Phenotypic Characterization

1. Phenotypic Characterization Harlan Howard, PhD

2. What are the direct and indirect risks posed to the GE animal? (e.g., can surveying the health and other phenotypic characteristics of the animal inform us with respect to risk to the animal and potential human food safety concerns?) Does the insertion of the rDNA construct pose a hazard to the animal, humans, other animals by feed, or the environment? Are there sequences that are likely to contain potential hazards to the animal, humans, or animals consuming food from that animal, or the environment? e.g., does the construct contain mobilizable sequences from viruses that may be endemic in that species? Describes the animal, construct, and proposed claim Phenotypic Characterization What hazards/risks have been identified in the hierarchical review?

3. Phenotypic Characterization Provides basis for • Animal safety evaluation • Hazard identification/utility for subsequent steps in process • Food safety • Environmental safety • Durability • Claim validation • Adjustments to product definition

4. Animal Health: Direct v Indirect/ Intended v Unintended Effects Direct Adverse Effect (Animal Health) • Adverse outcome from rDNA construct insertion • Insertional mutagenesis (disruption of coding region) Indirect Adverse Effect (Animal Health) perturbation from • Construct (insertion into regulatory region of genome) • Gene product perturbing the animal’s physiology Intended effects • Changes resulting from rDNA construct/gene product(s) • May or may not pose direct or indirect effects on food safety Unintended effects • Metabolic changes resulting from the interaction of the rDNA construct or its gene product(s) with the physiology of the animal • May or may not pose direct or indirect effects on food safety

5. Humans consume edible products from rDNA animals and possibly experience food consumption risks rDNA construct produces potential hazard(s) in rDNA animals to be used as food Hazard to What, Risk to Whom?

6. Phenotypic Characterization:Survey of Information-1 May include • Health, veterinary, and treatment records • Physiology • Clinical chemistry • Hematology • Gross/histological pathology

7. Phenotypic Characterization -2 • Performance (growth, lactation, reproduction) • Animal management procedures • Nutrition • Breeding management • Preventative health Determine need for additional studies, depending on unanswered risk questions

8. Phenotypic Characterization:ATryn Effect of introduction of rDNA construct? Safe for the animal? Does it still function as a goat? Health, Husbandry Data/Information Reviewed • Animal breeds, sources, disposition of investigational animals/products • Husbandry methods • Animal identification, housing, feed, milking, reproduction • Health management • Physical examinations, preventative procedures, biosecurity measures, routine health observations, necropsy • Milk production and composition • Production of rhAT in milk

9. Phenotypic Characterization:ATryn Conclusions • Quality housing; biosecure; highly contained • General health, growth, milk production, and reproduction of multiple generations the 155-92 line of goats comparable to non-GE herd-mates/historical comparators • Managed similar to non-GE herd-mates; no special management considerations over several generations • Milk composition of the 155-92 line of goats is comparable to non-GE herd-mates or historical comparators (except for the presence of rhAT)