FDA Regulation of Food from GE Crops

FDA Regulation of Food from GE Crops Patrick Cournoyer, Ph.D. U.S. Food and Drug Administration (FDA) Center for Food Safety and Applied Nutrition Office of Food Additive Safety

Overview Historical perspective: FDA s involvement in plant breeding and plant biotechnology FDA s regulatory approach: Legal authority related to food from GE plants How to consult with us: The types of data and information FDA evaluates Past consultations 2

Regulating plant breeding: A historical perspective 1938: The Federal Food Drug & Cosmetic Act 1958: Food Additive Amendment Food additives require approval Exempted: Substances whose uses are Generally Recognized as Safe (GRAS) 1970: Regulation on plant breeding and GRAS Emerging concerns cited: Glycoalkaloids in potatoes Endogenous defensive compounds Key vitamins and nutrients 3

Regulating plant breeding: A historical perspective 4

Regulating plant breeding: A historical perspective 1986 Coordinated Framework USDA EPA FDA Existing legal authorities sufficient Endogenous Substances Must not contain substances at levels that are harmful Including sufficient levels of key nutrients (1970) Added Substances Ingredients must meet safety criteria, may require FDA review and approval Including substances added through biotechnology (1984) 5

Regulating plant breeding: A historical perspective FDA s 1992 Statement of Policy: Foods Derived from New Plant Varieties FDA views on plant breeding in general Discussed new methods of biotechnology Endogenous Substances Must not contain substances at levels that are harmful Added Substances Ingredients must meet safety criteria, may require FDA review and approval Labeling Labeling must be truthful and not misleading (misbranding) Recommended consultation Flow charts to help developers determine if important safety and regulatory concerns exist 6

Overview Historical perspective: FDA s involvement in plant breeding and plant biotechnology FDA s regulatory approach: Legal authority related to food from GE plants How to consult with us: Data and information FDA evaluates Past consultations 7

Federal Food Drug & Cosmetic Act (FD&C Act) Core Provisions Labeling Labeling must be truthful and not misleading (misbranding) FD&C Act Safety Food must be safe (adulteration) Endogenous Substances Must not contain substances at levels that are harmful Added Substances Ingredients must meet safety criteria, may require FDA review and approval Legal without premarket approval If safety info is publically available and widely accepted by experts (GRAS) Premarket review required If safety info is NOT publically available or NOT widely accepted by experts 9

What does GRAS mean? GRAS: generally recognized, among experts qualified by scientific training and experience to evaluate its safety, as having been adequately shown through scientific procedures (or, in the case of a substance used in food prior to January 1, 1958, through either scientific procedures or experience based on common use in food) to be safe under the conditions of its intended use. (FD&C Act, Section 201(s)) 10

What does safe mean? With respect to added substances: Safe or safety means that there is a reasonable certainty in the minds of competent scientists that the substance is not harmful under the intended conditions of use. (Code of Federal Regulations 170.3(i)) 11

The FD&C Act applies to food from GE crops Labeling Labeling must be truthful and not misleading (misbranding) FD&C Act Safety Food must be safe (adulteration) Endogenous Substances Must not contain substances at levels that are harmful Added Substances Ingredients must meet safety criteria, may require FDA review and approval Legal without premarket approval If safety info is publically available and widely accepted by experts (GRAS) Premarket review required If safety info is NOT publically available or NOT widely accepted by experts 12

The FD&C Act applies to food from GE crops Endogenous Substances Must not contain substances at levels that are harmful Above 200 milligrams total glycoalkaloid per kilogram of potato Below 200 milligrams total glycoalkaloid per kilogram of potato 13

The FD&C Act applies to food from GE crops Added Substances Ingredients must meet safety criteria, may require FDA review and approval Legal without premarket approval If safety info is publically available and widely accepted by experts (GRAS) Premarket review required If safety info is NOT publically available or NOT widely accepted by experts Glyphosate tolerant corn with added CP4 EPSPS protein CP4 EPSPS 15

The FD&C Act applies to food from GE crops Labeling Labeling must be truthful and not misleading (misbranding) GE Soybean with increased levels of oleic acid 80% Oleic acid content in oil 60% Common or Usual Name 40% 75% 72% Must disclose material facts 20% 0% 25% New name: High oleic soybean oil 17

Overview Historical perspective: FDA s involvement in plant breeding and plant biotechnology FDA s regulatory approach: Legal authority related to food from GE plants How to consult with us: Data and information FDA evaluates Past consultations 18

Consulting with FDA Labeling Labeling must be truthful and not misleading (misbranding) FD&C Act Safety Food must be safe (adulteration) Endogenous Substances Must not contain substances at levels that are harmful Added Substances Ingredients must meet safety criteria, may require FDA review and approval Legal without premarket approval If safety info is publically available and widely accepted by experts (GRAS) Premarket review required If safety info is NOT publically available or NOT widely accepted by experts 19

Consulting with FDA Labeling Labeling must be truthful and not misleading (misbranding) Endogenous Substances Must not contain substances at levels that are harmful Added Substances Ingredients must meet safety criteria, may require FDA review and approval Consultation with FDA to resolve safety and regulatory questions before marketing 20

Consulting with FDA Developer submits safety and regulatory assessment FDA team of experts evaluates the data and information FDA requests additional information as needed Repeat until safety and regulatory questions are resolved FDA summarizes evaluation in a memo FDA ends the consultation by sending a letter to the developer Before sending us a submission for a final consultation Consult with us early! Consult with us often! Meet with us in person or by teleconference No cost 22

Elements of a Submission Basic Information Endogenous Substances Must not contain substances at levels that are harmful Trait description Crop uses Molecular characterization Trait stability Added Substances Ingredients must meet safety criteria, may require FDA review and approval Labeling Labeling must be truthful and not misleading (misbranding) 2 3 23

Elements of a Submission Basic Information Trait description Crop uses Molecular characterization Trait stability Characterize insertion(s), copy number Vector Backbone? New proteins from alternative open reading frames? Stability? 2 4 24

Elements of a Submission Basic Information Endogenous Substances Must not contain substances at levels that are harmful Compositional assessment: Added Substances Ingredients must meet safety criteria, may require FDA review and approval Labeling Labeling must be truthful and not misleading (misbranding) 2 5 25

Compositional Analysis Good stuff Bad stuff Key Nutrients Anti-Nutrients Endogenous Toxicants Endogenous Allergens proximates lectins glycoalkaloids soybean fatty acids raffinose stachyose gossypol wheat amino acids phytic acid glucosinolates rice minerals protease inhibitors benzyl isothiocyanate? vitamins cyanogenic glycosides isoflavones*??? 26

Compositional Analysis New GE variety Appropriate comparator (Grown concurrently) To characterize changes Reference varieties (Grown concurrently) To characterize existing variation Published data To characterize existing variation 27

Field trial design Compositional Analysis Number of locations, years? Need to represent range of conditions Number of replicates? Need to control for variables Need statistical power Field trials should be designed to answer necessary regulatory questions Case by case 28

Elements of a Submission Basic Information Endogenous Substances Must not contain substances at levels that are harmful Added Substances Ingredients must meet safety criteria, may require FDA review and approval Proteins: Toxicity, allergenicity Metabolites Labeling Labeling must be truthful and not misleading (misbranding) 2 9 29

Evaluating new substances for safety What is it? Prior knowledge What happens after consumption? (ADME) What do we know about potential toxicity? How much is safe to consume? Are feeding studies needed? NOAEL How much is consumed? Calculating exposure Are expected exposure levels safe? Margin of exposure 30

Elements of a Submission Basic Information Endogenous Substances Must not contain substances at levels that are harmful Added Substances Ingredients must meet safety criteria, may require FDA review and approval Labeling Labeling must be truthful and not misleading (misbranding) Common or usual name Material differences? 3 1 31

New Protein Consultations Potential unintended presence in food FDA issued guidance in 2006 to establish mechanism for FDA to evaluate new proteins before field testing 32

Overview Historical perspective: FDA s involvement in plant breeding and plant biotechnology FDA s regulatory approach: Legal authority related to food from GE plants How to consult with us: Data and information FDA evaluates Past consultations 33

Completed New Protein Consultations 34

Completed Consultations www.fda.gov/bioconinventory 35

Completed Consultations Crops (# of events) Radicchio (3) Alfalfa (3) Sugar beet (3) Tomato (7) Canola (18) Other* (14) Corn (45) Soybean (19) Cotton (25) Potato (35) Herbicide tolerance (52) * Squash (2), cantaloupe (2), apple (2), rice (2), papaya (2), plum (1), flax (1), wheat (1), creeping bentgrass (1) 36

Completed Consultations Traits (# of events) Disease resistance (R protein)* (1) Insect resistance (RNAi)* (1) Drought tolerance (1) Increased yield (2) Processing enzymes (5) Lower acrylamide potential (7) Altered composition (8) Delayed ripening (8) Reduced browning (9) Insect resistance Insect (Bt)* (71) resistance (Bt)* (71) Male sterility (13) Herbicide tolerance Herbicide tolerance (52) (52) Virus resistance (RNAi)* (19) * Plant-incorporated protectants regulated by EPA 37

Thank You FDA Home Page www.fda.gov FDA s Plant Biotechnology Consultation Program www.fda.gov/geplantfoods Food from GE Plants How FDA regulates Food from GE Plants Q&As Links to guidance and policy documents Listing of all completed consultations www.fda.gov/bioconinventory Documents from completed consultations Contact Patrick.Cournoyer@fda.hhs.gov Robert.Merker@fda.hhs.gov (Biotech program lead) Carrie.McMahon@fda.hhs.gov (New Protein Consultation Program lead) 38