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EU

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GRAS -------------------------------------------------------------1 -------------------------------------------------------------------------------72 Novel Food ---------------------------------------------------------122 Novel Food -------------------------------------------144 ------------------------------------------------------------------165

EU EU FDA FSA FFSA 1

() () () 2

18 12 12 16 FDA-CFSAN FICC() DANISCO.USA() Masaoka & Associates, Inc. EU 19 2 4 11 EFSA FSA Coutrelis & Associates () Ajinomoto Pharmaceuticals Europe Ltd() 3

substance labeling,claim,declaration ingredient (product) conventional food 4

Novel Food NDI Dietary Supplement GRAS Conventional food EU Novel Food PARNUTS Food Supplement 1-2 1 2 3 CoQ10 5

NDINew Dietary Ingredient GRAS Novel Food() 2 3 6

1 1958 (Food Additives Amendment, Section 409, Federal Food Drug and Cosmetic Act ) FDA (Delaney Clause) (Substances Generally Recognized As Safe, GRAS )GRAS GRAS Food Additives 21CFR170.3 Definitions GRAS FDA Guidance for Industry: Summary Table of Recommended Toxicological Testing for Additives Used in Food Low Toxicological Potential, Intermediate Toxicological Potential, High Toxicological Potential,12 ppb1000 ppb Concern Levels 2 Low(I)Intermediate(II)High(III) 2-1. 2-1 1 2 concernconcern Level 7

2-1 http://www.cfsan.fda.gov/~dms/opatxgui.html 1000 ppb 500 ppb 250 ppb 50 ppb 25 ppb 12 ppb A B C 2-1 8

Concern Levels Redbook 2000: Toxicological Principles for the Safety Assessment of Food Ingredients Chapter III. Concern Levels and Recommended Toxicity Studies GRAS (Generally Recognized as Safe) GRAS (Generally Recognized as Safe) 21CFR 170.30 (a)(1) 1958 1 1 GRAS (a)(2)gras the views of experts qualified by scientific training and experiences (b) 21CFR 2-2 PART 170 FOOD ADDITIVES Subpart BFood Additive Safety 170.30 Eligibility for classification as generally recognized as safe (GRAS). (a) General recognition of safety may be based only on the views of experts qualified by scientific training and experiences to evaluate the safety of substances directly or indirectly added to food: The basis of such views may be either (1) scientific procedures or (2) in the case of a substance used in food prior to January 1, 1958, through experience based on common use in food. General recognition of safety requires common knowledge about the substance throughout the scientific community knowledgeable about the safety of substances directly or indirectly added to food (b) General recognition of safety based upon scientific procedures shall require the same quantity and quality of scientific evidence as is required to obtain approval of a food additive regulation for the ingredient. General recognition of safety through scientific procedures shall ordinary be based upon published studies which may be corroborated by unpublished studies and other data and information. 9

GRAS GRAS FDA 1997 17 1958 FDA GRAS (GRAS Affirmation) GRAS GRASGRAS Notification GRASSelf determined GRAS Self affirmed GRAS GRAS GRAS GRAS Petition GRAS GRAS Notification GRAS GRAS Self determined GRAS 2-3 GRAS 1958 FDA GRAS 1969 FDA GRAS 370 1972-1980 1997 25 GRAS 1997 GRAS CAS GRAS NDINew Dietary Ingredient 1994 Dietary Supplement Health and Education Act: DSHEA 10

NDINew Dietary IngredientFDA 1994 Grandfathered substance 1994 10 15 75 FDA NDI NDI GRAS 21CFR190.6 Requirement for premarket notification NDI will reasonably be expected to be safe GRAS GRAS NDI 2-4 21CFR PART 190DIETARY SUPPLEMENTS Subpart BNew Dietary Ingredient Notification 190.6 Requirement for premarket notification. (b)(4) The history of use or other evidence of safety establishing that the dietary ingredient, when used under the conditions recommended or suggested in the labeling of the dietary supplement, will reasonably be expected to be safe, including any citation to published articles or other evidence that is the basis on which the distributor or manufacturer of the new dietary supplement will reasonably be expected to be safe. Any reference to published information offered in support of the notification shall be accompanied by reprints or photostatic copies of such references. If any part of the material submitted is in a foreign language, it shall be accompanied by an accurate and complete English translation; and 11

NDI 3 400 FDA 100 http://www.cfsan.fda.gov/~dms/ds-ingrd.html 4 1997 10 15 1958 GRAS (New Dietary Ingredient, NDI) GRAS GRAS (1997 ) FDA 1990 Nutrition Labeling and Education ActNLEA) Health Claims 1994 10 Dietary Supplement Health, and Education Act (DSHEA) / Structure/Function Claims Grandfather 30 FDA / 1997 FDA FDA Modernization Act National Academy of Science (NAS) Authoritative Statement 2 2003 Qualified Health Claims 3 1 / / 3 10 4 2 NDI 12

/ 2-5 / Nutrition Labeling and Education Act, NLEA 1990 21994 6 Significant Scientific Agreement FDA 12 1994 10 1999 10 2000 9 FDA FDA FDA 2-6 13

Dietary Supplement Health and Education Act, DSHEA 1990 21994 10 1997 1998 1999 2-7 (1) (2) (3) (4) / Structure/Function Claims FDA 14

health claims NLEA 2-8 DSHEA / Structure/Function ClaimsFDA FDA disease claimsfda 2000 1 6 health maintenance claims non-disease claims FDA claims for common, minor symptoms associated with life stages FDA express disease claims implied disease claims FDA 15

FDA FDA 2004 2007 OMBOffice of Management and Budget Food and Drug Modernization Act, FDAMA 1997 FDA National Academy of Science (NAS) Authoritative Statement FDAMA Qualified Health Claims 2000 FDA Consumer Health Information for Better Nutrition2003 10 2003 1 (1990) Significant Scientific Agreement ( ) 16

5 FDA Significant Scientific Agreement 2-10 BB (Qualified Health Claims) 2003 7 QHC 2006 Dietary Supplement and Nonprescription Drug Consumer Protection act 2006 12 6 12 22 FDA 1 5 12 6 6 17

270 HHSHealth and Human Services Serious Adverse Event (a) Adverse Event Serious Adverse Event Serious Adverse Event Report FDA (b) (c) 15 New Medical Information 1 new medical information15 (d) MedWatch 18

(e) 1 6 2 A B (f) (g) (h)preemption (g) (j) 1 2 1 270 HHSHealth and Human Services 19

NDI FDA objection FDA FDA ///// androstenedione 2004 3 FDA NDIs androstenedione androstenedione FDA androstenedione DSHEA DSHEA NDIs 2004 Anabolic Steroid Control Act 2005 1 androstenedione Ephedra sinica 94 10 15 /Ephedra sinica( )( )() Piper methysticum 20

Piper methysticum() 1 Piper methysticum 1 () 2007 3 NDI FDA 4 reasonably expected to be safe FDA reasonably expected to be safe FDA 1994 10 15 NDI FDA FDA 2000 6 2000 8 11 12 4 7 4 sn-12-dag 8 6 25 17 9 30 7 2002 8 21

DAG 2000 22

EU EU 1 EU EU Novel FoodPARNUTS 3-1 Novel Food EU Novel Food 1997 GMO GMO 1829/2003/EC 1830/2003/EC GMO PARNUTS EFSA Commission EU Directive 3-1 EU 1 EAS 2006 23

Novel Food Novel Food 1997/258/EC EU 1997 5 15 GMO 1997 1829/2003/EC 1830/2003/EC GMO 1. 2. 3. 1997 5 15 EU EU EU 3-2 3-3 3-2 EU EU EU EU Commission EFSAEFSA EU Commission EU Commission EU EUCommission 2007 EFSA EU 3-2 EU 3-3 24

EU Commission a cefsa EFSA d e Novel Food EU 2007 : a EUCommission b e c d EFSA 3-3 Novel Food EU 3-4 25

Novel Food Novel Food 1997515 EU EU? A. EU Commission EU Commission Commission B. EU Commission Commission25 EU EU Novel Food EU Commission EFSA EFSA EU Novel Food 3-4 EU EAS2006 EU 1997/618/EC 26

PARNUTS PARNUTSfood for particular nutritional uses; EU 89/398/EEC 1998 PARNUTS EU PARNUTS PARNUTS 1. 2. 3. 4. 5. PARNUTS EU 27

EU PARNUTS EU PARNUTS EU 2001/15/EC PARNUTS PARNUTS EU PARNUTS EU EFSA EFSA 2001 SCFEFSA EU PARNUTS 1989 EU 15 EU EU 5 28

1991 1997 2000 EU 2002 7 EU PARNUTS EU 3 2005 7 EU EU 2005 7 12 EFSA EFSA 7 12 31 EFSA EU EU EFSA EFSA EFSA EFSA 3-5 29

EU EUCommission C. EFSA 2007 a b : EFSA EU 3-5 1925/2006/EC 2007 12 30 30

a. RDA RDA RDA RDA b. 31

10% EU K DGCCRF EU 1970 2004 5 EU A D BVL 32

2000 10 2 2003 EU 2005 8 1 1990 2003 3 1994 MLX249MCA Boarder Substances MCA 2 Rapid Alert System for Food and FeedRASFFEC 178/2002/EC RASFF RASFF Alert notification 2 18 33

Information notification News notification RASFF 2006 10 Advisory Committee on Novel Food and Process(ACNFP) Web Mike Gasson FSA 20 EU 97/618/EC 34

OmegaTech FSA DHA DHA Gold 3 DHA gold - Application dossier Final Initial Opinion on DHA Gold Application for the Approval of DHA-rich Oil from OmegaTech(Germany) Schizochytrium sp. DHA-rich oil GRAS Schizochytrium sp. 1997 GM Advisory Committee 1.Novel Food 2.Novel Food 3. source organism 4. 5. 6. 7. 8. 9. 3 35

3 DHA DHA 36

172005 2 1 Novel Food in vitro in vivo FDA GRAS GRAS 37

FSA FDA Qualified Health Claim GRAS EU EU Novel Food EU EU 38

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