south east asia conference on current approaches to the environmental risk assessment of genetically engineered crops

june 27 29, 2011 Mvenpick Hotel Hanoi 83a ly tHuong kiet Street Hoan kieM DiStrict Hanoi vietnaM

The Center for Environmental Risk Assessment would like to thank the Biodiversity Conservation Agency of the Vietnam Environment Administration, Ministry of Natural Resources and Environment for their cooperation in organizing this conference. CERA would also like to than the International Life Sciences Institute, South East Asia Region for their support. Funding for this Conference was provided by the USDA Foreign Agricultural Services Emerging Markets Program.

Center for Environmental Risk Assessment ILSI Research Foundation 1156 Fifteenth Street N.W., Suite 200 Washington, D.C. 20005-1743 USA Tel: +1 (202) 659-3306; Fax: +1 (202) 659-3617 E-mail: info@cera-gmc.org URL: http://cera-gmc.org/ Copyright 2011 Center for Environmental Risk Assessment

Table of ConTenTs

Agenda. . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . 5 Speaker.Biographies. . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . 9 Michael A. Caprio, Ph.D. . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . 9 Flerida Cario, Ph.D. . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . 9 John M. Cordts, M.Sc. . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . 9 Monica Garcia-Alonzo, Ph.D. . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . 10 Alan Gray, Ph.D.. . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . 10 Ken-ichi Hayashi, Ph.D. . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . 10 Paul Keese, Ph.D. . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . 11 Robert Potter, Ph.D. . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . 11 Hector Quemada, Ph.D. . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . 11 Dolores A. Ramirez, Ph.D. . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . 12 Andrew Roberts, Ph.D. . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . 12 Patrick Rdelsheim, Ph.D. . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . 12 Jeff Stein, M.Sc. . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . 13 Annabel Waggoner, B.Sc. . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . 13 Abstracts. . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . 15 Problem Formulation: What is it and Why is it Important?. . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . 15 Generating Risk Hypotheses: The Importance of Distinguishing Between Ecological Research and Ecological Risk Assessment . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . 15 What Comes after Problem Formulation Completing the ERA . . . . . . . . . . . . . . . . . . . . . . . . . . 16 Data Quality, Acceptability and Transportability . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . 17 International Consensus on ERA of GM Crops: Contributions from the OECD . . . . . . . . . . . . . 18 Comparative Analysis of Information and Data Requirements for ERA . . . . . . . . . . . . . . . . . . . . . 18 What Does Molecular Characterization Contribute to the ERA?. . . . . . . . . . . . . . . . . . . . . . . . . . . 19 Collecting Data and Interpreting Results from Field Trials . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . 19 Gene Flow to Wild and Weedy Relatives . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . 20 Gene Flow in Centres of Origin: The Case of Rice (Oryza Sativa L.) . . . . . . . . . . . . . . . . . . . . . . . 20 Early Tier Lab Testing for Impacts on Non-Target Organisms . . . . . . . . . . . . . . . . . . . . . . . . . . . . . 21 Semi-field and Field Studies for Assessing Impacts on Non-Target Organisms. . . . . . . . . . . . . . . . . 21 Post Release Environmental Monitoring (PREM) . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . 22 PREM in Europe: What is Driving the Build-up of Requirements? . . . . . . . . . . . . . . . . . . . . . . . . 23 Australias Approach to PREM . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . 24 Insect Resistance Management: Past, Present and Future . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . 24 Appropriate Use of Models and Modeling in Development of IRM Plans . . . . . . . . . . . . . . . . . . . . 25

agenda

day 1 - june 27, 2011

Time Title Presenter

0900 0930

Welcome Inaugural addresses

Dr. Andrew Roberts, CERA, ILSI Research Foundation Dr. Nguyen The Dong, Deputy Director General, Vietnam Environment Administration, MONRE

1000

TEA Session.I:.Problem.Formulation.for.Environmental.Risk.Assessment.of.GE.Plants

1030 1100

Problem Formulation: What is it and Why is it Important? Generating Risk Hypotheses: The Importance of Distinguishing Between Ecological Research and Ecological Risk Assessment What Comes after Problem Formulation Completing the ERA Data Quality, Acceptability and Transportability LUNCH

Dr. Alan Gray, UK Center for Ecology and Hydrology, Emeritus Dr. Andrew Roberts, CERA, ILSI Research Foundation Dr. Monica GarciaAlonso, Estel Consult Ltd. Dr. Paul Keese, Office of the Gene Technology Regulator

1130 1200 1230

Session.II:.International.Approaches.to.ERA.of.GE.Crops 1330 1400 Status of ERA of GE Crops in South East Asia International Consensus on ERA of GM Crops: Contributions from the OECD Comparative Analysis of Information and Data Requirements for ERA TEA Session.III:.PreAssessment.Information.Used.in.ERA 1530 1600 1630 1700 What Does Molecular Characterization Contribute Mr. John Cordts, USDA APHIS BRS to the ERA? Protein Expression Data as Part of the ERA Open floor for questions Close of Day 1 Dr. Flerida Carino, University of the Philippines Dr. Flerida Carino, University of the Philippines Dr. Kenichi Hayashi, OECD Working Group, ViceChair, Emeritus, Japan Dr. Robert Potter, Robert Potter Consulting

1430 1500

day 2 - june 28, 2011

Session.IV:.Selected.Topics.in.ERA 0900 0940 1020 1100 1130 1210 1250 Collecting Data and Interpreting Results from Field Trials Gene Flow to Wild and Weedy Relatives Considering Gene Flow in Centers of Origin or Centers of Diversity TEA Early Tier Lab Testing of NonTarget Organisms Semifield and Field Studies for Assessing Impacts on NonTarget Organisms LUNCH Session.V:.Additional.Science.for.Oversight.of.GE.Plants 1400 1440 1520 1600 1630 1710 1750 1800 Post Release Environmental Monitoring (PREM) Dr. Alan Gray, Center for Ecology and Hydrology, Emeritus Ms. Annabel Waggoner, USEPA Dr. Monica GarciaAlonso, Estel Consult Ltd. Mr. Jeff Stein, Donald Danforth Plant Science Center Dr. Hector Quemada, Donald Danforth Plant Science Center Dr. Dolores Ramirez, University of the Philippines, Los Baos

PREM in Europe: What is Driving the Buildup of Dr. Patrick Rdelsheim, Perseus Requirements? Australias Approach to PREM TEA Insect Resistance Management: The Past, the Present and the Future Appropriate Use of Models and Modeling in Development of IRM Plans Open floor for questions Close of Day 2 Mr. Jeff Stein, Donald Danforth Plant Science Center Dr. Michael Caprio, Mississippi State University Dr. Paul Keese, OGTR

day 3 - june 29, 2011

Recurring.Issues.for.ERA.of.GM.Plants.(Panel.Sessions) 0900 Horizontal Gene Transfer Presenter: Dr. Paul Keese Panellists: Dr. Hector Quemada Mr. John Cordts Presenter: Mr. Jeff Stein Panellists: Dr. Rob Potter Dr. Flerida Carino

1000

Antibiotic Resistance Markers

1100 1130

TEA Herbicide Tolerance Management of GE Crops Presenter: Dr. Andrew Roberts Panellists: Dr. Paul Keese Dr. Monica GarciaAlonso

1230 1300

Open floor for questions CLOSE OF CONFERENCE

sPeaker biograPhies

MiChael a. CaPrio, Ph.d.

Dr. Caprio is a population geneticist in the Biochemistry, Molecular Biology, Entomology and Plant Pathology department at Mississippi State University. His particular interest is in the evolution of traits in heterogeneous habitats, in particular the evolution of resistance to transgenic crops. He has collaborated with the US Environmental Protection Agency (US-EPA) to develop several resistance models and risk assessments. He has worked extensively with probabilistic risk assessment models, using both deterministic and stochastic models to provide science-based risk assessments for both industry and the US-EPA.

flerida Cario, Ph.d.

Dr. Cario is the Physical Scientist member of the Philippine Department of Science and Technology Biosafety Committee. Before Executive Order 514 redefined the composition and function of the National Committee on Biosafety of the Philippines, she was the Physical Scientist of the committee for more than 14 years. A member of the pool of experts from which the Scientific Technical Review Panel of the Bureau of Plant Industry is drawn, she has been part of Philippine delegation to COP-MOP 4 and COP-MOP 5, and has participated in several symposia and in meetings of government-designated technical experts on biosafety. She co-authored a book detailing the history of the commercialization of biotech maize in the Philippines (Modern Biotechnology and Agriculture: A History of the Commercialization of Biotech Maize in the Philippines, STRIVE Foundation 2009). The book was translated into Thai in 2011. She has acted as faculty in several training programmes on food safety for the South Asia Biosafety Program and for the Philippine Department of Science and Technology. Dr. Cario is a full professor of biochemistry at the Institute of Chemistry, University of the Philippines, Diliman, and was a former director of the Institute of Environmental Science and Meteorology of the same University. She holds a Ph.D. from Texas A & M University and has worked extensively with insecticide resistance genetics, biochemistry and molecular biology.

john M. CordTs, M.sC.

Mr. Cordts has been a biotechnologist/risk assessor with the United States Department of Agriculture (USDA)/Animal and Plant Health Inspection Service (APHIS)/Biotechnology Regulatory Services (BRS) for over eight years. He is currently Branch Chief of the Plant Pests and Protectants Branch within the Environmental Risk Analysis Program in BRS. Until January 2010 he was responsible for risk assessment evaluations of field trial permit and notification applications and petitions requesting deregulation of particular genetically engineered plants. He was also responsible for the analysis and writing of environmental assessment documents associated with those petitions. He is currently responsible for overseeing the risk assessment work of a staff of seven biotechnologists. Prior to his work in USDA/APHIS, Mr. Cordts worked as a technician and scientist in USDA/ARS research laboratories for over twelve years at various locations around the United States (West Virginia, Florida, Washington D.C.). His research work revolved around developing genetically engineered varieties of woody plants and grapevines resistant to various plant diseases. Mr. Cordts also worked in Washington State for a small biotechnology company where he managed both lab and vineyard operations. He has co-authored
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over fifteen journal articles or book chapters. Mr. Cordts has an MBA from West Virginia University, an M.Sc. in botany from North Carolina State University, and a B.Sc. degree in horticulture from the University of Maryland, College Park.

MoniCa garCia-alonzo, Ph.d.

Dr. Garcia-Alonzo is the owner of Estel Consult Ltd., an independent regulatory affairs and risk assessment consultancy for agricultural biotechnology and crop protection that provides support for planning and conducting regulatory submissions, risk assessments and training courses. Prior to opening Estel Consult Ltd., Dr. Garcia-Alonzo worked for ICI (later Zeneca and later Syngenta) where she had appointments as entomologist, electrophysiologist, environmental risk assessor and senior regulatory affairs manager that garnered her extensive experience in agricultural biotechnology, ecology and risk assessment. Dr. Garcia-Alonzo earned a degree in Biology specialising in zoology and entomology and a Masters degree in insect physiology and ecology from the Consejo Superior de Investigaciones Cientificas (CSIC), Barcelona and a Ph.D. neurobiology and insect receptor electrophysiology from the University of Reading in the UK.

alan gray, Ph.d.

Dr. Alan Gray retired in 2003 as Director of the Centre for Ecology and Hydrology (CEH), Dorset, UK, following more than 35 years research in plant ecology and genetics, and more than 200 publications mainly on plant ecology, gene flow, population ecology and genetics and the conservation genetics of natural populations of plants. He is currently a CEH Research Fellow, Emeritus. Following a B.A. in Biology and Philosophy and a Ph.D. in Genetics at the University of Keele he joined the Nature Conservancys Merlewood Research Station in 1968, moved to ITE Norwich in 1970 and to Dorset in 1976 where he was appointed Head of Furzebrook Research Station in 1993 and Director CEH Dorset in 1999. He has been a visiting professor at the Universities of Southampton, Bournemouth, Stockholm and Groningen and has held a number of senior committee posts including Chairman of the Governing Body of the Institute of Grassland and Environmental Research, President of the Estuarine and Coastal Sciences Association, Vice President of the British Ecological Society and (currently) Chairman of the Royal Horticultural Societys Conservation and Environment Advisory Committee. He was awarded an OBE in 2003 for services to government and academic science. Dr. Gray has been involved in risk assessment for GMOs since 1990 undertaking research and providing independent advice to the UK Government. He was, first, a member (199499) and then Chairman (19992003) of ACRE (the Advisory Committee on Releases to the Environment) the UKs statutory advisory committee on GMOs. Since retirement he has continued his involvement with the biosafety of GM crops (e.g. on the UK GM Science Review), with science governance and peer audit, and has recently completed, with a co-author, a Flora of British Grasses. In the last two years he has taken part by invitation in GM Biosafety workshops in Argentina, South Africa, Brazil, Italy, South Korea, Mexico, New Zealand, Slovenia, Switzerland, Ukraine and Uganda. Dr. Gray is delighted to be visiting Vietnam.

ken-iChi hayashi, Ph.d.

Dr. Kenichi Hayashi worked for the Japanese Ministry of Agriculture, Forestry and Fisheries (MAFF) on biosafety aspects commencing in 1991 and, from 2004 to 2010, was the ViceChair, Impact Assessment Committee of GMO on Biological Diversity, jointly organized by MAFF and the Ministry of Environment. Dr. Hayashi was long involved in OECD activities as a member of the drafting committee of the so called ScaleUp document (1993) and from 1997 to 2009 as a ViceChair of the Working Group on
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Harmonization of Regulatory Oversight in Biotechnology. In the later 90s, he worked as a government expert for earlier works of the CBD on biosafety issues. Starting in the mid 80s, Dr. Hayashi worked for the Consultative Group on International Agricultural Research (CGIAR), as a Board Member of two CGIAR Centers (CIAT and ISNAR) and as a member of the Technical Advisory Committee (TAC). He also assisted some CGIAR centers on aspects of plant genetic resources. Domestically, he worked at research institutes of MAFF on areas such as the breeding of crop plants, genetic resources, photosynthesis and crop productivity, etc. His later assignments were as the Director General of the Tropical Agriculture Research Center and of the National Institute of Agrobiological Resources. Dr. Hayashi worked as the FAO Regional Rice Improvement Officer located in Thailand. In the early 60s, he was a visiting scientist at Botany Department, Rothamsted Experimental Station, UK. He earned his Ph.D. in Crop Science from the University of Tokyo.

Paul keese, Ph.d.

Dr. Keese is science advisor to the Office of the Gene Technology Regulator (OGTR), Australia, with responsibilities to develop and apply best practice risk analysis for the regulation of GMOs. He also promotes the application of emerging technologies in developing countries by addressing biosafety related issues.

roberT PoTTer, Ph.d.

With over 20 years of experience in plant biotechnology research on three continents, Dr. Potter has seen this technology move from academic research to commercial application. A Ph.D. from Rothamsted Experimental Station, UK was followed by Post-Doc positions in Norway and Australia and four years at Cornell University in the US. Research areas have included plant tissue culture and somaclonal variation, anther culture, developmental gene expression, plant-nematode interactions and the development and application of molecular markers in plant breeding. Recent experience in developing products for application in the developing world led to the realisation that regulatory affairs are currently the biggest hindrance to getting the technology into the hands of the farmers who need it the most. For the past six years Dr. Potter has been working as a consultant in regulatory affairs, supporting private sector product development as well as providing support to projects aimed at establishing biosafety systems in developing countries. Experience from both sides of the fence has led to a pragmatic outlook on how to manage regulatory systems in order to provide access for farmers with minimal risk to health and safety.

heCTor QueMada, Ph.d.

Dr. Quemada is the Director of the Biosafety Resource Network at the Donald Danforth Plant Science Center. This project provides regulatory expertise in support of crop development projects funded by the Bill and Melinda Gates Foundation. He is also the manager of the Biotechnology and Biodiversity Interface grant program, a component of the Program for Biosafety Systems, led by the International Food Policy Research Institute and funded by the United States Agency for International Development. For eleven years, he was the founder and principal consultant for Crop Technology Consulting, Inc., an agricultural biotechnology consulting firm offering services in technical assessment, product development, project management, and regulatory affairs. Before founding his consulting firm, he was the Associate Director of Biotechnology at Asgrow Vegetable Seed Company, where he led a group developing commercial transgenic crop varieties. Dr. Quemada has conducted biotechnology risk assessment research funded by the US Department of Agriculture, and under

11

contract to private companies. His consultancies have included technical and biosafety assessment for national biotechnology programs in India, Philippines, Uganda, Kenya, South Africa, Egypt and Indonesia.

dolores a. raMirez, Ph.d.

Dr. Ramirez is Professor Emeritus of Genetics and Plant Breeding at the University of the Philippines, Los Baos where she has had a long career. She has more than 125 publications and has advised more than 140 graduates. In addition to her work as professor, Dr. Ramirez as served as a member, and from 1996 to 2008 as CoChair, of the National Committee on Biosafety of the Philippines (NCBP), Department of Science and Technology, Philippines. She was also a member of the Board of Trustees of the International Maize and Wheat Improvement Center (CIMMYT), Mexico, and Vice President of the National Academy of Science and Technology, Philippines. She has also acted as Chair, External Evaluation and Advisory Board of the Program for Biosafety Systems (PBS), International Food Policy Research Institute (IFPRI); member, Committee on TWAS Prizes in the Agricultural Sciences, The Academy of Science for the Developing World (formerly, Third World Academy of Sciences, TWAS); and member of the Biosafety Committee of the Department of Science and Technology. At times over a span of 42 years Dr. Ramirez has been Editor-in-Chief of The Philippine Agriculturist; the founding editor of The Philippine Journal of Crop Science and, more recently, The Philippine Journal of Science. Dr. Ramirez has a B.S.A. from the University of the Philippines; an M.Sc. from the University of Minnesota, St. Paul, Minnesota; and a Ph.D. from Purdue University, West Lafayette, Indiana. Her area of specialization was plant genetics (biochemical genetics and cytogenetics).

andrew roberTs, Ph.d.

Dr. Roberts has been the Deputy Director of the Center for Environmental Risk Assessment (CERA), a part of the International Life Sciences Institute Research Foundation (ILSI RF), since December 2009. In addition to serving as the coordinator for the South Asia Biosafety Program (SABP), his responsibilities at CERA include managing expert panels, capacity building activities and authoring scientific papers related to CERAs mission of improving the environmental risk assessment of agricultural biotechnology through the application of sound science. Prior to joining CERA, Dr. Roberts worked at the US Department of Agriculture in several different capacities, all related to the regulation of agricultural biotechnology. He began his career at USDA as an AAAS Risk Policy Fellow in the Office of Science of Biotechnology Regulatory Services (BRS). After spending a year in the New Technologies office of the Foreign Agriculture Service, he returned to BRS to serve in the International Affairs branch, where he remained until joining CERA. Dr. Roberts received his Ph.D. in Cell and Developmental Biology from Rutgers University where he worked on signal transduction in the model nematode C. elegans.

PaTriCk rdelsheiM, Ph.d.

After obtaining a Ph.D. in biology, Dr. Rdelsheim started his career at a Dutch seed company. He then joined Plant Genetic Systems (PGS) N.V., Ghent, Belgium. After being in charge of product development and registration, he was appointed Director Regulatory Affairs and member of the Board.

12

Following the acquisition of PGS, he became Global Head of Biotechnology Regulatory Affairs for the AgrEvo group and remained in this function during the subsequent creation of Aventis S.A. and the acquisition by Bayer. In this function, he ensured the scientific argumentation for product safety and quality as well as the compliance with all regulatory acquirements related to genetic engineering. In 2003 he founded and became General Partner of Perseus BVBA, a service com-pany focused on biorisk management and related regulatory requirements. Biorisk management covers all aspects of biological safety and security such as risk assessment, containment requirements, training, audit, transport, waste handling and emergency preparedness. Dr. Rdelsheim combines a technical background with an in depth knowledge of the European regulatory requirements for biological material, including genetically modified organisms. As Perseus General Partner, he assists clients in complying with complex regulatory requirements on contained use, workers protection, pathogens, import and export, emergency planning, deliberate releases such as field trials and clinical trials and commercial applications. As an internationally recognized risk assessment and risk management expert, he has first hand experience obtaining approvals for and performing activities with genetically modified organisms in the European Union and internationally. He is involved in public biosafety research programmes and provides assistance in the defence of genetically modified products. He is contributing to the establishment of rational approaches for post market monitoring.

jeff sTein, M.sC.

Mr. Jeff Stein is a Biosafety Advisor in the Office of International Programs at the Donald Danforth Plant Science Center in St. Louis, MO, USA. In this role, Mr. Stein provides consultative services to a variety of agbiotech projects underway in Africa and Southeast Asia, facilitating the adoption of biosafety legislation and enabling regulations surrounding this technology. Prior to joining the Center, Mr. Stein spent 20 years in research and development at Syngenta Seeds, including as director if its biotechnology regulatory affairs team in North America.

annabel waggoner, b.sC.

Ms. Annabel Waggoner serves as an interdisciplinary regulatory scientist at the US Environmental Protection Agency (EPA) in the Office of Pesticide Programs Biopesticides and Pollution Prevention Division for over seven years. Originally hired through the EPAs Outstanding Scholar Program, Ms. Waggoner has since become the lead evaluator for conducting environmental risk assessments on the effects on non-target organisms (NTOs) from insect-resistant genetically modified (GM) transgenic crops (termed Plant-Incorporated Protectants or PIPs) for the regulatory approval of experimental field testing and commercial registrations of PIPs in the US. Ms. Waggoner offers the unique perspective as a risk assessor for reviewing both human health effects in GM food safety assessments and environmental risk assessment in context with the US EPAs federal statutes mandating the safety and protection goals of human health and the environment. She has much international experience in presenting EPAs regulatory and review process for PIPs to a variety of scientists from government, academia and the public and private sector. Back in the US, she provides similar guidance and technical expertise to visiting foreign delegations and post-doctoral fellows; as well as consults developers/applicants on the specific data requirements needed for their preparation of an acceptable data package. Ms. Waggoner is also designated as the lead writer for EPAs standard test guidelines for PIP studies on environmental fate and effects on NTOs, which is currently under development in conjunction with the proposed rule for the official federal codification of EPAs data requirements for registering PIPs.

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absTraCTs

ProbleM forMulaTion: whaT is iT and why is iT iMPorTanT?

Alan.Gray,.Ph .D .. Research Fellow, Emeritus, Centre for Ecology and Hydrology, Wallingford, UK, Email: ajg@ceh.ac.uk.

Assessment of the potential environmental impact of cultivating genetically modified (GM) crops now has a long and somewhat chequered history. Initially, with no global standard-setting body, environmental risk assessment (ERA) in many countries involved an attempt to establish that such crops were safe by discounting their adverse impact on a wide range of environmental and ecosystem services. Emphasising the complexity, interrelatedness and supposed fragility of biodiverse ecosystems, such approaches generated long lists of imaginable adverse effects or harms. (Ecologists were even asked to consider unimaginable harms!). Among the outcomes of this approach has been the generation of vast amounts of research aimed at better understanding this complexity but often of doubtful relevance to ERA, the burgeoning growth of the dossiers required to meet regulatory approval, and the fact that, in many areas ERA has moved very slowly and not very far beyond the what could go wrong? question. In recent years the wider application of a problem formulation (PF) approach has offered a more structured and targeted procedure. Derived from the risk assessment of agrochemicals, and boasting a literature that can be rather academic and jargon-rich, PF at its simplest is about framing the relevant questions and coming up with a plan to answer them. In this talk Dr. Gray introduces some of the key concepts in PF (e.g., protection goals, assessment endpoints, risk hypotheses) by asking four straightforward questions that he believes delineate the process and hopefully provide a helpful starting point for the ERA of novel crops. These are: 1. What do we want to protect (or not see harmed)? 2. Can we envision a way in which they could be harmed (by the cultivation of a particular crop)? 3. How can we assess whether they are likely to be harmed? and 4. Does it matter (what is the regulatory context)? Dr. Gray will illustrate this process with an example (the possible invasiveness of oilseed rape in the UK and Northern Europe).

generaTing risk hyPoTheses: The iMPorTanCe of disTinguishing beTween eCologiCal researCh and eCologiCal risk assessMenT
Andrew.Roberts,.Ph .D .. Deputy Director, Center for Environmental Risk Assessment, International Life Sciences Institute Research Foundation, Washington, DC, Email: aroberts@ilsi.org.

Although ecological risk assessment is a scientific endeavor, there are a number of defining characteristics that make it distinct from ecological research. An ecological risk assessment is an estimate of risk at a given point in time. It exists to support decision making and must be understandable to decision makers, relevant to the decision being considered and delivered in a timeframe that is appropriate for the decision. This is
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very different from ecological research, which is a slow and constant process for characterizing and refining our understanding of the way the natural world behaves. The first regulatory approvals for GE plants were issued in the mid 1990s, preceded by analyses of potential adverse environmental impacts. Over the last 15 years, the size of these ecological risk assessments has grown along with the amount of data that is generated in support of regulatory applications. The justification for much of this additional data has been driven by scientific, social and political controversy surrounding the use of GE technologies in the environment. However, this response relies on several faulty assumptions that confuse ecological risk assessment with ecological research. The result has been increasingly complex and costly risk assessments, which can confuse rather than clarify the decision-making process. Problem formulation is an important first step in risk assessment. It allows the assessor to identify the potential risks that will require attention from the assessment. A risk hypothesis is a defined and testable statement that can be either refuted or corroborated to provide evidence of risk or safety. By identifying risk hypotheses, which are likely to be informative, a risk assessor can focus the ecological risk assessment and the accompanying data on relevant considerations. This is important because an ecological risk assessment must be timely, transparent and accessible to decision makers. Proper identification of risk hypotheses can help a risk assessor avoid the pitfall of confusing ecological risk assessment with ecological research.

whaT CoMes afTer ProbleM forMulaTion CoMPleTing The era

Monica.Garcia-Alonzo,.Ph .D .. Consultant, Estel Consult Ltd., UK, Email: mgarcia@estelconsult.com.

As part of the regulatory approval process for commercial cultivation of genetically modified (GM) crops, many countries require an assessment of the potential adverse effects that these crops may have on human and animal health and the environment. The methodology to be used for these risk assessments has been a major subject of debate for many years. However, a conceptual framework is now widely accepted by risk assessors, regulators and the scientific community. The first step within this framework is problem formulation, which consists of collection of relevant information to address the key questions posed by regulatory requirements and an initial risk characterization that allows risk assessors to decide whether risk can be characterized with the information already available or whether more information needs to be collected. If more information is necessary to complete the risk assessment, problem formulation provides a useful tool for developing targeted analysis plans based on the formulation of testable hypotheses and the measurement of relevant endpoints. This ensures that the risk assessment is fit for purpose and addresses all relevant questions without wasting resources in producing data that does not bring additional information for decision making. One of the challenges when conducting an environmental risk assessment (ERA) for a regulatory submission is to have a clear understanding of the key questions that the assessment must address (protection goals). These are determined by local regulations and can vary from country to country. Once the key questions are established, the risk assessor must gather information already available in order to make an initial risk characterisation that will determine whether more data is needed or not and if so, an analysis plan is developed. However, for an ERA to really fulfil its purpose, the ERA must be presented in a clear and logical way so the rationale behind each of the risk conclusions can be easily followed by reviewers and hence facilitate the review and the decision making process for regulatory authorities. In this talk, the application of problem formulation for the preparation of high quality ERA for regulatory submissions will be discussed, as well as some key concepts and best practices.

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daTa QualiTy, aCCePTabiliTy and TransPorTabiliTy

Paul.Keese,.Ph .D .. Science Advisor, Office of the Gene Technology Regulator (Australia), Email: paul.keese@ health.gov.au.

Determining the quality of the data includes consideration of: Appropriateness. the degree to which the data are relevant and applicable to the risk assessment question; Reliability.  the accuracy and integrity of experimental design, methodology, and statistical analysis used to report data and conclusions; Transparency. the clarity and completeness with which all key data, methods and processes, as well as the underlying assumptions and limitations, are documented and available; Expertise. the standing of the author(s) or expert(s) presenting the data; Strength. how much data there is to support the conclusion in the scientific literature; whether there is conflicting data and the strength of the conflicting data; and Robustness. if data from disparate sources, experiments or researchers support similar conclusions.

Each piece of information may be ranked differently against these criteria and, where contradictory information exists, the risk assessor must judge the relative strength of each piece. Some information may be redundant or not of high enough value to be used as evidence. Factors that may influence the relevance and value of the information include whether the: Subject of the experiment is identical, similar or different to the gmo being assessed. Experiment is addressing a question relevant to the risk assessment. Experiment was performed locally or overseas.

Scientific papers published in peer-reviewed journals generally provide some assurance of quality; however, even such papers can vary in quality. It is important to check that the conclusions of the authors or experts presenting particular evidence are supported by associated data and by other data reported by different authors. A judgment may also be made about the expertise of the authors or experts presenting the data. Peer-reviewed papers are often regarded as high value evidence, but they are not automatically accepted and used in the risk assessment without further evaluation. Their appropriateness, transparency and robustness are all factors in determining how much reliance is placed on each piece of evidence. The combined weight of evidence may also influence the risk assessment, a single strong piece of information (as judged by the above criteria) may stand on its own or a number of weaker pieces of evidence may support each other in order for the risk assessor to have sufficient confidence in the information. In addition, judgment is needed to determine the sufficiency of the data to achieve a reliable and robust estimate of risk following a consideration of uncertainty. Collection and assessment of unnecessary or excessive data is an inefficient use of resources. Where a regulatory agency of another country has made an assessment of the same or a similar GMO, their findings can also be considered during the risk assessment. In addition, international agencies and agreements, such as the OECD or the Cartagena Protocol on Biosafety, produce documentation that contributes to harmonisation of regulatory activities between countries, which simplifies consideration of other countries assessments.

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It is important to consider not only the available information, but also uncertainty associated with the evidence. For example, if data regarding a proposed dealing with the GMO are unavailable, inconsistent or incomplete, the significance of that absence, inconsistency or incompleteness will be considered in the risk assessment process.

inTernaTional Consensus on era of gM CroPs: ConTribuTions froM The oeCd

Ken-ichi.Hayashi,.Ph .D .. Vice chair, emeritus, OECD working group.

The Organization for Economic Cooperation and Development (OECD) is an intergovernmental organization established in 1961 and has been promoting various activities to contribute to sound economic growth and development of member and non-member countries. Since the mid 1980s, OECD has been implementing various projects to promote international consensus on ERA of GM crops. In particular, the Scale-Up document was published in 1993 that established an important concept familiarity having enough information to judge and conduct science-based ERA , which constituted a fundamental pillar for ERA including the initiation in 1995 of the Working Group on Harmonization of Regulatory Oversight in Biotechnology (WG). A series of projects have subsequently been implemented with major outcomes of publications of valuable documents. These include: Biology Consensus Documents, Trait Consensus Documents, Unique Identifier, Points to Consider, Molecular Characterization, Low Level Presence (LLP) and Environmental Considerations. All of these documents have been and will be well-recognized and utilized for promoting consensus on ERA of GM crops in various sectors worldwide.

CoMParaTive analysis of inforMaTion and daTa reQuireMenTs for era

Robert.Potter,.Ph .D .. Consultant, Robert Potter Consulting, Ottawa, Canada, Email: rpotter@robpotterconsulting.com.

There is broad consensus on the kind of information required for food safety assessment, in part due to the international agreements on food safety brokered by the Codex Alimentarius Commission. In the absence of a similar body dealing with environmental risk analysis, there are no international agreements and the potential exists for quite different data being required. Finding out the extent of such differences would be useful to developers and regulators. A survey of published information requirements for environmental risk analysis of transgenic plants was supplemented by direct communication with regulatory staff in eight countries. This was supported by reviews of published applications (where these are available) to identify the type of data submitted by the developer. Data requirements were grouped by the areas of information into a broad area that was common to all assessments (food and feed and ERA) and data that was specific to ERA. The following list shows the broad outline of the information in each group.

Core.Characterization.. Host.and.Donor. Molecular.Analysis. Expressed.Material/Effect. Inheritance.and.Stability Environmental.Risk.Assessment

Phenotypic characterization Cultivation practices Gene flow to related plants or unrelated organisms Secondary and non-target adverse effects Other environmental interactions

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Overall, there is a very broad similarity between countries in the information requirements for the core characterization areas. Part of this is probably due to the fact that this same information is nearly always part of the food safety analysis, which conforms to Codex standards. In areas specific to ERA there are greater differences in the specific information requirements. In particular, there are usually fewer listed requirements in countries with less experienced regulatory systems, although it is likely that similar information to that submitted to other countries will be expected as similar dossiers will have been used by developers in the past. The gap between what is listed and what is expected may be an issue with submissions that do not originate in developed countries.

whaT does MoleCular CharaCTerizaTion ConTribuTe To The era?

Mr ..John.M ..Cordts,.M .Sc .. Branch Chief, Plant Pests and Protectants, Environmental Risk Analysis Program, Biotechnology Regulatory Services, Animal and Plant Health Inspection Service, United States Department of Agriculture, Email: john.m.cordts@aphis.usda.gov.

With the advent of the use of techniques of modern biotechnology, scientists have been able to introduce specific genes of interest into many plants and track and evaluate gene expression in these transformed plants. The molecular analysis of these plants typically includes a characterization of the inserted genes, expressed proteins and/or mRNA levels. Some data typically seen by US regulators includes Southern blots to characterize inserted DNA (or lack of plasmid backbone sequences), and some quantitative assessment of protein or RNA expression. Any one of several different methods is typically satisfactory to make these basic evaluations. Assessments for inheritance and stability within the plant genome are typically also required by national regulatory agencies. In consideration of the 20+ years of safe deployment of genetically engineered plants, it appears that extensive molecular characterization provides limited value to informing environmental risk assessments.

ColleCTing daTa and inTerPreTing resulTs froM field Trials

Jeff.Stein,.M .Sc .. Biosafety Advisor, Office of International Programs, Donald Danforth Plant Science Center, Email: Jstein@danforthcenter.org.

The conducting of confined field trials is an integral step in the research and development of genetically modified crop plants prior to commercial deployment. During this phase of research and development, individual transgenic events are evaluated for agronomic performance and trait efficacy under typical crop management conditions in geographic locations that the crop is anticipated to be planted commercially. The transgenic events are scrutinized for a broad range of traits and are evaluated side-by-side with their non-transgenic counterpart. Those events demonstrating superior trait expression while exhibiting no biologically-significant agronomic or phenotypic differences compared to controls are advanced to the next phase of commercial development. Confined field trials may also provide an opportunity to collect data relevant to an environmental risk assessment, conducted as a component of the regulatory review process. The nature and scope of any in-field study should be designed to answer specific questions regarding environmental risks when highly controlled laboratory-based studies do not satisfactorily address the data needs. Examples of potential data categories include assessing unintended changes in susceptibility to a pest or pathogen, alterations in reproductive phenotype that might lead to increased weediness potential, and studies relevant to assessing insect resistant management. Because of the inherent variability associated with studies conducted in the field, protocol and trial design are critical factors to be thoroughly investigated prior to initiating data collection for the environmental risk assessment.

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gene flow To wild and weedy relaTives

Hector.Quemada,.Ph .D .. Director, Biosafety Resource Network, Donald Danforth Plant Science Center, Email: hquemada@danforthcenter.org.

The risks posed by the possible outcrossing of specific transgenes into wild and weedy relatives are typically addressed in environmental risk assessment prior to a decision to allow commercial release of a transgenic crop. These risks can be systematically assessed, with application of problem formulation as a guide to identifying the critical information required. The typical approach to assessing risks posed by transgene flow to wild and weedy relatives will be presented, and examples of the application of this approach will be provided.

gene flow in CenTres of origin: The Case of riCe (oryza saTiva l.)
Dolores.A ..Ramirez,.Ph .D .. Professor of Genetics and Plant Breeding, emeritus, University of the Philippines, Los Baos, Email: daruplb@yahoo.com.

Gene flow refers to any movement of genes from one population to another resulting in a marked change in gene frequency. Gene flow within a population increases its genetic variation. On the other hand, gene flow across populations enhances genetic similarity of these populations, hence reducing the chances of speciation. Gene flow may be horizontal (between unrelated species) or vertical (between closely related species). Two centers of origin of rice have been identified: West Africa for Oryza glaberrima and Tropical and SubTropical Asia for Oryza sativa L. Oryza sativa L. originated from the wild grass Oryza rufipogon and is believed to be the product of continuous selection for desirable traits by early farmers. This may explain why there has been no drastic morphological modification or genome duplication during domestication. At present, the geographic ranges of O. sativa and O. rufipogon overlap throughout Asia. O. rufipogon has evolved and formed a complex of Oryza nivara (annual, photoperiod insensitive, self-fertilized and adapted to seasonally dry habitat) and Oryza rufipogon (perennial, photoperiod sensitive, largely cross-fertilized, and adapted to persistently wet habitat) and are widely distributed in South and Southeast Asia. There has been no major reproductive barrier between O. sativa, O. nivara, and O. rufipogon, hence a continuous gene flow between rice and these two wild relatives. A series of intermediate admixes have been observed. In addition, the weedy rice type or red rice (Oryza sativa L.f. spontanea) is a common weed in many rice fields and has been shown to be cross compatible with O. sativa. There are other Oryza species of the AA genome that have the potential to hybridize with rice and with each other, namely; O. longistaminata (a perennial species) and O. barthii (an annual species). These two species are widely distributed in South America. On the other hand, other species belonging to genomes BB, CC, BBCC, CCDD, EE, FF, GG, JJHH, and JJKK usually have significant reproductive isolation, making them unlikely to hybridize under natural conditions. Initially, two sub-populations of O. sativa were identified: Indica and Japonica. At present, based on morphological and molecular characterization, five sub-populations have been identified, namely; Indica, Aus/Boro, Tropical Japonica, Temperate Japonica, and Aromatic (Basmati/Sadri). No reproductive barriers between these sub-populations have been observed. Evidence of gene flow has been reported in the United States, China, and Europe. Natural outcrossing between rice and weedy rice ranged from 0.1 to 3. 2%. Experimental outcrossing resulted in 8 to 72% seed set. Other experiments to determine gene flow showed natural outcrossing between rice and O. rufipogon, O. nivara and O. sativa L.f. spontanea, with seed set ranging from 0.05 to 2.94%. The distances over which pollen flow were detected ranged from 30 to 110 meters.

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early Tier lab TesTing for iMPaCTs on non-TargeT organisMs

Annabel.Waggoner,.B .Sc .. Environmental Protection Specialist, Office of Pesticide Program, Biopesticides and Pollution Prevention Division, US Environmental Protection Agency, Email: waggoner.annabel@epamail.epa.gov.

Ms. Waggoners presentation will provide an overview of the Environmental Protection Agencys (EPA) current scientific review process for the environmental risk assessment of genetically engineered insect-resistant transgenic crops (termed plant-incorporated protectants or PIPs) for the purposes of regulatory approval of experimental field testing and commercial cultivation of these crops in the US. The presentation will discuss the tiered testing approach for determining potential adverse effects related to the use of PIPs on non-target organisms (NTOs) and the environment by utilizing early tier laboratory toxicity studies. The use of early tiered testing is structured so the potential for risk is first determined from estimates of hazard under worst-case exposure conditions by using extremely high test substance doses on suitable surrogate species that are representative of NTOs in the receiving environment. This testing scheme maximizes the ability to detect adverse effects on NTOs to provide a high degree of confidence in results, while avoiding unnecessary lines of investigation or duplicative testing that are not useful for the environmental risk assessment needs. Ms. Waggoners presentation will also discuss key points to consider and recommendations for the design and execution of early tier NTO laboratory studies that are important for the reconstruction, interpretation of results and the quality of information generated for the environmental risk assessment. These types of study design considerations help build scientific consensus of the types of data needed to make science-based regulatory decisions by establishing mutually-acceptable data and standards of acceptability for the overall purpose of international harmonization of data for evaluating the environmental effects of biotechnology in agriculture for both US and the international regulatory community.

seMi-field and field sTudies for assessing iMPaCTs on non-TargeT organisMs

Monica.Garcia-Alonzo,.Ph .D .. Consultant, Estel Consult Ltd., UK, Email: mgarcia@estelconsult.com

As part of the regulatory approval process for commercial cultivation of genetically modified (GM) crops, an assessment of the potential adverse effects that these crops may have on non-target organisms is usually required. The purpose of these assessments is to facilitate decision making, allowing regulatory authorities to establish if the risk posed by the GM crop is acceptable regarding the protections goals set in that regulatory system. This process is not unique to the risk assessment of GM crops, it is also applied to other types of products like plant protection products where a methodology based on a tiered testing approach has been used for many years. The tiered testing approach is structured such that risk is determined first from estimates of hazard and exposure under worst-case conditions. These early tier studies are conducted under controlled laboratory conditions where exposure can be guaranteed and doses can be given in excess of those encountered in the field to account for inter and intra species variation and provide an extra margin of safety. A lack of adverse effects in Tier I studies may provide enough confidence that there is no risk and no further data would be needed. However, in some cases, Tier I studies may reveal some adverse effects that could lead to risk to non-target organisms (NTOs) when exposed at field rates, in which case higher Tier studies can be conducted. These higher tier tests can be extended laboratory tests, semi-field tests or field tests, the terminology that refers to what type of study is considered in each Tier appears to differ depending on the regulatory system, but the methodology remains comparable in that the higher the Tier the more realistic the conditions. However the increase in realism comes with trade-offs that have to be taken into account when assessing the risk to NTOs.

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Extended laboratory tests can be tests conducted with plant material rather than microbially produced test substance. They provide a more realistic exposure, but do not allow testing at doses higher than those produced by that plant material. Semi-field tests are usually tests conducted with individual organisms or multiple organisms in field cages, or contained arenas, where exposure to the GM plant can be ensured (if it is going to occur) and the number of organisms under study can be controlled allowing the measurement of endpoints like mortality, rate of parasitism or predation, etc. However, like in extended laboratory tests, the levels of exposure will be limited to those present in the plant. Field trials are tests conducted at field scale where replicate plots are established and are subject to natural colonization and environmental conditions. NTOs are captured and the numbers captured are compared statistically between treatments in order to detect potential adverse effects. This results in large amounts of data gathered leading to complex analysis. Often, these tests are conducted under trial permits that establish containment measures that somehow compromise the realism compared with commercial production. For example in many countries isolation distances have to be respected, which force developers to conduct the trials in areas where the fauna will not represent the fauna normally found in that type of crop in a commercial production area. Also, the validity of the study will be subject to the colonization rates and the number of individuals present at the time of the trial, often compromising the analysis. In addition, even when effects are observed it is often difficult to interpret the results and establish a cause-effect. However, these trials are considered essential when risks have been identified at lower Tiers and there is a need to determine if the adverse effects detected in earlier Tiers will manifest under field conditions. In this talk the trade-offs between the different types of studies at the semi-field and field level will be discussed.

PosT release environMenTal MoniToring (PreM)

Alan.Gray,.Ph .D .. Research Fellow, Emeritus, Centre for Ecology and Hydrology, Wallingford, UK, Email: ajg@ceh.ac.uk.

A decade ago the UKs Advisory Committee on Releases to the Environment (ACRE) published its guidance on best practice in the design of post-market monitoring plans for GM crops (ACRE Guidance Note 16, 2001). Several of the principles behind this guidance were incorporated into subsequent legislation (including in the European Union (EFSA 2006)), most notably the division of post release monitoring into case-specific monitoring and general surveillance. Broadly speaking case-specific monitoring is to confirm any assumptions about potential environmental risks identified in the pre-market environmental risk assessment (ERA), whilst general surveillance is to identify the occurrence of any adverse effects that were not anticipated in that ERA. In this talk Dr. Gray will discuss these two types of monitoring using examples from Europe, where all applications for commercial release of a GM crop must be accompanied by an approved PREM plan. Affection for, and concern about, an essentially man-made and now highly protected environment, high food security, a generally risk-averse population, well-respected environmental and organic food lobbyists, and a regulatory system dedicated specifically to GMOs are among the many reasons why post release monitoring is mandatory. Whilst case-specific monitoring can be designed to test specific hypotheses derived from the initial ERA (e.g., to detect the emergence of resistant insect pests), general surveillance presents a number of problems in relation to the statistical limits of detection and the biological significance of the observed changes. These problems, and their implications for the design and execution of PREM plans and for changes in European agriculture, will be addressed.

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PreM in euroPe: whaT is driving The build-uP of reQuireMenTs?

Patrick.Rdelsheim,.Ph .D .. General Partner, Perseus BVBA, Email: patrick.rudelsheim@perseus.eu.

When the first European legal framework was established in 1990, it included all the elements guaranteeing safety for the environment and health associated with the development and placing on the market of genetically modified products. In spite of the successful conduct of a large number of trials and first product approvals, disparity between the European Member States on how certain aspects weigh in the risk assessment resulted in a deadlock situation. The regulatory framework was revised aiming to resolve the discerning views and thereby to facilitate the decision process. One of the introduced requirements was the obligation to implement a Post Release Environmental Monitoring (PREM) plan (also known as Post Market Environmental Monitoring) in order to trace and identify any direct or indirect, immediate, delayed or unforeseen effects on human health or the environment of GMOs as or in products after they have been placed on the market. The objectives of a monitoring plan were defined as to: confirm that any assumption regarding the occurrence and impact of potential adverse effects of the GMO or its use in the environmental risk assessment are correct, and identify the occurrence of adverse effects of the gmo or its use on human health or the environment which were not anticipated in the environmental risk assessment.

The first objective was subsequently elaborated as case-specific monitoring. It is based on identifying assumptions regarding the occurrence and impact of potential adverse effects of the GMO or its use that were made in the environmental risk assessment and that should be confirmed by a hypothesis driven monitoring effort. Where the conclusions of the risk assessment identify an absence of risk or negligible risk, case-specific monitoring would not be required. The second objective is not linked to specific features of the GMO and therefore has been introduced as a general requirement for all products. While at first sight an early warning system for unexpected negative impacts may look desirable, planning for potential effects or variables that cannot be foreseen or predicted is virtually impossible. Facing the difficulty of implementing general surveillance, different guidance notes have been published that elaborate on a combination of user (for plants this is the farmer) questionnaires, general monitoring networks, and review of ongoing research and development and scientific literature. The major challenges in designing general surveillance plans are to observe an unusual effect (clearly understanding that it is unusual), to determine whether the effect is adverse, and to determine whether the adverse effect is associated with the GMO and/or its use. During the presentation these methods, implementation challenges and the expected contribution to PREM will be discussed. Although the European Union has limited experience with the cultivation of GM crops and consequently has hardly evaluated PREM plans in practice, the effort that is required to establish and conduct PREM has increased since the inclusion of the provision in the legal framework. So far, case specific monitoring has only confirmed the assumptions and findings of the environmental risk assessment. The relevance of general surveillance continues to be highly debated. The recent mandate from the Commission to the European Food Safety Authority to again review and strengthen its PREM guidance is likely more an attempt to appease public opinion and to attract additional support from critical Member States.

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ausTralias aPProaCh To PreM

Paul.Keese,.Ph .D .. Science Advisor, Office of the Gene Technology Regulator (Australia), Email: paul.keese@ health.gov.au.

Post Release Environmental Monitoring (PREM) involves ongoing oversight of commercial releases, focused on informing the findings of the risk assessment and risk management plan and providing feedback into risk analysis. Some commercial release licences, particularly those requesting unrestricted release, may incorporate a requirement for ongoing oversight in the risk management plans, which may be achieved through identified PREM activities. Accordingly, the Australian Gene Technology Regulator may impose licence conditions that require the licence holder to supply, or enable the Regulator to collect, specific information on the progress of the release. This provides a mechanism for giving feedback in the risk analysis process. This includes verifying findings of the risk assessment and risk management plan by monitoring specific indicator(s) of harm that would usually have been identified in the risk assessment. Potential triggers for this component of post release review may include where the risk estimate is greater than negligible, or there is uncertainty (for example, lack of consensus among expert advisers). A second component of PREM is establishment and maintenance of an adverse experience/effects reporting page on the Office of the Gene Technology Regulator website to collect information about possible adverse effect(s) of a released GMO on the health of people and the environment. This could result in reports over the short and long term about any licence. Credible information would form the basis of further investigation. A third component of PREM is the review of risk assessment and risk management plans any time after the licence is issued. Such reviews would take into account any relevant new information or may be triggered by findings from either of the other components of post release review. The purpose of the review would be to ensure the findings of the risk assessment and risk management plan remained current. If the review findings justified either an increase or decrease in the initial risk estimate(s), or identified new risks to people or to the environment that needed managing, this could lead to review of the risk management plan and changes to the licence conditions. Alternatively, the review may be used in the consideration process leading to deregulation of the GMO.

inseCT resisTanCe ManageMenT: PasT, PresenT and fuTure

Jeff.Stein,.M .Sc .. Biosafety Advisor, Office of International Programs, Donald Danforth Plant Science Center, Email: Jstein@danforthcenter.org.

Crops genetically modified to be resistant to insect pests have been planted on millions of acres of farmland across the globe. These trait-enhanced crops provide tremendous value to farmers, delivering season-long protection against insect pests that translates into increased yield and improved quality of harvest. Their environmental benefits have been well documented, as the narrow-spectrum insecticidal proteins expressed in these crops have little if any adverse effects on non-target organisms, do not bio-accumulate in the soil or groundwater, and lack any worker-related safety issues often associated with the application of traditional insecticides. In order to preserve the long-term durability of these crops for future generations of farmers, technology developers have implemented comprehensive insect resistant management (IRM) programs. General practices to delay the onset of resistance typically include the deployment of crops that are highdose towards the target pest combined with the planting of a non-insecticidal refuge on each or nearby farm. However, IRM programs and their recommended practices need to be flexible and adaptable, taking into account such factors as pest biology and migration patterns, technology adoption rates, prevalence of alternative hosts, and local geography. In order to achieve a high rate of voluntary grower adoption, the
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recommended IRM activities should integrate into the prevailing crop management practices used by farmers in that region. To date, IRM programs for these crops have achieved success in both gaining a high rate of farmer compliance with recommended practices and thwarting resistance development in pest populations.

aPProPriaTe use of Models and Modeling in develoPMenT of irM Plans

Michael.A ..Caprio,.Ph .D .. Department of Biochemistry, Molecular Biology, Entomology and Plant Pathology, Mississippi State University, Email: mac24@msstate.edu.

The use of mathematical and simulation models to understand the processes important in the evolution of resistance in insects to toxins has a long history. This is in part because the goal of the modeling is to delay the development of the very thing one is attempting to study. In short, one wishes to study the problem of resistance without exacerbating the problem. Models have a number of roles, including identification of important parameters and focusing research efforts, the relative effectiveness of different IRM strategies, and tradeoffs between feasibility and effectiveness. For example, while a high dose/refuge strategy is almost always more effective than a seed-mixture strategy, in countries or regions where compliance with refuge requirements is likely to be low, implementation of a seed-mixture strategy may entail less risk. Exploration of IRM alternatives can be done with many types of models, ranging from simple selection models found in any population genetics textbook, to spatially implicit, deterministic models with few parameters, to spatially explicit, stochastic models with many parameters. Furthermore, each other these models can be used in several ways, from traditional scenario based risk assessments to probabilistic risk assessments. Both methods vary the parameters used in the models, but differ in how the parameters are varied. Probabilistic risk assessments require modellers to formally specify the uncertainty they have in parameters, and the result is expressed as a probability distribution such as the expected time for resistance to evolve. This allows the risk analyst to identify the likelihood of adverse effects (given the uncertainty specified) and to take appropriate action. In 2004, as part of the GMO Guidelines Project, Vietnamese scientists collaborated with an international group of scientists to conduct an environmental risk assessment associated with the challenges and opportunities of growing Bt-cotton in Vietnam. This group focused on the potential effects of irrigated Bt-cotton grown in the Binh Thuan region. Although there were numerous knowledge gaps, considerable information on the relative prevalence of various pests did exist and it was possible to propose an initial resistance management plan. A spatially implicit, deterministic model was used to incorporate available data as well as uncertainties in that data. Assuming prevalence of cotton in the current landscape, the risk of resistance evolving within 15 years was seen as relatively low, only occurring in 0.6% of the simulations. In contrast, if the most extreme predictions for the increase in cotton acreage were to occur (a 50 fold increase in cotton acreage), the risk of resistance evolving within 15 years increased to 43%. A spatially-explicit, complex simulation model of the US Midsouth Helicoverpa zea (Cotton Bollworm) represents the opposite end of the spectrum with regard to complexity and flexibility. This model incorporates over 50 different habitats such as whorl and ear stage corn, Bt and non-Bt cotton, soybeans, sorghum and various wild hosts. In cases of a polyphagous pest such as H. zea, IRM cannot focus on particular crops, but must follow the insect as it moves among host complexes that may vary in composition over the course of a season. Probabilistic risk assessment was again used with this model to identify changes in the risk profile with regard to resistance to transgenic plants. In one particular case of interest, the change from single-gen corn to dual gene corn with a reduced refuge size increased the risk of resistance evolving within 30 years from about 5% to 15%.

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