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

2. Universität Hamburg BIOGUM 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. Universität Hamburg BIOGUM 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. Universität Hamburg BIOGUM 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. Universität Hamburg BIOGUM 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. Universität Hamburg BIOGUM 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. Universität Hamburg BIOGUM 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. Universität Hamburg BIOGUM 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. Universität Hamburg BIOGUM 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. Universität Hamburg BIOGUM 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. Universität Hamburg BIOGUM 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. Universität Hamburg BIOGUM 12 US regulation: different GMOs Trait / OrganismAgencyreviewed for: Insect Resistance / USDAsafe to grow food cropEPAsafe for the environment and human consumption (PIPs) FDAsafe to eat (except for PIPs) and wholesomeness Herbicide tolerance /USDAsafe to grow food cropEPAuse of the companion herbicide FDAsafe to eat and wholesomeness Modified oil content /USDAsafe to grow food cropFDAsafe to eat and wholesomeness Modified flower colourUSDAsafe to grow ornamental crop

13. Universität Hamburg BIOGUM 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. Universität Hamburg BIOGUM 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. Universität Hamburg BIOGUM 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. Universität Hamburg BIOGUM 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. Universität Hamburg BIOGUM 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. Universität Hamburg BIOGUM 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. Universität Hamburg BIOGUM 19 Ende des Vortrages!

20. Universität Hamburg BIOGUM 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. Universität Hamburg BIOGUM 21 US regulation: Agencies AgencyResponsibility in case of gm plants: USDAplant pests, All gm plants which are plant pests gm crop plants withor which carry DNA from a plant plant pest risks,pest (CaMV, Agrobacterium) are veterinary biologicsdefined as “regulated articles” EPAmicrobial pesticides,Substances produced in a plant plants producing toxic through genetic engineering with substances,the intention to control pests (PIP) plant-incorporated protectants (PIP) FDAfood, feed, food Voluntary consultations, additives, drugs, guidance on safety tests, medical devices, responsibility rests with the cosmeticsproducer

22. Universität Hamburg BIOGUM 22 Toxicity assessment AgencyAim of regulation Toxicity assessment (what/how) USDANo significant planta) Impact on non-target organisms pest risk should result (beneficial, endangered species) from the widespread b) field observations, planting of GMP nutritional composition EPASafety of PIPs for mana) 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 FDAFoods and feed froma) Impact on humans and animals GMP should be as safeb) nutritional composition, known and nutritious as their toxicants, feeding tests, parental species history of safe use

23. Universität Hamburg BIOGUM 23 Allergenicity assessment AgencyAim of regulation Allergenicity (aim/method) USDANo significant planta) worker safety pest risk from the b) evaluation based on a planting of GMP literature survey EPASafety of PIPs for mana) 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 FDAFoods and feed froma) 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