

“As safe as food we eat every day”

• Clones: Food from cattle, swine, and goat clones that meet federal and state requirements is as safe as food from conventional animals that meets the same requirements

• Clone Progeny: Food from clone offspring poses no additional risk compared with food from other animals

Animal Cloning - RA Conclusions: Food Consumption Risks

• Final release January 15, 2008– USG has no further scientific concerns

• USDA working with industry for “smooth and orderly market transition”– Continues voluntary moratorium on introduction of food from

clones into food supply

– Supply chain management plan driven by industry

Animal Cloning - Current Status

1. Overview of Animal Biotechnology• Introduction - Animal Biotechnology• Animal Cloning• Genetically Engineered (GE) Animals

From Tools to Traits………Ag

ricul

tura

lBi

omed

ical

/Hig

h Va

lue

((( (((

Conformation

Meat/milk quality

EnvironmentalTolerance

↑ ProductivityDisease

resistanceMeat/milk composition

Environmental footprint

Hardiness

Fertility/Fecundity

Biopharm

Xenotransplant

HiVal Products

Disease models cells

organs

tissues

devicesbiologics

drugs

QTL

MAB

CNV

GWAS

Microinjection

Nuclear transfer

Metab-olomics

Prote-omics

Genomics

Breeding

Phenotypeassays

• Enhanced Food Quality/Agronomic Traits/Environmental Benefits– Cows Producing Milk with Long Shelf

Life/Digestibility – Omega-3 Fatty Acid Pork – Milk for Cheese Making

• Animal Health– Mastitis-Resistant Dairy Cows – BSE-Resistant Cattle– Other disease resistance

GE Animal: Products (1)

• Products for Human Therapeutic Use– Chickens/Cattle/Goats for pharmaceutical production – Swine as Xenotransplantation Sources– Cattle/Goats producing anti-biowarfare agents

• Mixed-Use High-Value Products– Goats producing spider silk– Cows producing highly specific

antibody:functional molecule products

GE Animal: Products (2)

• Companion Animals– GloFish

GE Animals: (3)

•GE Animals

http://www.fda.gov/animalveterinary/developmentapprovalprocess/geneticengineering/geneticallyengineeredanimals/default.htm

• Cloning

http://www.fda.gov/AnimalVeterinary/SafetyHealth/AnimalCloning/default.htm

Links to the Website

Adrianne.Jacobs@fda.hhs.gov

Contact Information

AI: Artificial InseminationARTS: Assisted Reproductive TechnologiesBSE: Bovine Spongiform EncephalopathyCNV: Copy Number VariationGE: Genetically EngineeredGWAS: Genome-Wide Association StudiesLOS: Large Offspring Syndrome MAB: Marker Assisted BreedingNT: Nuclear TransferQTL: Quantitative Trait LociRA: Risk AssessmentUSDA: United States Department of AgricultureU.S. FDA: United States Food and Drug AdministrationUSG: United States Government

Acronyms