Biotechnology Risk Assessment

and Risk Reduction

Sally McCammonBiotechnology Regulatory

ServicesAnimal and Plant Health Inspection Service, USDA

U.S. Coordinated Framework for the Regulation of

Biotechnology

FDA

USDA

EPA

Federal System

APHIS – Regulates the development and field testing of genetically engineered products for safe agricultural use

EPA – Ensures that genetically engineered products classified as pesticides are used safely

FDA – Ensures that food products are safe and wholesome

Trait Viral resistance in

food crop Herbicide tolerance

in food crop Herbicide tolerance

in ornamental crop Modified oil content

in food crop Modified flower

color in ornamental crop

Agency USDA, EPA, FDA

USDA, FDA (EPA)

USDA (EPA)

USDA, FDA

USDA

APHIS Biotechnology Regulatory Services (BRS)

June, 2002 - formed Internal Review Process Keep pace with evolving technology

Regulatory program based on science Rigorous and reasonable

Dedicate resources and increase capacity

BRS Organization

O ffice o f S c ien ce

C om p lian ce

P erm its

R isk A ssessm en t

R eg u la to ry D ivis ion

R eg u la to ry C ap ac ity B u ild in g

In te rn a tion a l P o lic y

R eg u la to ry P o lic y

F orecas tin g an d P rog ram D eve lop m en t

P o lic y C oord in a tion D ivis ion

O ffice o f D ep u ty A d m in is tra to r

Office of Science

Scientific input to policy, regulations, and assessments

Improve public understanding of scientific base of regulatory policy and decisions

Strong working relationships with scientific and technical infrastructure

APHIS Statutes and Regulations

1987 USDA-APHIS - 'Plant Pests; Introduction of

Genetically Engineered Products' 1993

USDA-APHIS - Notification Procedures 1997

USDA-APHIS - Simplification of Requirements and Procedures

2000 Plant Protection Act

1986-1997 2001 2002

RESEARCH FIELD –

TESTING

ANIMAL VACCINES

ENVIRONMENTAL

IMPACTS

FOOD SAFETY

PHARM PLANTS

ANIMALS

INSECTS

1977-1986

HISTORY OF REGULATIONS AND POLICY STATEMENTS

Plant Variety Development

LABORATORY / GREENHOUSE

FIELD TESTING

VARIETY DEVELOPMENT

COMMERCIALIZATION

Animal and Plant Health Inspection Service

Regulated Status (“regulated articles”) 1. Importation and Interstate Movement 2. Field Testing/Confined Cultivation

Permits - 120 day review; more details Notifications - 30 day review; simplified;

certain traits and weeds excluded>For both – State concurrence; sites

inspected; field data reports

Non-regulated Status Petitions - 180 days, comprehensive scientific

reviews Extensions – comprehensive scientific review; some

administrative steps are streamlined.

APHIS Oversight of Confined Field Tests – Notification or

Permit Confined to field test site & no

persistence in environment Physical & reproductive isolation Termination, devitalization, disposal

protocols Post-harvest monitoring and land use Inspections Review records

Petition for Determination of Non-Regulated Status

USDA-APHIS

Petitionreceived,logged into database

Team reviews: Technical completeness

Deficiency letter sent

Petition withdrawnor denied

Petitionamended

FR noticeseeking public comment

EA written, OGC review

FR noticeseeking comment onthe EA

Determinationwritten – Petition Approved

No

Yes

60 days

30 days

APHIS Approvals: 1987 -APHIS Approvals: 1987 -20032003

Field Tests:Field Tests: 9700 authorizations9700 authorizations 39,000 sites39,000 sites

Petitions for Non-regulated Status:Petitions for Non-regulated Status: 90 Petitions90 Petitions

58 Granted58 Granted 24 Withdrawn24 Withdrawn 8 Pending8 Pending

APHIS Evaluation

Biology and genetics of the plant, Nature and origin of the genetic

material used, Possible effects on other organisms

in the environment and agricultural products.

Petition Requirements

Crop biology and taxonomy description Genotypic differences Phenotypic differences Field test reports for all releases

conducted under permit or notification Relevant experimental data,

publications, and unpublished data upon which to base a determination

Unfavorable data and information

APHIS Evaluation of Effects

Potential for creating plant pest risk; Disease and pest susceptibilities; Expression of gene products, new enzymes,

or changes to plant metabolism; Weediness and impact on sexually

compatible plants; Agricultural or cultivation practices; Effects on non-target organisms; and Potential for gene transfer to other

organisms

Research Needs

National Academy of Sciences Biotechnology Risk Assessment

Grants Program Agricultural Biotechnology Risk

Analysis Task Force Kay Simmons detail to APHIS

National Academy of Sciences

1987

White Paper

1989

Field Testing Genetically Modified Organisms: Framework for Decisions

2000

Genetically Modified Pest Protected Plants

National Academy of Sciences

2002

Environmental Effects of Transgenic Plants

2004

Biological Confinement of Genetically Engineered Organisms

National Academy of Sciences

Ecological Research (PIPS) - 2000

Major goal for traditional and transgenic pest-protected plants Enhance agricultural productivity and

foster more sustainable agricultural practices

Enhance preservation of biodiversity Decrease potential for health

problems associated with PIPs

National Academy of Sciences

Ecological Research (PIPS)2000 Plant Incorporated Protectants (PIPS)

Bt and Virus-resistance Agricultural practices

Impacts of PIPS of nontarget organisms compared with impacts of standard and alternative agricultural practices

Encourage uses of resistance management practices if transgenic variety threatens utility of existing uses of pest protectant or functional equivalent

National Academy of Sciences

Ecological Research (PIPS) - 2000 Molecular basis of pest-plant interactions

+ population ecology & genetics of target pests to develop ecologically and evolutionarily sustainable approaches to the use of pest-protected plants

Specific expression systems that lessen nontarget exposure and delay pest adaptation

Monitor ecological impacts of pest-protected crops on long term basis

National Academy of Sciences

Ecological Research USDA should research, publicize,

and periodically revise lists of plant species with feral populations or wild relatives

National Academy of Sciences

Ecological Research - 2002 Improvement in risk analysis

methodologies Improvement in transgenic methods to

reduce risks and improve environmental benefits

Develop and improve monitoring for effects in environment

Social, economic, and value-based issues affecting environmental impacts

Research Needs………………..Research Needs………………..

ISSUES

Risks vs hazards vs phenomena Scientific issues Public perception

Field testing vs unconfined release Adventitious presence

Intended vs Unintended effects Baselines, comparators, endpoints

Staying on Course

Conceptual Framework Build upon rationales Concept of Familiarity – baselines Plant X trait X environment

Identify Issues Biodiversity – centers of origin Monitoring

Phenomenology vs Hazard Identification Monarchs

Framing the Issues

Paradigms based upon pesticides Hazard X exposure = risk assessment Non-target effects – assumes target

and toxicity Resistance management – post-

decision management

Molecular Impact of Transgenes

Impact of transformation methodologies

Location of insertion Impact of deletions Epistatic or pleiotropic effects Genomics, proteomics,

metabolomics Stability

Traits

Biotic and abiotic resistances, nutritional enhancement, pharmaceuticals and industrials

Can they be categorized regarding agricultural and environmental effects? Toxicity Fitness Unintended effects at molecular>ecological systems

levels Stacked genes

Multiple genes in crop plants Cumulative genes in wild relatives

Weediness/Invasiveness

Baseline research – factors leading to Characteristics associated with

invasiveness and associated environmental factors

Plant fitness characteristics Semi-domesticated species with wild

relatives Sunflower, Sorghum, Turf grasses, Trees

Impact of biotic and abiotic resistances on fitness of relatives

Gene Flow Field Testing and Unconfined

Release Outcrossing – factors & comprehensive

data Pollen dispersal, viability, inter-crop

fertilization, rate and kinds of gene flow with wild relatives

Database on cross fertilization Scale Reduction

Factors that reduce or prevent outcrossing New tools and approaches

Risk Management – Field Testing

Compliance Methodologies for promoting & tracking

compliance with protocols Verify if current protocols for confinement

are effective Refinement of biological, physical, &

temporal measures Technologies for cleaning & removing

seed from equipment Development of commercial-scale

shipping & storage containers

Risk Management

Alternative crops to food and feed crops for pharmaceutical or industrial products Do not cross with commodity crops No wild or weedy relatives or do not cross with

relatives Bioconfinement technologies

GURTS Male sterility Seed sterility

Issues

Framing the issues Traits Weediness Unintended effects Ecological endpoints Centers of origin Gene flow Confinement Impact of scale Risk assessment methodologies

Regulatory Issues Related to Science

Domestic - Many new products

- New regulatory challenges

- Risk mitigation research

- Credibility

International - Standards for safety not in place

- Differences in perceived risk

- Precautionary Principle

- Traceability

APHIS Biotech Website:APHIS Biotech Website:http://www.aphis.usda.gov/biotech/

US Government Website:US Government Website:http://www.usbiotechreg.govhttp://www.usbiotechreg.gov