Representing the Plant Science Industry

Field Trials of Experimental, Genetically Engineered Plants

CropLife International Compliance Management Programme for Confined

Field Trials

Issues that we are NOT dealing with during this workshop

Globalization

Risks

Benefits

Grower Satisfaction

Public Trust

RegulatoryOversight

Labelling Testing andTraceability

CommodityMarkets

SegregationIdentity Preservation

Openness andTransparency

RiskCommunication

SocialAcceptability

Confined Trials

· For 2004, it is estimated that total acreage 200 million – a 20% increase over 2003

· More than 8.25 million farmers are growing transgenic crops, 90% of these are resource-poor farmers in developing countries

· The percentage growth in area between 2003 and 2004 in developing countries (35%) was almost 3X greater than for industrialized countries (13%)

Continued growth in GM crop area

Global Area of Transgenic Crops(Source: Clive James, 2004)

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Distribution of GM crops by country

· In 2004, six countries grew 98% of the global GM crop area– USA – 59%– Argentina – 20%– Canada – 6%– Brazil – 6%– China – 5%– Paraguay – 2% 0

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1996 1998 2000 2002 2004

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Acreage of Transgenic Crops by Country

(Source: Clive James, 2004)

USA Argentina Canada China

· Nearly all of the area planted to transgenic crops is accounted for by four crops, which in 2004 were represented by:– Soybean – 60%– Maize – 23%– Cotton – 11%– Canola – 6%

Distribution of GM crops by crop

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Global Acreage by Crop(Source: Clive James, 2004)

Soybean Maize Cotton Canola

· Of the global aggregate area of these 4 crops (710 M acres) in 2004, 29% was planted to biotech varieties.

· In 2004, the global market value of biotech crops was estimated at $4.7 billion, representing 16% of the $30 billion global commercial seed market

Global adoption of GM soy, cotton, canola & maize

Global Area Adoption Rates by Crop

(Source: Clive James, 2004)

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Transgenic Total

· Broader application of plant biotechnology products needs a system in place to permit the safe conduct of confined field trials.

· Capability to safely perform confined trials is equally important in both industrialized and developing countries.

· A system must exist whereby locally developed and foreign applications can be assessed and evaluated for potential biosafety impacts.

Global snapshot: Africa

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Global snapshot: Asia

Global snapshot: Central & Eastern Europe

I think we should change this to Europe including the new accession states

Global snapshot: Central & South America

Regulatory framework for confined field trials in the Philippines

Roles

CBI

Timeframes

Terminology

· Contained use (laboratory, greenhouse, screenhouse)

· Confined environmental release (field test)

· Unconfined environmental release (commercialization)

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What is a confined field trial?

· A confined field trial is a small-scaleexperimental field trial of a genetically engineered plant species carried out to collect the data necessary for a complete environmental risk assessment that is performed under terms and conditions that mitigateimpacts on the surrounding environment

Trials we are all familiar with

· Breeders’ trials (experimental)– Agronomic evaluation of new crosses– Evaluation of new germplasm, perhaps

imported from elsewhere· Variety registration trials

– Performance trials, demonstration of merit (value)

· Plant breeders’ rights trials– DUS – demonstration of distinctness,

uniformity, and stability

Purpose of confined field trials

· For the breeder – to collect agronomic performance data (efficacy of the modification, yield, etc), same as for a conventional trial

· To collect data to complete the environmental risk assessment– Secondary effects on non-target organisms– Morphological characterization – seed dissemination,

dormancy of seed, germination rate, time to maturity, disease and pest resistance

· To generate data for variety registration

Purpose of confined field trials (cont’d)

· To produce material for livestock feed performance trials

· To produce material for food safety evaluations (raw seed/grain and derived fractions)– Nutritional compositional analysis (proximates, amino

acids, fatty acids, minerals, vitamins, etc)– Levels of endogenous antinutrients, toxicants, and

allergens· Data are usually collected from trials in multiple

locations, representing a range of growing conditions, and over multiple years

Confined field trials

Most lines in confined field trials do NOTend up as products

ContainedLaboratory

Experimentation

ConfinedField Trial

Experimentation

100’s – 1000’sPotential Lines

10 - 100Potential Lines

1 – 4 Lines Submitted forUnconfinedApproval

New trait moved into10 – 100 varieties usingTraditional breeding

Post-approvalUse of new line

In breeding programs

Application forUnconfined (commercial)

Release

Application forConfined Field

Trial

Risk management approach

· The necessity of being able to safelyevaluate plants of uncertain risk cannot be over emphasized.

· A crucial distinction between unconfined environmental releases and confined trialsthat has not been sufficiently appreciated in some countries, either by regulators, national biosafety committees, or capacity builders and trainers.

Risk management approach

· At the level of an unconfined release, the focus must be on rigorous risk assessmentas the intent is widespread introduction of the modified plant into agriculture, usually with few or no restrictions.

· Conversely, for confined trials the risks may not yet be fully understood without data collected during the trial, hence the focus must be on risk management – the terms and conditions that are necessary to permit safe trial conduct.

Risk = Exposure x Hazard

· The risk management approach recognizes that hazards may not fully understood for field trials, so the focus is on preventing exposure by implementing specific mitigation measures

· Risk assessment is about hazardidentification and characterization, and exposure estimation

· Hazards can be:– Probabilistic– Hypothetical– Speculative

“3-Ps” of risk management for field trials

Aim to:

· Prevent dissemination of new genes in experimental transgenic plant into and within the environment (ieprevent pollen-mediated gene flow)

· Prevent the persistence in the environment of the experimental transgenic plant and any progeny plants

· Prevent the introduction of the experimental transgenic plant (or products) into the livestock feed and human food pathways

Confined trial process

Application Permit Planting Harvest/Termination Completion

TechnicalReview

RegulatoryDecisionLegal AuthorizationWith Terms & Conditions

Regulatory Inspections

Current Season Post-Harvest Period

Preventing dissemination of new genes

· Impose conditions of reproductive isolation on all plants within the trial site

· Practically, reproductive isolation = means used to control the movement of pollen from the trial site

· Ensures that new genes are not introgressedinto neighbouring plants of the same or a sexually compatible species

Purpose of reproductive isolation

· Prevent dissemination of new genes in experimental transgenic plant into and within the environment – prevent pollen-mediated gene flow and seed dispersal

· Three main methods– Spatial isolation– Physical isolation– Temporal isolation

GrapesTransgenicmaize

40 footBorder50 foot

FallowConfined maize trials in

the U.S.

Cotton

Preventing persistence in environment

· Imposing conditions of post-harvest land use restriction and post-harvest monitoring for volunteers– i.e. no planting of the same plant species

· Period of post-harvest restriction depends on the plant species– ie: seed dormancy characteristics

· Volunteers, related species and weedy relatives (where applicable) must be removed from the post-harvest site before flowering

Preventing introduction into food/feed chain

Controlling the· movement of plant material onto and off of the trial

site (transport and cleaning of any machinery used)· storage of plant material· disposal of residual or excess plant material on the

trial site – excess planting materials, material remaining after harvest, material from roguing, detasseling or deflowering activities

· disposition of any material retained after harvest

Terms & conditions + inspection & enforcement· The questions asked in applications for a

confined field trial should relate directly to confinement issues

· All of the provisions under the “3-Ps” should be reflected in the terms and conditions of authorization of a confined field trial

· Adherence to the terms and conditions must be verified through inspection / auditing by the regulatory authority

Safety record

· The combination of science-based risk management T&Cs plus adequate inspection will contribute to the safe conduct of confined field trials

· Over the last 17 years (since 1987), more than 15,000 field trials have been conducted in numerous countries around the world

· There is not a single documented example of actual “harm” to the environment or to people or animals

Contingency planning

· Applicants should be asked to provide contingency plans for responding to accidental breaches of confinement

· Key elements should include– The procedure for notifying the regulatory

authority– Measures for destroying the transgenic plant– Supervision and safety procedures– Communication strategy– Diagnostic methods to trace back if

necessary

Developing a regulatory system

Considerations:

· Stipulating the permissible means of achieving reproductive isolation (crop by crop)

· Defining schedules (intervals) for current season and post-harvest monitoring

· Defining periods of post-harvest land use restriction (crop by crop)

· Defining record-keeping requirements – activity based

· Levels of inspection – current season, post-harvest period, facilities

Common requirements of a regulatory system

· Clarity

· Transparency

· Consistency

· Workability and enforceability

· Adaptability

Clarity

· Unambiguous (ie: scope and objectives)

· Clear differentiation between different activities (ie: contained use, confined trials, unconfined releases, commodity imports/exports) – different application and review processes

· Clear division of responsibilities between government ministries (ie: food/feed vs. environment, etc)

· Clear interrelation with other existing regulatory systems (ie: seeds regulations, plant import and quarantine, etc)

Transparency

· The applications system for permits and/or authorizations must be clearly communicated– When and where applications are to be submitted– What is to be included in the application (ie: information

requirements)– Time standards for review and reporting

· How is science advice provided and taken into account– External review, expert panels, government science

evaluators· Basis of regulatory decision-making

– How are decisions made and by whom– Independence and impartiality

· What information is to be disclosed to the public and when· Treatment of confidential business information

Workability

· System must be practical, effective, and efficient

· Triggers and procedures must work

· Requirements and standards must be achievable

· Complexity should be commensurate with activity and level of risk

· Levels of inspection and auditing should be consistent with available resources – human, financial, infrastructure

Categories of information

· Administrative

· Unmodified host organism

· Transgenic plant

· Trial site location

· Trial protocol – purpose of the trial

Administrative information

· Who is the applicant? – this is the legally responsible person; the person to which all future correspondence is addressed

· Is this a new application or a renewal?· Is any material intended for experimental

evaluation in livestock feed?· Does the applicant want to retain any

material from the trial?· Other permits obtained/required (Import

Permit, use of unregistered pesticides)

The unmodified plant

· Information on the biology of the unmodified host plant

· May only be required if the regulator does not already have a biology document for that plant species

· Fertility, phenotypic characteristics, habitat, normal cultivation and breeding practices

· Knowledge of the unmodified plant is crucial to designing rational methods of reproductive isolation

The transgenic plant

· Based on scientific understanding of the function of the introduced gene(s), we need to address two main questions:

· 1. Will the standard conditions of reproductive isolation for the unmodified plant also apply for the transgenic plant?– Is the introduced gene anticipated to affect some

aspect of the plant’s reproductive biology?– Is the gene integrated within the nuclear genome?– Do we expect that the introduced DNA would give rise

to a pathogenic agent?

The transgenic plant (cont’d)

2. Have we knowingly introduced an allergen or toxin?– If so, additional risk mitigation measures

may be necessary (i.e. some protection for workers handling that material) or increased level of inspection may be necessary to ensure that no material is entering food/feed supply

The trial site

· Location of the trial site· Field manager· How is the trial site being marked?· Are there any sexually compatible wild species in

the vicinity?· Land use and responsible person during post-

harvest period· Is it on agricultural land or is it part of a “natural

ecosystem”? – is it near to, or part of, a protected area? Are there any endangered species in the area?

Trial protocol

· Purpose of the trial· Proposed methods of reproductive isolation· How is transport, planting, monitoring and

harvesting going to be carried out?· Is any plant material to be retained after the

trial? (for experimental use) · Public notification?

Relevant questions

· Focus on issues of relevance to reproductive isolation – i.e., mitigating gene flow through outcrossing

· Focus on issues related to controlling the movement, handling, and fate of all plant material

· Focus on issues related to control over the trial site

· Everything else is “nice to know” not “need to know” for confined trials

Adaptability

· New applications of biotechnology are evolving rapidly and regulatory requirements and/or guidelines must be able to adapt quickly

· Technical requirements should be defined in guidelines or directives rather than in statutory regulations or laws

· Flexibility must exist to accommodate case-by-case variations

· As confidence and experience grows with particular (trait x species) combinations, provisions for expedited or ‘short-track’ reviews desirable – may be especially true in the case of confined field trials

Administrative

· Receipt of applications and processing

· Issuing legally binding authorization (permit or letter of authorization) stipulating terms and conditions of authorization

· Coordinate with other permit issuers (Plant Import, Pest Control)

· Coordinate inspection and enforcement activities (24 x 7) including administrative and monetary penalties

· Receipt and handling of reports – record of planting, record of harvest/termination, end of trial report

· Publication of notices/reports – record of decision, compliance information, summary statistics

· Single point of contact

Technical evaluation

· Access to specific scientific expertise – plant breeding, plant physiology, plant pathology, molecular biology (case by case)

· Science-based risk mitigation measures (terms and conditions of authorization)

· Advice for risk management

Inspection and enforcement

· Legal powers of an inspector – enter, detain, seize, examine records

· Trained inspection staff – specific training for inspecting confined field trials

· Diagnostic and testing capability – required in the case of trace-back or verification

· Able to take enforcement action – require trial destruction

· Emergency response

Final messages

· Confined and unconfined activities are distinct and there should be a separate review and approval process for each

· The questions that need to be considered for confined trials ARE different to the questions for unconfined release

· Confined field trials CAN be performed safely and routinely