US regulation of gm foods

1. US regulation of gm foods Dr. Susanne Stirn Forschungsschwerpunkt Biotechnik, Gesellschaft und Umwelt (FSP BIOGUM)Universität Hamburg, Ohnhorststr. 18, 22609 Hamburgstirn@botanik.uni-hamburg.de

2. US regulation Basis of regulation: • Process of biotechnology poses no special risks. • Foods derived from biotechnology should be regulated in the same way as traditional foods. Therefore: • The same laws are applicable. • Three federal agencies have responsibility: • US Department of Agriculture (USDA) • Environmental Protection Agency (EPA) • Food and Drug Administration (FDA)

3. US Department of Agriculture (USDA) • Basis of regulation: Protecting the US agriculture from agricultural pests and noxious weeds (Federal Plant Pest Act) • Gm plants:All plants carrying DNA from an organism considered to be a plant pest (Agrobacterium, CaMV) are defined as “regulated articles”. • Stepwise procedure for deliberate release of gm plants: • Field trial authorisation (physical confinement), • Determination of non-regulated status (required for unrestricted release and movement in the US).

4. USDA[2/3] • A petition for nonregulated status must consider: • harm to other organisms (beneficial & non-target org.), • increase in weediness, • adverse effects on the handling, processing or storage of commodities, • threat to biodiversity. • No tests requirements laid down in the Federal Plant Pest Act. • Generally performed tests to exclude toxic effects: • data from field experiments on the lack of toxic effects on animals (counting), • comparison of the nutritional composition with a conventional counterpart.

5. USDA [3/3] 61 gm plants are no longer regulated by USDA (August 2003). These include: • 10x maize (HT, IR), • 10x tomatoes (PQ), • 4x soybeans (HT), • 4x oilseed rape (HT), • 3x cotton (HT), • 3x potatoes (IR, VR).

6. Environmental Protection Agency (EPA) • Basis of regulation: Manufacture, sale and use of pesticides; environmental safety as well as tolerance levels for presence in foods • Gm plants:Substances produced in a living plant to control pests (plant-incorporated protectants [PIPs]) (e.g. Bt-toxins, viral proteins) • In general, the data requirements for a registration of PIPs are based on those for microbial pesticides.

7. EPA [2/3] • These general data requirements include: • product characterisation, • mammalian toxicity (acute oral toxicity), • effects on non-target organisms (avian, aquatic species, beneficial insects, soil organisms), • allergenicity potential (AA sequence homology, heat / processing stability, in vitro digestibility in gastric fluids), • environmental fate, and, if appropriate, • insect resistance management. • The exact data requirements for a registration are developed on a case-by-case basis.

8. EPA [3/3] 8 plant-incorporated protectants (PIPs) have been registered by EPA (June 2003): • Bt Cry IA(b) in maize (2x), • Bt Cry IA(c) in cotton, • Bt Cry IIIA in potato, • Bt Cry 1F in maize, • Bt K Cry IA(c) in maize (2x), • Potato Leaf Roll Virus replicase in potato (Monsanto)

9. Food and Drug Adimistration (FDA) • Basis of regulation: - Whole foods are under post-market authority. - A premarket-approval is only necessary when substances are added to foods that are not “generally recognised as safe” (GRAS)  Food additive petition. • Gm plants:- No pre-market approval necessary. - All food crops on the market have undergone voluntary consultations.- Responsibility (liability) rests with the companies. • Nevertheless, the FDA developed guidance documents for the industry.

10. FDA [2/3] • Summary information on the following topics are discussed: • the source of the introduced genetic material, • information on the agronomic and quality attributes of the plant, • genetic analysis of the modification, • evaluation of the safety of the newly introduced proteins - toxicity (known toxicants, “history of safe use”, feeding tests) - allergenicity (AA sequence homology, in vitro- digestibility), • chemical analysis of important nutrients and toxicants.

11. FDA[3/3] 55 consultations on gm plants for human food and/or animal feed use have been completed by the FDA. These include: • 14x maize (HT, IR, MS), • 10x oilseed rape (HT, PQ, MS), • 6x cotton (HT, IR), • 5x tomatoes (PQ), • 4x potatoes (IR, VR). • 3x soybeans (HT, PQ).

12. US regulation: different GMOs Trait / Organism Agency reviewed for: Insect Resistance / USDA safe to grow food crop EPA safe for the environment and human consumption (PIPs) FDA safe to eat (except for PIPs) and wholesomeness Herbicide tolerance / USDA safe to grow food crop EPA use of the companion herbicide FDA safe to eat and wholesomeness Modified oil content / USDA safe to grow food crop FDA safe to eat and wholesomeness Modified flower colour USDA safe to grow ornamental crop

13. Safety tests performed by the companies Despite the differences in regulation in the USA and the EU, the tests on food safety are similar. • The FDA guidelines are explicitly based on the “concept of substantial equivalence” of the OECD and the principles developed by FAO/WHO. • Most of the gm plants intended for deliberate release and food use in the EU have previously been approved in the USA. • The companies have sometimes performed additional tests to ensure consumer confidence (e.g. livestock feeding tests).

14. Differences in safety tests between USA and EU? Two interesting argumentation lines of FDA: • High oleic soybeans (DuPont) “not materially different ... from soybeans already on the market”. • Safety assessment focussed on • molecular characterisation and • compositional analysis to exclude unexpected effects. • No toxicity assessment of the altered oil quality because of “history of safe use” (conventionally bred high oleic soybeans and the lack of known toxicity of oleic acid in other species).

15. Differences in safety tests between USA and EU? Not yet decided in the EU. Potential scenario: • According to the concept of substantial equivalence “without substantial equivalence”: • safety assessment of the introduced protein, • the changed fatty acid profile, • potential unexpected effects, and • exposure of consumers (aggregate exposure, vulnerable consumer groups, bioavailability of nutrients).

16. Differences in safety tests between USA and EU? • Virus-resistant plants (coat protein mediated)No registration with EPA necessary. • Long history of human consumption in virus-infected plants (higher virus levels than in transgenic plants). • FDA is looking at nutritional composition and unexpected effects. • Safety assessment of virus-resistant plants in the EU?

17. Summary[1/2] The regulatory approaches towards gm foods in the US and the EU are totally different: • USA: Gene technology as an extension of traditional breeding methods (including mutagenesis, wide crosses and cell fusion) no specific laws required • EU: Specific risks attributed to genetic engineering  new regulations implemented for all “genetically modified organisms” (including all organisms which can not be obtained by sexual crosses  protoplast fusion, mutagenesis and wide crosses)

18. Summary[2/2] Safety assessments are essentially the same: • USA: Food safety is the interest of the companies due to unlimited liability. • EU: Food safety is determined by government agencies (main responsibility) with general test requirements laid down in the regulations. • Internationally:Detailed test requirements have been developed by OECD, FAO/WHO, Codex Alimentarius.

19. Ende des Vortrages!

20. Summary The extent to which more traditional breeding methods are considered safe is different: • USA: unintended effects happen also with more traditional breeding methods (mutation breeding, wide crosses), breeders have successfully eliminated plants exhibiting unexpected adverse effects  no regulatory oversight necessary • EU: Some of the risks are common to genetic engineering and traditional breeding methods (unintended effects)  regulation for all “genetically modified plants” (include all plant characteristics which could not be achieved through sexual crosses)

21. US regulation:Agencies Agency Responsibility in case of gm plants: USDA plant pests, All gm plants which are plant pests gm crop plants with or which carry DNA from a plant plant pest risks, pest (CaMV, Agrobacterium) are veterinary biologics defined as “regulated articles” EPA microbial pesticides, Substances produced in a plant plants producing toxic through genetic engineering with substances, the intention to control pests (PIP) plant-incorporated protectants (PIP) FDA food, feed, food Voluntary consultations, additives, drugs, guidance on safety tests, medical devices, responsibility rests with the cosmetics producer

22. Toxicity assessment Agency Aim of regulation Toxicity assessment (what/how) USDA No significant plant a) Impact on non-target organisms pest risk should result (beneficial, endangered species) from the widespread b) field observations, planting of GMP nutritional composition EPA Safety of PIPs for man a) Impact on non-target organisms and the environment (beneficial, birds, fish, honey- (analogous to bio- bees, invertebrates) chemical pesticides) b) acute oral toxicity, AA sequence homology with known toxins FDA Foods and feed from a) Impact on humans and animals GMP should be as safe b) nutritional composition, known and nutritious as their toxicants, feeding tests, parental species history of safe use

23. Allergenicity assessment Agency Aim of regulation Allergenicity (aim/method) USDA No significant plant a) worker safety pest risk from the b) evaluation based on a planting of GMP literature survey EPA Safety of PIPs for man a) Food safety of PIPs and the environment b) IFBC-concept: (analogous to bio- - amino acid sequence homology, chemical pesticides) - in vitro digestibility, - stability to heat and processing FDA Foods and feed from a) Food safety (except for PIPs) GMP as safe and b) allergenic substance not present nutritious as their in the new food or parental species - AA sequence homology and - in vitro digestibility