Safety and Regulation in Agricultural Biotechnology

MUPGRET Workshop

Comprehensive safety assessments

Integrated (coordinated) framework involves three federal agencies to ensure biotech product safety. USDA: environmental safety EPA: environmental, food and feed

safety for pest-protected products. FDA: feed and food safety.

Public participation

Solicited by USDA, EPA and FDA at several steps in the process.

Small-scale to commercial testing.

Food and Drug Administration

Voluntary Labeling Indicates whether foods have or have

not been developed using transgenic technology.

Pre-market notice concerning food resulting from transgenic technology.

www.access.gpo.gov/su_docs/aces/aces140.html

Comprehensive international safety assessments in key export markets

European Union Director of EU

Canada Canadian Food Inspection Agency

Japan Ministry of Agriculture, Forestry, and

Fisheries; Ministry of Health and Welfare

Safety is a comparison of Risks and Benefits All technologies are evaluated relative to:

Consequences of their implementation Consequences of their non-

implementation Comparison to safety of alternative

technologies Context of current and historical practices Benefit to human, animal and

environmental health

Minimizing risk

Comprehensive hazard analysis Risk identification Assessment (evaluation) Risk/benefit consideration Develop risk management plan Effective training and

communication

Assessing Safety

Standard is “reasonable certainty that no harm will result from intended uses under the anticipated conditions of consumption”.

Remember

Food is not inherently safe. Safety is based on experience. Relative, not absolute safety.

Substantial Equivalence

“as safe as” Compare transgenic products to

conventional products.

Hazard identification

Toxicity Allergenecity Safety of antibiotic resistance

markers Nutritional equivalence Compositional equivalence Lack of unintended effects

Safety-Genetic and Protein Map of vector and its

components Position and size of

“novel” DNA Function of gene in

plant Source of gene Inheritance and

stability of trait

Changes in amino acid sequence relative to native protein

Expected expression Compare to known

toxin/allergens Test in mice In vitro digestibility

test

Compositional Equivalence

Fatty acid Amino acid Vitamin Mineral Anti-nutrient

How does this compare to the How does this compare to the variation present among conventional variation present among conventional varieties?varieties?

Comparison to toxin/allergens

Compared in global database against >100,000 proteins.

“Macro” analysis of entire protein “Micro” analysis of small stretches

of protein (eg. 600 comparisons for the Bt protein).

Allergenicity 1-2% of adults are affected by food

allergies. Eight major allergens:

Peanut Milk Soy Wheat Shellfish Fish Egg Tree Nuts

Toxicity Assessment

Once safety is established, EPA tests for secondary metabolic activity

These products are labeled because they have different composition due to the change in protein.

Testing in Mouse

Cry1Ac (Cotton, Tomato)4200mg/kg

Cry3A (Potato)5200mg/kg

Cry1b (Corn)4000mg/kg

CP4 EPSPS (Soybean) 572 mg/kg

CROPS Coordinated screening and testing Regulatory review Other scientific experiments and

trials Performance feedback from growers Stewardship and monitoring to

ensure responsible use. www.cast-science.org/biotechnology/

index.html

Coordinated screening and testing

Initial screening Early field testing Experimental use permits

Regulatory review

USDA Composition, Germination, Seed

longevity, Growth and Reproduction, Outcrossing, Fitness Assessment, Herbicial Activity, Field Observation

EPA Plant gene expression, toxicology,

environmental fate

Other scientists

Land Grant Universities Private Institutions Private Foundations

Performance Feedback

Compare transgenic and conventional in field setting

Environmental stewardship New paradigms, ex. Return of

beneficial insects.

Stewardship and Monitoring

Non-target populations Risk management plan Monitor use accordance with

requirements.

Nine chances to say no! Biosafety Committee USDA Greenhouse

Approval USDA Field Trial

Authorization USDA Authorization

for transport to field trials

USDA Permit to Commercialize

EPA Experimental Use Permit

EPA Food Tolerance Determination

EPA Product Registration

FDA Review

International Agencies Food and Agriculture Organization

and World Health Organization say: “products of plant biotechnology are

not inherently less safe than those developed by traditional breeding”

“same food safety considerations” “extensive testing provides equal or

greater assurance of safety”

What is risk?

Chance that something will happen over a certain period of time.

Factors that can affect risk: Age Gender Genetic constitution Environment

Risk and New Technology

Public view leans toward no risk associated with new technology.

Two case studies: New fuel source New appliance

Death Rates for 1998Rank Cause % ♂:♀ AM:C

1 Heart Disease 31.0 1.8 1.5

2 Cancer 23.2 1.4 1.3

3 Cerebrovascular disease 6.8 1.1 1.8

4 COPD 4.8 1.4 0.8

5 Accidents 4.2 2.4 1.2

6 Pneumonia and flu 3.9 1.5 1.4

7 Diabetes melitus 2.8 1.2 2.4

8 Suicide 1.3 4.3 0.5

13 Homicide 0.8 3.5 5.7

Another way to look at health risk

See Overheads

Risk assessment examples

Life insurance Auto insurance Statistics for disease Cigarette smoking Food—E. coli