Phenotypic Characterization Harlan Howard, PhD

Describes the animal, construct, and proposed claim 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? Does the insertion of the rDNA construct pose a hazard to the animal, humans, other animals by feed, or the environment? 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?) Phenotypic Characterization What hazards/risks have been identified in the hierarchical review?

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

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

Hazard to What, Risk to Whom? 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

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

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

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

Phenotypic Characterization: ATryn Conclusions Quality housing; biosecure; highly contained General health, growth, milk production, and reproduction of multiple generations the 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 line of goats is comparable to non-GE herd-mates or historical comparators (except for the presence of rhAT)