applications, mandates and other activities Irina Olaru 8 th GMO - - PowerPoint PPT Presentation

Irina Olaru 8th GMO Network Meeting 23 May 2017

Update from EFSA on GMO applications, mandates and

• ther activities

2

 Applications under 1829/2003

 Under Articles 5 and 17  Renewals under Articles 11 and 23

 Guidance documents and explanatory notes  External mandates  Procurement and grants

EFSA ACTIVITIES ON GMO

3

APPLICATIONS Applications under 1829/2003, Art 5 & 17 Completeness check (5) Risk assessment (32) Finalised (80) Withdrawn (24)

4

APPLICATIONS

Crop

Maize (21) Soybean (8) Cotton (5) Oilseed rape (3)

APPLICATIONS UNDER 1829/2003, ART 5 & 17 – CC + RA PHASE (37)

5

APPLICATIONS

Level of stacking

Singles (13) 2-event stacks (6) 3-event stacks (6) 4-event stacks (7) 5-event stacks (3) 6-event stacks (2)

M (2) S (2) C (1) O (1) M (1) S (3) C (2) M (6) S (1)

M (3) M (2)

APPLICATIONS UNDER 1829/2003, ART 5 & 17 – CC + RA PHASE (37)

M (7) S (2) C (2) O (2)

M=maize S=soybean C=cotton O=oilseed rape

6

Renewal applications under 1829/2003, Art 11 & 23

 Under risk assessment: 6 (OSR GT73; OSR MS8, RF3

and MS8 x RF3; maize GA21; sugar beet H7-1; maize NK603 x MON 810; maize 1507 x NK603)

 Finalised: 2 (maize 1507 and maize 59122)

APPLICATIONS

7

Guidance documents under development or recently finalised

 Low Level Presence GD – item 4.4 of the agenda  Allergenicity GD – item 5.1 of the agenda

Explanatory notes

 Literature review – item 4.3 of the agenda  Next Generation Sequencing – item 5.2 of the agenda

GUIDANCE DOCUMENTS AND EXPLANATORY NOTES

8

 MON810 PMEM annual reports – item 6.2 of the agenda  Additional information on maize Bt11 x MIR162 x MIR604 x

GA21 (Application 66) – finalised March 2017

 Additional information on maize 5307 (Application 95) –

received in December 2016, on-going

 Additional information on maize 3272 (Application 34) –

received in April 2017, on-going EXTERNAL MANDATES

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 Impact of teosintes – item 6.3 of the agenda  Scientific assistance on Bohn et al., 2016 in relation to the risk

assessment of genetically modified Bt crops

 Scientific assistance on the commentary published by Kruse-

Plass et al. (2017), in relation to the risk assessment of the GM Bt Maize crops EXTERNAL MANDATES

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Sequencing mandates

 Finalised: 3 (maize GA21, maize MIR604, maize 59122)  On-going: 2 (soybean 305423, soybean 40-3-2)

EXTERNAL MANDATES

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Contractor support on:

• Bioinformatics
• Statistical analyses
• Toxicological analyses

 Literature review of baseline information to support the risk

assessment of RNAi-based GM plants – finalised, item 7.2 of the agenda

 Literature review of baseline information on RNAi that could

support the food/feed and environmental risk assessment of RNAi-based GM plants – on-going PROCUREMENT AND GRANTS

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23 May 2017 8th GMO Network Meeting Elisabeth Waigmann

Risk assessment of subcombinations

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 IR 503/2013 (Annex II, 2.2):

“for stacked GM plants, whose cultivation is associated with the production of GM material containing various subcombinations of events (segregating crops), the application shall include all subcombinations independently of their origin which have not yet been authorised.”

“In such case, the applicant shall provide a scientific rationale

justifying that there is no need to provide experimental data for the concerned subcombinations or, in the absence of such scientific rationale, provide the experimental data”

BACKGROUND

3

‘subcombinations’ = lower stacks containing combinations of up to N-1 of the events present in the high stack

 Subcombinations can be obtained in two ways:  By segregation in the progeny of the high stack  through targeted breeding programs, by conventional

crossing BACKGROUND

4

F1 AxBxCxD (high stack) Harvested F2 kernels will contain:

• high stack AxBxCxD
• 3-event subcombinations: AxBxC;

AxBxD; AxCxD; BxCxD

• 2-event subcombionations: AxB;

AxC; AxD; BxC; BxD; CxD

• singles: A; B; C; D.

Segregation will

• ccur on the cob

Subcombinations obtained by segregation from the high stack BACKGROUND

hemizygous

5

Subcombinations obtained through targeted breeding programs

Example subcombination AxBxD: BACKGROUND

AxB D (done by breeding company) F1: AxBxD hemizygous

targeted breeding program x F1: AxBxD hemizygous marketed to farmers

6

 Define a GMO Panel approach for the risk assessment

• f subcombinations independently of their origin, i.e.
• btained by segregation or through targeted breeding

programs, as required in IR 503/2013

 GMO panel approach will be published as an annex to

the May 2017 plenary meeting minutes, in line with the EFSA goal to provide transparency in the risk assessment process

 Covers maize and oilseed rape

GOAL

7

Subcombinations obtained by segregation in the progeny of the high stack (e.g. F2 generation in harvested grains/seeds)

 present in F2 grain/seed mixture of the high stack  not intended to be further propagated  are an integral part of the assessment of the high stack

the assessment of sub-combinations occurring by segregation needs no further consideration. RISK ASSESSMENT STRATEGY

8

Subcombinations obtained through targeted breeding programs

 stacks in themselves which can be bred, produced and

marketed independently of the higher stack The strategy to assess these sub-combinations needs further consideration RISK ASSESSMENT STRATEGY

9

The assessment of subcombinations needs to encompass intended and unintended effects, as for any other stack

 Intended effects - directly linked to the objective(s) of the

genetic modification(s)

 Unintended effects - not directly linked to the objective(s) of

the genetic modification(s). On the basis of current knowledge

• f the introduced trait(s), these can be either expected or

unexpected RISK ASSESSMENT STRATEGY

10

The challenge:

 these subcombinations may not even exist at the moment of

submission of the high stack application,

  experimental data to identify intended and unintended

effects might not be available.

 it is also possible that some of these subcombinations have

been the object of past applications and assessed by the EFSA GMO Panel RISK ASSESSMENT STRATEGY

11

The GMO Panel considers that the assessment of subcombinations

• btained through targeted breeding programs can be performed
• n the basis of:

 RA of the single events;  RA of the high stack;  RA of relevant specific subcombinations (if available);  specific data/information that may be required on a case-by-

case basis. RISK ASSESSMENT STRATEGY

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Assessment of:

 intended and expected unintended effect(s)

linked to the genetic modification

 unexpected unintended effect(s) potentially

linked to the genetic modification RISK ASSESSMENT STRATEGY

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Intended and expected unintended effect(s) linked to the genetic modification When the RA has identified effects linked to the single events or the high stack, the risk associated to particular subcombinations can be anticipated. Two scenarios:

a)

An effect linked to specific subcombinations is expected

• Effect relevant to safety of the subcombinations

additional data is requested

• Effect not relevant to safety of the subcombination no

additional data needed

b)

No effect linked to specific subcombinations of the events is expected no additional data needed

RISK ASSESSMENT STRATEGY

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Unexpected unintended effect(s) potentially linked to the genetic modification



If an unexpected unintended effect is identified for the high stack and/or any of the single events, it is assessed as an expected unintended effect, and its associated risk in specific subcombinations

• f the events is considered as described previously



If no unexpected unintended effect is identified, the assessment will be performed on the basis of the available information no additional data needed

RISK ASSESSMENT STRATEGY

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 The opinion will report (i) the assumptions made to

complete the assessment of subcombinations, (ii) possible remaining uncertainties, as well as (iii) if appropriate, strategies to reduce such uncertainties. Example of implementation of the strategy can be found in the scientific opinion on application 119. RISK ASSESSMENT STRATEGY

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23-24 May 2017 – GMO RA Network MTG – Yann Devos (EFSA GMO Unit)

Explanatory note on literature searching

2

3

 Submission types

 GMO market registration applications (APs) submitted

under Regulation (EC) No 1829/2003 before and after the Implementing Regulation (EU) No 503/2013 (IR) entered into force [GMO APs]

 Annual post-market environmental monitoring reports

• n GMOs authorised for commercial cultivation in the

EU [annual PMEM reports]

 GMO APs for the renewed market authorisation of

authorised GM food/feed under Regulation (EC) No 1829/2003 [renewal APs]

SCOPE OF EXPLANATORY NOTE

4



GMO APs submitted after the IR came into force

 IR requires a systematic review (SR) covering the 10

years before the submission of the GMO AP

 GMO APs submitted before the IR came into

force

 Complement GMO APs with relevant findings published

in the scientific literature during the regulatory review process

SCOPE OF EXPLANATORY NOTE

5

 Annual PMEM reports

 European Commission’s authorisations require to

actively screen relevant scientific publications

 Renewal APs

 EFSA GMO Panel (2015) requires to search all scientific

databases relevant for the three main areas of the risk assessment in a comprehensive and structured manner, in order to retrieve new scientific information relevant to the safety of the GMO for market renewal

SCOPE OF EXPLANATORY NOTE

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 Observations

 Applicants have undertaken literature searches to

various degrees of rigour

 Lack of clarity on how to address the SR requirement

• f the IR

AIM OF EXPLANATORY NOTE

7

 Aim

 To clarify the scope and methodology for literature

searching

 To give recommendations on how to conduct, report

systematic/extensive literature searches, and present the results of any scoping reviews

 To complement EFSA (2010) on the application of SR

methodology to food/feed safety assessments to support decision making, with GMO-specific guidance

AIM OF EXPLANATORY NOTE

8

 Applicants

 To provide a more rigorous and

standardised/harmonised approach to literature searching

 To perform more consistent and sensitive literature

searches, and improve reporting

 To minimise biases (such as publication bias)

 Risk assessors and regulators

 To provide guidance on how to check/appraise

systematic/extensive literature searches

INTENDED USERS OF EXPLANATORY NOTE

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 Scoping reviews



GMO APs submitted after the IR came into force

 Systematic/extensive

literature searches

 GMO APs submitted

before the IR came into force

 Annual PMEM reports  Renewal APs

STRATEGY OF EXPLANATORY NOTE

10

 Scoping reviews



GMO APs submitted after the IR came into force

 IR requires a SR  Not always useful/necessary to perform SR  IR allows for derogation  Reasoned justification required  Outcome of scoping review can determine

whether it is useful to perform SR and for which topics

STRATEGY OF EXPLANATORY NOTE

11

 Framework consisting of five successive steps

1.

Identifying review questions and clarifying their purpose (Section 3.1)

2.

Searching for/identifying relevant studies (Section 3.2)

3.

Selecting studies (Section 3.3)

4.

Extracting high level data of the relevant studies (Section 3.4 – only applicable to scoping reviews)

5.

Summarising and reporting the data, and considering the implications of findings (Section 3.5)

STRUCTURE OF EXPLANATORY NOTE

12

 Appendices

 A – Categories of information/data requirements  B – Search strategy examples (#4)  C – Examples of web-based databases that can contain

relevant information supporting the risk assessment of GMOs

 D – Requirements for undertaking scoping reviews

applicable to systematic/extensive literature searchers

STRUCTURE OF EXPLANATORY NOTE

13

 Problem to address should be specified in the form

• f clear, unambiguous and structured questions

 Link to GMO risk assessment context

 Review questions should be broken down into their

key elements to guide the development of search terms and structure the search:

1.

Structured questions (e.g. PICO, PECO)

2.

Information/data requirements outlined in relevant GMO Panel guidance documents, EFSA explanatory notes and IR (see Appendix A)

• 1. IDENTIFY REVIEW QUESTIONS/CLARIFY THEIR PURPOSE

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1.

Structured questions (e.g. PICO, PECO)

 “Does either the GMO and derived food/feed products,

• r the intended trait(s), have adverse effects on

human and animal health and the environment?”

 P = population [human/animal health/environment]  I/E = intervention/exposure [GMO, derived

food/feed products, intended trait(s)]

 C = comparator  O = outcome [adverse effects]

• 1. IDENTIFY REVIEW QUESTIONS/CLARIFY THEIR PURPOSE

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2.

Information/data requirements outlined in relevant GMO Panel GDs, EFSA explanatory notes and IR (see Appendix A)



Examples



Protein expression data



90-day feeding studies in rodents



Laboratory/greenhouse feeding bioassays with representative non-target organisms



…

• 1. IDENTIFY REVIEW QUESTIONS/CLARIFY THEIR PURPOSE

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 Literature searching involves:

1.

Developing a search strategy

2.

Identifying information sources to search

• 2. SEARCH FOR/IDENTIFY RELEVANT STUDIES

17

1.

Developing a search strategy



Approaches to develop searches



Single search strategy



Series of focused search strategies



Search strings (link to key elements of review questions)



See Appendix B

• Search terms
• Search functions
• Search operators
• 2. SEARCH FOR/IDENTIFY RELEVANT STUDIES

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1.

Developing a search strategy



Language



Time period



Reference study searches



List of reference studies



Results of searches with reference studies



Appraisal (EFSA critical appraisal tool [CAT])

• 2. SEARCH FOR/IDENTIFY RELEVANT STUDIES

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2.

Identifying sources of scientific literature

 Electronic bibliographic databases  Mandatory  At least two multi-disciplinary databases for

complementarity (e.g. Web of Science Core Collection, Scopus, CAB Abstracts, Medline)

 Optional  Searching more specialist/subject-specific

databases (e.g. Agricola)

• 2. SEARCH FOR/IDENTIFY RELEVANT STUDIES

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2.

Identifying sources of scientific literature

 Internet searches (limit publication bias)  Mandatory  Internet pages of relevant key organisations

involved in GMO risk assessment (e.g. FDA, USDA, US EPA)

• 2. SEARCH FOR/IDENTIFY RELEVANT STUDIES

21

2.

Identifying sources of scientific literature

 Internet searches (limit publication bias)  Optional  Scientific literature that is not indexed in

electronic bibliographic databases via general search engines such as Google scholar (check first 200-300 hits)

 Web-based databases known to contain

information specifically on effects of GMOs (examples given in Appendix C)

• 2. SEARCH FOR/IDENTIFY RELEVANT STUDIES

22

2.

Identifying sources of scientific literature

 Manual searches  Mandatory  Checking reference list from recent relevant

reviews, methodological publications and scientific opinions

 Optional  Hand-searching key journals or assessing

journal contents pages

 Citation searching

• 2. SEARCH FOR/IDENTIFY RELEVANT STUDIES

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 Determining “relevance”

 Set eligibility/inclusion criteria to determine relevance

• f the retrieved studies

 Table 1 gives examples of eligibility/inclusion

criteria

 Reliability of relevant studies is assessed later in the

process

• 3. SELECT STUDIES

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• 3. SELECT STUDIES

25

• 3. SELECT STUDIES

26

 Process (2 stages)

1.

Rapid assessment based on title-abstract-keywords

2.

Detailed assessment of full-text documents

 Quality assurance

 Relevant screening performed by more than 1 reviewer  Ensure inter-reviewer agreement  Resolve disagreement

• 3. SELECT STUDIES

27

 Classification of studies retrieved

 Relevant studies  To summarise and consider those for reliability  Non-relevant studies  Give reason(s) for exclusion based on

eligibility/inclusion criteria

 Unobtainable studies & studies with unclear relevance  Describe (unsuccessful) methods used to try to

• btain a copy of the study

 Give justification of why relevance cannot be

definitively determined

• 3. SELECT STUDIES

28

 Data extraction [only for scoping reviews]

 Purpose  Enable applicants to describe the overall volume,

strength and direction of the studies

 Possible variables  Authorship, year of publication, source, title of the

study, objective of the study, experimental design, main results, conclusion, protection goal considered, applicable category of information/data requirement, whether adverse effects are reported

• n human/animal health and/or the environment, …
• 4. EXTRACT HIGH LEVEL DATA OF RELEVANT STUDIES

29

 Summarising and reporting the data

 Search methods and outcomes  Results of study selection process  See template tables 2 to 5  Narrative synthesis/summary of relevant studies,

describing their overall volume, strength and direction [only applicable to scoping reviews]

 See template tables 6

• 5. SUMMARISE AND REPORT

30

 Considering implications of the findings

 Value of undertaking SR [only applicable to scoping

reviews]

 Implications for risk assessment  To assess the reliability and implications for the risk

assessment of all relevant studies retrieved after detailed assessment of full-text documents for relevance: ordered by category of information/data requirement(s) (see template Table 7)

• 5. SUMMARISE AND REPORT

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 Applicability of the explanatory note

 Six months after publication date of the note  New submissions submitted after 10 OCT 2017  Except for:  Extensive/systematic literature searchers previously

submitted to EFSA that do not comply with minimum quality standards

 Updates of extensive/systematic literature

searchers previously submitted to EFSA

TRANSITION PHASE

32

 EFSA’s completeness checklist

 To be completed by applicants  To ensure adequate reporting to facilitate appraisal and

reproducibility

 How?  Appendix to EFSA’s updated submission

guidance on applications for authorisation of GM plants under Regulation (EC) No 1829/2003

 Attached to GMO Panel/EFSA questions asking

for updated or revised literature searches

COMPLETENESS CHECKLIST

33

 Explanatory note may/will be revised:

 when experience is gained in its application  in view of any amendments to the IR

FUTURE UPDATES OF EXPLANATORY NOTE

34

ACKNOWLEDGEMENTS

 Thank you for your attention  EFSA wishes to thank the following for the support

provided to this scientific output: Elisa Aiassa, Fernando Álvarez, Hermann Broll, Giacomo De Sanctis, Antonio Fernandez Dumont, Andrea Gennaro, Anna Lanzoni, Nikoletta Papadopoulou, Konstantinos Paraskevopoulos and Matthew Ramon, and experts of the GMO Panel standing Working Groups

• n Molecular Characterisation, Food/Feed, and

Environmental Risk Assessment for inspiring discussions that helped to develop the explanatory note to the guidance

35

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Guidelines on possible derogation of existing requirements for applications of GM food and feed at low levels submitted under Regulation (EC) No 1829/2003

Anna Lanzoni 8th GMO Network Meeting 23 May 2017

2

 Introduction  The mandate on GMO Low Level Presence (LLP)  Project plan and schedule  Stakeholders engagement  EU Member States consultation  The draft guidance: key points  Q&A

ROADMAP

3

 Introduction  The mandate on GMO Low Level Presence (LLP)  Project plan and schedule  Stakeholders engagement  EU Member States consultation  The draft guidance: key points  Q&A

ROADMAP

4

 Mandate from European Commission

Mandate on possible derogation of existing requirements for applications of GM foods and feeds at low levels submitted under regulation (EC) No 1829/2003

 Received by EFSA in 2014  Clarification requested to EC  Accepted by EFSA in 2015 (EFSA-Q-2015-00432)

THE MANDATE ON GMO LOW LEVEL PRESENCE (LLP)

5

PROJECT PLAN AND SCHEDULE LLP

Sept 2017 July 2015 2 May-13 June 2017 (6-week) Sept 2016

1st draft guidance

EU MS consultation Public consultation

2nd draft guidance

GMO Panel Guidance

28 Oct–9 Dec 2016 (6-week) Apr 2017

Josep Casacuberta Adinda De Schrijver Achim Gathmann Mikolaj Gralak Elsa Nielsen Francesco Visioli - Chair Jean-Michel Wal Yann Devos Antonio Fernandez Anna Lanzoni –Task leader Claudia Paoletti Konstantinos Paraskevopoulos Hearing expert: Thomas Frenzel

LLPWG

6

 Introduction  The mandate on GMO Low Level Presence (LLP)  Project plan and schedule  Stakeholders engagement  EU Member States consultation  The draft guidance: key points  Q&A

ROADMAP

7

 Two-step approach  Dedicated EU Member States Consultation

28 October - 9 December 2016

 Public Consultation

• ngoing, ending 13 June 2017

STAKEHOLDERS ENGAGEMENT

8

 The process

EU MS CONSULTATION

EFSA LLP WG Advisory Forum EFSA Focal Points MS Competent Authorities under 1829/2003 EFSA Focal Points

9

EU MS CONSULTATION

 The tools

10

 240 comments  summarised replies will be provided in a Technical report

with those from Public Consultation

EU MS CONSULTATION

 The outcome

11

 Main comments

 Readibility  Scientific contents  reassurance on the appropriateness on most EFSA proposals  relevant scientific points raised  Risk management issues EC involvement

 Threshold  Scope (“large size” fruit/vegetables)  Asynchronicity/asimmetry & mutual recognition

EU MS CONSULTATION

12

 Introduction  The mandate on GMO Low Level Presence (LLP)  Project plan and schedule  Stakeholders engagement  EU Member States consultation  The draft guidance - key points  Q&A

ROADMAP

13

 Improved instructions for use  Not a stand-alone document!

This document is intended to assist applicants … by indicating which technical requirements of Annex II of Regulation (EU) No 503/2013 are necessary and which are not, in this case providing justification, in order to conclude on the safety of a GMO in a LLP application This document supports Regulation (EU) No 503/2013 and it is not intended to serve as a stand-alone guidance DRAFT GUIDANCE – IMPROVED READIBILITY VS V1

See: 3.1 Introduction

14

NOT A STAND-ALONE DOCUMENT

15

 GMO at maximum 0.9% per ingredient  point of entry  consumer  GMO at >0.9% per ingredient : not in the remit of this

guidance

 e.g. GM fruits and vegetables constituting either a full

portion or part of a consumed portion, resulting in an exposure of consumers (or animals) higher than 0.9% to that GMO DRAFT GUIDANCE - SCOPE

See: 1.2 Interpretation of the Terms of Reference

16

 LLP application: covers a request for the authorisation of a

GMO present at a level of maximum 0.9% per ingredient in any food and/or feed, submitted under Regulation (EC) 1829/2003

 LLP GMO: the GMO subject of the LLP application  LLP Ingredient: the mixture of the LLP GMO and the same

plant species and/or derived product, at the predefined proportion of a maximum of 0.9% and 99.1% respectively DRAFT GUIDANCE - DEFINITIONS

See: 1.2 Interpretation of the Terms of Reference

17

 Stand-alone dossier  Comprehensive characterisation of the

transformation event (intended trait)

 Fit-for purpose assessment driven by:

low exposure under acute/chronic scenarios

DRAFT GUIDANCE - SCIENTIFIC DRIVERS

18

MAIN “DEROGATIONS” FROM REGULATION (EU) 503/2013 – AT A GLANCE

Molecular characterisation

• Expression of the insert

Singles: only edible parts Stacks: not routinely needed

• RNAi off targets

Not necessary Comparative assessment

• ONLY for output traits, hypothesis-driven situations, de novo compounds
• Targeted compositional analysis, not full list of OECD consensus docs compounds
• No equivalence test necessary
• Greenhouse/field trials acceptable
• # sites
• No agronomic and phenotypic characteristics assessment on a routine basis
• Codex-aligned studies acceptable

Food Feed Assessment

• No 90-day studies
• No endogenous allergens measurements on a routine basis
• No nutritional assessment

19

 Environmental Risk Assessment: case-specific  varying depending on the biology of the plant

species, the intended trait(s), the potential receiving environments, and interactions among all three IN ADDITION

20

 Not mandatory on a routine basis  Since in LLP situations the level of exposure of consumers

and animals to the LLP GMO is defined to be at a maximum 0.9% per ingredient, not all differences in comparative analysis endpoints between the LLP GMO and the plant (and/or derived product) constituting the remaining part of the ingredient may be relevant

 Why? Which difference might be relevant in LLP?

FOCUS ON COMPARATIVE ANALYSIS

See 3.2.3.3 Comparative analysis

21

 The level of an endogenous compound in a LLP ingredient is

determined by:

 the level of such endogenous compound in the LLP GMO

(and/or derived product)

 the level of such endogenous compound in the plant (and/or

derived product) constituting the remaining part of the ingredient.

 The ratio between these two levels determines the extent to

which the level of the compound of the LLP GMO impacts the overall level of that compound in the LLP ingredient FOCUS ON COMPARATIVE ANALYSIS

See 3.2.3.3 Comparative analysis

22

FOCUS ON COMPARATIVE ANALYSIS

LLP ingredient LLP GMO remaining part of the ingredient

+ =

endogenous compound

Case 1 Case 2 Case 3

23

FOCUS ON COMPARATIVE ANALYSIS

Level of a compound in LLP GMO/ level

• f

the compound in the ingredient without the LLP GMO Level of the compound in LLP ingredient/ level of the compound in the ingredient without the LLP GMO

0.991 0.001 0.991009 0.01 0.99109 0.1 0.9919 1 1 10 1.081 20 1.171 50 1.441 90 1.801 100 1.891 200 2.791

Table 1: Impact of variations in the levels of an endogenous compound in a LLP GMO on the level

• f the same compound in a LLP ingredient.

Case 1 Case 2 Case 3

See 3.2.3.3 Comparative analysis

24

 On the basis of the current knowledge, the GMO Panel is of

the opinion that variations in the level of compound(s) in LLP GMOs are generally not large enough to impact on the nutritional or safety characteristics of the LLP ingredient POSSIBLE EXCEPTIONS

 GMOs with output traits developed to improve nutrition  GMOs expected to show compositional changes on the basis

• f precedent investigations

FOCUS ON COMPARATIVE ANALYSIS

See 3.2.3.3 Comparative analysis

25

 Therefore:  No comparative assessment on a routine basis  Compositional analysis only if:

 the intended trait targets the composition of the LLP GMO (output

trait)

 a hypothesis for a relevant compositional change can be

formulated based on available information from the hazard identification (e.g. unintended compositional changes anticipated by the precedent analyses)

 compounds are de novo produced in the LLP GMO

 No comparative analysis of agronomic/phenotypic

characteristics FOCUS ON COMPARATIVE ANALYSIS

See 3.2.3.3 Comparative analysis

26

 Implementation  Targeted compositional analysis  No full list of OECD consensus doc compounds  Conditions maximising expected change(s), based on

available knowledge

 field trials, greenhouse studies  Equivalence test not considered necessary

FOCUS ON COMPARATIVE ANALYSIS

See 3.2.3.3 Comparative analysis

27

 Comparative assessment studies performed under

non-EU regulatory frames: applicability in LLP applications

 studies conducted in accordance with Codex (Codex

Alimentarius, 2009) could support the assessment

 studies not aligned to requirements of Codex are not

considered appropriate by the GMO Panel. FOCUS ON COMPARATIVE ANALYSIS

 

See 3.2.3.3 Comparative analysis

28

 Testing of whole genetically modified food and feed

(Regulation [EU] No 503/2013; Annex II. II, 1.4.4 subsections 1.4.4.1-1.4.4.3)

 the GMO Panel considers that a 90-day feeding study is

not needed to corroborate information on the toxicological characteristics of the whole LLP GM food and feed in rodents and/or to reduce the remaining uncertainties, considering the limited exposure to the LLP GMO FOCUS ON TOXICOLOGY

See 3.2.3.4 Toxicology

29

 The assessment of the allergenicity of food or feed

from the LLP GMO should be conducted in the case changes in the levels of endogenous allergens are expected in the LLP GMO, possibly impacting the allergenicity of the LLP ingredient

 In such situations, relevant identified endogenous

allergens should be analysed and the assessment should indicate whether the GMO could impact the allergenicity of the LLP ingredient FOCUS ON ALLERGENICITY

See 3.2.3.5 Allergenicity

30

 Considering that the scope of LLP applications is

limited to a level of maximum 0.9% of a LLP GMO per ingredient a nutritional assessment is not considered necessary on a routine basis, unless relevant changes in the levels of food and feed constituents from the LLP GMO are expected FOCUS ON NUTRITIONAL ASSESSMENT

See 3.2.3.6 Nutritional assessment

31

 In the case of multiple LLP applications for LLP GMOs showing

similar traits, the possible cumulative contribution from the various LLP GMOs to the ingredient should be taken into consideration in the risk assessment

 the relative contribution to the ingredient of each of these

taken into account to allow an estimation of their total contribution via the addition of the respective trait-related constituent(s)

 Case-by-case, on the basis of compositional analysis outcome

CUMULATIVE RISK ASSESSMENT

See 3.2.5.3 Cumulative risk assessment

32

Thank you Questions?

33

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STAY CONNECTED!

Allergenicity guidelines

(EFSA-Q-2014-00547)

Antonio Fernandez Dumont 8th GMO Network Meeting 23 May 2017

2

• Self-task activity (initiated by EFSA)
• Non-IgE-mediated immune adverse reactions to foods
• In vitro protein digestibility
• Endogenous allergenicity
• Stakeholders engagement
• EFSA Workshop (June 2015)
• Public consultation (July-September 2016)
• EFSA Info Session (November 2016)
• «Focus group» interactive consultation body

Allergenicity guidelines

3

Non-IgE-mediated immune adverse reactions to foods

• Risk Assessment to focus on celiac disease
• Clear cause-effect relationship
• Risk assessment considerations
• Stepwise approach
• Annex A
• Additional considerations
• Examples

Allergenicity guidelines

4

Allergenicity guidelines

5

Allergenicity guidelines

6

• Risk assessment considerations
• Usefulness of protein digestion
• Types of in vitro digestibility tests
• An interim phase needed – EFSA procurement
• Annex B
• Additional considerations for the interim phase
• Examples

Allergenicity guidelines

In vitro protein digestibility

7

Allergenicity guidelines

8

Allergenicity guidelines

9

• Relevant crops for the analysis
• Relevant allergens to be quantified
• Methodology
• Data interpretation
• Annex C
• Additional considerations
• Examples

Allergenicity guidelines

Endogenous allergenicity

10

Allergenicity guidelines

11

Thank you very much for your attention!

Allergenicity guidelines

Acknowledgement: EFSA would like to thank the members of the Allergenicity Working Group: Eigenmann Philippe, Epstein Michelle, Hoffmann- Sommergruber Karin, Koning Frits, Lovik Martinus, Mills Clare, Moreno F. Javier, van Loveren Henk, Wal Jean-Michel; the EFSA trainee Selb Regina and the EFSA staff member Fernandez Dumont Antonio for the scientific discussions and the preparation of the guidance document

Presented by Nikoletta Papadopoulou GMO Unit Parma, 23-24 May 2017

Explanatory Note on Next Generation Sequencing

2

This presentation represents the state of discussion at the time of the GMO Network meeting, 23-24 May 2017, and does not necessarily reflect the final

• utcome.

3

NEXT GENERATION SEQUENCING (NGS)

Library Construction Cluster Amplification Alignment and data analysis (reference genome) Sequencing

Genomics (whole genome sequencing, exome sequencing, de novo and targeted sequencing) Transcriptomics (total RNA and mRNA sequencing, targeted RNA sequencing, small RNA and ncRNA sequencing) Epigenomics (Methylation sequecning, ChIP sequencing, ribosome profiling)

4

NGS is used for the molecular characterisation of the GM plant insert, in the context of GMO applications for EU market authorization, and specifically for:

• Characterisation of the T-DNA insertion site in the

plant genome and its junction sites

• Detection of backbone plasmid in the GM plant genome
• Generational stability/integrity of a T-DNA

NGS IN GMO APPLICATIONS

5

 To provide recommendations on the information that should be submitted in GMO applications so that EFSA can perform its quality assessment  To provide a standardised approach to NGS

AIM OF THE NOTE TO GUIDANCE

6

PREPARATION OF THE NOTE TO GUIDANCE

Consultation by the Molecular Characterisation WG experts Experience from assessing applications using NGS Published literature

7

I.

Sequence data and quality

II.

Read depth: Whole genome sequencing approach or Sequence capture approach

• III. Read alignment to a reference genome
• IV. Description of data and processing

DESCRIPTION OF QUALITY PARAMETERS FOR RA

8

• Library construction methods and sequencing

platforms

• Paired or single-end read sequencing, but for

characterisation of integration sites: longer read lengths are required.

• Junction read analysis involves detection of chimeric

reads (mapped to insert and host genome)

• Number and quality statistics of reads (FASTQC)/run
• I. SEQUENCE DATA AND QUALITY

9

• Whole genome sequencing approach
• Calculation of the number of reads required to

cover the genome to a specified depth: e.g. by Lander-Waterman algorithm

Coverage =

𝑜𝑣𝑛𝑐𝑓𝑠 𝑝𝑔 𝑠𝑓𝑏𝑒𝑡∗𝑠𝑓𝑏𝑒 𝑚𝑓𝑜𝑕𝑢ℎ 𝑓𝑡𝑢𝑗𝑛𝑏𝑢𝑓𝑒 𝑕𝑓𝑜𝑝𝑛𝑓 𝑡𝑗𝑨𝑓

• Identification approach by Willems et al, 2016

(statistical framework for estimating the probability of sequencing junction reads)

• Sequence capture approach to enrich for target

sequences

• II. READ DEPTH

10

• Genome coverage:

The degree of validation of sequence coverage is greatly dependent on:

• the organism in question
• the availability of genomic resources

Examples are provided in the Note to Guidance

• III. READ ALIGNMENT TO A REFERENCE GENOME

11

 Read numbers per sequencing run (raw and

calculated/probability formula)

 Data on coverage of reference genes (from read

alignment)

 Number of reads when trimmed or removed during

analysis

 Description of bioinformatics analysis; step-by step  Parameters and versions of software used

• IV. DESCRIPTION OF DATA AND PROCESSING

12

NOTE TO THE GUIDANCE ON NGS- PUBLICATION Publication: June 2017 EFSA webinar: 11th July 2017

13

 Simon Moxon  Molecular Characterisation (MC) WG Experts  GMO Unit Colleagues

ACKNOWLEDGMENTS

Assessment of site representativeness

Andrea Gennaro and Giacomo De Sanctis 23 May 2017 8th GMO Network ERA break-out session

2

 PART 1  The objective of this presentation  The importance of site selection  The site representativeness in the EFSA 2011 FF

guidance and IR 503/2013

 Strategy proposed in the EFSA 2015 agro/pheno

guidance

 PART 2  Classification of the cultivation conditions  Graphical representations  Assessment of representativeness of selected sites  Conclusion on site representativeness

OUTLINE

3

To present a strategy to assess the representativeness of the selected sites where the field trials are conducted

OBJECTIVE

4

WHY SITE REPRESENTATIVENESS IS IMPORTANT

Molecular characterisation Agro/Pheno Compositional

Comparative approach is followed to identify intended and unintended differences between GM plant and the conventional counterpart The risk assessment of GM plants starts with hazard identification (as part of problem formulation)

Selected sites Field trials conditions Test materials Intended and unintended changes

5

… WHICH ARE THE IMPLICATIONS OF SITE SELECTION? Seedling – Vegetative phase – Reproductive phase - Harvest

Seeds FIELD TRIAL Seeds

Agronomic and phenotypic characterisation Compositional analysis

 This information is used to drawn conclusions on

materials produced under conditions different from those tested to support the specific application

6

EFSA Guidance on RA of food and feed from GM plants and Implementing regulation (EU) 503/2013



Each field trial shall be replicated at a minimum of eight sites



The replication at each site is the number of results obtained for each test material; the replication should never be less than four at any site.

HOW MANY SITES AND REPLICATES

7

EXPERIMENTAL DESIGN: THE MINIMAL REQUIREMENTS 8 sites, 1 GM plant, 1 comparator, 6 reference varieties (3 per site) Randomised Block Design

GM CC Ref Single plant Plot Single row Number of plants/plot is related to the phenotypic characteristics of the crop and to the applied agricultural practices

Block1 Block2 Block3 Block4

8

 be representative of the range

• f receiving environments

where the crop will be grown, thereby reflecting relevant meteorological, soil and agronomic conditions; the choice should be explicitly justified.

THE PRINCIPLES OF SITE SELECTION

 reflect the different

meteorological and agronomic conditions under which the crop is to be grown; the choice shall be explicitly justified.

From the EFSA guidance and IR, it is clear the importance of site selection and its justification The different sites selected for the field trials shall

EFSA Guidance on RA of food and feed from GM plants 2011 Implementing regulation (EU) 503/2013

9

Site selection justification in import & processing applications: …field trial sites were selected in areas where the crop is typically cultivated in the USA OR …the selection was based on the representativeness of the region for the crop production and the availability of GLP compliant test sites Site selection and/or the representativeness of the sites selected by the applicants in frequently challenged by MS. It was considered important:

 more clarity to applicants on how sites should be selected  more transparency in the assessment of site

representativeness SITE SELECTION NOT SUFFICIENTLY JUSTIFIED

10

The agro/pheno guidance provides recommendations on how to select and manage the field trials The principle to be follow is:



The selection should be able to capture enough variability within the set of possible receiving environments in which the test materials can be grown To agro/pheno guidance requests specific information to support the appropriateness of site selection such as:



geographical location



agrometeorological data



soil characteristics



crop management practices

SITE REPRESENTATIVENESS IN THE AGRO/PHENO GD

11

EXAMPLE OF SITE SELECTION

Step I: delineate the boundary within which sites for the trials could be selected (e.g. acreage) Step II: further delineation of boundaries based on additional factors (e.g. maturity group that is related to the tested materials)

12

EXAMPLE OF SITE SELECTION Step III: sites identification, including sites outside optimal growing area 3 examples for a soybean (maturity group III)

Representative Variable Appropriate for the GM line

        

13

Key factors to evaluate site representativeness of selected sites (requested in agro/pheno GD):



geographical locations



meteorological conditions



soil characteristics



management practises

REPRESENTATIVENESS OF SELECTED SITES

How?



Multi-factors



Transparent



Repeatable



Component of expert judgement What?



Representative of likely REs



Variable



Inside the limits where the GM will be grown

14

Sys et al. 1993 Land evaluation part III crop requirements Based on Land suitability classification from FAO (1976)

HOW WE EVALUATE METEO CONDITIONS

Classes: S1 subcat. 0  optimal areas S1 subcat. 1  near optimal areas S2  suboptimal areas S3  marginal areas N1  not suitable but susceptible to correction N2  not suitable

15

HOW WE EVALUATE METEO CONDITIONS

Classes: S1 subcat. 0  optimal areas  dark green S1 subcat. 1  near optimal areas  light green S2  suboptimal areas  yellow S3  marginal areas  brown N1  not suitable but susceptible to correction  grey N2  not suitable  black

100% 0%

16

EXAMPLE OF METEOROLOGICAL CONDITIONS



Representative



Variable



Inside the limits where the GM will be grown

  



Representative



Variable



Inside the limits where the GM will be grown

  

17

HOW WE EVALUATE SOIL CONDITIONS

Classes: S1 subcat. 0  optimal areas S1 subcat. 1  near optimal areas S2  suboptimal areas S3  marginal areas N1  not suitable but susceptible to correction N2  not suitable

18

EXAMPLE OF SOIL CONDITIONS



Representative



Variable



Inside the limits where the GM will be grown

  



Representative



Variable



Inside the limits where the GM will be grown

  

19

HOW WE EVALUATE CROP MANAGEMENT

Field crops, usual planting and harvesting dates - USDA report, 2010.

Crop management should be representative of the likely REs:



Planting and harvesting timing



Treatments (e.g. herbicide, type and timing)



Fertilization (amount and timing)



Irrigation (amount and timing)



Tillage (type and timing)



Crop history

20

SELECTION OF REPRESENTATIVE SITES

Historical climatic conditions (average over 30 years)

21

REPRESENTATIVE CONDITIONS ON FIELD TRIALS

Meteorological conditions and crop management applied during the year(s) of field trials

22

 Site representativeness is fundamental to drawn any

conclusion on comparative assessment of GM plants

 Conclusion on site representativeness takes into

account a multi-factors assessment

 Graphical tools could facilitate the expert judgements

making decisions transparent and repeatable

 Site representativeness requires expert judgments

CONSIDERATION ON SITE REPRESENTATIVENESS 1/2

23

 Applicant might select appropriate sites, but end up with

no representative conditions (meteorological and/or crop management during the field trials)

 meteorological  additional years as foreseen by the

agro/pheno GD

 crop management  additional field trials with

representative management

 Meteorological and soil conditions figures will be published

soon with submission GD CONSIDERATION ON SITE REPRESENTATIVENESS 2/2

24

 

THANK YOU FOR YOUR ATTENTION

EFSA Scientific Opinion Annual 2015 PMEM report on cultivation of maize MON810

Fernando Álvarez, GMO Unit 8th GMO Network meeting Parma 23 May 2017

2

Bt maize cultivation in the EU

20 40 60 80 100 120 140 160 1998 1999 2000 2001 2002 2003 2004 2005 2006 2007 2008 2009 2010 2011 2012 2013 2014 2015

SP SK RO PO PO GE FR CR

103xha

1.5%

Total maize area

92%

Slovakia 104 ha Portugal 8 017 ha Czech Republic 997 ha Romania 2.5 ha Spain 107 749 ha

19

Opt

• uts

Bt-176 MON810

5

Countries in 2015

3



Since 1998



>100 varieties registered



~90% Bt maize in EU



~25% global adoption rate



Highest adoption rate in Ebro valley  ''Hot spot area''

Bt maize cultivation in Spain

67% 81% 88%

>10000 >5000-10000 >1000-5000 >100-1000 >0-100

MON810 ha Castañera et al. 2016.PLOS ONE 11(5): e0154200 Source: Avances

4

Lepidopteran pests of maize in the EU

Corn borers

Ostrinia nubilalis (ECB) Sesamia nonagrioides (MCB)

5

Annual PMEM reports maize MON810

• From 2005, Monsanto submits to the EC annual PMEM reports

according to Annex VII of Directive 2001/18/EC

• From 2009, EC requests the GMO Panel to assess annual PMEM reports

 Scientific Opinions (SOs) on 2009-2015 PMEM reports (EFSA PMEM GD 2006, 2011)

To monitor changes in susceptibility to Cry1Ab for the assessment of the ‘high-dose/refuge’ strategy ‒ EuropaBio harmonised insect resistance management (IRM) plan To identify unanticipated adverse effects caused by the cultivation of maize MON810 ‒ Farmer questionnaires (FQs) ‒ Literature searching & assessment scientific publications

Case-Specific Monitoring (CSM) General Surveillance (GS)

6

Dose-response

• Diet-overlay assays
• MIC50 and MIC90
• Reference lab strain
• 1. Insect Resistance Monitoring
• Changes in baseline susceptibility
• Field sampling ECB and MCB from 3 areas
• Three sampling sites per area
• ~450 larvae per area
• Lab assays with F1 larvae

Case-specific monitoring

Insect Resistance Management Plan

• Based on the high-dose/refuge strategy
• EuropaBio, 2003 (MON810, Bt11, 1507)

Diagnostic dose

• Since 2013
• MIC99
• RR individuals

Maize MON 810

SS SS SS RR RS

Non-Bt maize Non-Bt maize

X X

ECB collection 2004-2013

7

Case-specific monitoring

Insect Resistance Management Plan

• Based on the high-dose/refuge strategy
• EuropaBio, 2003 (MON810, Bt11, 1507)
• 2. Farmer Alert System
• Report unexpected damages caused

by target pests

• Stewardship activities
• Follow-up studies to confirm

resistance

Remedial plan in case of failure

• Procedures for unexpected damage / Confirmation of resistance / Remedial actions

Dose-response

• Diet-overlay assays
• MIC50 and MIC90
• Reference lab strain

Diagnostic dose

• Since 2013
• MIC99
• RR individuals

Detection ≤3% Frequency R alleles

• 1. Insect Resistance Monitoring
• Changes in baseline susceptibility
• Field sampling ECB and MCB from 3 areas
• Three sampling sites per area
• ~450 larvae per area
• Lab assays with F1 larvae

8

Case-specific monitoring – 2015

• Crucial to delay resistance evolution
• Requirements
• 20% non-Bt maize refuge (>5 ha)
• ≤750 m from Bt maize field
• Compliance in Spain
• Through FQs
• 212 farmers in 2015
• 93% compliance
• Consent holder & MS to develop

appropriate information systems of GMO cultivation

20 40 60 80 100 2006 2007 2008 2009 2010 2011 2012 2013 2014 2015 90

Implementation of non-Bt maize refuges

Compliance (%)

9

Case-specific monitoring – 2015

Field sampling of ECB/MCB populations



Larvae (F0) collected from refuges and conventional maize fields

• ECB: Northeast and Central Iberia (3 sites at each area)
• MCB: Northeast Iberia (3 sites)



Larvae reared in the lab and bioassays conducted with progeny (F1)

• ECB: 152-180 larvae reached adult stage (~40% field-collected)
• MCB: 195 adults (37%) were used to obtain F1 larvae for assays



Insufficient # larvae sampled/represented in the bioassays as F1

10

Case-specific monitoring – 2015

Field sampling of ECB/MCB populations



Larvae (F0) collected from refuges and conventional maize fields

• ECB: Northeast and Central Iberia (3 sites at each area)
• MCB: Northeast Iberia (3 sites)



Larvae reared in the lab and bioassays conducted with progeny (F1)

• ECB: 152-180 larvae reached adult stage (~40% field-collected)
• MCB: 195 adults (37%) were used to obtain F1 larvae for assays



Insufficient # larvae sampled/represented in the bioassays as F1

11

Case-specific monitoring – 2015

Concentration-response assays

1 2 3 4 5 6 7 8 9 2005 2006 2007 2008 2009 2010 2011 2012 2013 2014 2015 North East Lab ref strain Resistance ratio 5 10 15 20 25 30 35 40 2005 2006 2007 2008 2009 2010 2011 2012 2013 2014 2015 North East Lab ref strain Resistance Ratio

MIC50 (95% CI) 

7-10 concentrations of purified Cry1Ab and F1 larvae (diet overlay assay)



Estimation MIC50 and MIC90 (with 95% CI) by Probit analysis



Calculation of Resistance Ratios (RR = MICfield population / MIClab ref strain)

12

Case-specific monitoring – 2015

Diagnostic-concentration assays



Bioassay conducted since 2013 – Standalone from 2016 onwards?



Diagnostic concentration: MIC99 (derived from baseline data)

• ECB:48.2 ng Cry1Ab/cm2
• MCB: 28.2 ng Cry1Ab/cm2



No resistant individuals identified (~96 larvae tested/area/year)



Actual limit of R allele frequency that could be detected < 3% threshold  Recommendation to increase sampling effort

Species Population Season Moulting inhibition (% ± SE)

ECB North East Iberia 2013 100 2015 100 Central Iberia 2013 100 2015 100 MCB North East Iberia 2013 97 ± 2 2015 100

13

Case-specific monitoring – 2015

Farmer alert system

 System allowing farmers to report complaints on

product performance

 Including unexpected crop damage caused by target pests

 300 complaints received during 2015 season  None of the related to infestation by ECB/MCB  Useful complement to the info provided by the lab

assays

Additional info needed to appraise usefulness:

• Appropriate communication mechanisms
• Fit-for-purpose educational programs

14

General surveillance – 2015

Farmer questionnaires



261 farmers surveyed in 2015: 212 from Spain and 49 from Portugal



Similar methodology compared to previous years

 Previous EFSA recommendations on sampling and reporting apply



The analysis of the 2015 FQs did not show any unanticipated adverse effects related to maize MON810 plants and their cultivation



2,627 questionnaires have been completed over 10 yrs. (2006-2015)

• EFSA previously recommended to perform stat analysis of pooled data
• Monsanto’s intention is to publish such analysis in a peer-reviewed journal

15

General surveillance – 2015

Literature searching



• Lit. search to retrieve studies published btw. JUN 2015 – MAY 2016



(Slightly) Revised protocol based on:

• EFSA Guidance on systematic review methodology (EFSA, 2010)
• Previous GMO Panel recommendations



Two databases: WoS Core Collection and CABI CAB Abstracts



Similar search strategy as previous years



18 relevant publications identified in 2015:

• 5 Food and feed safety
• 13 ERA/Risk management



No new info that would invalidate previous FF and ERA conclusions on maize MON810



Recommendation to follow EFSA’s explanatory note on literature searching (EFSA, 2017)

FF/MC ERA/Risk management

150 73 PMEM 2009-2015

16

• The data reported do not indicate any adverse effects on

human and animal health or the environment arising from the cultivation of maize MON 810 during the 2015 growing season

• The GMO Panel therefore concludes that the CSM and GS activities
• f maize MON 810 as carried out by the consent holder do not

provide evidence that would invalidate previous GMO Panel evaluations on the safety of maize MON 810

• Some methodological limitations were identified:

 Insect resistance monitoring activities – Do not provide sufficient sensitivity for an early detection of potential resistance

• f target pests in the field

 Farmer questionnaires – The sampling frame questionnaires does not allow the assessment of the representativeness of the results

EFSA Scientific Opinion Annual PMEM maize MON810 – 2015

Conclusions

17

• Sampling target pests
• To increase the sampling efforts (to achieve the recommended threshold)
• To focus in north-east Iberia (highest selection pressure)

‒ Annual sampling of both corn borers ‒ Three zones of ~10×10 km where adoption rate >60% for 3 years  Info on non-GM and maize MON 810 cropping areas at an appropriate scale should be made available by MS

• Laboratory bioassays
• Measurement endpoints – Provide LC and MIC values
• Reference laboratory strain – Refreshment
• Confirmatory experiment with maize leaves – Negative control & add info
• Disclose raw data
• Farmer alert system
• To provide additional info to appraise its usefulness and
• Implementation of non-Bt refuges
• To increase level of compliance (especially in regions of high adoption)

EFSA Scientific Opinion Annual PMEM maize MON810 – 2015

Recommendations – CSM

18

• Farmer questionnaires
• Previous recommendations on survey design and reporting
• To provide the pooled analysis from the surveys obtain over the last ten

years  To confirm that no unintended effects caused by the cultivation of maize MON 810 have been observed.  To evaluate the farmer questionnaire methodology for the detection of unintended effects

• Literature search
• To follow the recommendations given in the EFSA’s explanatory note to the

guidance on literature searching (EFSA, 2017)

EFSA Scientific Opinion Annual PMEM maize MON810 – 2015

Recommendations – GS

19

PMEM Working Group

Acknowledgements

EFSA GMO Unit

• Michele Ardizzone
• Yann Devos
• Antonio Fernández-Dumont
• Salvatore Arpaia
• Barbara Manachini
• Antoine Méssean (chair)
• Jeremy Sweet

EFSA AMU Unit

• Marios Georgiadis
• Laura Martino

23-24 May 2017 – GMO RA Network MTG – Yann Devos (EFSA GMO Unit)

Teosinte in the EU – Are there any implications for the ERA of GM maize for cultivation?

2

3

 Teosinte found in maize fields in the EU

 Spain  Ebro Valley (Aragón)  Region of Cataluña (to a lesser extent)  Since 2009  France  Region of Poitou-Charentes  Since 1990

CONTEXT

4

 EFSA was requested by EC to assess whether

 “on the basis of the elements provided by this letter,

the existing scientific literature and any other relevant information,

 new evidence emerges which would change the

conclusions and recommendations of the EFSA opinions

• n cultivation of genetically modified maizes MON810,

Bt11 and 1507 and GA21”

 Timeline

 Mid June 2016  September 2016

MANDATE OF THE EUROPEAN COMMISSION (EC)

5

 Materials

 Documents supplied and translated by the European

Commission (mostly grey literature)

 Available relevant scientific literature

 Methods

 Narrative review of relevant scientific literature (non-

systematic search)

 Problem formulation exercise (pathways of harm)  Consultation of representatives of the Competent

Authority of Spain

MATERIALS AND METHODS

6

 In centres of origin

 Teosinte is native to Mexico and Central America  Direct wild ancestor of maize  Many teosinte species and subspecies are rare and

endangered, requiring conservation actions

 Other teosinte species and subspecies are widely

distributed, and occur in agricultural fields, where they are considered non-aggressive weeds

 In some regions, teosinte is grown for forage/feed

purposes

PROTECTION GOAL

7

 Outside centres of origin

 Teosinte is not indigenous, but has become

naturalised/established in some countries

 Teosinte does not represent an environmental entity of

concern requiring protection

 Instead, it is occasionally cultivated for its forage, or

considered a weed

 In infested agricultural fields, teosinte is subject to

control and/or eradication measures

PROTECTION GOAL

8

 Problem formulation exercise focusing on possible

pathways to harm

 EFSA explored whether plausible pathways to harm

from the cultivation of maize MON810, Bt11, 1507 and GA21 can be hypothesised for situations where GM maize and teosinte would grow sympatrically, focusing

• n specific areas of risk typically considered in ERA of

GM plants

APPROACH

9

 Effects of vertical gene flow

 Hybridisation potential (teosinte to maize >> maize to

teosinte)

 Altered persistence/invasiveness of GM maize ×

teosinte hybrids

 Cross-pollination of maize by GM maize × teosinte

hybrids

 Interactions of GM maize × teosinte hybrids with  Other organisms (target and non-target)  The abiotic environment and biogeochemical

processes

APPROACH

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 Pathways to harm

 For each of the pathways considered, it is unlikely that

environmental harm will be realised

 Previous outputs

 No information indicating the necessity to revise the

previous ERA conclusions and risk management recommendations for maize MON810, Bt11, 1507 and GA21 made by the GMO Panel

CONCLUSION

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 Previous outputs

 EFSA considers that the previous GMO Panel risk

assessment conclusions and risk management recommendations on maize MON810, Bt11, 1507 and GA21 for cultivation remain valid and applicable

 To ensure effective long-term management of teosinte

and maize × teosinte hybrids that acquired glyphosate tolerance through vertical gene flow from maize GA21, and avoid exacerbating weed problems, EFSA recommends that integrated weed management reliant

• n multiple tactics is deployed when growing maize

GA21 in association with GLY

CONCLUSION

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 Trtikova et al. (2017)

 Teosinte in Europe – Searching for the origin of a novel

• weed. Scientific Reports, 7, 1560

 Authors genotyped Spanish teosinte plants  Genetically distinct from teosinte taxa from Mexico

and Nicaragua, and maize

 Teosinte × maize hybrids  Origin unclear (EU or country of origin)  Study under assessment internally

NEW STUDY

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ACKNOWLEDGEMENTS

 Thank you for your attention  EFSA wishes to thank Yann Devos for the preparatory

work on this scientific output, and Magdalena Ibáñez Ruiz, Antoine Messéan, Lucía Roda Ghisleri, Jeremy Sweet and Elisabeth Waigmann for the support provided to this scientific output

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