2009 korea slikker_korea_발표용(1)


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2009 korea slikker_korea_발표용(1)

  1. 1. Advances in Approaches to Food and Drug Safety Assessment William Slikker, Jr., PhD, ATS National Center for Toxicological Research U.S. Food and Drug Administration Jefferson, ArkansasThe views expressed in this presentation do not necessarily reflect those of the FDA. 1
  2. 2. NCTR is UniqueEstablished in January 1971 by ExecutiveOrder as a non-regulatory nationalresource owned and managed withinDHHS by FDA to conduct integratedtoxicological research and fosterinteragency, academic, and industrialcollaboration in support of risk assessmentneeds related to public health. 2
  3. 3. NCTR VisionNCTR is an internationally recognized FDA research center thatprovides innovative, vital scientific technology, training, andtechnical expertise to improve public health.NCTR—in partnership with researchers from government,academia, and industry—develops, refines, and applies currentand emerging technologies to improve safety evaluations ofFDA-regulated Products.NCTR fosters international and intragovernmental cooperationto improve and protect public health and enhance the quality oflife for the American people. 3
  4. 4. Department of Health and Human Services Food and Drug Administration National Center for Toxicological Research HHS … NIH FDA CDC …CBER CDER CDRH CFSAN CTP CVM NCTR ORA 4
  5. 5. FDA Strategic GoalsStrengthen FDA for today and tomorrow– Science foundation– Partnerships and communicationImprove Patient and Consumer Safety– Strengthen science foundation– Provide patients access to risk benefit informationIncrease Access to New Medical and Food Products– Critical Path to Personalized Nutrition and MedicineImprove the Quality and Safety of ManufacturedProducts and the Supply Chain– Modernize science-based standards and tools to provide high quality manufacturing processing and duplication 5
  6. 6. NCTR Strategic GoalsInnovative toxicology forregulatory decisionsPromote personalizedmedicine and nutritionBioinformaticsFood safetyMentorship/training 6
  7. 7. NCTR/FDA Research StrategyFocus research resources on: – Regulatory issues to enhance decision making – Technical innovations to speed FDA-regulated product review and safety assessment 7
  8. 8. Primate 9 BSL-3 ARL Bld. FDA Disaster NTP/FDA Photx.Laboratories Suites Recovery Laboratories FDA Nano Core FacilityBio-Imaging Center Dietary General Animal Preparation Housing Visitor Housing 23 Pathology Laboratories82 Accredited animal and 123 experimental laboratories / 1M sq ft. in 30 buildings 8
  9. 9. Department of Health and Human Services Food and Drug Administration National Center for Toxicological Research Office of the Director William Slikker, Jr. Ph.D. Office of Research Coordinating Council Jeanne F. Anson Fred Beland, Ph.D. Jim Kaput, Ph.D. Paul Howard, Ph.D. NCTR Executive Officer & Dir., Division of Dir., Division of Personalized Assoc. Dir. for Assoc. Dir. for Office of Planning Biochemical Toxicology Nutrition & Medicine Scientific Coordination & Resource Management Martha Moore, Ph.D. Donna Mendrick, Ph.D. Thomas F. Flammang, Ph.D. Margaret Miller, Ph.D. Dir., Division of Genetic & Dir., Division of Senior Advisor Assoc. Dir. for Reproductive Toxicology Systems Toxicology for Science Regulatory Activities Jeff Carraway, DVM Jennings Partridge Vicky Ross-Barsh, Carl Cerniglia, Ph.D. Dir., Division of Assoc. Dir. for Regulatory Assoc. Dir. for Dir., Division of Microbiology Veterinary Services Compliance & Risk Management Executive Programs & Services Merle Paule, Ph.D.Dir., Division of Neurotoxicology 9
  10. 10. Advancing FDA ScienceNanotechnologyFood SafetyCritical PathBio-imagingNutrition and ObesityRegulatory ScienceBioinformatics 10
  11. 11. ArrayTrack™: An Integrated Solution for Omics Research Clinical and nonclinical data OH HO HMicroarray data Chemical data ArrayTrack™Proteomics data Public data Metabolomics data 11
  12. 12. Results from the MicroArray Quality Control (MAQC) StudySix research paperspublished in Nature Biotechnology on Sept andOct 2006 MAQC Main Paper Validation of Microarray Results RNA Sample Titrations One-color vs. Two-color Microarrays External RNA Controls Rat Toxicogenomics Validation Nat. Biotechnol. 24(9) and 24(10s), 2006 137 Participants from 51 Organizations 12
  13. 13. An Array of FDA EndeavorsIntegrated Nature of VGDS, ArrayTrack™, MAQC, and Best Practice Document E-Submission VGDS MAQC ArrayTrack™ 13
  14. 14. Bio-Imaging at FDA 14
  15. 15. Bio-Imaging at NCTR/FDAMicroPET Biospec MRI23 cm bore 7 Telsa, 30 cm bore 15
  16. 16. Pediatric AnestheticsKetamine, a non-competitive NMDA receptorantagonist, has been used as a general pediatricanesthetic for surgical procedures in infants.Ketamine is one of the most commonly used agentsfor mild sedation in pediatric emergencydepartments, endoscopy suites, catheterizationlaboratories, radiology suites, and intensive careunits. 16
  17. 17. A Control (24-hr) B Ketamine (24-hr) C Control (24-hr) D Ketamine (24-hr) E Control (24-hr) Control (24- hr)E F Ketamine (24-hr) Slikker et al., 2007 17
  18. 18. 25 * Caspase 3-Positive Neuronal Cells ControlEffects of * Ketamine-infused 20ketamine- 15induced 10anesthesia 5on the 0 300frontal * Silver-staining (Grain Density) 250cortex of the 200developing 150 *monkey 100 50 0 25 Fluoro-Jade C-Positive Neuronal Cells 20 * * 15 10 5 Slikker et al., 2007 0 GD 122 PND 5 PND 35 PND 5 (24-hr) (24-hr) (24-hr) (3-hr) 18
  19. 19. (B)(C) Zou et al., 2009 19
  20. 20. ABC Slikker et al., 2007 20
  21. 21. Dorsal Left Right VentralDrs. Xuan Zhang (NCTR), Marc Berridge (UAMS), Tucker Patterson,Glenn Newport, Cheng Wang, and Merle Paule (NCTR) 21
  22. 22. Dynamic Uptake of [18F]-AnnexinV 4 Control Ketamine 3 SUV Ratio 2 1 0 0 10 20 30 40 50 60 70 80 90 100 110 120 Time (s)N=7 SUV=total radioactivity in ROI x body weight / injection dose 22
  23. 23. Nanotechnology at NCTR, ARL/ORANanotechnology“Will eventually impact all Centers of the FDA”– Component of regulated products– Contaminant in regulated products– Challenge to our safety assessment paradigmNanotechnology Working Group– Coordinate NCTR’s and ARL/ORA’s participation in FDA’s nanotechnology effortNanotechnology Core Facility– Support NCTR research efforts and serve as FDA core 23
  24. 24. Nanotechnology at NCTR, ARL/ORA Overall StrategyResearch projects requested by FDA Centers (protocol-based studies)– FDA resources– through NTP IAG– through CRADA, MOU, etc Support/Resources Engage/Dialogue – NCTR/ORA Nanotechnology – FDA – NNI Core Facility – NTP/NIEHS – OECD – UALR – EPA – DOD – UAMS – SOT – UA 24
  25. 25. Nanotechnology Core FacilityResources (on site, purchased, or funds available)– Transmission electron microscope (TEM)– HPLC with light scatter detection– Confocal microscopy (fluorescence detection)– Confocal microscopy (Raman and FTIR detection)– High resolution darkfield microscopy (hyperspectral detection)– Atomic force microscope– Particle size analyzers (1 nm -1 mm)– Inductively coupled plasma mass spectrometer (ICP-MS)– BET material surface analyzer– Wavelength dispersive X-ray fluorescence spectrometer– Sample preparation for electron microscopy 25
  26. 26. Collaborations with Agencies/Universities/ Research FacilitiesIAGs CRADAs– Environmental Protection Agency (EPA) – Argus Research Laboratories– Federal Aviation Administration (FAA) – Primedica Corp– National Institute of Environmental Health – AstraZeneca Science (NIEHS) – Litmus– National Cancer Institute (NCI) – LLCPI– National Institutes of Health (NIH)/National – Pfizer, Inc. Institute of Environmental Health Science – RxGen, Inc. (NIEHS) – SAS Institutes, Inc.– Environmental Protection Agency (EPA)/National Health and Environmental – Sigma Tau Research, Inc. Effects Research Laboratory (NHEERL) – University of Illinois– National Institutes of Health (NIH)/National – University of Arkansas at Little Institute of Child Health and Human Rock Development (NICHD) – University of Arkansas for– National Institutes of Health (NIH)/National Medical Sciences Toxicology Program (NTP) 26
  27. 27. FDA/NIEHS IAG..…to conduct comprehensive toxicological assessments on selected FDA andNIEHS high priority chemicals nominated to the National Toxicology Program…FDA Nominations NTP/NIEHS Nominations Chloral Hydrate (CFSAN) Endocrine Active Chemicals Fumonisin B1 (CFSAN) – Methoxychlor Malachite Green (CVM) – Genistein (CFSAN) Urethane/Ethanol (CFSAN) – Nonylphenol (CDER) Riddelliine (CFSAN) – Vinclozolin α & β Hydroxy Acids (CFSAN)* – Ethinyl Estradiol (CDER) – Glycolic Acid Riddelliine (CFSAN/Adducts) – Salicylic Acid Aloe vera (NCI-Oral & Dermal) Ephedra (NCI/ODS - CFSAN) AIDS Therapeutics Retinyl Palmitate (CFSAN) – Zidovudine (AZT) Ketamine (CDER) – Nevirapine (NVP) Bisphenol A (CFSAN) – Lamivudine (3TC) Acrylamide (CFSAN) – Nelfinavir (NFV) Bitter Orange (CFSAN) – Efavirenz Usnic Acid (CFSAN) Glucosomine/Chrondroitin Di-(2-ethylhexyl) Phthalate (CFSAN) (CBER/CDRH) AZT P53 ko Mouse Study (CDER) Permanent Makeup Pigments (CFSAN) 27
  28. 28. FDA and kFDA CollaborationThe letter of agreement was signedNCTR/FDA and NITR/KFDA Joint Workshop onToxicogenomics - July 15-16, 2009– kFDA Participants: Drs. Sue Nie Park, Hong-Ki Min, Ki-Suk Park, Ho-Sang Jeong, and Wan-Seob ChoCollaborative projects– Liver Toxicity Knowledge Base (Dr. Weida Tong at NCTR and Dr. Ho-Sang Jeong at kFDA) 28