environmental assessment of genetically engineered animals at cvm (fda) animal biotechnology...
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Environmental Assessment of Genetically Engineered Animals at CVM (FDA)
Animal Biotechnology Interdisciplinary GroupCenter for Veterinary Medicine
U.S. Food and Drug Administration
Evgenij A. Evdokimov, MS, PhD
June 4, 2015
Major Statutes Governing Regulation of GE Animals
Federal Food, Drug, and Cosmetic Act (FD&C Act) Products are regulated; not processes GE animals are regulated under New Animal Drug
Provisions of the Act*
National Environmental Policy Act (NEPA) Procedural; major agency’s actions trigger NEPA
assessment
*Regulated article - article intended to affect the structure or function of the animal (e.g., rDNA construct)
Guidance for Industry 187*
Regulated article = article intended to affect
the structure or function of the animal
(e.g., rDNA construct) Covers all types of GE animals All GE animals in a lineage are covered Event-based, case-by-case evaluation Enforcement discretion and approval paths New Animal Drug Application (NADA) means mandatory
approval prior to marketing Post-market surveillance
*http://www.fda.gov/AnimalVeterinary/DevelopmentApprovalProcess/GeneticEngineering/GeneticallyEngineeredAnimals/default.htm
Are there significant direct or indirect effects from introduction of the GE animal into the environment?
Basis for satisfying NEPA requirements.
Hierarchical Risk-Based Evaluation
Finding of No Significant Impact
(FONSI)
NEPA Process Overview
Regulated Article
May Significantly
Affect
Environmental Impact
Statement (EIS)
NoSignificant
Effects
Record of Decision (ROD)
Environmental Assessment (EA)
BiologicalContainmentPhysical
Containment
Source(s)Escape or
Introduction
Able to Survive
Impact on Target Resources in the Environment
(habitats, wildlife)
Dispersion
Direct and Indirect Effects
Accessible Environments
Able to Reproduce
Establishment
Spread of Transgene(s)
Wild Conspecifics
Feral Relatives
Net Fitness
Geographical/ Geophysical Containment
Conceptual Framework for Environmental Assessment
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Environmental Assessment: General Risk Questions
For a specific GE animal (population) containing a specific regulated article….
– What is the intent (free release or contained use)?• If contained use - what is the likelihood of escape?
– What is the likelihood of survival in the receiving environment?
– What is the likelihood of establishment and reproduction?– What are potential consequences/effects to the environment
associated with introduction/inadvertent release?
Considered in context of an appropriate comparator on a case-by-case basis
Potential Environmental Hazards and Harms
Hazard Harm
Does the rDNA construct introduce any hazardous elements into the animal (e.g., viral or mobilizable sequences, sequencing encoding pathogens or toxins, vectors) (Characterized in Molecular Characterization steps)
Increased probability of new pathogenic recombinants
Do introduced traits affect species fitness or adaptation(Characterized in Phenotypic Characterization)
Increased probability of disruption of existing ecosystems due to establishment of a GE animal in the environment
Fitness
• Fitness affects survival and reproduction
• Net fitness components include– Juvenile and adult viability – Age at sexual maturity – Female fecundity/male fertility/mating success
Impacts
• Pathogen / disease transfer• Genetic disturbance• Resource competition• Displacement• Habitat destruction• Predation
Population changes
Community/Ecosystem disruptions
Consequences of Introduction, Escape, and Dispersion
Will depend largely on:• Specific physical locations of production or release;
• Extent of containment (if applicable);– Physical/mechanical– Biological (e.g., sterility, monosex)– Geographical/geophysical (environmental conditions)– Domestication of species (ability to become feral)
• Mobility of species
Areas of interest
Potential risks associated with introduction of GE animals into the environment that are function of the introduced trait
– Longevity;– Mating behavior;– Stability of genotype and phenotype over time;
Areas of interest
• Do we always need containment for GE animals?
– GE terrestrial livestock intended for food use?– GE animals for population control?– GE animals receiving gene therapy treatment?
• What risks do we guard against?
• Is gene flow a risk per se?
