Development of GM crops in the EU. Key Issues for the Assessment of GMO by the European Food Safety Authority (EFSA)

Lucía Roda GhisleriLRoda@mma.esDirección General de Calidad y Evaluación Ambiental

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.

Genetically Modified Organism(GMO)

‘Genetically modified organism (GMO) means anorganism, 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)

Biosafety Food Safety‘Put in place politics and measures focused on the health and the environment protection’.

‘Protection of life and human beings, of the human health and the animal welfare, the environment and the consumer interests’.

Risk Analysis based on available scientific studies.

Risk Assessment based on existing scientific data.

PRECAUTIONARYPRINCIPLE

‘CASE BY CASE’

‘STEP BY STEP’

Confined use Experimental trials Commercialisation

Precautionary Principle in the EU:Risk Analysis

Risk 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.

Deliberate Release into the EnvironmentField 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(under controlled conditions))

GoalGoal: Identification and assessment , case by case, of potential adverse effects of GMO, either by direct or indirect, immediate or delayed effects, on human health and the environment.

National Assessment and Authorisation ProcedureDeliberate Release: Field Trials

ONE MONTH

THREE MONTHS

0

50

100

150

200

250

300

1991 1992 1993 1994 1995 1996 1997 1998 1999 2000 2001 2002 2003 2004 2005 2006 2007 2008 2009 2010 2011

4

66

89

166

213

239

264244

238

129

88

56

8272 78

139

9590

110

77

45

Notificactions of Field Trials with GMOby Year in the EU (November 2011)

www.gmoinfo.jrc.ec.europa.eu

0

100

200

300

400

500

600591

568

295

238191

182

136113

56 5632 27 23 22 19 16 15 6 3 2 2 1

Notifications of Filed Trials by Countries in the EU(November 2011)

www.gmoinfo.jrc.ec.europa.eu

0

100

200

300

400

500

600

700

800

900

1000 929

388

337 319

77 8262 35 37 31 22 19 15 10 9 8 8 8

GM Plants Tested in the Field in the EU(2011)

0

10

20

30

40

50

60

70

1993 1994 1995 1996 1997 1998 1999 2000 2001 2002 2003 2004 2005 2006 2007 2008 2009 2010 2011

3

129

19

41

47

42

11

18 18

41

20

26

4346

49

63

49

28

Experimental Field Trials with GMOs conducted in Spain(1993 - 2011)

58%13%8%

5%5% 3%

2% 1%

GMP tested in the field (1993-2011)

Maize

Cotton

Sugar beet

Rice

Potato

Tomato

Wheat

Citrus

Soybean

Melon

Tobacco

Sunflower

Poplar

Prunus

Oilseed rape

Strawberry

Eucalyptus

Main Traits introduced in GMP in Spain(1993-2011)

32%

26%

15%

15%

3%2% 2% 2%

1% HT + IRHerbicide toleranceChanges in compositionInsect resistanceVirus resistanceAndrosterilityFertilityDrought toleranceAntibiotic resistanceFungal resistanceHeat stressBiofuel

Placing on the Market of GMP

The 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.

Directive 2001/18/ECDecentralised procedure for the approval of import, processing and/or cultivation

1) Submission Submission of the of the

Application Application by the by the

NotifierNotifier

2) Study and assessment 2) Study and assessment by the by the Competent Competent Authority of the Authority of the Member StateMember State(Lead country)(Lead country)

3) Study and 3) Study and revision by the revision by the

Competent Competent Authorities of all Authorities of all Member StatesMember States

YesYes

No

4) 4) EFSA OpinionEFSA Opinion(European Food Safety Authority)(European Food Safety Authority)

SíApproval

No

No

5) Decision of the 5) Decision of the Regulatory Committee Regulatory Committee de los de los EstadosEstados MiembrosMiembros

YesYes

Yes

Approval

No

6) Decision of the 6) Decision of the CounsilCounsil of Ministersof Ministers of the of the Environment Environment of the Member Statesof the Member States

7) 7) DecisioDecisio by the by the European European CommisionCommision

No

YesYes

Approval

YesApproval

No

Commitology after ‘Lisboa Treaty’March 2011

Regulation (EC) Nº 1829/2003Centralised Procedure for the la Commercialisation of

GM Food and Feed (can include cultivation)

1) Notifier complete1) Notifier completethe Application:the Application:Technical Dossier +Technical Dossier +Risk AssessmentRisk Assessment

EFSA OpinionEuropean Food Safety Authority))

No

4) Decision of the Scientific Committee of the Food4) Decision of the Scientific Committee of the FoodChain and Animal Health of the Member StatesChain and Animal Health of the Member States

(SCFCAH)(SCFCAH)Sí

Yes

Approval

No

5) Decision of the Council of Ministers of the5) Decision of the Council of Ministers of theAgriculture of the Member StatesAgriculture of the Member States

6) Decision by the European Commission

No

Yes

Approval

YesApproval

No

2) Submission to allMember StatesCompetent Authorities

Consultation to allCompetentAuthorities

‘One door-one key’

Commitology after ‘Lisboa Treaty’March 2011

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

VACCINES

VEMIE VETERINAR CHEMIE

ENFERMEDAD AUJESZKY

AUJESZKY DISEASE VACCINATION

FROM

1992

TO

1998

RABORALRHONE-MERIEUX

ORAL LIVE VACCINE AGAINST RABIE IN FOX

KIT OF ANÁLYSIS VALIO LTD.(Streptococcus thermophilus)

DETECTION OF ANTIBIOTICS IN MILK

TOBACCO SEEDS(Cultivation/Tobacco Industry)

SEITABROMOXINIL TOLERANCE

6 OILSEED RAPE(Seed production)

PLANTGENETIC SYSTEMS

GLUFOSINATE TOLERANCE

SOYA (A 5403)(Import and processing)

MONSANTO GLIFOSATE TOLERANCE

CHICCORY(Cultivation)

BEJO ZADENANDROESTERILITY/

GLUFOSINATE TOLERANCE

8 MAIZES(Import and processing)(Only 3 for Cultivation)

MONSANTOSYNGENTA

PIONEER/DOWBAYER CROPSCIENCE

RESISTENCIA AL TALADROHERBICIDE TOLERANCE

4 CARNATIONS(Cultivation)

FLORIGENE EUROPE B.V. LONGEVITY

1 POTATO(Cultivation /industrial uses)

BASF PLANT SCIENCE CHANGES IN STARCH CONTENT 2010

COMMUNITY REGISTER OF GENETICALLY MODIFIEDFOOD AND FEED

REGULATION (EC) Nº 1829/2003

AUTHORISZATION 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 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)

http://ec.europa.eu/food/dyna/gm_register/index_en.cfm

EVENT: Unique DNA recombination used for the regeneration of a whole genetically modified plant

Sequential Scientific Risk Assessment(‘step by step’)

Post Market monitoring (C) to measure effects (adverse or not)

Lab/greenhouse assays (A) to identify hazards

Field trials (B)To assess Risks (hazard x exposure)

Deliberate release into the environmentConfined use

Directive 2009/41/EC

Directive 2001/18/EC

Directive 2001/18/EC and/orRegulation (EC) Nº 1829/2003

Step 1: Identification of characteristics which may cause adverse effects (direct,indirect, immediate or delayed, and cumulative effects) on the human health and the environment.(Characteristics of the GMO, intended release or use including its scale, the receivingenvironment and the interaction between these).Step 2: Evaluation of the potentialconsequences of each adverse effects ifit occurs.

Step 3: Evaluation of the likelihood of the occurrence of each identified adverse effects.

Step 4: Estimation of the risk posed by each characteristic of the GMO

Step 5: Application of management strategies for risk from deliberate release of the GMO.

Step 6: Determination of the global risk of the GMO.

Methodology for Environmental Risk Assessment (Field Trials)

Potential Impact of the GMO on the HumanHealth and the Environment

1. 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 material

11. Changes in management, including, where applicable, in agricultural practices

The EFSA Role in Risk Assessment

• Establishment of EFSA in 2002 (Regulation (EC) Nº 178/2002) and located in Parma, Italy

Main goals:• Improving EU food safety• Re-building consumer confidence in EU food safety

http://www.efsa.europa.eu

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

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)

EFSA Guidance for the RA of GMOsEFSA 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

Principles for ERA of GM Plants

Scientifically sound

Transparency

Sequential steps

Comparative approach

Case-specific

Tiered approach

Iterative

Scientific incertitude

Food and Feed Safety Assessmentin the EU

Main 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

Safety and Nutritional Assessment - I

Parental PlantHistory of use,

Origin, Habitat, Characteristics

Donor organism

DNA with new genes

Genetic ModificationProcess

Genetically Modified Plant

Comparative analysis of GM plants and derived food and feed and conventional counterpart(s)compositional, phonotypical and agronomical analysis

HAZARD IDENTIFICATION

Safety and Nutritional Assessment - II

Intended differencesNew gene products

Compositional alterations

Unintended differences?Agronomical and compositional

alterations

Safety evaluation ofsingle compounds

RISK CHARACTERISATION

Safety and nutritional evaluationof the whole GM plant and

derived food and feed

Toxicity in vivo/in vitro,allergenicity, bioinformatics

90-daysrodent feeding trialsLivestock feeding trials

EXPOSURE ASSESSMENT

CONCLUSIONS ON SAFETY

HAZARD CHARACTERISATION

ERA Templ(at)e

Env.ironmental Risk Assessment

Parental plant & GM trait

Molecular characterization

Compositional Analysis

Agronomic/phenotyp. Characters.

Plant/environment interaction

‘Pillar Task‘: Decrease uncertainty about unintended effects due to genetic modification

Knowledge = Stone

(Graph Dr. Bartsch)

6 steps

34Conclusions ERA & PMEM

Persistence &invasiveness

HGTTO

Impact of cultivation practices

Impact on biogeochemical processes

Human and

animal health

5 cross-cutting considerations

Comparators, Receiving environment, General statistics, Long-term effects, Stacked events

Step 1

Step 2

Step 6

Step 3

Step 5

Step 4

Strategies for ERA of GM plants

NTO

4-5-6-7-8 Compendium of ERA

G. Human and animal health

F. Biogeochemical processes

E. Farming practices

D. Non‐target organisms (NTOs)

C. Target organisms (TO)

B. Horizontal gene transfer

A. Persistence and invasiveness

(6) Overall risk evaluation & conclusion

(5) Risk mitigation strategies

(4) Risk characterisation

(1) Problem formulation

(2) Hazard characterisation

(3) Exposure characterisation

Plant‐environment interactions

Agronomic/phenotypic data

Compositional data

Molecular data

Event‐specific data sources (4)

Areas of risk or concern (7)ERA strategies (8) ‐

Principles & approaches

I. Science‐basedII. Transparency

III. Sequential stepsIV. Comparative approach

V. Case‐specificVI. Tiered approach

VII. IterativeVIII. Scientific incertitude

Cross‐cutting considerations (5)

I. Choice of comparatorII. Receiving environment(s)

III. General statistical considerationsIV. Long‐term effects

V. Stacked transformation events

Graph by Yann Devos

Commercial VarietyRegistration

Commercial cultivation

EPA ASSESSMENT

FDA ASSESSMENT

Commercial Cultivation in the USA

SAFETY ASESSMENT BY EU MMSS Field Trial

in the UE

USDA ASSESMENT

Lead Country Assessment+ 26 Member StatesDirective 2001/18/EC

EFSA AssessmentRegulation (EC) Nº1829/2003

GMFood

GM Feed

GMO ApprovalDirective 2001/18/EC or

Regulation (EC) 1829/2003

GM

MONITORING PLANS

FOOD/FEED/CULTIVATION

% Bt maize

0 %

< 5 %

5-25 %

25-50 %

50-75 %

2010: 76.575 ha Bt maize (23% of the total maize, 329.000 ha of grain maize) 101 varieties of GM maize registered in the Spanish Catalogue17 companies marketing these varieties in Spain.

1998: first 2 varieties of Bt maize (Bt 176 from Syngenta)

2010

GM maize crop in SpainGM maize crop in Spain

2011: 97.326 ha Bt maize (26.5% of the total grain maize)106 varieties of GM maize registered in the Spanish CatalogueSeveral companies marketing these varieties in Spain.

Area of GM maize

0

20.000

40.000

60.000

80.000

100.000

120.000

1998 1999 2000 2001 2002 2003 2004 2005 2006 2007 2008 2009 2010 2011Year

Hec

tare

s

Spanish legislation for the registration of commercial varieties since 1998 going ahead of what was included later in the Directive 2001/18/EC.

Monitoring Plan for Applicants

Case SpecificMonitoring 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

Bt176 varieties(1998-2005)

MON810 varieties (from 2003)

PostPost--market monitoring for Bt maize in Spainmarket monitoring for Bt maize in SpainRequirements for ApplicantsRequirements for Applicants

Public Research Studies for Bt-maize. Bt-176 (1998-2005) and MON810 (2003-2010)

MARM (CNB) + public research institutions (CSIC, Universities) MARM (CNB) + public research institutions (CSIC, Universities)

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).

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: 459-463Farinós et al., 2004. Entomol. Exp. Appl. 110: 23-30

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.

Potential effects on non-target arthropods

Arthropod fauna in maize fields

The abundance and composition of non-target arthropods in maize fields vary between years and localities

Natural enemies are exposed to the Cry1Ab toxin expressed in Bt maize

No detrimental effects have been found in field trials on commercial Bt-maize fields

No negative effects on “worst-case scenario” laboratory assays

De la Poza et al. (2005) Crop Protection 24: 677-684Farinós et al. (2008). Biological Control 44: 362-371

Alvarez-Alfageme et al. (2008). Transgenic Research, 17: 943-954Alvarez-Alfageme et al. (2009). J. Insect Physiol. 55: 143-149García et al. (2010). Biological Control 55: 225-233

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 rhizobacterial communities of Bt maize (genetic microarrays) FingerprintingVal, G., Marín, S. and Mellado, R.P. 2009. Microbial Ecology 58,108-115.

CNB

Positive spots

http://ec.europa.eu/research/biosociety/pdf/a_decade_of_eu-funded_gmo_research.pdf

http://www.marm.es/es/calidad-y-evaluacion-ambiental/temas/biotecnologia/PLAN_DE_SEGUIMIENTO_mar_2011_tcm7-147305.pdf

New Politics on GMO in the EUConclusions 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 Member States to decide on cultivation of GMO

Barroso, in September 2009, indicated that it should be possible to combine an EU authorisation system, based on science, with freedom for Member States to decide whether or not they 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 increaseflexibility to Member States on GMO cultivation in all or part of their territory• Revision of all the existing legislation

THANK YOU!THANK YOU!