2. Biotechnology Risk Assessment and Risk Reduction Sally McCammon Biotechnology Regulatory Services Animal and Plant Health Inspection Service, USDA

3. U.S. Coordinated Framework for the Regulation of Biotechnology FDA USDA EPA

4. Federal System APHIS – Regulates the development and field testing of genetically engineered products for safe agricultural use EPA – Ensures that genetically engineered products classified as pesticides are used safely FDA – Ensures that food products are safe and wholesome

5. Trait Viral resistance in food crop Herbicide tolerance in food crop Herbicide tolerance in ornamental crop Modified oil content in food crop Modified flower color in ornamental crop Agency USDA, EPA, FDA USDA, FDA (EPA) USDA (EPA) USDA, FDA USDA

6. APHIS Biotechnology Regulatory Services (BRS) June, 2002 - formed Internal Review Process Keep pace with evolving technology Regulatory program based on science Rigorous and reasonable Dedicate resources and increase capacity

7. BRS Organization

8. Office of Science Scientific input to policy, regulations, and assessments Improve public understanding of scientific base of regulatory policy and decisions Strong working relationships with scientific and technical infrastructure

9. APHIS Statutes and Regulations 1987 USDA-APHIS - 'Plant Pests; Introduction of Genetically Engineered Products' 1993 USDA-APHIS - Notification Procedures 1997 USDA-APHIS - Simplification of Requirements and Procedures 2000 Plant Protection Act

10. 1986-19972001 2002 RESEARCHFIELD – TESTING ANIMAL VACCINES ENVIRONMENTAL IMPACTS FOOD SAFETY PHARM PLANTS ANIMALS INSECTS 1977-1986 HISTORY OF REGULATIONS AND POLICY STATEMENTS

12. Plant Variety Development LABORATORY / GREENHOUSE FIELD TESTING VARIETY DEVELOPMENT COMMERCIALIZATION

13. Animal and Plant Health Inspection Service Regulated Status (“regulated articles”) 1. Importation and Interstate Movement 2. Field Testing/Confined Cultivation Permits - 120 day review; more details Notifications - 30 day review; simplified; certain traits and weeds excluded >For both – State concurrence; sites inspected; field data reports Non-regulated Status Petitions - 180 days, comprehensive scientific reviews Extensions – comprehensive scientific review; some administrative steps are streamlined.

14. APHIS Oversight of Confined Field Tests – Notification or Permit Confined to field test site & no persistence in environment Physical & reproductive isolation Termination, devitalization, disposal protocols Post-harvest monitoring and land use Inspections Review records

15. Petition for Determination of Non- Regulated Status USDA-APHIS Petition received, logged into database Team reviews: Technical completeness Deficiency letter sent Petition withdrawn or denied Petition amended FR notice seeking public comment EA written, OGC review FR notice seeking comment on the EA Determination written – Petition Approved No Yes 60 days 30 days

16. APHIS Approvals: 1987 -2003 APHIS Approvals: 1987 -2003 Field Tests: Field Tests: 9700 authorizations 9700 authorizations 39,000 sites 39,000 sites Petitions for Non-regulated Status: Petitions for Non-regulated Status: 90 Petitions 90 Petitions 58 Granted 58 Granted 24 Withdrawn 24 Withdrawn 8 Pending 8 Pending

17. APHIS Evaluation Biology and genetics of the plant, Nature and origin of the genetic material used, Possible effects on other organisms in the environment and agricultural products.

18. Petition Requirements Crop biology and taxonomy description Genotypic differences Phenotypic differences Field test reports for all releases conducted under permit or notification Relevant experimental data, publications, and unpublished data upon which to base a determination Unfavorable data and information

19. APHIS Evaluation of Effects Potential for creating plant pest risk; Disease and pest susceptibilities; Expression of gene products, new enzymes, or changes to plant metabolism; Weediness and impact on sexually compatible plants; Agricultural or cultivation practices; Effects on non-target organisms; and Potential for gene transfer to other organisms

21. Research Needs National Academy of Sciences Biotechnology Risk Assessment Grants Program Agricultural Biotechnology Risk Analysis Task Force Kay Simmons detail to APHIS

22. National Academy of Sciences 1987 White Paper 1989 Field Testing Genetically Modified Organisms: Framework for Decisions 2000 Genetically Modified Pest Protected Plants

23. National Academy of Sciences 2002 Environmental Effects of Transgenic Plants 2004 Biological Confinement of Genetically Engineered Organisms

24. National Academy of Sciences Ecological Research (PIPS) - 2000 Major goal for traditional and transgenic pest-protected plants Enhance agricultural productivity and foster more sustainable agricultural practices Enhance preservation of biodiversity Decrease potential for health problems associated with PIPs

25. National Academy of Sciences Ecological Research (PIPS) 2000 Plant Incorporated Protectants (PIPS) Bt and Virus-resistance Agricultural practices Impacts of PIPS of nontarget organisms compared with impacts of standard and alternative agricultural practices Encourage uses of resistance management practices if transgenic variety threatens utility of existing uses of pest protectant or functional equivalent

26. National Academy of Sciences Ecological Research (PIPS) - 2000 Molecular basis of pest-plant interactions + population ecology & genetics of target pests to develop ecologically and evolutionarily sustainable approaches to the use of pest- protected plants Specific expression systems that lessen nontarget exposure and delay pest adaptation Monitor ecological impacts of pest-protected crops on long term basis

27. National Academy of Sciences Ecological Research USDA should research, publicize, and periodically revise lists of plant species with feral populations or wild relatives

28. National Academy of Sciences Ecological Research - 2002 Improvement in risk analysis methodologies Improvement in transgenic methods to reduce risks and improve environmental benefits Develop and improve monitoring for effects in environment Social, economic, and value-based issues affecting environmental impacts

29. Research Needs……………….. Research Needs………………..

30. ISSUES Risks vs hazards vs phenomena Scientific issues Public perception Field testing vs unconfined release Adventitious presence Intended vs Unintended effects Baselines, comparators, endpoints

31. Staying on Course Conceptual Framework Build upon rationales Concept of Familiarity – baselines Plant X trait X environment Identify Issues Biodiversity – centers of origin Monitoring Phenomenology vs Hazard Identification Monarchs

32. Framing the Issues Paradigms based upon pesticides Hazard X exposure = risk assessment Non-target effects – assumes target and toxicity Resistance management – post-decision management

33. Molecular Impact of Transgenes Impact of transformation methodologies Location of insertion Impact of deletions Epistatic or pleiotropic effects Genomics, proteomics, metabolomics Stability

34. Traits Biotic and abiotic resistances, nutritional enhancement, pharmaceuticals and industrials Can they be categorized regarding agricultural and environmental effects? Toxicity Fitness Unintended effects at molecular>ecological systems levels Stacked genes Multiple genes in crop plants Cumulative genes in wild relatives

35. Weediness/Invasiveness Baseline research – factors leading to Characteristics associated with invasiveness and associated environmental factors Plant fitness characteristics Semi-domesticated species with wild relatives Sunflower, Sorghum, Turf grasses, Trees Impact of biotic and abiotic resistances on fitness of relatives

36. Gene Flow Field Testing and Unconfined Release Outcrossing – factors & comprehensive data Pollen dispersal, viability, inter-crop fertilization, rate and kinds of gene flow with wild relatives Database on cross fertilization Scale Reduction Factors that reduce or prevent outcrossing New tools and approaches

37. Risk Management – Field Testing Compliance Methodologies for promoting & tracking compliance with protocols Verify if current protocols for confinement are effective Refinement of biological, physical, & temporal measures Technologies for cleaning & removing seed from equipment Development of commercial-scale shipping & storage containers

38. Risk Management Alternative crops to food and feed crops for pharmaceutical or industrial products Do not cross with commodity crops No wild or weedy relatives or do not cross with relatives Bioconfinement technologies GURTS Male sterility Seed sterility

39. Issues Framing the issues Traits Weediness Unintended effects Ecological endpoints Centers of origin Gene flow Confinement Impact of scale Risk assessment methodologies

40. Regulatory Issues Related to Science Domestic - Many new products - New regulatory challenges - Risk mitigation research - Credibility International - Standards for safety not in place - Differences in perceived risk - Precautionary Principle - Traceability

41. APHIS Biotech Website: http://www.aphis.usda.gov/biotech/ US Government Website: http://www.usbiotechreg.gov