1. Development of GM crops in the EU.Key Issues for the Assessment of GMO by theEuropean Food Safety Authority (EFSA) Lucía Roda Ghisleri LRoda@mma.es Dirección General de Calidad y Evaluación Ambiental
2. EU Legislation on GMOs in the EU• Directive 2009/41/EC on the contained use of genetically modified microorganisims.• Directive 2001/18/EC on the deliberate release into the environment of genetically modified organisms and repealing.• Regulation (EC) Nº 178/2002 laying down the general principles and requirements of food law, establishing the European Food Safety Authority (EFSA) and laying down procedures in matters of food safety.• Regulation (EC) Nº 1829/2003 on genetically modified food and feed.• Regulation (EC) Nº 1830/2003 concerning the traceability and labelling of genetically modified organisms and the traceability of food and feed products produced from genetically modified organisms• Regulation (EC) Nº 1946/2003 on transboundary movements of genetically modified organisms.• Recommendation (EU) (2010/C 200/01) on guidelines for the development of national co-existence measures to avoid the unintended presence of GMOs in conventional and organic crops.
3. Genetically Modified Organism (GMO) ‘Genetically modified organism (GMO) means an organism, with the exception of human beings, in which the genetic material has been altered in a way that does not occur naturally by mating and/or natural recombination’- Recombinant nucleic acid techniques- Micro-injection, macro-injection and micro-encapsulation- Cell fusion(Artícle 2 of Directive 2001/18/EC)
4. Biosafety Food Safety ‘Put in place politics and ‘Protection of life and human measures focused on the beings, of the human health and the health and the animal welfare, the environment environment protection’. and the consumer interests’.Risk Assessment based on Risk Analysis based on availableexisting scientific data. scientific studies. PRECAUTIONARY PRINCIPLE ‘CASE BY CASE’ ‘STEP BY STEP’ Confined use Experimental trials Commercialisation
5. Precautionary Principle in the EU: Risk AnalysisRisk assessment: Identification of the potential adverse effects in a scientifically sound manner (uncertainties),Risk management: political decision deciding the acceptable level of risk for the society and deciding whether take an action or not.Risk communication: Decision making process have to be transparent and take into account all stakeholders.
6. Deliberate Release into the Environment Field Trials with GMOs Directive 2001/18/EC‘Any intentional introduction into the environment of a GMO or a combination of GMOs for which no specific containment measures are used to limit their contact with and to provide a high level of safety for the general population and the environment (under controlled conditions)Goal: Identification and assessment , case by case, of potentialadverse effects of GMO, either by direct or indirect, immediate or delayedeffects, on human health and the environment.
7. National Assessment and Authorisation Procedure Deliberate Release: Field Trials ONE THREE MONTH MONTHS
8. Notificactions of Field Trials with GMO by Year in the EU (November 2011) www.gmoinfo.jrc.ec.europa.eu300 264 244 239 238250 213200 166150 139 129 110 95100 89 88 90 82 78 77 72 66 56 4550 4 0 1991 1992 1993 1994 1995 1996 1997 1998 1999 2000 2001 2002 2003 2004 2005 2006 2007 2008 2009 2010 2011
9. Notifications of Filed Trials by Countries in the EU (November 2011) www.gmoinfo.jrc.ec.europa.eu 591600 568500400 295300 238 191 182200 136 113 56 56100 32 27 23 22 19 16 15 6 3 2 2 1 0
10. GM Plants Tested in the Field in the EU (2011)1000 929 900 800 700 600 500 388 400 337 319 300 200 77 82 62 35 100 37 31 22 19 15 10 9 8 8 8 0
13. Main Traits introduced in GMP in Spain (1993-2011) HT + IR 1% 2% 2% 2% Herbicide tolerance 3% Changes in composition 32% Insect resistance15% Virus resistance Androsterility 15% Fertility 26% Drought tolerance Antibiotic resistance Fungal resistance Heat stress Biofuel
14. Placing on the Market of GMPThe Notifier has two options to submit the Application: Under the Part C procedure of Directive 2001/18/EC on deliberate release of GMO, or Under Regulation (CE) Nº 1829/2003 on genetically modified food and feed.
15. Directive 2001/18/ECDecentralised procedure for the approval of import, processing and/or cultivation 7) Decisio by the Yes Approval European Commision No No Commitology after 6) Decision of the Counsil of Ministers of the Yes ‘Lisboa Treaty’ Approval March 2011 Environment of the Member States No 5) Decision of the Regulatory Committee Yes Approval de los Estados Miembros Yes 4) EFSA Opinion No (European Food Safety Authority) No 3) Study and Yes 1) Submission 2) Study and assessment Sí revision by the of the by the Competent Competent Approval Application Authority of the Authorities of all by the Member State Member States Notifier (Lead country) No
16. Regulation (EC) Nº 1829/2003 Centralised Procedure for the la Commercialisation of GM Food and Feed (can include cultivation) Yes 6) Decision by the European Commission Approval No Commitology after Yes 5) Decision of the Council of Ministers of the ‘Lisboa Treaty’ Approval March 2011 Agriculture of the Member States NoNo 4) Decision of the Scientific Committee of the Food Yes Chain and Animal Health of the Member States Approval (SCFCAH) Sí EFSA Opinion European Food Safety Authority)) No Consultation to all 1) Notifier complete Competent the Application: 2) Submission to all Authorities Technical Dossier + Member States Risk Assessment ‘One door-one key’ Competent Authorities
17. PLACING ON THE MARKET OF GMO IN THE EUROPEAN UNION (DIR. 90/220/EEC and DIR. 2001/18/EC) (http://ec.europa.eu/environment/biotechnology/authorised_prod_1.htm) GMO/USES COMPANY/SCOPE GENETIC MODIFICATION YEAR VEMIE VETERINAR AUJESZKY DISEASE CHEMIE VACCINATION ENFERMEDAD AUJESZKY VACCINES RABORAL ORAL LIVE VACCINE AGAINST RHONE-MERIEUX RABIE IN FOX KIT OF ANÁLYSIS VALIO LTD. DETECTION OF ANTIBIOTICS IN (Streptococcus thermophilus) MILK TOBACCO SEEDS SEITA(Cultivation/Tobacco Industry) BROMOXINIL TOLERANCE FROM 1992 6 OILSEED RAPE PLANT GLUFOSINATE TOLERANCE (Seed production) GENETIC SYSTEMS TO SOYA (A 5403) 1998 MONSANTO GLIFOSATE TOLERANCE (Import and processing) ANDROESTERILITY/ CHICCORY BEJO ZADEN GLUFOSINATE TOLERANCE (Cultivation) MONSANTO 8 MAIZES SYNGENTA RESISTENCIA AL TALADRO (Import and processing) PIONEER/DOW HERBICIDE TOLERANCE (Only 3 for Cultivation) BAYER CROPSCIENCE 4 CARNATIONS FLORIGENE EUROPE B.V. LONGEVITY (Cultivation) 1 POTATO BASF PLANT SCIENCE CHANGES IN STARCH CONTENT 2010 (Cultivation /industrial uses)
18. COMMUNITY REGISTER OF GENETICALLY MODIFIED FOOD AND FEED REGULATION (EC) Nº 1829/2003AUTHORISZATION 40 transformation events (import/processing, food and feed; only 2 for cultivation): 7 COTTONS (MON1445, MON15985, MON15985 x MON1445, MON531, MON 531 x MON1445, LLCotton25 y GHB614) 23 MAIZES (Bt11, DAS1507, DAS1507 x MON863, DAS59122, GA21, MON810, MON863, MON863 x NK603, MON863 x MON810, NK603, NK603 x MON810, T25, etc...) 3 OILSEED RAPE (GT73, MS8-RF3-MS8 x RF3 y T45) 3 SOYA BEENS (MON40-3-2, A2704-12 y MON89788) 1 SUGAR BEET (H7-1) 1 POTATO (EH92-527-1) 2 MICROORGANISMS (pCABL- Brevibacterium lactofermentum y pMT742 o pAK729 – Saccharomyces cerevisiae) EVENT: Unique DNA recombination used for the regeneration of a whole genetically modified plant http://ec.europa.eu/food/dyna/gm_register/index_en.cfm
19. Sequential Scientific Risk Assessment (‘step by step’) Confined use Deliberate release into the environment Lab/greenhouse Field trials (B) Post Market assays (A) To assess Risks monitoring (C) to to identify hazards (hazard x exposure) measure effects (adverse or not) Directive 2001/18/EC Directive 2001/18/EC and/orDirective 2009/41/EC Regulation (EC) Nº 1829/2003
20. Methodology for Environmental Risk Assessment (Field Trials)Step 1: Identification of characteristics which may cause adverse effects (direct,indirect, immediate or delayed, and cumulative effects) on the human health and theenvironment.(Characteristics of the GMO, intended release or use including its scale, the receivingenvironment and the interaction between these).Step 2: Evaluation of the potential Step 3: Evaluation of the likelihood ofconsequences of each adverse effects if the occurrence of each identifiedit occurs. adverse effects.Step 4: Estimation of the risk posed by each characteristic of the GMOStep 5: Application of management strategies for risk from deliberate release of theGMO.Step 6: Determination of the global risk of the GMO.
21. Potential Impact of the GMO on the Human Health and the Environment1. Survival and invasiveness increased2. The spread of the GMO(s) in the environment3. The transfer of the inserted genetic material to other organisms4. Phenotypic and genetic instability5. Interactions with other organisms (target or non-target organisms)6. Disease to humans, animals and plants including allergenic or toxic effects7. Effects on the dynamics of populations of species in the receiving environment and the genetic diversity of each of these populations8. Altered susceptibility to pathogens facilitating the dissemination of infectious diseases and/or creating new reservoirs or vectors9. Compromising prophylactic or therapeutic medical, veterinary, or plant protection treatments10. Effects on biogeochemistry (biogeochemical cycles), particularly carbon and nitrogen recycling through changes in soil composition of organic material11. Changes in management, including, where applicable, in agricultural practices
22. The EFSA Role in Risk Assessment• Establishment of EFSA in 2002 (Regulation (EC) Nº 178/2002) and located in Parma, ItalyMain goals:• Improving EU food safety• Re-building consumer confidence in EU food safety http://www.efsa.europa.eu
23. EFSA Tasks and ApproachEFSA’s tasks:• Deliver sound scientific opinion on food safety to the risk managers• Ensuring close collaboration between national bodies (National Biosafety Committees and Competent Authorities)• Engage and exchange information with the many different stakeholders• Risk communication: Providing the right information to consumers, government, industrial, NGO and other stakeholders at the right timeEFSA Approach:• Scientific excellence• Independence• Transparency/openness• Close collaboration with Member States• Building consumer confidenceEFSA Structure:• Management Board• Advisory Forum• Executive Director and Staff• Scientific Committee and Panels
24. EFSA Scientific Panels• Additives and products or substances used in animal feed (FEEDAP)• Animal health and welfare (AHAW)• Biological hazards (BIOHAZ), including BSE-TSE-related risks• Contaminants in the food chain (CONTAM)• Dietetic products, nutrition and allergies (NDA)• Food additives and nutrient sources added to food (ANS)• Food contact materials, enzymes, flavourings and processing aids (CEF)• Genetically modified organisms (GMO)• Plant health (PLH)• Plant protection products and their residues (PPR)• Scientific Committee (SC)
25. EFSA Guidance for the RA of GMOs EFSA Scientific Panel on GMO• Guidance on post-market environmental monitoring of GM Plants (2011). Updated version of 2006.• Guidance on the risk assessment of genetically modified microorganisms and their products intended for food and feed use (2011). Updated version of 2006.• Guidance for risk assessment of food and feed from GM plants (2011)• Guidance on selection of comparators for the risk assessment of GM plants (2011).• EFSA Guidance Document on the Environmental Risk Assessment of GM plants (2010).• Working Document of the GMO Panel on the interplay between Directive 2001/18/EC (GMOs) and Directive 91/414/EEC (Plant Protection Products) (2008).• Guidance Document for the risk assessment of genetically modified plants containing stacked transformation events by the Scientific Panel on Genetically Modified Organisms (GMO) (2007)• Guidance document for the renewal of authorisations of existing GMO products by the Scientific Panel on Genetically Modified Organisms (GMOs) (2006
26. Principles for ERA of GM Plants Scientifically sound Transparency Sequential steps Comparative approach Case-specific Tiered approach Iterative Scientific incertitude
27. Food and Feed Safety Assessment in the EUMain criteria:1. Identification of differences between the GM and non-GM crop2. Assessment of the environmental and/or food/feed safety and nutritional impact of identified differences • Concept of Familiarity • Concept of Substantial Equivalence • Comparative Safety Assessment
28. Safety and Nutritional Assessment - I Donor organism Parental Plant History of use, Origin, Habitat, Characteristics DNA with new genes Genetic Modification Process Genetically Modified Plant HAZARD IDENTIFICATIONComparative analysis of GM plants and derived food and feed and conventional counterpart(s) compositional, phonotypical and agronomical analysis
29. Safety and Nutritional Assessment - II HAZARD CHARACTERISATION Intended differences Unintended differences? New gene products Agronomical and compositionalCompositional alterations alterations Safety and nutritional evaluation Safety evaluation of of the whole GM plant and single compounds derived food and feed Toxicity in vivo/in vitro, 90-daysrodent feeding trialsallergenicity, bioinformatics Livestock feeding trials EXPOSURE ASSESSMENT RISK CHARACTERISATION CONCLUSIONS ON SAFETY
30. ERA Templ(at)e Env.ironmental Risk Assessment Knowledge = Stone Plant/environment interaction Agronomic/phenotyp. Characters. Compositional Analysis Molecular characterization ‘PillarTask‘: Decrease uncertainty about unintended effects due to genetic modificationParental plant & GM trait (Graph Dr. Bartsch)
31. Strategies for ERA of GM plants 5 cross-cutting considerations Comparators, Receiving environment, General statistics, Long-term effects, Stacked events6 steps Persistence & invasivenessStep 1 HGT TOStep 2 NTO Impact of cultivation practicesStep 3 Impact on biogeochemicalStep 4 processesStep 5 Human andStep 6 animal health Conclusions ERA & PMEM 34
32. 4-5-6-7-8 Compendium of ERA ERA strategies (8) ‐ Areas of risk or concern (7) Principles & approaches I. Science‐based G. Human and animal health II. Transparency III. Sequential steps F. Biogeochemical processes IV. Comparative approach V. Case‐specific VI. Tiered approach E. Farming practices VII. Iterative VIII. Scientific incertitude D. Non‐target organisms (NTOs) C. Target organisms (TO) Cross‐cutting considerations (5) B. Horizontal gene transfer I. Choice of comparator II. Receiving environment(s) A. Persistence and invasivenessIII. General statistical considerations IV. Long‐term effects (6) Overall risk evaluation & conclusion V. Stacked transformation events (5) Risk mitigation strategies (4) Risk characterisation Event‐specific data sources (4) (2) Hazard (3) Exposure characterisation characterisation Plant‐environment interactions (1) Problem formulation Agronomic/ phenotypic data Compositional data Molecular data Graph by Yann Devos
33. USDA ASSESMENT Commercial Cultivation in the USA EPA ASSESSMENT FDA ASSESSMENT SAFETY ASESSMENT BY Field Trial EU MMSS in the UEGM MONITORING PLANS FOOD/FEED/CULTIVATION Lead Country Assessment EFSA Assessment + 26 Member States Regulation (EC) Nº Directive 2001/18/EC 1829/2003 Commercial Variety Registration GMO Approval GM Directive 2001/18/EC or GM FeedCommercial cultivation Regulation (EC) 1829/2003 Food
34. GM maize crop in Spain Area of GM maize 2010 120.000 100.000 80.000Hectares 60.000 40.000 20.000 0 Year 1998 1999 2000 2001 2002 2003 2004 2005 2006 2007 2008 2009 2010 2011 1998: first 2 varieties of Bt maize (Bt 176 from Syngenta) % Bt maize 2010: 76.575 ha Bt maize (23% of the total maize, 329.000 ha of grain maize) 0% 101 varieties of GM maize registered in the Spanish Catalogue <5% 17 companies marketing these varieties in Spain. 5-25 % 2011: 97.326 ha Bt maize (26.5% of the total grain maize) 25-50 % 106 varieties of GM maize registered in the Spanish Catalogue 50-75 % Several companies marketing these varieties in Spain.
35. Post-market monitoring for Bt maize in Spain Requirements for ApplicantsSpanish legislation for the registration of commercial varieties since 1998 goingahead of what was included later in the Directive 2001/18/EC. Bt176 varieties MON810 varieties (1998-2005) (from 2003) Monitoring Plan for Applicants Case Specific Monitoring of corn borer resistance Potential effects on non-target arthropods Potential effects on soil microorganisms Potential effects on digestive tract bacteria (only for Bt-176) General Surveillance Farmer questionnaires (only MON810) Seed sales by localities. Distribution. Buyers. Information to farmers on specific measures for GM cultivation
36. Public Research Studies for Bt-maize. Bt-176 (1998-2005) and MON810 (2003-2010) Ecology of corn borers in Spain and susceptibility to Bt maize and Bt toxin. Ecological risk assessment of transgenic maize. Assessment of the potential ecological risks of transgenic maize Mid and long-term monitoring of the potential ecological risks of insect resistant transgenic crops (maize and cotton) Centro de Investigaciones Biológicas (CSIC). Gene transfer from transgenic maize to the microbial population in the planting soil and effects on soil populations. Centro Nacional de Biotecnología (CSIC).MARM (CNB) + public research institutions (CSIC, Universities)
37. Susceptibility to Cry1Ab in Spanish populations Sesamia nonagrioides LC50 values of field populations collected from 1999 to 2009 ranged between 3 and 30 ng Cry1Ab/cm2 Ostrinia nubilalis LC50 values of field populations collected from 1999 to 2009 ranged between 3 and 40 ng Cry1Ab/cm2 No significant changes in the susceptibility to Cry1Ab over time González-Núñez et al., 2000. J. Econ. Entomol. 93: 459-463 Farinós et al., 2004. Entomol. Exp. Appl. 110: 23-30
38. Potential effects on non-target arthropods Pedro Castañera, Félix Ortego, CSIC (Agreement MARM-CSIC)Compa CB (Bt-176): 2000-2005Varieties MON810: 2005-2010Objectives:-Arthropod fauna in maize fields.-Exposure of non-target arthropods to Bt toxins.-Field trials to assess abundance and diversity of non-target arthropods.-Laboratory assays to test worst-case scenarios.
39. Arthropod fauna in maize fieldsThe abundance and compositionof non-target arthropods inmaize fields vary between yearsand localitiesNatural enemies are exposed to De la Poza et al. (2005) Crop Protection 24: 677-684 Farinós et al. (2008). Biological Control 44: 362-371the Cry1Ab toxin expressed in BtmaizeNo detrimental effects havebeen found in field trials oncommercial Bt-maize fieldsNo negative effects on “worst-case scenario” laboratory assays Alvarez-Alfageme et al. (2008). Transgenic Research, 17: 943-954 Alvarez-Alfageme et al. (2009). J. Insect Physiol. 55: 143-149 García et al. (2010). Biological Control 55: 225-233
40. Potential effects on soil microorganisms (2004-2009)1) A lack of detection of gene transfer from Bt-maize to culturable soil bacteria was demonstrated by PCR analysis. Badosa et al, 2004. FEMS Microbiology Ecology 48: 169-178.2) Development of a detection system of molecular structure differences in Positive spots rhizobacterial communities of Bt maize (genetic microarrays) Fingerprinting Val, G., Marín, S. and Mellado, R.P. 2009. Microbial Ecology 58,108-115. CNB
42. New Politics on GMO in the EU Conclusions of the Council of December 2008 under the French Presidency • The legal framework was comprehensive • The need to better implement the existing provisions, notably as concerns cultivation. • Need to evaluate the current legislation • Need to evaluate the socio-economic impact of GMO • EFSA Guidance for the assessment of environmental risks New approach of the Commission with regards GMO cultivation 13 Member States called the Commission to prepare proposals to give freedom to MemberStates to decide on cultivation of GMO Barroso, in September 2009, indicated that it should be possible to combine an EUauthorisation system, based on science, with freedom for Member States to decide whether or notthey wish to cultivate GM crops in their territory In July 2010, the Commission makes a proposal compound by three steps: • New Recommendation on coexistence (already published) • Legislative amendment: Regulation that amends the Directive 2001/18 that increase flexibility to Member States on GMO cultivation in all or part of their territory • Revision of all the existing legislation