FDA Commissioner’s Fellowship Program Class of 2012

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FDACommissioner’sFellowshipProgram2012Fellows

Bazaco,Michael…………………………………. 9 Khatiwara,Anita………………………………. 18

Chigurapati,Srinivasulu…………………….. 10 Lin,Carol…………………………………………. 19

Chintagari,NarendranathR……………….. 11 Marasa,Bernard………………………………. 20

Duan,Peng………………………………………... 12 Mishra,Niharika…………………..………….. 21

Eustaquio,Trisha………………………………. 13 Pan,Yuzhuo…………………………….……….. 22

GacchinaJohnson,Carmen…………………. 14 Revollo,Javier………………………………….. 23

Haerian,Krystl…………………………………... 15 Tam,Justina……………………………………... 24

Hirneisen,Kirsten……………………………… 16 Yong,Carolyn…………………………………… 25

Keller,Paul………………………………………... 17 Zhao,Yuequin…………………………………... 26

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FDACommissioner’sFellowshipProgram2012Preceptors

Alayash,Abdu……………………………………. 28 Paredes,Angel………………………………….. 37

Berkower,Ira…………………………………….. 29 Rorer,Eva………………………………………… 38

Chen,Ii‐LunandAaronson,Wendy……... 30 Street,Debra……………………………………. 39

Clavet,Charles…………………………………… 31 Tiwari,Ram……………………………………… 40

Dobrovolsky,Vasily……………………………. 32 Williams‐Hill,Donna……………………….... 41

Hammack,Thomas…………………………….. 33 Zhang,Lei………………………………………… 42

Khan,Saeed……………………………………….. 34 Zhao,Ping………………………………………... 43

Larkin,John……………………………………….. 35

Liachenko,Serguei……………………………... 36 RegenerativeMedicineProject:Cavanaugh,KennethJ,Durfor,Charles,andOh,Steven…………………………………..

44‐46

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FDACommissioner’sFellowshipProgram2012PreceptorsandFellowsProjectslistedby

RegulatorySciencePriority Area

FDA’sRegulatorySciencePriorityAreasarearticulated in theStrategicPlanforAdvancingRegulatoryScienceatFDA.

ModernizeToxicologytoEnhanceProductSafety

4projectsareassociatedwiththisareaFellowsandPreceptorsinthisarea:

SrinivasuluChigurupatiandSergueiLiachenko(NCTR)

NarendranathChintagariandAbduAlayash(CBER) TrishaEustaquioandAngelParedes(NCTR) JavierRevolloandVasilyDobrovolsky(NCTR)

StimulateInnovationinClinicalEvaluationsandPersonalizedMedicinetoImproveProductDevelopmentandPatientOutcomes

2projectsareassociatedwiththisareaFellowsandPreceptorsinthisarea:

PengDuanandLeiZhang(CDER) YuzhuoPanandPingZhao(CDER)

EnsureFDAReadinesstoEvaluateInnovativeEmergingTechnologies

4projectsareassociatedwiththisareaFellowsandPreceptorsinthisarea:

CarmenGacchinaJohnsonandKennethCavanaugh,CharlesDurfor,andStevenOh(CDRHandCBER)

PaulKellerandIraBerkower(CBER) CarolLinandEvaRorer(CDRH) CarolynYongandKennethCavanaugh,CharlesDur‐

for,andStevenOh(CDRHandCBER)

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FDACommissioner’sFellowshipProgram2012PreceptorsandFellowsProjectslistedby

RegulatorySciencePriority Area

HarnessDiverseDatathroughInformationSciencestoImproveHealthOutcomes

2projectsareassociatedwiththisareaFellowsandPreceptorsinthisarea:

KrystlHaerianandIi‐LunChenandWendyAaronson (CTP) YueqinZhaoandRamTiwari(CDER)

ImplementaNewPrevention‐FocusedFoodSafetySystemtoProtectPublicHealth

4projectsareassociatedwiththisareaFellowsandPreceptorsinthisarea:

MichaelBazacoandDebraStreet(CFSAN) KirstenHirneisenandDonnaWilliams‐Hill(ORA) AnitaKhatiwaraandThomasHammack(CFSAN) NiharikaMishraandJohnLarkin(CFSAN)

FacilitateDevelopmentofMedicalCountermeasurestoProtectAgainstThreatstoU.S.andGlobalHealthandSecurity

2projectsareassociatedwiththisareaFellowsandPreceptorsinthisarea:

BernardMarasaandSaeedKhan(NCTR) JustinaTamandCharlesClavet(ORA)

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CBERPreceptor FellowAbduAlayash NarendranathR.Chintagari IraBerkower PaulKellerKennethJ.Cavanaugh, CarolynYongCharlesDurfor,andStevenOhCDERPreceptor FellowLeiZhang PengDuanPingZhao YuzhuoPanRamTiwari YueqinZhao CDRHPreceptor FellowKennethJ.Cavanaugh, CarmenGacchinaJohnsonCharlesDurfor,andStevenOhEvaM.Rorer CarolLin CFSANPreceptor FellowDebraA.Street MichaelBazacoThomasS.Hammack AnitaKhatiwaraJohnW.Larkin NiharikaMishra

FDACommissioner’sFellowshipProgram2012PreceptorsandFellowsbyCenter

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CTPPreceptor FellowIi‐LunChenand KrystlHaerianWendyAaronsonNCTRPreceptor FellowSergueiLiachenko SrinuChigurupatiAngelParedes TrishaEustaquioSaeedKhan BernardMarasaVasilyDobrovolsky JavierRevolloORAPreceptor FellowDonnaM.Williams‐Hill KirstenHirneisenCharlesR.Clavet JustinaTam

FDACommissioner’sFellowshipProgram2012PreceptorsandFellowsbyCenter

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FDACommissioner’sFellowshipProgram2012Fellows

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Scienti icandProfessionalBackgroundPh.D. Epidemiology UniversityofPittsburgh 2012M.S. FoodScienceandTechnology VirginiaTech 2004B.S. Biology VirginiaTech 2001 Biology UniversityofSouthCarolina ResearchInterestsMichael’sresearchinterestsfocusmainlyontheepidemiologyoffoodborneillnessanditsapplicationtofoodsafety.Hehasworkedontheoptimizationofenvironmentalsamplingtechniques for pathogens. In addition, he has assessed pathogen ecology in processingplantswhilecompletinghisMSatVirginiaTech.Hisdoctoralresearch focusedonsocialepidemiology.Speci ically,hedevelopedareliableinstrumenttomeasureneighborhoodcontentednessinadolescentsusingstatisticalinference.Inaddition,helookedattheas‐sociationbetweenthismeasureandphysicalactivityandscreentimeinadolescents.Healsoworkedonstatisticaldevelopmentofatrajectoryanalysismodelfortraumaticbraininjurytreatmentandevaluation,aswellasinfectiousdiseaseepidemiologyprojectscon‐cerningnosocomialinfectionsandvaccinecoverage.Healsoactedastheteachingfellowforthreeyearsandwasinvolvedwiththedevelopmentandexecutionofvariousgraduatelevelepidemiologycourses.Publichealthcommunicationandlearningisalsoamajorin‐terestofhis.Commissioner’sFellowshipProjectOverviewTemporalTrendsinOutbreakAttributionofProduceandJuicesComparedtoOtherFoodGroupsFDA Regulatory Science Priority Area: ImplementaNewPrevention‐FocusedFoodSafetySystemtoProtectPublicHealthMichaelwillbelookingattemporaltrendsintheattributionoffoodbornediseasesinvar‐iouscommodity/pathogencombinations.

MichaelC.Bazaco,Ph.D.,M.S.

CenterforFoodSafetyandAppliedNutrition(CFSAN)Of iceofAnalyticsandOutreach(OAO)

Preceptor:DebraStreet,Ph.D.,M.P.H.

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Scienti icandProfessionalBackground2010‐2012 ResearchScientist:NationalInstituteonAging,NIH,Baltimore,MD& CollegeofMedicine,UniversityofCentralFlorida,OrlandoFL2008‐2010 ResearchScientist:CollegeofMedicine,UniversityofCentralFlorida, OrlandoFL2005‐2008 Postdoctoral Visiting Fellow, National Institute on Aging, NIH, Baltimore, MD1997 PhD,CollegeofVeterinaryScience,Rajendranagar,AP,India1991 MVSc,CollegeofVeterinaryScience,Tirupati,AP,India1987 DVM,CollegeofVeterinaryScience,Tirupati,AP,IndiaLicensesandCerti ication:HeislicensedbyAVMAtopracticeVeterinaryMedicineinUSA;Heisalsocerti iedbyNIHinClinicalPharmacologyandClinicalTrials.ResearchInterestsHisresearchinterestsarebroadlyinstudyingthemechanismsinvolvedinneuronaldam‐age,relatedtoagingandchronicneurodegenerativediseasessuchasAlzheimer‘s,Parkin‐son’sandALS.Also,studyingmolecularbasisofglioblastomastoidentifynoveldrugtar‐getsanddevelopingnewanimalstudyprotocolsinNeuro‐OncologyandNeuroscience.Heis lookingforwardtolearnmoreaboutregulatoryscienceintheCommissioner’sfellow‐shipprogramtoprotect&promotethepublichealthandexpandskillsetinidenti icationofnovelneurotoxicitybiomarkersthroughMagneticResonanceImaging(MRI)andMag‐neticResonanceSpectroscopy(MRS).Commissioner’sFellowshipProjectOverviewCon irmativeNeuropathologystudieswithMRIImagingandInformaticsFDA Regulatory Science Priority Area: ModernizeToxicologytoEnhanceProd‐uctSafety DevelopmentofMRI/MRSbiomarkersofneurotoxicity in laboratoryanimals.Prototypicneurotoxiccompoundswillbeusedtoinducebrainlesionswiththeintentofidentifyingassociatedmetabolicchangesinaffectedtissue.Evaluationofquantitativeimaging(MRI/MRS, positron emission tomography) for identifying new potentially translational bi‐omarkersandpredictorsofsafetyandef icacy.

SrinuChigurupati,D.V.M.,Ph.D.

NationalCenterforToxicologicalResearch(NCTR)

Preceptor:SergueiLiachenkoM.D.,Ph.D.

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Scienti icandProfessionalBackground2010 PostdoctoralAssociate;YaleUniversity2008‐09 PostdoctoralfellowandResearchAssociate;OklahomaStateUniversity2007 PhD(VeterinaryBiomedicalSciences):OklahomaStateUniversity2002 M.V.Sc(Pharmacology):AnandAgriculturalUniversity1999 B.V.Sc&A.H,SriVenkateshwaraVeterinaryUniversityResearchInterestsDr. Chintagari’s research interestsmainly focused on understanding the pathophysiology of lungfunctioning.Hisdoctoralresearchunraveledtheroleof lunglipidraftsinsurfactantsecretion.Healso studied multiple acute lung injury diseases such as Acute Respiratory Distress Syndrome(ARDS),Ventilator‐inducedlunginjury(VILI)andhyperoxia‐mediatedlunginjury.Hisotherinter‐ests include fetal lung development and its anamolies such as Congenital Diaphramatic Hernia(CDH), Bronchopulmonary Dysplasia (BPD). Recently, he investigated the therapeutic ef icacy ofTransientReceptorProtein(TRP)receptorsinamelioratingirritant‐inducedskininjuryinmice.Hiscurrent researchwill investigate hemoglobin‐based oxygen carriers (HBOC)‐induced lung injury.Thepresentstudiesmightrevealmechanismstomitigatetheirpulmonarytoxicity.Commissioner’sFellowshipProjectOverviewInvestigationofHemoglobin‐inducedpulmonarytoxicityFDA Regulatory Science Priority Area: ModernizeToxicologytoEnhanceProductSafety Bloodtransfusionisacommonlyusedcriticallifesavingprocedureinintensivecareunits.Massivetransfusionandredbloodcelllysisinsicklecelldiseaseandthalassemiareleaseshemoglobinintothevasculature.Excessiveamountsofcellfreehemoglobinareinjurioustomultipletissues.Lungsareoneofthehighlyperfusedtissues.Theyarepotentiallyexposedtohighconcentrationsofacellularhemoglobinnotonlyinhemolyticdiseasesbutalsoduringacutelunginjury.Thepresenceofexcessacellularhemoglobinmightaffectlungfunctioning.Thepresentstudyishencedesignedtostudy the toxicity of hemoglobin on lung epithelial cells invitro and invivo. Understanding themechanismsofhemoglobin‐inducedepithelial injurymightenableustodevisestrategiestomini‐mizethepulmonaryinjury.Ourstudymightalsoprovidevaluableinputindevelopinghemoglobinbasedoxygencarrierswhicharesafeandeffective.

NarendranathChintagari,BVSc&AH(DVM),MVSc,Ph.D.

CenterforBiologicsEvaluationandResearch(CBER)

Preceptor:AbduI.Alayash,Ph.D.

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Scienti icandProfessionalBackground1994‐1998B.S.inPharmaceuticalScience ChinaPharmaceuticalUniversity2001‐2007Ph.D.inNeuroscience StateUniversityofNewYorkatBuffalo2007‐2012ResearchAssistantProfessor Rutgers,StateuniversityofNewJerseyResearchInterestsDr.Duan’sresearchareasincludedrugtransporterfunctionalregulationandtransporterassociateddrug‐druginteractions(DDIs)studies.Heisinterestedinutilizingthecurrentknowledgeandunderstandingoftransporterfunctionsandregulationmechanismstoin‐vestigateandpredictclinicalDDIstoassistregulatoryreviewandthedevelopmentofreg‐ulatoryguidance.Dr.Duanhasextensiveexperienceinmolecularbiology,neuroscience,andpharmaceuticalsciences.Commissioner’sFellowshipProjectOverviewConstructionofaDrugTransporterDatabaseandUtilizationof thePhysiologically‐BasedPharmacokinetic (PBPK) Modeling and Simulation to Predict and Analyze Transporter‐mediatedDrug‐drugInteractions(DDIs)FDA Regulatory Science Priority Area: StimulateInnovationinClinicalEvalua‐tionsandPersonalizedMedicinetoImproveProductDevelopmentandPatientOutcomesTransporter‐Mediated DDIs, caused by competition of the same transporter pathwaysamong co‐administrated drugs, can lead to signi icant changes in the safety or ef icacypro iles of the affecteddrug. Therefore, assessing the clinical relevance of transporter‐mediateddruginteractionshasbecomeanintegralpartofriskassessmentsduringdrugdevelopmentandregulatoryapprovalprocesses.Adatabasecontainingtransporterinfor‐mation fromNDA/IND submissionswill be a very helpful resource to reviewers. FDA’s2012draftguidanceondruginteractionshasrecommendedtheapplicationofmodelingandsimulationinthepredictionofDDIrisk.Inthisproject,atransporterdatabasemainlybasedontheinformationfromNDA/INDsubmissionswillbeconstructed.Inaddition,abestpracticedocumentoninvitrotransporterassayswillbetohelpimprovequalityofinvitro transporter studies and aid transporter study review. Finally, mechanistic staticmodelsaswellasdynamicPBPKmodelswillbeconstructedtoevaluateDDIriskassociat‐edwithstatindrugsthatinvolveseveraltransportersandmetabolizingenzymes.

Peng(Vincent)Duan,Ph.D.

CenterforDrugEvaluationandResearch(CDER)Of iceofTranslationalSciences(OTS)Of iceofClinicalPharmacology(OCP)

Preceptor:LeiZhang,Ph.D.

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Scienti icandProfessionalBackground2007‐2012 Ph.D.BiomedicalEngineering,PurdueUniversity,WestLafayette,IN2011 Consultant,Nanovis,WestLafayette,IN2009 SummerIntern,DowAgroSciences,Indianapolis,IN2005‐2007 ResearchAssociate,Cyntellect,SanDiego,CA2003‐2005 ResearchAssociate,Acidophil,SanDiego,CA2000‐2004 B.S.BioengineeringwithminorinMathematics,UniversityofCalifornia,SanDiego,

LaJolla,CAResearchInterests Engineeringnanomedicaldevices Nanotoxicologyandtheenvironmentalimpactofnanotechnology Developmentofmethodologiesforthephysicochemicalandbiologicalcharacterizationofnov‐

elnanomaterials Scienti icandregulatoryissuesofnanomaterial‐basedproducts Nanotechnologyeducation Developmentof3DelectronmicroscopytechniquesfortoxicologicalresearchCommissioner’sFellowshipProjectOverviewAssessmentofmitochondrialultrastructureandfunctionafterketaminetreatmentinthedevelopingratbrainFDA Regulatory Science Priority Area: ModernizeToxicologytoEnhanceProductSafe‐ty Ketamine, an FDA‐approved N‐methyl‐D‐aspartate (NMDA) receptor antagonist, is commonlyusedforgeneralpediatricanesthesia.Accumulatingevidenceindicatesthatcontinuousexposuretoketamine inducesextensiveneuronalcelldeath in thedevelopingbrainsofexperimentalani‐mals.Littleisknown,however,abouttheoverallchangesinthemitochondrialultrastructurethatmayaccompanythedistincteventsinthiscelldeathprocess.Thus,2Dand3Dmethodsofelectronmicroscopy(EM)willbeutilizedtoexaminealterations in themitochondriaultrastructureafterketaminetreatmentandthencorrelatethemtomitochondrial(dys)functionintherodentmodel.This projectwill allow the development of new EM techniques thatmay provide critical infor‐mationfor irstdetectingandthenunderstandingtherelativerisksassociatedwiththeuseofket‐amine and the subsequent impacton regulationof similar anesthetic agents. SuchpowerfulEMmethodologiescanalsobeusedinavarietyofFDAstudies,inwhichstructureplaysacriticalroleinstudyingdrugornanomaterialinteractions.

TrishaEustaquio,Ph.D.

NationalCenterforToxicologicalResearch(NCTR)

Preceptor:AngelM.Paredes,Ph.D.

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Scienti icandProfessionalBackground2010‐2012 ImagingScienceTrainingPostdoctoralFellow

NationalInstitutesofHealth(NIH),Bethesda,MD2010 Ph.D.Bioengineering

ClemsonUniversity,Clemson,SC2006 B.S.MaterialsScienceandEngineering

MichiganStateUniversity,EastLansing,MI

ResearchInterestsCarmen’sresearch interestsarecardiovascularregenerativemedicine, intravascular image‐guidedthera‐pies,andlocaldrugdelivery.Hergraduateresearchfocusedonregenerativemedicinefortreatmentofex‐tracellularmatrixdegradationfromvasculardisease.Sheutilizedanimalmodelsthatrecapitulatedvaryingstages of clinical abdominal aortic aneurysms (AAA), and then therapeutically delivered biomolecularagentstothederivedcells.Thesebiomoleculesstimulatedextracellularelasticmatrixrepairwithsigni i‐cantsuccess.Thechallengesofsustaineddeliveryofsuchtherapeuticagentstoatargetpathologiclocation,suchasthesiteofAAA,sparkedherinterestinlocaldrugdelivery.Therefore,shepursuedanopportunityto expand her expertise into the ield of image‐guided therapies and local drug delivery for her post‐doctoraltraining.Carmen’spostdoctoralresearchprojectsincludedimage‐guidedlocalembolicanddrugdeliveryforlivercancertherapy,lowtemperaturesensitiveliposome(LTSL)drugdeliveryandhighinten‐sityfocusedultrasound(HIFU)forenhancedthrombolysis,MR‐guidedHIFUfortargeteddrugdeliveryofLTSLs in a tumormodel, and aminimally‐invasive large animalmodel of AAA for testing endovasculartherapeuticdevices. Inallof theseprojects, she focusedonunderstanding thebiologic response to localtherapy.Commissioner’sFellowshipProjectOverviewOpportunitiesandchallengesinapplyingexistingbiocompatibilitystandardsforthesafetyevaluationofcar‐diovasculardevice‐biologiccombinationproductsFDA Regulatory Science Priority Area: EnsureFDAReadinesstoEvaluateInnovativeEmergingTechnologiesStandardapproachesforevaluatingthebiologicsafetyofaproductmaynotbeappropriateorsuf icientlyinformativefordevice‐biologiccombinationproducts.Forthisproject,Carmenwilladdressthefollowingissuesforcardiovasculardevice‐biologicproducts:

1)Whenthecurrentmethodsofevaluatingbiocompatibilityprovidemeaningfulandsuf icientdata2)Whatcriteriashouldbemetsothatmeaningfulandsuf icientbiocompatibility/preclinicaldatacanbebasedonpublishedliteratureofsimilarproducts

3)Underwhatconditionsandhowsamplepreparationmethodsshouldbemodi iedtoprovidemoreaccurateevaluationofbiocompatibility(e.g.,studiesoncomponentsratherthana inalproduct)

4) Underwhat conditions additional / new tests should be considered to augment the current bio‐materialbiocompatibilitytestmethods

Carmenwillreviewthedataavailableforinvestigationalandapprovedproductswiththeultimategoalofsuggesting updated biocompatibility testing guidelines for cardiovascular device‐biologic combinationproducts.

CarmenGacchinaJohnson,Ph.D.

RegenerativeMedicineProjectCenterforDevicesandRadiologicalHealth(CDRH)

CenterforBiologicsEvaluationandResearch(CBER)

Preceptors:KennethJ.CavanaughJr.,Ph.D.(CDRH),CharlesDurfor,Ph.D.(CDRH),andStevenS.Oh,Ph.D.(CBER)

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Scienti icandProfessionalBackground2009‐2012 ColumbiaUniversity,DepartmentofBiomedicalInformatics, NLMfundedgraduatestudent(M.S.,BiomedicalInformatics)2009 U.S.HouseofRepresentatives,Of iceofHon.LucilleRoybal‐Allard, WREICongressionalFellow2008 NationalInstituteofHealth,ClinicalCenter,

LaboratoryforInformaticsDevelopment,PostdoctoralFellowEducation: M.D.,UniversityofMarylandSchoolofMedicine; M.S.,Biotechnology,JohnsHopkinsUniversity;B.S.,BiologicalSciences,UMBCResearchInterestsDr.Haerian’sresearchpriortojoiningtheFDAwasfocusedonthesecondaryuseofElec‐tronicHealthRecorddata for thedetectionofpharmacovigilanceanddrug repurposingsignals.Herresearchincludedmethodstoimprovecaptureofclinicalresearchdata,auto‐matedphenotype extraction, andmethods to reducenoise and confounding in big datasets.AttheFDA,herhopeistotranslatefundamentalclinicalandinformaticsknowledgeandmethodstoorganize,structure,andlabeldocumentsgermaneandrelevantforspeci ‐icclinicalthemesforrapidreviewandevaluationbyCTPscientists.Commissioner’sFellowshipProjectOverviewStreamliningTobaccoIndustrySubmissionstotheFDACenterforTobaccoProductsFDA Regulatory Science Priority Area: HarnessDiverseDatathroughInfor‐mationSciencestoImproveHealthOutcomesThefellowshipprojecthastwomaincomponents,the irstistodevelopadraftguidancefor standardizedelectronic submissions toCTPand the second is toutilizedataminingtechniques tostudycon identialhealthdocumentssubmitted toCTPunder theTobaccoControlAct.Currentstandards,suchastheeCTDandCDISC,thatareinuseatotherFDAcentersforelectronicsubmissionswillbeevaluatedforpotentialutilityatCTP.Thefellowwillplanaworkshoponelectronicsubmissionstandardsforindustryandinterestedpar‐ties. Researchworkwill include applying preprocessing and data‐mining techniques toexplorealargecorpusofcon identialindustrydocumentstoidentifycollectionsofdocu‐mentsandstudiesrelevanttoscienti icreviewers.Thefellowwillalsoparticipateintheclinicalreviewofinvestigationaltobaccoproductapplications.

KrystlHaerian,M.D.

CenterforTobaccoProducts(CTP)Of iceofScience(OS)

Preceptors:Ii‐LunChen,M.D.and

WendyAaronson

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Scienti icandProfessionalBackground2008‐2012 Ph.D.FoodMicrobiology,UniversityofDelaware,Newark,DE2006‐2008 M.S.FoodScience,UniversityofDelaware,Newark,DE2002‐2006 B.S.Biochemistry/CellBiology,BucknellUniversity,Lewisburg,PAResearchInterestsKirsten’s research interests encompass a variety of topics in the ield ofmicrobial foodsafety. Hergraduateresearchfocusedontheinteractionofentericviralpathogenswithfresh produce in the pre‐harvest environment aswell as post‐harvest processing treat‐ments.CurrentresearchprojectsasaCommissioner’sFellowswillfocusondevelopmentandvalidationofmethodstestingforpathogensinfoodmatrices.Commissioner’sFellowshipProjectOverviewDevelopingaUniversalEnrichmentBrothforFoodborneBacterialPathogensFDA Regulatory Science Priority Area: ImplementaNewPrevention‐FocusedFoodSafetySystemtoProtectPublicHealthSuccessfulpreventionoffoodborneillnessrequiresthedevelopmentofrapidandreliablepathogendetectionmethodsfortestingoffoods.Dependingonthefoodmatrixandtargetpathogen, different pre‐enrichment broths are usedwhen following the BacteriologicalAnalyticalManual(BAM)forsamplepreparationpriortoconventionalculturingoffood‐bornebacterial pathogens. Thepreparation ofmultiple pre‐enrichment broths is laborintensive,timeconsumingandcostly,andtheneedtousemultipleenrichmentbrothsisamajorroadblockwhentryingtodeveloprapidmethodsdesignedformulti‐targetpatho‐gendetectionsuchasmultiplexqPCR.Theobjectiveofthisresearchprojectistodevelopa universal enrichment broth to simultaneously propagatemultiple foodbornebacterialpathogensincludingGramnegativeandGrampositivepathogensinfoodmatrices.Auni‐versalenrichmentbrothcombinedwithmultiplexqPCRdetectionwill reducemediare‐quirementsandsampleanalysistimeinadditiontoresultinginahigh‐throughput,stream‐linedapproach. Thismethodwill increasethecapacityofdetectingmultiplepathogenswhichiscritical totherapiddetectionofpathogens infoodsamplesbypublichealth la‐boratories.

KirstenHirneisen,Ph.D.

Of iceofRegulatoryAffairs(ORA)

Preceptor:DonnaWilliams‐Hill,Ph.D.

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Scienti icandProfessionalBackground PostdoctoralFellowship:2007‐2012;LaboratoryofStructuralBiologyResearch,NIAMS/

NIH CornellUniversity,2007:Ph.D.,Genetics&Development CarnegieMellonUniversity,2001:B.S.,BiologicalSciencesResearchInterestsDr.Keller’sprimaryresearchinterestisthestudyofvirusesandotherinfectioushumanpatho‐gens,withaparticularemphasisonretrovirusessuchasHIV‐1.Forhisdoctoralresearch,Dr.Kellerstudiedtheassemblypathwayofretrovirusesusingmolecularbiology,genetic,andim‐agingtechniques.InhispostdoctoralworkatNIH,Dr.Kellerfocusedoninvestigatingretroviralmaturationand its inhibitionusing three‐dimensional electronmicroscopy techniques.As anFDACommissioner’sFellow,Dr.KellerlooksforwardtoapplyinghismolecularandstructuralbiologyexperiencetothedesignofpotentialHIV‐1vaccineantigensandeffectivedeliveryvec‐tors.Commissioner’sFellowshipProjectOverviewDesigningHIV‐1VaccineImmunogensbyStabilizinggp120withanExposedCD4ReceptorBind‐ingSiteFDA Regulatory Science Priority Area: EnsureFDAReadinesstoEvaluateInnovativeEmergingTechnologiesMorethan30yearsafterthe irstdescriptionofthedisease,HIV/AIDSremainsaglobalhealthpandemic.Despitedecadesof research, there isnoeffectivevaccineagainstHIV infection,orcureforthosealreadyinfectedwiththevirus.ThesurfaceglycoproteinofHIV‐1,Env(gp120),utilizesseveralstrategiestoevadeeffectiveimmunerecognition,includingstructuralplasticity,sequence variability, and epitope shielding.Nevertheless, gp120 is the target ofmost knownbroadlyneutralizingantibodies(nAbs)againstthevirusduetoitscriticalroleinvirusbindingandentrytohostcells.Thegoalofthisprojectistousestructuralbiology‐guidedmutagenesistoinvestigatethedesignofHIV‐1vaccineimmunogensbasedongp120.Byengineeringastabi‐lizedminimalgp120constructthatretainstheCD4receptorbindingsite(CD4bs)activitybuteliminatesstructuralplasticityandshielding,westrivetocreateanantigenthatavoidsEnv’snaturaldefensemechanisms,ishighlyimmunogenic,andisabletoelicitnAbsagainstprimaryHIV‐1isolates.Inaddition,wearedevelopingnovelformsofgp120thataresmallenoughforexpressioninaliveviralvector,yetretaintheCD4bstargetfornAbs.ThisworkwillcontributetotheFDA’sknowledgeofeffectivevaccineantigendesign,aswellasprovideinsighttoassistinregulatoryreviewofpotentialvaccinecandidates.

PaulW.Keller,Ph.D.

CenterforBiologicsEvaluationandResearch(CBER)DivisionofViralProducts,Of iceofVaccines

Preceptor:IraBerkower,M.D.,Ph.D.

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Scienti icandProfessionalBackground2007‐2012 Ph.D.,CellandMolecularBiology,UniversityofArkansas,Fayetteville,AR2005‐2007 M.S.,CellandMolecularBiology,UniversityofArkansas,Fayetteville,AR2001‐2005 VeterinaryPractitioner,Gangtok,Sikkim,India1996‐2001 B.V.Sc.&A.H.,(≈DVM)BachelorofVeterinarySciencesandAnimal Husbandry,AcharyaN.G.RangaAgriculturalUniversity,Hyderabad,IndiaResearchInterestsDr.Khatiwara’sresearchinterestsliesinthe ieldsofMicrobiology,MolecularBiology,FoodSafe‐ty,andPublicHealth.HerdoctoralresearchfocusedonfunctionalgenomicsofSalmonellaTyphi‐muriumtoidentifyconditionallyessentialgenes.Thesegenescouldbeanimportantresourceforbetterunderstandingtheabilityofbacteriatosurvive/persistinvariousenvironmentsincludingfoodmatricesandfoodcontactsurfaces.Theknowledgegainedcouldassistindevelopingstrate‐giestopreventbacterialcontaminationoffood.HerresearchinterestsatFDAistobuilduponheracademic and research experience and apply various microbiological and molecular biologicaltechniquesforthedevelopmentof improvedmethodsofdetectionof food‐bornepathogens.ShebelievesthelaboratoryresearchexperiencealongwithregulatoryexperiencesheexpectstogainhereatFDAwillimparttheskills/knowledgethatisessentialtoworkforthebettermentandsafe‐guardingofhumanhealth.

Commissioner’sFellowshipProjectOverviewDevelopmentandvalidationofanenvironmental testingmethod for thedetectionofL.monocyto‐genesinfoodprocessingenvironment

FDA Regulatory Science Priority Area: Implement a New Prevention‐Focused FoodSafetySystemtoProtectPublicHealth

Effective environmental testing procedures are critical for identifying source of contaminationduring an outbreak. Recently L.monocytogenes has been implicated in amajormulti‐state out‐break associated with contaminated cantaloupes and it is the deadliest foodborne outbreak inmorethanadecade.Theinvestigationofthisoutbreakidenti iedtheprocessingenvironmentasasourceofcontamination.ThecurrentFDABacteriologicalAnalyticalManual(BAM)containsana‐lyticalmethodsforthedetectionofL.monocytogenesinvariousfoodmatrices.However,therearenovalidatedmethodsforenvironmenttestingofthepathogensbyFDA.Herresearchprojectwillfocusonthedevelopmentandvalidationof testingprocedures includingsamplecollection,han‐dling, enrichment, screening, isolation and con irmation of L.monocytogenes in food processingenvironment,especially foodcontact surfaces.Theenvironmental testingandmonitoringproto‐colsforthepathogenwillguideindustrytodevelopeffectivesanitationprocedurestoensuresafe‐tyof inalfoodproducts.

AnitaKhatiwara,Ph.D.

CenterforFoodSafetyandAppliedNutrition(CFSAN)

Preceptors:ThomasHammack,M.S.

19

Scienti icandProfessionalBackground2010–2011 Attendingophthalmologist,Queens‐LongIslandMedicalGroup,P.C.2009–2010 Fellowshipinglaucoma,Mt.SinaiMedicalCenter,NewYork2006–2009 Residencyinophthalmology,NewYorkMedicalCollege‐St.VincentCatholic MedicalCenter,Manhattan2005–2006 Internshipinmedicine,UniversityofMarylandMedicalCenter2005 M.D.,UniversityofMarylandSchoolofMedicine2000 B.A.inbiology,WashingtonUniversityResearchInterestsTechnologicalinnovationinophthalmologicaltherapeuticshasbeenemergingatarapidpaceoverre‐centyears,withongoingregulatoryandeconomicimplications.Drawinguponmypreviousclinicalex‐periencesasacomprehensiveophthalmologistandglaucomaspecialist,Iwouldliketoexplorethere‐ciprocatingeffectsbetweentheseinnovationtrends,federalregulationandpublichealthwhilelearningaboutthepremarketregulatoryprocessesforophthalmicdevicesubmissions.Commissioner’sFellowshipProjectOverviewDevelopmentofaGuidanceDocumentforOphthalmicOpticalCoherenceTomographyImagingDevicesFDA Regulatory Science Priority Area: EnsureFDAReadinesstoEvaluateInnovativeEmerg‐ingTechnologiesThe rapid pace of developments in diagnostic ophthalmic imaging technology over the past severalyearshasbeenaccompaniedbyanincreaseinrelatedmarketingsubmissions,particularlyfordevicesemployingopticalcoherencetomography(OCT)technology.However,appropriateendpointsandstrat‐egies for theassessmentofnewophthalmicOCTdevice functionsandclaimsremainunclear.EvenastheseOCTdevicesassertincreasingimportancetoclinicians,noguidanceexistsforFDAstafforindus‐try onhow to evaluate advances in ophthalmicOCT technology and related labeling claims.A recentworkshop jointly sponsored by the FDA and the American Glaucoma Society invited stakeholders(clinicians,academicians,andindustry)todiscussregulatoryscienceaspectsofandstrategiesforchar‐acterizing and assessing the performance of OCT devices used for the diagnosis andmanagement ofglaucoma.Theobjectivesofthisprojectaretoutilizethefeedbackobtainedfromtheworkshopandtoincorporateitintoaguidancedocumentforindustryandstafftoimprovethequalityandconsistencyofpre‐marketsubmissionsforophthalmicOCTdevices.Asaregulatoryagency,theFDAisresponsibleforadvancingpublichealthbyfacilitatingthedevelopmentofproductinnovationsandthepublic’saccessto accurate, science‐based information necessary for appropriate use of medical devices. One of thewaystomeet theseregulatorygoals is topromoteconsistency in thepathtoproductclearancewhilemaintainingclearscienti icstandardsofproductvalidation,reliability,andusability.ProgresstowardsapublishedguidancedocumentwillcontributetotheFDA’soverallpublichealthmission.

CarolLin,M.D.

Center:CenterforDevicesandRadiologicalHealth(CDRH)

Preceptor:EvaRorer,M.D.

20

Scienti icandProfessionalBackground2010‐2012 ResearchAssociate,HIV‐1Vaccine,TheCatholicUniv.of America(CUA),WashingtonDC2007‐2010 Post‐DoctoralAssociate,LaboratoryofCellular&MolecularImmunology, NIA‐IRP;NationalInstituteofHealth,Baltimore,MD 2003‐2007 Ph.D.MolecularPathology,UniversityofMaryland Baltimore,MD 2001‐2003 ResearchAssociate,DeptofSurgery,Universityof Maryland,Baltimore,MD1999‐2001 M.Sc.Mol.Biology,VrijeUniversiteitBrussel,Belgium1997‐1999 ResearchAssistant,InternationalLivestockResearch Institute(ILRI),Nairobi,Kenya1993‐1997 B.Sc.(Biochemistry)JKUAT,Nairobi,KenyaResearchInterestsDr. Marasa’s research interests are primarily in cellular signaling, gene expression pro iling, siRNA/microRNA gene therapy and characterization of disease biomarkers. He is also interested in learningaboutFDA’sregulatoryscienceandpoliciesespeciallyinrelationtotoxicologicalevaluationofbiologics,drugsandgenetherapyproducts.Hiscurrentresearchis focusedontheanalysisofglobalcellulargeneexpressionandmicroRNApro ilingonthepulmonary,cutaneousandIntestinalprimarycellsuponinfec‐tionwithavirulentanthraxstrainBacillusanthracis.HisPh.D.researchfocusedoncloningandcharacter‐izingTRPCcalciumionchannelsanddownstreamcellularsignalingpathwaysinintestinalepithelialcells.Inhispost‐doctoraltrainingattheNIA‐NIH,hisresearchfocusedprimarilyonroleofRNABindingPro‐teins(RBPs)andmicroRNAsinpost‐transcriptionalgeneregulationduringcellularsenescence.AtCUA,hewasmainlyinvolvedindesigninganovelHIV‐1ENVgeneimmunogenandengineeringbacteriophageT4capsidsforuseasapotentialHIV‐1vaccineplatform.Commissioner’sFellowshipProjectOverviewGene expressionpro iling inpulmonary,gastrointestinaland cutaneous epithelial cell linesafter infectionwithBacillusanthracisSterneFDA Regulatory Science Priority Area: FacilitateDevelopmentofMedicalCountermeasurestoProtectAgainstThreatstoU.S.andGlobalHealthandSecurityAnthraxdiseasemanifestsitselfinthreeforms,whichdifferinseverity;howeverthecauseofthediffer‐encesinseverityanddiseaseoutcomeispoorlyunderstood.Theoutcomeofthediseaseisprobablyde‐pendentupontheinteractionofanthraxtoxinswithcellulartargetsatthesiteofinfection.Tofullyunder‐standcausesofseveritydifferencesamongthetheeformsofanthraxdiseasemanifestations;weseektostudythewholegeneexpressionpro ileofthepathogen;B.anthracisandhostcellstoidentifykeyintra‐cellularsignalingandpro‐in lammatoryresponsepathwaysinvolvedineachformofthedisease.Evalua‐tionof thesedownstreamsignalingpathwaysmay leadto identi icationofnewpotentiallytranslationalbiomarkers of anthrax diseasewhich FDA can utilize for the expeditious development and licensing ofproductstodiagnose,treatorpreventanthraxfollowingexposure.

BernardSMarasa,Ph.D.

NationalCenterforToxicological.Research(NCTR)DivisionofMicrobiology

Preceptor:SaeedAKhan,Ph.D

21

Scienti icandProfessionalBackground2011‐2012 Postdoctoralassociate,ThePennsylvaniaStateUniversity2011 Ph.D.Agricultural&BiologicalEngineering,ThePennsylvaniaStateUniversity2003 M.Tech.DairyandFoodEngineering,IndianInstituteofTechnology,Kharagpur, India2000 B.Tech.AgriculturalEngineering,OrissaUniversityofAgriculture&Technology (OUAT),Bhubaneswar,India.ResearchInterestsMyresearchinterestisintheareaoffoodprocessengineering,primarilyfocusedonprocesses‐tablishmentandvalidation.Iaminterestedinstudyinginactivationofpathogenicmicroorganismsinfoodbyvariousemergingtechnologiesanddevelopmentofmathematicalmodelsforriskanaly‐sis.DuringmyPhD.Iworkedondevelopmentofpredictivemodelsforinactivation,injuryandre‐coveryoffoodbornepathogeninUHTwholemilkfollowinghighpressureandtemperaturetreat‐ment.MyM.Techprojectworkinvolved,designanddevelopmentofanasepticpackagingmachineforsterilizedmilk.Commissioner’sFellowshipProjectOverviewValidationofExtrusionProcessingforInactivationofSalmonellainLowMoistureModelFoodsFDA Regulatory Science Priority Area: Implement a New Prevention‐Focused FoodSafetySystemtoProtectPublicHealthDuring thepast several decades, numerousoutbreaksof salmonellosis have been linked to lowmoisture foods such aspeanut butter, treenuts, dry seasoning, powered infant formula, cereal,andpet food.Among theseoutbreaksmanyareassociatedwithextruded foodproductssuchascereals,snackfoodsandpetfoods.Thus,anurgentneedexistsforminimizationofmicrobialsafe‐tyhazardsinextrudedfoodproducts.EradicationofSalmonellabythermaltreatmentisdif icultdue to thehigh thermal resistanceofSalmonella at lowmoisturecontentorwateractivity (aw).Moreover, the reported extrusion studies describingmicrobial inactivation lack comprehensivedatainvaryingmoisturecontentandtemperature.Ourgoalistoevaluatetheef icacyofextrusionasaninactivationstepforSalmonellaindifferentfoodsoverarangeofmoistureandtemperature.Themainobjectivesoftheresearchare1)IdentifythemostresistantSalmonellastrainfromadi‐verse collectionof food, clinical and environmental isolates associatedwith lowmoisture foodsand related outbreaks; 2) Determine themicrobial inactivation kinetics of Salmonella(most re‐sistantstrainobtainedfromobjective1)inlowmoisturefoodmatricesofvaryingmoisturecon‐tentandthecompositionofstarch,proteinandfatcontent.3)Studythemicrobialinactivationef i‐cacyofapilot‐scaleextruderoverarangeofmoistureandtemperatureandpredicttheminimumprocessconditionstoachieveatargetreductionofSalmonellabydevelopingandvalidatingasta‐tisticalmodel.

NiharikaMishra,Ph.D.

CenterforFoodSafety&AppliedNutrition(CFSAN)

Preceptor:JohnLarkin,Ph.D.

22

Scienti icandProfessionalBackground2008‐2012 PostdoctoralResearchAssociate,PharmaceuticalSciences,StateUniversity ofNewYorkatBuffalo,NY2006‐2008 VisitingScholar,Urology,TohokuUniversityHospital,Japan2002‐2007 Ph.D.Pathology&Pharmacology,JilinUniversity,China1997‐2002 M.D.Medicine,NormanBethuneCollegeofMedicine,JilinUniversity,ChinaResearchInterests Population‐based,physiologically‐basedpharmacokinetic(PBPK)modeling. Drugmetabolizingenzymes,transportersanddrugdruginteraction. Pharmacokineticsandpharmacodynamicsmodelingandsimulation.Throughmyeducationalandprofessionaltraining,Ihaveacquiredin‐depthknowledgeinpreclinical and clinical pharmacokinetics and pharmacodynamics. My current researchinterests involve the best practice of physiologically based pharmacokinetic models indrugdevelopmentandregulation.Commissioner’sFellowshipProjectOverviewEstablishingAKnowledge‐baseofPhysiologically‐basedPharmacokinetic(PBPK)ModelstoSupportRegulatoryReviewFDA Regulatory Science Priority Area: StimulateInnovationinClinicalEvalua‐tionsandPersonalizedMedicinetoImproveProductDevelopmentandPatientOutcomesPhysiologically‐basedpharmacokinetic(PBPK)modelisaneffectivetoolduringdifferentstages of drug development by facilitating decision making. By integrating drug‐dependentandsystem(physiology)‐dependentinformation,PBPKmodelcanhelpusun‐derstandthe interactionbetweendrugmoleculeandthephysiologicalsystemthrougha“predict‐learn‐con irm” cycle. Recently, drug industries have adopted PBPKmodels tosupporttheirIND/NDAsubmissions.MyprojectistoestablishaPBPKmodelknowledgebasebysummarizingexperiencegainedinrecentreview/researchintheOf iceofClinicalPharmacology. The extensive information accumulated in the knowledge base will im‐proveourunderstandingofphysiologyanddrugbehavior,whichinturncontributessci‐enti ic ield. The established knowledge‐base is expected to have signi icant impact onregulatoryreview.

YuzhuoPan,Ph.D.

CenterforDrugEvaluationandResearch(CDER)Of iceofTranslationalSciencesOf iceofClinicalPharmacology

Preceptor:PingZhao,Ph.D.

23

Scienti icandProfessionalBackground2011‐2012 Scientist,NationalInstituteofEnvironmentalHealthSciences,NationalIn‐

stitutesofHealth,ResearchTrianglePark,NC.2006‐2011 IRTAFellow,NationalInstituteofEnvironmentalHealthSciences,National

InstitutesofHealth,ResearchTrianglePark,NC.2001‐2006 PhDinMolecularCellBiology,WashingtonUniversityinSt.Louis,MO.1997‐2000 BSinGenetics,UniversityofWisconsin‐Madison,WI.ResearchInterestsDr.Revollo’sinterestsinvolvethestudyofgenomicandtranscriptionalchangeselicitedbyenvironmental stimuli. In the recent past—through next generation sequencing tech‐niques—he has studied how nuclear receptors alter the transcriptional landscape(exome)ofcellsandtissues.He isnowapplyingthesetechnologiesanddevelopingnewones to study how toxic compounds affect the exome aswell as the genetic stability ofcells.Commissioner’sFellowshipProjectOverviewCharacterizationoftheTK9Exomeby454NextGenerationSequencingFDA Regulatory Science Priority Area: ModernizeToxicologytoEnhanceProd‐uctSafety Nextgenerationsequencing(NGS)referstoanumberoftechnologiesthathavemadese‐quencingofnucleicacidsfastandaffordable.Whiletheyarecommonlyusedtosequenceentiregenomes,NGScanalsobedirectedtostudyasubsetofgeneticmaterial,suchasex‐omes,ortheareasofthegenomethatencodeproteinsandnon‐codingRNAs.Dr.Revollois employingNGS to ind, catalogue, and characterizemutations createdbyexposure totoxins and localized in the exomes of cell lines commonly used for toxicological assays(e.g., TK6). His indingswould inform regulatory agencies about the reliability of thesecellsfortoxicologicalassaysandestablishanewtechniquetoassesstoxicityinagenome‐widescale.

JavierRevollo,Ph.D.

NationalCenterforToxicologicalResearch(NCTR)

Preceptor:VasilyDobrovolsky,Ph.D.

24

Scienti icandProfessionalBackgroundTheUniversityofArizona:B.S.inBiosystemsEngineering,2002‐2006TheUniversityofTexasatAustin:Ph.D.inBiomedicalEngineering,2006‐2012ResearchInterestsJustina’sresearchinterestsfocusondetectingpathogensusingmolecular‐speci iccontrastagents.Traditionalmethodsofdetectingpathogensinthebodyinvolveusingradioactiveand luorescentlabels,butradioactiveimagingisdose‐limitingand luorescentimagingislimitedinopticalstability.Tomaketheseimagingmethodsmoreef icient,metalnanopar‐ticlescanbeusedasrobustmolecularmarkersbecausetheyarebiocompatibleandopti‐callystable.Justina’sresearchexperiencehasfocusedonusinggoldnanoparticlestode‐tectbothcancerinvivoandviralproteinmarkersexvivo.Commissioner’sFellowshipProjectOverviewRapidDetectionofPathogensusingNanoparticlesfunctionalizedwithAptamers,withReal‐timeAnalysisFDA Regulatory Science Priority Area: FacilitateDevelopmentofMedicalCoun‐termeasurestoProtectAgainstThreatstoU.S.andGlobalHealthandSecurityAmajorchallengeincounteringanoutbreak,whetherfromacontaminatedfoodsupplyorfromabioterrorattack,isalackofamethodtoprovidepopulation‐basedrapiddiagnos‐ticsandreal‐timemonitoring.Onesteptoovercomingthischallengeistouseapoint‐of‐care (POC)device,which is amobiledevice that can rapidlydetectpathogens. CurrentPOCdevices,however,donotallowforreal‐timemonitoring,andtypicallydetectonlyasinglepathogen.Justina’sprojectaimstodetectvirusesandfoodpathogensbydevelopingamultiplexedlateral low‐basedPOCdevicethatwillbeusedwithamobilephoneappli‐cationtoallowforreal‐timeepidemiologyanalysis.

JustinaTam,Ph.D.

Of iceofRegulatoryAffairs(ORA)

Preceptor:CharlesClavet,Ph.D.

25

Scienti icandProfessionalBackground2011 Ph.D.Bioengineering&Biotechnology, EcolePolytechniqueFederaledeLausanne(EPFL)2000 M.S.E.ChemicalEngineering,JohnsHopkinsUniversity1998 B.S.E.BiomedicalEngineeringandB.S.E.ChemicalEngineering, JohnsHopkinsUniversityResearchInterestsDr.Yong’sresearchbackgroundliesinlymphaticbiology,tissueengineering,interstitial luidandtissuemechanics,andsurfacescience.Herdoctoralresearchaimedtocharacterizethelymphaticendothelium,inparticular,itsfunctional‐adaptiveresponsetobiologics(VEGF‐C)andbiophysicalstimuli( luidshearstress)andtherebyelucidatetheactiveroleoflymphaticsintheregulationoftissue luiddrainage,in lammation,andpathophysiologicalconditionssuchasedema. Herworkemployedinvitro3‐Dregenerativemodelsof thetissuespace, incorporating interstitial low,toinvestigategeneregulationinlymphangiogenesisandangiogenesisandtode ineprinciplesforthe(re‐)generationofvascularizedengineered tissue. Shewasalsoactively involved inprojects in‐vestigatingthemechanismsof lymphogenoustumorcellmetastasisandhowthebiophysical tu‐mormicroenvironmentcanin luencethisprocess.Commissioner’sFellowshipProjectOverviewEvaluationofregenerativemedicinedevicesthatproduceabiologicalproductatthepatientpoint‐of‐care:AssessmentofdeviceandoutputcontrolsandenhancementofFDAreviewFDA Regulatory Science Priority Area: EnsureFDAReadinesstoEvaluateInnovativeEmergingTechnologiesDevicesusedatthepatient“point‐of‐care”(POC)toprocessautologousbiologicalmaterialarebe‐comingincreasinglyprevalentinthe ieldofregenerativemedicine.Thesedevicesareaprimeex‐ampleofemergingcell therapy‐basedtechnologiesthatposebothscienti icandregulatorychal‐lenges in ensuring their safe use in the clinical setting. The challenges are in part attributed tocomplexitiesrelatedtoestablishingdevicecontrolswhichmayincludeparametersfordeviceper‐formancetestingandadditionalcharacterizationofthebiologicaloutput,appropriateforagivenintendeduseoftheproduct.Therefore,thismulti‐centerprojectaimstoidentifyandde ineneces‐sarycontrolsfordeviceandcorrespondingbiologicaloutputtoensurethatthequalityoftheout‐putfromsuchPOCdevicesmeetspublichealthandregulatoryneeds.Ananticipatedoutcomeisasetofrecommendationsonscience‐basedapproachestoproductdevelopmentandregulatoryre‐viewforcertainPOCdevicesrelevanttoregenerativecellulartherapies.

CarolynYong,Ph.D.

Multi‐CenterFellowshipinRegenerativeMedicineCenterforBiologicsEvaluationandResearch(CBER)CenterforDevicesandRadiologicalHealth(CDRH)

Preceptors:KennethJ.CavanaughJr.,Ph.D.(CDRH),Charles

Durfor,Ph.D.(CDRH),andStevenS.Oh,Ph.D.(CBER)

26

Scienti icandProfessionalBackground2005‐2010AssistantProfessor,EasternVirginiaMedicalSchool,VA2010Ph.D.ComputationalandAppliedMathematics,OldDominionUniversity,VA2005M.S.ComputationalandAppliedMathematics,OldDominionUniversity,VA2000B.S.Statistics,ShanghaiUniversityofFinanceandEconomics,ChinaResearchInterestsSignalDetection;LikelihoodRatioTest;Bayesianmethods;Bene itRiskassessment.Commissioner’sFellowshipProjectOverviewLikelihoodRatioTest(LRT)forSafetySignalDetectionsinClinicalTrialsFDA Regulatory Science Priority Area: HarnessDiverseDatathroughInfor‐mationSciencestoImproveHealthOutcomes Thelikelihoodratiotest(LRT),recentlydevelopedbyHuang,ZalkikarandTiwari(2011),forsignaldetectionfromlargedrugsafetyobservationaldatabases,suchasAdverseEventReportingSystem(AERS)databaseestablishedbytheU.SFoodandDrugAdministrationis showntocontrolboth the type‐Ierrorand falsediscoverrate (FDR).AnextensionofLRTtoZero‐In latedPoisson(ZIP)modelbasedLRTisalsobeingdevelopedbytheseau‐thors, inordertomodeltheextrazerocountsinthelargedatamatrix.BoththeoriginalLRTandZIPmodelbasedLRTmethodshavebeendevelopedandappliedtoobservationalstudydatabases.ThegoaloftheprojectistodevelopLRTtestsfordetectingthesignalsofAEsinclinicaltrialdataenvironment.

YueqinZhao,Ph.D.

CenterforDrugEvaluationandResearch(CDER)

Preceptor:RamTiwari,Ph.D.

27

FDACommissioner’sFellowshipProgram2012Preceptors

28

Background Ph.D.(1978) DSc(2010) 23yearsemploymentwithFDAResearchInterestsHemoglobin‐basedoxygencarriers(HBOCs)alsoknownas“bloodsubstitutes”arebeingdevelopedtoreducetheneedforredbloodcelltransfusionsinemergencytraumaresusci‐tation,surgeryandseveralotherindications.DespiteconsiderableadvancesinthedesignandmanufactureofHBOCs, safety issuescontinue toslow theprogressof this the ield.Ourlaboratoryhasfocusedonthebiochemicalandphysiologicalbasisofoxidativetoxici‐tiesandhasestablishedadirectlinkbetweentheredox(reduction‐oxidation)activityofHBOCsandtheirsafetypro ilesinvivoandinvivo.Antioxidativeaswellasoxidativeinac‐tivation clearance interventions are being explored as possible protective strategies incontrollingHboxidativesidereactions

AbduI.Alayash,Ph.D.

CenterforBiologicsEvaluationandResearch(CBER)LaboratoryofBiochemistryandVascularBiology

DivisionofHematology

29

BackgroundOverthepast25years,wehaveworkedonregulatingtheproductsofbiotechnology,in‐cludingthe irstrecombinantderivedvaccine,the irstmonoclonalantibodyinman,andpeptidetestkitsforHIV.Inthelab,weareusingmolecularimmunologytoolstounder‐standandenhancetheimmuneresponsetovaccineantigens.Twocurrentapproachestoenhancevaccinepotencyinclude:assemblyofvirus‐likeparticlevaccineswithorwithoutattachedcytokines,andproteinexpressionbyliveattenuatedviralvectors.ResearchInterests1.Virus‐likeparticlevaccinesforHIV,gp120structure,cytokineenhancedvaccines.2.LiveattenuatedviralvectorstodeliverHIVantigens.

IraBerkower,M.D.,Ph.D.

CenterforBiologicsResearchandEvaluation(CBER)LabChief,LabofImmunoregulation

DivisionofViralProducts,Of iceofVaccines

30

BackgroundIi‐LunChenisaClinicallead/SeniorMedicalOf icerworkingwithFDAfor4years.Pedia‐tricianandAssistantClinicalProfessorofPediatricsatGeorgeWashingtonSchoolofMedi‐cine.WendyAaronson isHealth Scientist andDirector of theRegulatory Science InformaticsTeam. Shehas33yrsofFDAexperience. MS inMicrobiology fromUniversityofMary‐land,CollegeParkResearchInterests(IC)Interestedinhealtheffectsofnewtobaccoproductssuchashookahsande‐cigarettes.(WA) Interested in coordinating, developing, and using standard terminology and datastandardstoimprovedataqualityandfacilitateregulatorydecision‐making.

Ii‐LunChen,M.D.CenterforTobaccoProducts(CTP)

Of iceofScience

Workinginconjunctionwith:

WendyAaronsonCenterforTobaccoProducts(CTP)

Of iceofScience

31

Background B.S.Microbiology,UniversityofRhodeIsland M.S.Microbiology,UniversityofRhodeIsland FDAexperience‐20yearsResearchInterestsMyinterestoverthepast20yearshasfocusedonregulatoryissuesinmicrobiologyrelat‐edtoimportantpublichealthconcerns.

CharlesR.Clavet,M.S.

Of iceofRegulatoryAffairs(ORA)

WinchesterEngineeringandAnalyticalCenter(WEAC)Winchester,MA

32

Background 1988M.S.,Biotechnology.MoscowInstituteofPhysicsandTechnology(Russia). 1994Ph.D.,MolecularBiology.ShemyakinInstituteofBioorganicChemistry,Russian

AcademyofSciences(Moscow,Russia). 1994–1998,PostdoctoralFellow,OakRidgeInstituteforScienceandEducation

(ORISE)(OakRidge,TN). FDAexperience15yearsResearchInterestsFindingsolutionstoissuesfacingregulatoryscienceusingthemostadvancedtechnologyandinstrumentation.Developingandimprovingtoolsforassessmentofsafetyandidenti‐icationofpotentialhazards(i.e.,carcinogens)intheproductsregulatedbytheU.S.FDA. Invivoandinvitrogenetictoxicology Geneticengineering Transgenictechnology High‐throughput lowcytometry Regulatoryscience

VasilyN.Dobrovolsky,Ph.D.

DivisionofGeneticandMolecularToxicologyNationalCenterforToxicologicalResearch(NCTR)

33

Background M.S.PoultryScience.1992fromTheUniversityofMarylandResearchInterests:DevelopmentandvalidationofenvironmentaltestingmethodsforthedetectionofL.mon‐ocytogenesandCronobacterinfoodprocessingenvironment

ThomasHammack,M.S.

Chief,MicrobialMethodsDevelopmentBranchDivisionofMicrobiology

Of iceofRegulatoryScienceCenterforFoodSafetyandAppliedNutrition(CFSAN)

34

Background Ph.D. FDAExperience:14YrsResearchInterestsAntimicrobial Resistance in bacteria, gene expression pro iling, and anthrax disease bi‐omarkers

SaeedKhan,Ph.D.

DivisionofMicrobiologyNationalCenterforToxicologicalResearch(NCTR)

35

JohnW.Larkin,Ph.D.

CenterforFoodSafetyandAppliedNutrition(CFSAN)

36

Background M.D./Ph.D.inbiochemistry/pharmacology(RussianStateMedicalUniversityandNa‐

tionalCenterforBioactiveCompounds,Moscow,Russia) 7.5yearswithP izer,Inc(Sr.PrincipalScientist,HeadofMRI) 2.5yearswithFDA(DirectorofBio‐Imaging)MentorshipExperience:3summerstudents,1graduatestudent,3postdoctoralfellows.ResearchInterests UtilizationofMagneticResonanceImagingandSpectroscopy(MRI/MRS)inpreclinical

studydesign. Imagingbiomarkersofneurotoxicity Translationalbiomarkersofaddiction NovelMRI/MRSdataacquisitionandanalysis

SergueiLiachenko,M.D.,Ph.D.

BioImagingLab/DivisionofNeurotoxicologyNationalCenterforToxicologicalResearch(NCTR)

37

Background Ph.D.,Microbiology,UniversityofTexas,1993 NationalCenterforMolecularImaging,BaylorCollegeofMedicine,Houston,TX(1994‐

2004) AssistantProfessorandDirectorHighResolutionCryo‐ElectronMicroscopyFacility,

DepartmentofPathology&LaboratoryMedicine,UniversityofTexasHealthSciencesCenter,Houston,TX(2005‐2011)

DirectorofElectronMicroscopyGroup,NCTR(2011‐present)ResearchInterestsNanotechnologyinvolvesthestudyandmanipulationofcertainnano‐scaledmaterials(~1‐100nm)foruseinmanufacturedproducts.Someoftheseproductsincludepharmaceuti‐calsandmedicaldevices,andfromtheFDApointofview,thepotentialadverseeffectofthesematerials on human health is very important. For instance,many nanomaterialssuchasnano‐silver,nano‐gold,andnano‐ironarebeingdevelopedasdrugdelivery/organtargeting systems. My research goal is to use electronmicroscopy (EM) and computeraided3Dimagereconstructiontoinvestigatethestructuralbasisofhumancellularinter‐actionwithnanomaterials. Asnanomaterials are introduced into amammalian system,knowledgeof theuptake,distribution,anddispositionof thenanomaterial is critical forunderstandingpotentialbene itandrisk.Wewillbeusingastate‐of‐the‐artFEGScanningElectronMicroscope(SEM)withanovelnewauto‐ultramicrotomeserialsectioningdevice(Gatan 3Veiw2) to look at the 3D structure of cells and organelles treated with nano‐materials. Inparticular,weareinterestedinthedistributionofnanomaterialwithintheanimalmodelandtheeffectsthesematerialshaveatthecellularandorganlevel.

AngelM.Paredes,Ph.D.

DirectorofElectronMicroscopyGroup,NCTR/ORANano‐technologyCoreFacility

Of iceofScienti icCoordinationNationalCenterforToxicologicalResearch(NCTR)

38

BackgroundDr. Rorer ensures consistency of clinical reviews of ophthalmic devices across twobranchesoftheDivisionandhelpsresolvecomplexanddif icultissuesinvolvingophthal‐micdevicesubmissions.Dr.RorerhasextensiveexperienceinophthalmicdevicereviewandisrecognizedbytheCenterforherexpertiseasaclinicalreviewer.

EvaRorer,M.D.

ChiefOphthalmicMedicalOf icerDivisionofOphthalmic,NeurologicalandENTDevices

Of iceofDeviceEvaluation(ODE)CenterforDevicesandRadiologicalHealth(CDRH)

39

Background Ph.D.‐Epidemiology, M.P.H.‐Epidemiology 17yearsofFDAemploymentResearchInterests Improvingcharacterizationofadverseeventsreportedbypassivesurveillance, Improvingattributionmethodsforassociatingillnesswithspeci icfoods, Chronicdiseaseepidemiology

DebraStreet,Ph.D.,M.P.H.

Chief,EmergencyResponse&SurveillanceBranchDivisionofPublicHealthandBiostatistics

CenterforFoodSafetyandAppliedNutrition(CFSAN)

40

Background M.S.&Ph.D.(MathematicalStatistics),FloridaStateUniversity Fellow,AmericanStatisticalAssociation Member,InternationalStatisticalInstitute PreviousEmployment:MathematicalStatisticianandProgramDirector,Surveillance Researchprogram,NCI/NIH(2000‐2008); Professor&Chairman,DepartmentofMathematics,UniversityofNorthCarolina,Char‐

lotte,NC(1994‐2000); Asst./Assoc./Professor,DepartmentofMathematics,UniversityofNorthCarolina,

Charlotte,NC(1986‐1994); Asst.Professor,IndianInstituteofTechnology,Bombay(2002‐2006);VisitingLectur‐

er,UCSantaBarbara(1981‐1982,1985‐1986).ResearchInterestsDevelopment of statisticalmethods for i) clinical trials; and ii) signal detection in drugsafetysurveillance.

RamC.Tiwari,Ph.D.

AssociateDirector,Of iceofBiostatistics

CenterforDrugEvaluationandResearch(CDER)

41

Background 1975,B.S.Biology,magnacumlaude,ChemistryMinorNorthernIllinoisUniversity,

DeKalb, 1980,M.S.Biology,IllinoisInstituteofTechnology,Chicago,IL. 1992,Ph.D.Microbiology,UniversityofSouthernCalifornia,LosAngeles,CA. 1992‐1995,Post‐doctoralFellowDepartmentofHumanOncology,UniversityofWis‐

consin,Madison,WI. FDAEmployee:12/31/2000ResearchInterestsProjectscenterondevelopmentofmolecularmethodstodetectpathogensinfoods:1. Detectionofhighriskpathogens(selectagents) includingBacillusanthracis,YersiniapestisandFrancisellatularensisusingBSL‐3safetyprocedures;2. Assessingemerging technologies for therapiddetectionofbacterialandviralpatho‐gens3..Improvingcurrentculturalenrichmenttechniquestoenhancethedetectionoftar‐getbacterialpathogensinfoods.

DonnaWilliams‐Hill,Ph.D.

Of iceofRegulatoryAffairs(ORA)Paci icRegionalLaboratorySouthwest

42

Background Ph.D.inBiopharmaceuticalSciences,UniversityofCalifornia,SanFrancisco PharmaceuticalIndustryExperience–4years FDAExperience–11yearsResearchInterestsMy research interests include role of transporters in drug interactions, phar‐macogenomicsofmetabolizingenzymesandtransporters,interplayofdrugmetabolizingenzymesand transporters, effectof renalorhepatic impairmentonenzymesand trans‐porters,andpharmacokinetics/pharmacodynamics.Membrane transporters represent ~15% of the human genome of approximately 30Kgenes.Thesetransportersareexpressedinmanytissuessuchastheintestine, liver,kid‐neyandbrain,andplaykeyrolesindrugabsorption,distributionandexcretion.Assuch,transporterscanaffect thepharmacokineticsandpharmacodynamicsofadrugwhetheractingaloneor inconcertwithdrugmetabolizingenzymes. Increasingnumberofexam‐ples in the literature and regulatory reviews have demonstrated that drug interactionsand polymorphisms involving transporters can affect safety or ef icacy of therapeutics,e.g., organic cation transporting polypeptides (OATPs) and cholesterol lowering statindrugs.Transportersrepresentanemergingareaforregulatoryresearch.IleadaTrans‐porter Scienti ic Interest Group (SIG) in the Of ice of Clinical Pharmacology/Of ice ofTranslationalSciencestoconductregulatoryresearchprojectsinthetransporterareaandwehavegenerateddatatosupportregulatoryguidancedevelopment,e.g.,FDA’srecentlypublished draft drug interaction guidance (http://www.fda.gov/downloads/Drugs/GuidanceComplianceRegulatoryInformation/Guidances/UCM292362.pdf, February2012).

LeiZhang,Ph.D.

SpecialAssistanttoOf iceDirectorImmediateOf ice

Of iceofClinicalPharmacology(OCP)Of iceofTranslationalSciences(OTS)

CenterforDrugEvaluationandResearch(CDER)

43

Background Ph.D.–DrugMetabolismandPharmacokinetics Pharmaceuticalindustryexperience–6years FDAExperience–3.5yearsResearchInterestsUse of population‐based, physiologically‐based pharmacokinetic (PBPK) modeling andsimulationstofacilitateregulatoryreviewofclinicalpharmacologyissues.

PingZhao,Ph.D.

Of iceofClinicalPharmacology(OCP)Of iceofTranslationalSciences(OTS)

CenterforDrugEvaluationandResearch(CDER)

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Background BachelorofChemicalEngineeringwithMinorsinChemistryandBiology,Villanova

University Ph.D.inBioengineering,UniversityofPennsylvania FDAexperience–8yearsResearchInterestsDr.CavanaughistheChiefofthePeripheralVascularDevicesBranch(PVDB),DivisionofCardiovascularDevices(DCD),Of iceofDeviceEvaluation(ODE),CenterforDevicesandRadiologicalHealth(CDRH),apositionhehasheldsince2008. PVDB isresponsible forthepre‐marketreviewofallcardiovasculardevicesusedoutsidetheheartandbrain,in‐cluding vascular stents, vascular and endovascular grafts, inferior vena cava ilters, andangioplastycatheters.Manyofthesedevicesincorporatebiologiccomponents(e.g.vascu‐largraftsinvolvingproteincoatingsororiginatingfromanimaltissue)orarecombinationproducts involving substantial device and drug components (e.g. drug‐eluting stents ordrug‐coatedangioplastyballoons).From2003to2008,Dr.Cavanaughwasabiomedicalengineerandscienti icreviewerinPVDB, focusingon the reviewof carotid and renal artery stents andembolicprotectiondevices,combinationproducts,anddeliverysystemsforcellandgenetherapies.Heholdsabachelor'sdegreeinchemicalengineeringwithminorsinbiologyandchemistry,andaPh.D.inbioengineering.Hisdissertationalresearchfocusedonlunginjurymechanics.

KennethJ.CavanaughJr.,Ph.D.

CenterforDevicesandRadiologicalHealth(CDRH)Of iceofDeviceEvaluation(ODE)DivisionofCardiovascularDevices

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Background B.S.(Chemistry)CollegeofWilliamandMary Ph.D.(BioorganicChemistry)UniversityofVirginia

ResearchInterestsDr.DurforisanexpertregulatoryreviewerinthePlasticandReconstructiveSurgeryDe‐vicesBranch (PRSB),DivisionofSurgical,OrthopedicandRestorativeDevices (DSORD),Of ice of Device Evaluation (ODE), Center for Devices and Radiological Health (CDRH).Dr.Durforhas served in thePlastic andReconstructiveSurgeryDevicesBranchofODEsinceJune26,1994.Previously,hewasemployed,(sinceNovember8,1988),bytheCen‐ter for Biologics Evaluation and Research (CBER) and the National Institutes of Health(NIH)withinthePublicHealthService(PHS).Hewasalsotheleadreviewerforthe irstcellulardeviceproductstoreceivePMA(Apligraf)andHDE(OrCel)approvals.PRSB reviews 510(k)s, IDEs, HDEs and PMAs seeking approval for devices for: woundhealing(e.g.,acuteburnwoundsandchroniculcers)andsofttissuerepair(e.g.,facial,per‐itonealandlungtissues)aswellasseveralbiologicalanddrugproductscontainingdevicematerialsthroughInterCenterconsults.Manyofthesedevicescontaincomponentscom‐posedofphysiologicalmaterials(e.g.,cells,proteinsandpolysaccharides)orbiosynthetic(e.g.,insitucrosslinkingorpolymerizing)materials.Dr.Durfor'sexperienceincludesreg‐ulationofmammaliancellcultureproductsandinsitupolymerizingmedicaldevices,re‐search on protein structure/function, and considerable exposure to clinical trial designissues(e.g.,from200‐2001heservedastheChairmanoftheInterCenterClinicalWoundHealingGroup).HeiscurrentlytheCDRHexperton“thechemistryandmanufacturingofbiosynthetic,cellularandtissue‐derivedmedicaldevicesforsofttissuerepair.”

CharlesN.Durfor,Ph.D.

ExpertReviewerDivisionofSurgical,OrthopedicandRestorativeDevices

Of iceofDeviceEvaluation(ODE)CenterforDevicesandRadiologicalHealth(CDRH)

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Background Ph.D.,UniversityofMichigan PostdoctoralFellowship,JohnsHopkinsUniversitySchoolofMedicineandMassachu‐

settsInstituteofTechnology Faculty,TuftsUniversitySchoolofMedicine FDAExperience–Since2007ResearchInterestsDr. Oh serves as Team Lead for device evaluation in the Division of Cellular and GeneTherapies. His areas of regulatory expertise include device‐biologic combination prod‐ucts, tissue engineered products, andmedical deviceswith regenerative or therapeuticindications.Heprovidesleadershipinreachingvariousregulatorydecisionsonproductssubmittedformarketing,clinical investigation,orclassi ication. Healsoactivelypartici‐patesinpolicydevelopmentandstafftrainingforthesecombinationproductsaswellasdevicesthatproducebiologicastheoutput.Dr.OhspentsometimeinCDRHservingasavisitingreviewscientistfromCBER. ThisuniqueexperiencehasbeencrucialtoDr.Oh’sunderstandingandappreciationofbalancedapproachestobiologicanddeviceregulation.UponreturningtoCBERfromCDRH,Dr.OhhasfoundedDeviceBiologicsInterestGroup(DBIG)in2008providingaforumtoregulatorystaffinCBERandCDRHtolearnandex‐changeideasaboutregulations,policies,standards,technologies,andreviewpracticesap‐plicabletodevicesanddevice‐biologiccombinationproducts. Hecontinuesintheefforttoharmonizescienti icreviewpracticesandstandardsforcombinationproductsandde‐vicesregulatedbyCBERandCDRH.

StevenS.Oh,Ph.D.

TeamLead,DeviceandCombinationProductDivisionofCellularandGeneTherapies

Of iceofCellular,TissueandGeneTherapiesCenterforBiologicsEvaluationandResearch(CBER)