2nd Excipient Workshop: Focus on Excipient Quality, Compendial Testing, and Regulatory Impact November 17-18, 2015 USP Meetings Center, Rockville, Maryland USA

2nd Excipient Workshop: Focus on Excipient Quality, Compendial Testing, and Regulatory Impact

November 17-18, 2015 USP Meetings Center, Rockville, MD USA

Preliminary Agenda (Updated November 15, 2015)

DAY ONE: Tuesday, November 17, 2015 8:00 – 8:30 a.m. Registration and Coffee 8:30 – 8:45 a.m. Welcome and Introductions SESSION I Strategy to Bring USP-NF Excipient Monograph Specifications Up to Date Moderator: Jeffrey Medwid, Ph.D., Government Liaison, USP Excipient Monographs 2 Expert Committee 8:45 – 9:15 a.m. Keynote Presentation

Joseph Kushner, IV, Ph.D., Pfizer Inc. Industry Perspective

9:15 – 9:45 a.m. Presentation 1: FDA /OPQ IID Issues and Potential Resolutions Katherine Ulman, DOW Corning

USP Perspective 9:45 – 10:10 a.m. Presentation 2: Challenges and Opportunities in Excipient Monograph

Development and Update Kate Houck, Ph.D., Chair, USP Excipient Monographs 2 Expert Committee

10:10 – 10:40 a.m. Break

Regulatory Perspective

10:40 – 11: 10 a.m. Presentation 3: FDA CDER Inactive Ingredient Database: Goals and Progress Susan Zuk, U.S. Food and Drug Administration (FDA)

Academic Perspective 11:10 – 11:40 p.m. Presentation 4: Global Excipient Databases – NIPTE Overview Stephen Hoag, Ph.D., Member, General Chapters Physical Analysis Expert

Committee. University of Maryland, School of Pharmacy 11:40 – 11:45 a.m. PQRI Survey Results on Excipient Variability (poster presentation) Lawrence H. Block, Ph.D., Vice-Chair, USP Excipient Monographs 2 and General Chapters Physical Analysis Expert Committees 11:45 – 12:00 p.m. Q & A (15 min) 12:00 – 1:00 p.m. Networking Lunch

 

2nd Excipient Workshop: Focus on Excipient Quality, Compendial Testing, and Regulatory Impact November 17-18, 2015 USP Meetings Center, Rockville, Maryland USA

SESSION II Challenges and Opportunities in Excipient Monograph Development and Update Moderators: Hong Wang, Ph.D., USP Senior Scientific Liaison, Excipients / Kevin Moore, Ph.D., USP Manager, Pharmacopeial Harmonization Topic 1: USP Up-to-Date for USP-NF monographs Regulatory Perspective 1:00 – 1:30 p.m. Presentation 5 (FDA): FDA Perspective on Excipient Monograph Up-to-Date

Steven Wolfgang, Ph.D., Government Liaison, USP Excipient Monographs 1 Expert Committee

USP Perspective

1:30 – 2:00 p.m. Presentation 6: What Does USP-NF Up-To-Date Mean for Excipients? R. Chris Moreton, Ph.D., Vice-Chair, USP Excipient Monographs 1 Expert

Committee

Industry Perspective 2:00 – 2:30 p.m. Presentation 7: Challenges and Opportunities in Development of Novel

Excipients and Monographs in USP Shaukat Ali, Ph.D., BASF

2:30 – 3:00 p.m. Break Topic 2: Global Harmonization Activities for Excipients 3:00 – 3:30 p.m. Presentation 8: USP Update on Pharmacopeial Harmonization Activities Lawrence H. Block, Ph.D., Vice-Chair, USP Excipient Monographs 2 and General Chapters Physical Analysis Expert Committees (USP)

3:30 – 4:00 p.m. Presentation 9: Pharmacopoeial Discussion Group (PDG) Update on Harmonization Activities – Japanese Pharmacopoeia (JP)

Hiroshi Tokunaga, Ph.D. (PMDA)

4:00 – 4:30 p.m. Presentation 10: EP Update on Harmonization Activities – European Pharmacopeia

Professor Anne Gayot (EDQM) 4:30 – 5:00 p.m. Roundtable Discussion / Q & A (30 min) – Challenges and Opportunities for

Harmonization, Update and Development of Excipient Specifications Moderator: Jiasheng Tu, Ph.D.

5:00 p.m. Adjourn

 

2nd Excipient Workshop: Focus on Excipient Quality, Compendial Testing, and Regulatory Impact November 17-18, 2015 USP Meetings Center, Rockville, Maryland USA

DAY TWO: Wednesday, November 18, 2015 8:00 – 8:30 a.m. Registration and Coffee SESSION III Challenges and Opportunities in Development and Update of Excipient Monographs Used for Biologics Drug Applications Moderator: R. Chris Moreton, Ph.D., Vice Chair, USP Excipient Monographs 1 Expert Committee / Catherine Sheehan, MS., MS., USP Senior Director, Excipients 8:30 – 9:00 a.m. Keynote Presentation: Integrity of Supply – Shifting Paradigms Marla Phillips, Ph.D., Xavier Health

USP Perspective

9:00 – 9:30 a.m. Presentation 1: Understanding USP’s Role with Excipients Used in Biologics: Identifying Gaps in Current Excipient Monographs and Developing Monographs for Missing Excipients

Thiago C Carvalho, Ph.D., Member, USP Excipient Monographs 1 Expert Committee

Regulatory Perspective

9:30 – 10:00 a.m. Presentation 2 (FDA): FDA Review of Excipient Submissions in BLA Laurie Graham, U.S. FDA

10:00 – 10:30 a.m. Break 10:30 – 11:00 a.m. Presentation 3 (FDA): The Scientific and Regulatory Basis for the Management

of Excipient Data During the Review of Biotechnology-Derived Drugs Ashutosh Rao, Ph.D., U.S. Food and Drug Administration (FDA)

11:00 – 11:30 a.m. Q &A (30 min)

Industry Perspective

11:30 – 12:00 p.m. Presentation 4: Ensuring an Excipient is Suitable for its Intended End Use; An Excipient Manufacturer’s Perspective Dora Meissner, M.S., BioSpectra

12:00 – 1:00 p.m. Networking Lunch

Industry Perspective (Cont’d.) 1:00 – 1:30 p.m. Presentation 5: Drug Product Manufacturer’s Perspective on the Use of

Pharmaceutical Excipients in Biologics Finished Final Product / Formulation; Focusing on the Characterization of Surfactants Y. John Wang, PhD., Genentech

1:30 – 2:00 p.m. Presentation 6: Impact of Raw Material Variability for Upstream Processes to Drug Substance Performance Attributes Colleen Alexander, Ph.D., BMS

 

2nd Excipient Workshop: Focus on Excipient Quality, Compendial Testing, and Regulatory Impact November 17-18, 2015 USP Meetings Center, Rockville, Maryland USA

2:00 – 3:30 p.m. Parallel Breakout Sessions: Rationalization of Terminology used in the

manufacturing of Biologics, including Drug Substance (upstream/downstream processing) and Drug Product (final formulations) aspects. To discuss / understand when compendial grade materials are necessary in the manufacture of Biologics. Parallel breakout sessions will explore and report back on learnings relating to the use of the current terminology and provide recommendations / path forward. Moderator: Jiasheng Tu, Ph.D.

3:30 – 4:00 p.m. Break Closing Summary 4:00 – 4:15 p.m. Session I 4:15 – 4:30 p.m. Session II 4:30 – 4:45 p.m. Session III 4:45 p.m. Workshop Concludes

2ndExcipientWorkshop:FocusonExcipientQuality,

CompendialTesting,andRegulatoryImpact

SpeakerandModeratorInformation(alphaorder)

U . S . P H A R M A C O P E I A L C O N V E N T I O N

ColleenM.Alexander,Ph.D.ScientistBristol‐MyersSquibbEastSyracuse,NY,USAColleenAlexanderisaScientistintheMaterialSciencegroupwithinManufacturingSciencesandTechnology(MS&T)atBristol‐MyersSquibb(BMS)inEastSyracuse,NY.ColleenfocusesprimarilyontheRawMaterialssub‐functionwithinMaterialScience.Inthisrole,sheprovidesrawmaterialssupporttobiologicsdrugsubstancemanufacturing,aswellassupportintheauthoringofregulatoryfilingsandinternaldocuments.ColleenjoinedBMSin2014andhasmostrecentlyworkedasaPostdoctoralResearchAssociateintheChemistryDepartmentattheUniversityofMassachusettsatAmherst.ColleenholdsaPh.D.inChemistryfromSyracuseUniversity,aB.S.inBiochemistryfromStateUniversityofNYatOswego,andaB.A.inPsychologyfromMcGillUniversity.

PresentationAbstractPresentation6:ImpactofRawMaterialVariabilityforUpstreamProcessestoDrugSubstancePerformanceAttributesWednesday,November18,2015,1:30–2:00p.m.Theimpactofrawmaterialvariabilityontheupstreammanufacturingofabiologicsdrugsubstance(DS)processisdiscussedinthispresentation.Rawmaterialvariabilityisexploredwithin‐lot,lot‐to‐lot,andasafunctionoftime.TheimpacttoDSmanufacturingismeasuredforrelevantparameters,includingseveralprocessperformanceattributes(PAs).Inthefirststudy,metalswerequantifiedusingICP‐MSinupstreamrawmaterials,demonstratingbothwithin‐lotandlot‐to‐lotvariabilityofcoppercontent.Tofurtherexploretheimpactofcoppercontentvariability,apilotscaleupstreammanufacturingstudythatincluded7xand20xcoppersupplementationrelativetothecoppercontentofthecontrolconditionwascompleted.Viablecelldensity(VCD)ofthecellculturewasenhanced1.4foldand1.9‐foldrelativetothecontrolforthe7xand20xcopperconditions,respectively.Percentviabilitywasenhancedforbothhighcopperconditions.Thepercentviabilityremained>80%forbothhighcopperconditionscomparedto<40%forthecontrol.Titerwasalsoenhancedsignificantlyforbothhighcopperconditions.Furthermore,titerforthe7xcopperconditionwascomparabletomanufacturingscaledatawhichutilizedahighcopperrawmateriallot.Inaseparatestudy,vitaminsandaminoacidswerequantifiedincellculturemediausingHPLC‐MS.Variabilityofselectvitaminsandaminoacidswasdemonstratedasafunctionofmediaage.Forexample,folicacidconcentrationdeclinedoverthe12monthmediashelflife,ultimatelyreaching<12%ofitstheoreticalconcentration.Inasmallscalefollowupstudy,mediaageandfolicacidcontentwereevaluatedfortheirresponsetowardspecificPAs:VCD,percentviability,titer,and

2ndUSPExcipientWorkshop:FocusonExcipientQuality,CompendialTesting,andRegulatoryImpactNovember17‐18,2015,USPMeetingsCenter,Rockville,Maryland,USA

glycosylation.Atsmallscale,newermedia(1month)increasedVCD,percentviability,titer,andglycosylationrelativetooldmedia(11months).Increasedfolicacidcontent(folicacidspikedintooldmedia)increasedglycosylationrelativetocontrol(agedmedia).Manufacturingscaledatawasconsistentwiththesmallscalestudy,anddemonstrateda>15%increaseintiterusingnewmediacomparedtoagedmedia.Inanotherretrospectiveanalysisofmanufacturingdata,theimpactofmediaageandcomponentvariabilitywasexploredforadifferentcellculturemedium.Lot‐to‐lotvariabilityofasinglemediacomponentwasidentifiedandwasfoundtocorrelatewithreducedtiter.Mediaageat≥6monthscorrelatedwithreducedtiter.Theresultsfromthesestudiesenhancetheknowledgeofhowrawmaterialsimpactmanufacturingandareusefulforidentifyingstrategicmaterial‐relatedchangestosupportprocessimprovements.

2ndUSPExcipientWorkshop:FocusonExcipientQuality,CompendialTesting,andRegulatoryImpactNovember17‐18,2015,USPMeetingsCenter,Rockville,Maryland,USA

ShaukatAli,Ph.D.TechnicalSupportManagerBASFCorporationFlorhamPark,NJ,USAShaukatAlihasover21yearsofexperienceinthepharmaceuticalindustriesincluding11yearsatBASF,wherehesupportssolubilization,instantandmodifiedreleaseplatforms,andAPIs.Dr.Ali’sareasofexpertiseincludesoliddispersions,liposomedrugdelivery,controlledrelease,transdermal,andfilmdevelopmenttechnologies.Dr.Aliisamemberoftheeditorialadvisoryboardsof,AmericanPharmaceuticalreviews,BiopharmaAsia,ContractPharma,DrugDelivery&Development,InternationalJournalofPharmaceuticalInvestigation,JournalofPharmaceuticalSciencesandPharmacology,andJournalofAnalytical&PharmaceuticalResearch.HeisalsoamemberofUSPpanelofexpertsforGeneralChapters‐PhysicalAnalysis.HereceivedhisPh.D.inChemistryfromtheCityUniversityofNewYorkandpursuedhispostdoctoraltrainingattheUniversityofMinnesotaandCornellUniversity.Hehasauthoredover37scientificarticlesandistheinventorin14USpatents.

PresentationAbstractChallengesandOpportunitiesinDevelopmentofNovelExcipientsandMonographsinUSPTuesday,November17,2015,2:00–2:30p.m.Compendialrequirementsofnovelexcipientsandtheir“firsttouse”informulationhavebeensubjectofcontinuedinterestbyboththeexcipientanddrugmanufacturers.Suchchallengeshavebeenunderestimated,andthusfindingthecommonsolutionsatbothsides,stemmingfromexcipient’ssafetyoracceptancebytheindustry,havebeenunsettled.CoupledwithregulatoryandFDArequirements,thoseissuesfurtherdiscouragedinnovationbyexcipientmanufacturers,whichinturnhassloweddowntheindustryinaddressingthechallengeseitherwithcontinuedsurgeinnumberofpoorlysolublecompounds,inareasoftaste‐maskingofbitterAPIsorfindingtheappropriateexcipientsforimprovingtheperformanceofadesireddosage.Notably,thesechallengesmaynotbeaddressedwiththestandardexcipientsandtherefore,thepharmaindustrywillcontinuetodependuponthenovelexcipientsthatmeetdesiredsafetyandperformance,andtechnologicaladaptablefordevelopingbetterandsmartermedicinesfortomorrow.Thatwillinevitablychallengetheregulatoryagencies.BASFcontinuestotakeasteeperpathandinnovatenewexcipients,knowingthattheapprovalofdrugswithnovelexcipientswilltakemuchlongerthanthosedevelopedwiththestandardexcipients.Itischallengingbutimportanttoaddresstheindustry’sneedswheremostdesirable.Soluplus®andKollicoat®Smartseal

2ndUSPExcipientWorkshop:FocusonExcipientQuality,CompendialTesting,andRegulatoryImpactNovember17‐18,2015,USPMeetingsCenter,Rockville,Maryland,USA

weredevelopedtomeetexactlythoseneedsinaddressingsolubilityandbioavailabilitychallengesanddesigningbetterdosageswithtastemaskedAPI’s,respectively.Bothhaveyetnotbeenapprovedindrugproducts.ThispresentationwillfocusontechnicalunderstandingofselectedinnovativeexcipientsandtheirperformancesinthedesiredformulationdosagesThechallengesindevelopmentofdosagewithnon‐compendialexcipientssuchasSoluplus®andKollicoat®Smartseal,andtheiracceptancenotonlybytheindustrybutalsobyregulatoryagencies,willbediscussedwithcommoninterestsandhowtoembracethenovelexcipientsindrugproductswithoutbeinglistedinFDA’sinactiveingredientdatabase.ThepresentationwillhighlightchallengesandopportunitieswithdevelopingNFmonographsinUSP.

2ndUSPExcipientWorkshop:FocusonExcipientQuality,CompendialTesting,andRegulatoryImpactNovember17‐18,2015,USPMeetingsCenter,Rockville,Maryland,USA

LawrenceH.Block,Ph.D.USPAffiliation:Vice‐Chair,USPExcipientMonographs2andGeneralChaptersPhysicalAnalysisExpertCommitteesProfessor Emeritus of Pharmaceutics DuquesneUniversity Pittsburgh,PA,USALawrenceH.Block,Ph.D.,isProfessorEmeritusofPharmaceuticsattheMylanSchoolofPharmacyandGraduateSchoolofPharmaceuticalSciencesatDuquesneUniversity.Dr.BlockwaseducatedattheUniversityofMarylandwhereheearnedhisB.S.inPharmacy,M.S.,andPh.D.degrees.Dr.BlockisaFellowofboththeAmericanAssociationofPharmaceuticalScientists(AAPS)andtheAmericanPharmacistsAssociation‐AcademyforPharmaceuticalResearchandScience(APhA‐APRS).HeisamemberofAAPS,APhA‐APRS,theControlledReleaseSociety,theNewYorkAcademyofSciences,andtheSocietyofRheology.Dr.BlockisaPastChairofboththeTeachersofPharmaceuticsSectionoftheAmericanAssociationofCollegesofPharmacyandtheBasicPharmaceuticalSciencesSectionoftheAPhA‐APRS.HecurrentlyservesasCo‐ChairoftheExcipientMonographs2ExpertCommitteeoftheUSPandisalsoamemberoftheUSPGeneralChapters‐PhysicalAnalysis(GC‐PA)ExpertCommittee.Inaddition,Dr.BlockservesasChairoftheRheologySubcommitteeoftheGC‐PA.Arecipientin2000oftheDuquesneUniversityPresident'sAwardforExcellenceinScholarship,Dr.Blockhasauthoredmorethan100publicationsandmentoredmorethan70post‐baccalaureatePharm.D.,M.S.,andPh.D.researchstudentsinthecourseofhisprofessionalcareer.Hisresearchinterestsembraceexcipienttechnology,rheology,drugandcosmeticdeliverysystems,pharmaceuticalengineering,biopharmaceutics,andpharmacokinetics.HehasservedasaVisitingScholaratKobeGakuinUniversityinKobe,JapanandVisitingProfessorofPharmaceuticalSciencesattheCenterforPharmacogeneticsattheUniversityofPittsburghSchoolofPharmacy.SteeringCommitteeMemberPresentationAbstractPQRISurveyResultsonExcipientVariability(posterpresentation)Tuesday,November17,2015,11:40–11:45a.m.Excipientvariabilityhaslongbeenatopicofconcernamongpharmaceuticalmanufacturersandformulators.But,liketheweather,"…everybodytalksaboutit,butnobodydoesanythingaboutit".Butisexcipientvariabilityinevitableandirremediable?Toexploreandunderstandexcipientvariabilitybetter,PQRIrecentlyinitiatedasurveyofthepharmaceuticalindustryintendedtoassesstheextentoftheproblemanditsimpactonpharmaceuticalmanufacturingandproductperformance.Althoughsurveyparticipationwasmorelimitedthanhadbeenhopedfor(n=49),theresultscorroboratetheexpectationsofmanyexcipient

2ndUSPExcipientWorkshop:FocusonExcipientQuality,CompendialTesting,andRegulatoryImpactNovember17‐18,2015,USPMeetingsCenter,Rockville,Maryland,USA

experts:Excipientvariabilityissuesonacommercialscalehavebeenexperiencedbymanyexcipientusers:Inmanyinstancestherewasaneedtoreformulateorreengineertheaffectedproduct(s).AnextensivereviewoftheliteratureonexcipientvariabilitywillbethesubjectofaforthcomingPQRIpublication.Subsequently,aPQRIworkshoporwebinarwillprovideforumsforfurtherdiscussionandexplorationofexcipientvariabilityanditsramifications.Ultimately,theseactivitieswillfacilitatetheprovisionofrecommendationsforbestpracticesforthepharmaceuticalindustry,pharmaceuticalexcipientmanufacturers,andregulatoryauthorities.Presentation8:USPUpdateonPharmacopeialHarmonizationActivitiesTuesday,November17,2015,3:00–3:30p.m.ThistalkwillprovideanoverviewofthecurrentofinternationalharmonizationfromaUSPperspective.Globalharmonizationofpharmacopeialspecificationsofexcipientshasbeenagoalofpharmacopeias,inresponsetorequestsfromindustrytoeliminateredundanttestingacrossmultipleregions.TheseeffortsbeganwiththePharmacopeialDiscussionGroup(PDG),whichworkonharmonizingselectedstandardsforgeneralchaptersandexcipientmonographswiththeUSP,EuropeanPharmacopeia,andJapanesePharmacopeia.USP'scurrenteffortstothisendareexemplifiedinthispresentationnotonlybytheformalPDGprocessbutalsobycollaborationsthroughWHOonthedevelopmentoftheGoodPharmacopeialPractices(GPhP),aswellasadditionalinformalprospectiveharmonizationactivitieswithotherpharmacopieas

2ndUSPExcipientWorkshop:FocusonExcipientQuality,CompendialTesting,andRegulatoryImpactNovember17‐18,2015,USPMeetingsCenter,Rockville,Maryland,USA

ThiagoCarvalho,Ph.D.USPAffiliation:Member,USPExcipientMonographs1ExpertCommitteeResearchInvestigatorBristol‐MyersSquibbNewBrunswick,NJ,USAThiagoCarvalho,Ph.D.,iscurrentlyaResearchInvestigatorinDrugProductScience&TechnologyatBristol‐MyersSquibb.Hehasover6yearsofexperienceinthepharmaceuticalindustry,workingwithdevelopment,techtransferandmanufacturingofproteintherapeuticsaswellasinthedrugproductdevelopmentofsmallmolecules.HeholdsaB.Pharm.DegreefromFederalUniversityofMinasGerais,Brazil,andaPh.D.degreeinPharmaceuticsfromtheUniversityofTexasatAustin.Dr.Carvalhohaspublishedseveralpeer‐reviewedmanuscriptsandorganizedmultiplescientificsymposiaandwebinars.Heisthe2015PastChairoftheAAPSExcipientsFocusGroupandcurrentlyservesatthe2015‐2020USPExcipientMonographsExpertCommittee.SteeringCommitteeMemberPresentationAbstractPresentation1:UnderstandingUSP’sRolewithExcipientsUsedinBiologics:IdentifyingGapsinCurrentExcipientMonographsandDevelopingMonographsforMissingExcipientsWednesday,November18,2015,9:00–9:30a.m.Forthe2015‐2020USPCouncilofExpertsrevisioncycle,theUSPisinvestingtobringtheUSP‐NFUptoDate.Aspartofthiseffort,theUSP‐NFmonographswillberevisedtobecurrent,relevantandsuitablefortheirintendeduse.ThegreatmajorityofBiologicsproductsaredeliveredviainjectionandthusrequirebioburdenandendotoxincontrolswithappropriateacceptancelimits.MonographsforexcipientsusedinBiologicsformulationsshouldthuscomplywithrequirementsforparenteralproducts.Currently,therearemonographsforexcipientsusedinparenteralformulationswithconsiderablegaps.Someexamplesformonographsrequiringmodernizationare:inconsistencieswithregardstobioburdenandendotoxinlimits;existingexcipientsbeingrecentlyusedininjectabledosageforms;obsoletetechnologiestodetectimpurities;andneedtoaddtestsfornewlyfoundimpuritiesthatmayaffectdataanalysisand/orproductquality.Inaddition,someexcipientsusedinBiologicsformulationsaremissingmonographs.Theobjectiveofthistalkistobringsomeofthesegapstolightandtoinitiatea

2ndUSPExcipientWorkshop:FocusonExcipientQuality,CompendialTesting,andRegulatoryImpactNovember17‐18,2015,USPMeetingsCenter,Rockville,Maryland,USA

discussiononhowtoapproachmodernizingthesemonographs.

2ndUSPExcipientWorkshop:FocusonExcipientQuality,CompendialTesting,andRegulatoryImpactNovember17‐18,2015,USPMeetingsCenter,Rockville,Maryland,USA

AnneGayot,Ph.D.ProfessorUniversityofLille2FacultyofPharmacyEuropeanPharmacopoeiaLille,FranceProfessorAnneGayotisinco‐chargeofthePharmaceuticalIndustryLaboratoryattheUniversityofLILLE‐France.

Thislaboratory,beyonditsteachingactivitiesinthefieldofthedevelopmentandproductionofpharmaceuticalproducts,studiesthesolidstatepropertiesandpropertiesoftheparticulatesolidoftherawmaterialsusedintheformulationofdrugs.

Itstudiesthephysicalpropertiesofexcipientsandactivesubstanceswithrespecttothefunctionalitycharacteristics.

ProfessorAnneGayotwasuntilreorganizationoftheFrenchagencymemberandvice‐presidentoftheFrenchMarketingauthorizationcommitteeSheisnowmemberoftheFrenchPharmaceuticalandGenericworkinggroupattheFrenchAgency.SheparticipatestothewritingoftheguidelineonPharmaceuticalDevelopmentofMedicinesforPediatricuse.ProfessorAnneGayothasbeeninvolvedintheFrenchPharmacopoeiathentheEuropeanPharmacopoeiasince1980.AsanexpertofpowdertechnologyattheEuropeanPharmacopeia,shewasveryactiveintheelaborationofmonographsconcerningtheparticle–size,thesurfaceareadeterminations.ShewasnominatedasamemberoftheFrenchPharmacopoeiaCommissionandbelongsnowtothePharmaceuticalpreparations–IndustrialPharmacygroup.ShewasamemberofthecellulosegroupandamemberoftheP.A.T.GroupoftheEuropeanPharmacopoeiafrom2008–2012.Since2005,shehasbeenamemberofthefunctionalityrelatedcharacteristicsgroup.Shehasbeenchairmanofthisgroupsince2007.ShepreparedherPh.D.attheUniversityofLille(1981).Itconcernsmicrocapsulesofactivatedcharcoalforrenalpatients.Herscientificworkconcernscauterizationofsolidparticles,extrusion‐spheronisation,powderforinhalation.Sheusesasaninvitedspeakertogiveconferencesonthepharmaceuticaldevelopment,theprocessvalidation,thepowdersforinhalation.

2ndUSPExcipientWorkshop:FocusonExcipientQuality,CompendialTesting,andRegulatoryImpactNovember17‐18,2015,USPMeetingsCenter,Rockville,Maryland,USA

SheisinchargeofthemasterinindustrialpharmaceuticsattheUniv.ofLille2.

PresentationAbstractPresentation10:UpdateonHarmonizationActivities–EuropeanPharmacopeiaTuesday,November17,2015,4:00–4:30p.m.TheauthorpresentstheEuropeanDirectorateforthequalityofMedicinesandHealthcare(EDQM)oftheCouncilofEurope.ItsupportstheCommissionintheelaborationandrevisionoftextsoftheEuropeanPharmacopoeia.ThePharmacopoeiaEuropeanisengagedinaprocessofharmonizationwiththeJapanesePharmacopoeiaandtheUnitedStatesPharmacopoeiawithinaninformalstructurereferredtoasthePharmacopoeialDiscussionGroup(PDG).Thecellulosederivativesarepartoftheprogramofharmonization.Thepolymershavecomplexrheologicalproperties.Theviscositycanbedeterminatedwithdifferentapparatus,givinganabsoluteorrelativevalue.Theharmonizationofthedeterminationoftheviscosity,especiallyofcellulosederivatives,isanimportantsubject.Veryoften,theviscosityisrelevantasF.R.C.forsomefunctionsofthesepolymers.TheinterestsoftheF.R.C.inaqualitybydesignpharmaceuticaldevelopmentareoutlined.ThepresentworkoftheF.R.C.groupofthePharmacopoeiaEuropeanrelativetosurfactantsispresented.

2ndUSPExcipientWorkshop:FocusonExcipientQuality,CompendialTesting,andRegulatoryImpactNovember17‐18,2015,USPMeetingsCenter,Rockville,Maryland,USA

LaurieGrahamLeadBiologistU.S.FoodandDrugAdministration(FDA)SilverSpring,MD,USABiographyforthcoming.

PresentationAbstractPresentation2(FDA):FDAReviewofExcipientSubmissionsinBLAWednesday,November18,2015,9:30–10:00a.m.Abstractforthcoming.

2ndUSPExcipientWorkshop:FocusonExcipientQuality,CompendialTesting,andRegulatoryImpactNovember17‐18,2015,USPMeetingsCenter,Rockville,Maryland,USA

StephenW.Hoag,Ph.D.USPAffiliation:Member,GeneralChaptersPhysicalAnalysisExpertCommitteeProfessorUniversityofMaryland,SchoolofPharmacyBaltimore,MD,USAStephenW.HoagisaprofessorattheUniversityofMaryland,BaltimoreSchoolofPharmacy.Hisprimaryresearchinterestsaretabletcompaction,dosageformdevelopment,controlledreleasepolymers,excipientfunctionality,excipienttesting,formulationofnutritionalsupplements,botanicalproductsandNIRspectroscopyapplicationsinPAT.WorkingwiththeFDA,NIPTEhewasaco‐principleinvestigatoroftheteamthatcreatedtheexcipientdatabaseonpharmahub.org.Dr.HoagisamemberofNIPTE,USPCounselofExperts,SteeringCommitteefortheHandbookofPharmaceuticalExcipients,theeditorialboardofthejournalofPharmaceuticalDevelopmentTechnologyandanAAPSFellow. PresentationAbstractPresentation4:GlobalExcipientDatabases–NIPTEOverviewTuesday,November17,2015,11:10–11:40a.m.Successfulmanufacturingofpharmaceuticaldosageformsandtheresultanttherapeuticefficacydependsonthephysical,chemicalandmechanicalpropertiesofthedrugsubstanceandexcipients.Physicalpropertiesarelinkedtofinalproductqualityattributessuchaspurity,uniformity,dissolution,stability,appearanceandmechanicaldurability.Despiteawarenessoftheimportanceofphysicalandmechanicalproperties,manyfundamentalquestionsaboutexcipientfunctionalitystillneedtobeanswered.Tobeginansweringthesequestions,anexcipientdatabasewascreatedtoconsistentlycatalogandorganizeexcipientproperties.Databasesofmaterialpropertiesareverycommoninotherfieldsofengineering,andthesestandardizedandreliablematerialpropertiesareindispensabletoengineerswhoaredesigningproductsandindustrialprocesses.Inaddition,excipientscanbevariable,becausetheyarederivedfromnaturalproductsorsyntheticallymodifiednaturalproductsandareavailablefrommultiplevendors;asaresult,theirphysicalpropertiesmayvaryfromlot‐to‐lotandvendor‐to‐vendor,andifthisnaturalvariabilityifnotaccountedfor,itcancausemanufacturingproblemsthatseeminglyappearunpredictablythroughoutthelifecycleofadrugproduct.Thus,anothergoalofthedatabaseistocatalogtheintrinsicvariabilityofexcipientsfromvendor‐to‐vendorandlot‐to‐lot.Thiswillmakeiteasierforformulationstodeterminetheintrinsicvariablyintheirexcipientsandhowthisvariabilitycouldimpactproductquality.Theoverallgoaloftheexcipientdatabaseistocatalogmaterialpropertiesandusageinformationthatwouldbeusefulforformulationdevelopmentandtheevaluationof

2ndUSPExcipientWorkshop:FocusonExcipientQuality,CompendialTesting,andRegulatoryImpactNovember17‐18,2015,USPMeetingsCenter,Rockville,Maryland,USA

formulationsbyregulators.Inthispresentationthestructureandfeaturesofthedatabasewillbediscussed.

2ndUSPExcipientWorkshop:FocusonExcipientQuality,CompendialTesting,andRegulatoryImpactNovember17‐18,2015,USPMeetingsCenter,Rockville,Maryland,USA

KateHouck,Ph.D.USPAffiliation:Chair,USPExcipientMonographs2ExpertCommitteeAssociateDirector,AnalysisandTechnologyAstellasPharmaTechnologyNorman,OK,USADr.KateHouckisthechairoftheExcipientMonograph2committeeandtheAssociateDirectorofAnalysisandTechnologyatAstellasPharmaTechnologiesinNormanOklahomawhereshedirectstheAnalyticalDevelopment,QualityControl,StabilityandMicrobiologygroups.Shehasover25yearsofexperienceinthepharmaceuticalindustrywithexperienceinawiderangeofpharmaceuticaldosageformsaswellasdrugsubstancesandexcipients.Dr.HouckhasalsoworkedatTheDowChemicalCompany,SyntexChemicals(nowRocheColorado),CellTherapeutics,ScheinPharmaceutical,AlkermesandPPD.ShehasworkedasavolunteerfortheUnitedStatesPharmacopeiaontheexpertcommitteeforexcipientmonographsforthelast10yearsandhasvolunteeredforanumberoflocalandnationalorganizations.Dr.HouckearnedaB.S.inChemistryfromCreightonUniversityandaPh.D.inAnalyticalChemistryfromtheUniversityofArizona.

SteeringCommitteeMemberPresentationAbstractPresentation2:ChallengesandOpportunitiesinExcipientMonographDevelopmentandUpdateTuesday,November17,2015,9:45–10:10a.m.Aswenearthecelebrationof200yearsoftheUSP,itisimportantthatwearelookingnotonlyatthepastbutalsoatthepresentandfutureneedsofthehealthcareindustry.Bringingtheexistingexcipientmonographstoup‐to‐date,inadditiontothedevelopmentofmonographsfornewexcipientsisimportanttoprovidingastablesupplyofqualitypharmaceuticalproductstoaglobalmarketplace.Changesinthepharmaceuticalindustrysuchasincreasedgenerics,shifttowardbiologics,andincreasedoutsourcingdemandthattheUSP‐NFstandardsaremaintainedtocurrentstateoftechnology.Asthepharmaceuticalindustryfindsnewusesforexistingexcipients,theup‐to‐dateexcipientsmonographsmustcontaincertaincriticalqualityattributesthatsupportthenewuses.Newmonographsshouldbedevelopedfornovelexcipientsthatareneededtosupportemergingtechnologies.Inthischangingenvironment,theroleoftheinactiveingredientdatabase(IID)indeterminingwhatmonographsrequirechangesandwhatnewmonographsshouldbedevelopediscrucialtomaintaining

2ndUSPExcipientWorkshop:FocusonExcipientQuality,CompendialTesting,andRegulatoryImpactNovember17‐18,2015,USPMeetingsCenter,Rockville,Maryland,USA

theUSP‐NFstandards.Additionally,theIIDhasthepotentialtobeagreatresourceofinformationhelpingusersdetermineswhetheranewlyaddedexcipientorachangetoanexistingexcipientimpactsdosageforms/routesofadministrationordosageamounts.Thistalkwillcoverabackgroundoftherequirementsfordevelopingnewmonographsandupdatingexistingmonographs,theimpactoftheIIDnomenclature,functionality,andcompletenessonexcipientsmonographdevelopmentandupdate,andfinallydiscussthechangesrequiredfromtheIIDtobettersupportthemaintenanceofUSP‐NFcompendialstandards.

2ndUSPExcipientWorkshop:FocusonExcipientQuality,CompendialTesting,andRegulatoryImpactNovember17‐18,2015,USPMeetingsCenter,Rockville,Maryland,USA

JosephKushner,IV,Ph.D.SeniorPrincipalScientistPfizer,Inc.Groton,CT,USADr.KushnerreceivedaB.S.inChemicalEngineeringfromArizonaStateUniversityandcompletedaM.S.andPh.D.inChemicalEngineeringfromtheMassachusettsInstituteofTechnology,conductingresearchinthefieldofultrasound‐mediatedtransdermaldrugdelivery.SincejoiningPfizerin2006asaresearchscientistintheDrugProductDesigngroup,Dr.Kushnerhasledresearcheffortstobetterunderstandtheroleofexcipientvariabilityonsmallmoleculedrugproductrobustness,aswellastoprogressmodelingofthelubricationblendingprocess.Theseresearcheffortshaveledtonovelmethodsforassessingexcipientlot‐to‐lotvariabilityandthedevelopmentofalubricantblendingprocessscale‐upmodel,bothofwhichhavebeenusedtosupportthedevelopmentofPfizerdrugproducts.Dr.Kushnerhasauthoredseveralpublicationsandpresentationsinthefieldsoftransdermaldrugdeliveryandsolidoraldosageformdesignanddevelopment,includinglubricationunderstandingandexcipientvariability.Previously,hehasgiveninvitedtalksonexcipientvariabilityconceptsatworkshopshostedbyNIPTE,Patheon,andtheAAPSChicagolandRegionalGroup.HeisalsocurrentlyinvolvedwiththeInternationalPharmaceuticalExcipientCouncil(IPEC)QbDandExcipientCompositioncommittees.Throughthisinvolvement,hehasprovidedperspectivesonexcipientvariabilityindrugproductmanufacturingfromanexcipientuserperspectiveduringIPEC‐ledtrainingsessionswiththeFDAOfficeofGenericDrugsandanIPEC‐sponsoredWebinarseriesonExcipientVariabilityandQuality‐by‐Designdrugproductdevelopment.Dr.KushnerisamemberofbothAIChEandAAPS,andalsoservesasaScientificAdvisorfortheJournalofPharmaceuticalSciences.PresentationAbstractKeynotePresentationTuesday,November17,2015,8:45–9:15a.m.Excipientsareanessentialcomponentofrobust,commercialpharmaceuticaldrugproducts.Therefore,understandingthepotentialimpactofvariabilityinexcipientmaterialattributesondrugproductmanufactureandperformanceisanintegralpartofdrugproductdesignanddevelopment.Casestudiesincorporatingexcipientvariabilityunderstandingintothedrugproductdesignanddevelopmentprocesswillbereviewed.Thesecasestudiesareintendedtohighlightthechallengesdrugproductdevelopersmayencounterwhileevaluatingtheimpactthatexcipientvariabilitymayplayintheperformanceofdrugproductsandjustifyingexcipient‐relatedaspectsofthedrugproductcontrolstrategy.

2ndUSPExcipientWorkshop:FocusonExcipientQuality,CompendialTesting,andRegulatoryImpactNovember17‐18,2015,USPMeetingsCenter,Rockville,Maryland,USA

JeffreyMedwid,Ph.D.USPAffiliation:GovernmentLiaison,USPExcipientMonographs2ExpertCommitteeSeniorCMCReviewChemistU.S.FoodandDrugAdministration(FDA)SilverSpring,MD,USAJeffreyB.Medwid,Ph.D.,hasover35years’experienceinthepharmaceuticalIndustry.JeffmovedtoNewYorkin1980tojoinAmericanCyanamid(Lederle),whichbecameWyethandisnowpartofPfizerwherehemadehiscareerinpharmaceuticaldevelopmentthereforovertwenty‐sevenyears.Dr.MedwidretiredfromWyeth(nowPfizer)asaDirectorinAnalyticalR&DinMarch2007toformCMCPharmaceuticalConsultants,LLC.Aspresident,heconsultedforanumberofpharmaceuticalcompanies,includinganotabletriptoChinaforon‐sitefacilityevaluationsin2008.JeffjoinedtheFDAinOctober2008.InhiscurrentpositionasaSeniorCMCQualityReviewer,Jeff’sprimaryroleisreviewingtheCMCsectionsforNewDrugs.HeisalsoveryinvolvedwithAAPS,IPEC,andUSP(FDALiaisontoUSP)inlearningandhelpingtopresenttheFDAperspectiveontheroleofExcipientsfromaQbDpointofview.

SteeringCommitteeMemberModeratorSession1:StrategytoBringUSP‐NFExcipientMonographSpecificationsUptoDateTuesday,November17,2015,8:45a.m.–12:00p.m.

2ndUSPExcipientWorkshop:FocusonExcipientQuality,CompendialTesting,andRegulatoryImpactNovember17‐18,2015,USPMeetingsCenter,Rockville,Maryland,USA

DoraMeissner,M.S.DirectorofRegulatoryAffairsBioSpectraBangor,MS,USADoraMeissneristheDirectorofRegulatoryAffairsforBioSpectrawhichisheadquarteredinBangor,PA.ShereceivedherB.S.inChemistryfromtheUniversityofPittsburghandiscurrentlypursuingaMaster’sDegreeinQualityAssuranceandRegulatoryAffairsfromTempleUniversity.DorabeganworkingatBioSpectraasaQualityControlAnalystin2004.ShehasdedicatedherprofessionalcareertounderstandingandadvancingthequalityandregulatorystandardsofBioSpectra,aleadingmanufacturerofExcipientsandActivePharmaceuticalIngredients.DuringherelevenyearsatBioSpectra,DorahasbeenresponsiblefortheQuality,SafetyandRegulatoryaspectsofthecompany’soperationsatthreedifferentmanufacturingfacilities.InhercurrentroleasDirectorofRegulatoryAffairs,DoraisresponsibleformanagingQualityControl,QualityAssurance,EnvironmentalHealthandSafety,InformationTechnologyandInformationSystems.Additionally,DoraisresponsibleforthemanagementofBioSpectra’sglobalrawmaterialsupplychain.

PresentationAbstractPresentation4:EnsuringanExcipientisSuitableforitsIntendedEndUse;AnExcipientManufacturer’sPerspectiveWednesday,November18,2015,11:30a.m.–12:00p.m.Anunderstandingofthequality,identity,purityandgradeofanexcipientisessentialtoassureitssuitabilityfortheintendedenduse.Therearemanyparameters,controlsandanalyticaltestsnecessarytoverifyandprovethatanexcipientismanufacturedinaccordancewithdesiredquality,uniformityandcompliance.Theseparametersallowaningredienttoconsistentlymeetthedefiningspecificationsforuseinthemanufactureofadrugproduct.Informationprovidedthroughresourcesisavailabletomanufacturersandenduserstoaidinharmonizingexpectations,testingcriteriaandcompliancerequirements.Resources,suchastheUSPMonograph,areusedtoprovideguidelinesforqualifyingandapprovingthequalityandenduseofaningredient.Thispresentationwilldiscusstheinformationandtoolsthatanexcipientmanufacturershouldusetosupporttheintendedenduseofanexcipient.Thispresentationwillalsoprovideabroadoverviewofhowanexcipientmanufacturercanensureitsproductsaresuppliedwiththenecessaryattributesfortheirintendeduse.Specificcasestudieswillalsobediscussedduringthispresentation.

2ndUSPExcipientWorkshop:FocusonExcipientQuality,CompendialTesting,andRegulatoryImpactNovember17‐18,2015,USPMeetingsCenter,Rockville,Maryland,USA

KevinMoore,Ph.D.Manager,PharmacopeialHarmonizationUSPRockville,MD,USAKevinistheManager,PharmacopeialHarmonizationwithresponsibilitiesastheUSPtechnicalleadforallofUSP’sglobalharmonizationactivities.ThisincludesleadingtheUSdelegationtothePharmacopeialDiscussionGroup,whichworkstoharmonizeGeneralChaptersandExcipientMonographswithrepresentativesfromtheUnitedStatesPharmacopeia,theEuropeanPharmacopeia,andtheJapanesePharmacopeia.Inaddition,KevinworkstocoordinatethetechnicalactivitieswithinUSPforUSP’sprospectiveharmonizationinitiativesfordrugsubstance,drugproduct,andexcipientmonographs,aswellassupportUSPactivitiesincollaborationwithWHOinthedevelopmentoftheGoodPharmacopeialPractices(GPhP).KevinholdsaPh.D.inInorganicChemistryfromtheUniversityofPennsylvaniaandaB.S.inChemistryandBiologyfromLeMoyneCollege.ModeratorSession2:ChallengesandOpportunitiesinExcipientMonographDevelopmentandUpdateTuesday,November17,2015,1:00–2:30p.m.

2ndUSPExcipientWorkshop:FocusonExcipientQuality,CompendialTesting,andRegulatoryImpactNovember17‐18,2015,USPMeetingsCenter,Rockville,Maryland,USA

R.ChrisMoreton,Ph.D.USPAffiliation:Vice‐Chair,USPExcipientMonographs1ExpertCommitteePartnerFinnBritConsultingWaltham,MA,USADr.Moretonisaformulationscientistwithover30yearspharmaceuticalindustryexperience.Hehasformulatedawiderangeofdifferentdrugproducts,bothforclinicalandcommercialuse,includingtablets,capsules,injections,creams,ointments,suppositoriesandpessariesandhastakenproductsfrompreformulationthroughtocommercialmanufacture.InadditionhehasworkedinQA,QCandRegulatoryAffairsforanexcipientanddrugdeliverycompany.Dr.MoretonhasworkedwithIPECovermanyyears,initiallyinEuropeandlaterintheUS.HewasamemberoftheIPECTeamthatpreparedtheinitialIPECGuideonGoodManufacturingPracticesforBulkPharmaceuticalExcipients,andhasalsohelpeddraftseveralotherIPECGuides.HeisapastChairofIPEC‐Americas.Dr.MoretonisamemberoftheEditorialAdvisoryBoardforPharmaceuticalTechnologyandalsofortheJournalofExcipientsandFoodChemicals.Hehasauthoredandco‐authoredscientificpapers,articlesandbookchapters,andlecturedextensivelyintheareasofexcipients,drugdelivery,preformulationandformulationatuniversities,trainingcoursesandsymposiaintheU.S.,EuropeandJapan.SteeringCommitteeMemberPresentationAbstractPresentation6:WhatDoesUSP‐NFUp‐To‐DateMeanforExcipients?Tuesday,November17,2015,1:30–2:00p.m.Underthe‘USP‐NFuptodate’initiativetheEM1Expertcommitteewillbeworkingtoensurethatnewandexistingmonographsarecurrent,relevantandsuitablefortheirintendeduse.Thispresentationwillreviewhowthisimpactsexcipientmonographsandthenfocusonmonographupdatingactivities,andhowtheCommitteewillbelookingtoupdatemonographs.Inadditionthelikelyimpactofnewanalyticaltechnologieswillalsobediscussed.ModeratorSession3:ChallengesandOpportunitiesinDevelopmentandUpdateofExcipientMonographsUsedforBiologicsDrugApplicationsWednesday,November18,2015,8:30–3:30p.m.

2ndUSPExcipientWorkshop:FocusonExcipientQuality,CompendialTesting,andRegulatoryImpactNovember17‐18,2015,USPMeetingsCenter,Rockville,Maryland,USA

MarlaPhillips,Ph.D.Director,XavierHealthXavierUniversityCincinnati,OH,USA

Marla joined Xavier University in 2008 as the Director of Xavier Health, where she leads initiatives with FDA officials and Pharmaceutical and Medical Device professionals. Marla began working in the pharmaceutical industry for Merck in 1996 as a Senior Project Chemist in the Analytical Methods Development group, became Manager of the Quality Control Laboratory for the Philadelphia plant site, and ultimately served as the Head of Quality Operations at the Merck North Carolina facility. She holds a B.S. in Chemistry from Xavier University, and a Ph.D. in Organic Chemistry from the University of North Carolina – Chapel Hill.

PresentationAbstractKeynotePresentation:IntegrityofSupply–ShiftingParadigmsWednesday,November18,2015,8:30–9:00a.m.XavierUniversityhasbeenleadingtheIntegrityofSupplyinitiativesince2012withrepresentationfromFDA,pharmaceuticalandmedicaldevicemanufacturers,andsuppliers.Thegoalofthisworkistoincreasethereliabilityofthesupplychainandtoincreaseproductconfidence.Majorparadigmshiftshavebeendiscoveredthroughtheseinitiativesthatareresultinginthedevelopmentofimpactfulsolutions.Attendeeswillunderstandhowtheparadigmshiftscanaltercurrentpracticesintheircompaniestoday.

2ndUSPExcipientWorkshop:FocusonExcipientQuality,CompendialTesting,andRegulatoryImpactNovember17‐18,2015,USPMeetingsCenter,Rockville,Maryland,USA

AshutoshRao,Ph.D.Chief,LaboratoryofAppliedBiochemistryU.S.FoodandDrugAdministration(FDA)SilverSpring,MD,USADr.AshutoshRaoistheActingChiefoftheLaboratoryofAppliedBiochemistryandSupervisoryDrugQualityReviewerintheDivisionofBiotechnologyReviewandResearch,OfficeofBiotechnologyProductsatOPQ/CDER/FDA.Dr.RaoreceivedhisB.PharmfromtheUniversityofBombayandPh.D.inmolecularpharmacologyfromtheUniversityofTexasM.D.AndersonCancerCenterinHouston,TX.PriortojoiningtheFDAin2006,Dr.Raocompletedpost‐doctoralfellowshipsinbiochemistryandmolecularbiologyattheNationalCancerInstituteinBethesda,MD.Dr.Raoiscurrentlyresponsiblefortheregulationoftherapeuticproteinssuchasenzymes,monoclonalantibodies,andcytokines,andservesasanexpertreviewerforbiomarkersrelatedtooncologyorneuromuscularindications.HealsoservesonFDAworkinggroupstodevelopregulatorypolicyonthedevelopmentandvalidationofanalyticalmethodsduringmanufacture,novelexcipients,referencestandards,andonsurrogatemarkersforacceleratedapproval.Dr.Raoalsodirectsalaboratoryresearchprogramthatinvestigatesthestructure‐activityrelationshipbetweenproteinoxidationanddrugsafetyandefficacy.Hehasauthoredseveralpeer‐reviewedarticlesondrugdevelopment,metal‐catalyzedoxidationoftherapeuticproteins,biomarkersofcancerchemotherapy,andFDAregulatoryguidances.

PresentationAbstractPresentation3:TheScientificandRegulatoryBasisfortheManagementofExcipientDataDuringtheReviewofBiotechnology‐DerivedDrugsWednesday,November18,2015,10:30–11:00a.m.Abstractforthcoming.

2ndUSPExcipientWorkshop:FocusonExcipientQuality,CompendialTesting,andRegulatoryImpactNovember17‐18,2015,USPMeetingsCenter,Rockville,Maryland,USA

CatherineM.Sheehan,M.S.,M.S.SeniorDirector,Science‐ExcipientsUSPRockville,MD,USAMs.SheehanjoinedUSPin2001.SheiscurrentlytheSeniorDirector,Science‐Excipients,UnitedStatesPharmacopeiaConvention,Rockville,MD.Inhercurrentrole,shesupportsexcipientsstandardsettingactivitiesoftheUSPCouncilofExpertsfortwoExcipientMonographExpertCommittees.HerresponsibilitiesincludeworkingwithstakeholdersonthedevelopmentandupdateofexcipientmonographsandrelatedgeneralchaptersincludingtheupdateofhighpriorityexcipientsaspartofUSPscollaborationwiththeFDAMonographModernizationTaskGroup.SheisalsoresponsiblefortheharmonizationactivitiesofexcipientmonographsandgeneralchaptersthroughthePharmacopeialDiscussionGroupandispartoftheUSPdelegationtothePharmacopeialDiscussionGroup.Ms.SheehanholdsbothanM.S.RegulatorySciencedegreeandM.S.MolecularBiotechnologydegreefromTheJohnsHopkinsUniversity,Baltimore,USA.

ModeratorSession3:ChallengesandOpportunitiesinDevelopmentandUpdateofExcipientMonographsUsedforBiologicsDrugApplicationsWednesday,November18,2015,8:30a.m.–3:30p.m.

2ndUSPExcipientWorkshop:FocusonExcipientQuality,CompendialTesting,andRegulatoryImpactNovember17‐18,2015,USPMeetingsCenter,Rockville,Maryland,USA

HiroshiTokunaga,Ph.D.TechnicalExpertPharmaceuticalsandMedicalDevicesAgencyTokyo,JapanHehadthirty‐sixyears’experienceintheNationalInstituteofHealthSciencesandworkedatqualitycontrolofpharmaceuticalsandexcipients.Afterretiring,hestartstoworkinPharmaceuticalsandMedicalDevicesAgency.HeisoneofJPExpertCommitteeonExcipientandoneoftherepresentativesofJPinPDG.HeleadsactivelythequalitycontrolofexcipientsandtheInternationalharmonization.

PresentationAbstractPresentation9:PharmacopoeialDiscussionGroup(PDG)UpdateonHarmonizationActivities–JapanesePharmacopoeia(JP)Tuesday,November17,2015,3:30–4:00p.m.Inthispresentation,theactivitiesofPDGarereportedfromthepasttothenearfuture.PDGhasthreePharmacopoeialbodiesasEP,USP,andJPandWHOasobserver.PDGhasbeenestablishedin1989andcontinuestoworkfor26years.Thefirstsign‐offoftheharmonizeddocumentwasSDS‐PAGE.ICHapprovedtheICHQ6AAgreementfortheSpecificationsfornewdrugson1999andalsoestablishedtheICHQ4Bforevaluatingforinter‐regionalregulatoryacceptanceon2003.ICHQ4Bactivitiesstoppedtoworkon2011.PDGhastheWorkingProceduresfromStage1toStage6;Stage1istheIdentificationofmonograph,Stage2isitsInvestigation,Stage3istheProposalforExpertCommitteeReview,Stage4isitsofficialInquiry,Stage5isitsconsensusofsign‐off,andStage6isitsregionaladoptionandimplementation.ICHnominated15generalchaptersontheprogramofICHQ6A.WhenhavingdiscontinuedtheICHQ4Bon2011,ICHadopted14generalchaptersexcept“color”onPharmacopoeia.PDGTokyomeetingwashostedbyJPinTokyo,Japan,30June–1July,2015.PDGselected36generalchaptersand62excipient’smonographs.Atpresent,29ofthe36GeneralChaptersand48ofthe62excipientmonographsonthecurrentworkprogrammehavebeenharmonised.Sign‐offsatthismeetingincludedarevisedmonographon“Povidone”inordertorefineconditionsforimpuritytestingofmonomers(1‐vinyl‐2‐pyrrolidoneand2‐pyrrolidone)andtoaddidentitytestingbyinfraredspectroscopyasaharmonisedattribute.In‐depthdiscussionsonanumberofadditionalitemscurrentlyontheworkprogrammetookplacewithaviewtoresolvingoutstandingissuesandadvancingtheitemstowardsign‐off.Withregardto“Chromatographychapter”,asafollow‐upfromrecentPDGdecisionsonPDGprocessimprovement,ateleconferencewithexpertsfromthe3regionshadtakenplaceinMayandallowingsignificantprogresstobemadeintheresolutionofmajorstickingpoints.ThecoordinatingpharmacopoeiawillworkontheresolutionofanumberofotheritemswiththeaimoffinalisingaStage4draftfor

2ndUSPExcipientWorkshop:FocusonExcipientQuality,CompendialTesting,andRegulatoryImpactNovember17‐18,2015,USPMeetingsCenter,Rockville,Maryland,USA

publicinquiryforthenextPDGmeeting.Withregardto“Copovidone”,thecoordinatingpharmacopoeiawillsendoutadraftforpublicconsultationinJulyforthethreepharmacopoeiastopublishaccordingtotheirrespectiveschedules.ThethreepharmacopoeiasexchangedinformationontheirrespectiveapproachesfortheimplementationoftheICHQ3Dguideline.Inaddition,PDGconfirmedtheircommitmenttoharmonisethegeneralchapterontestingproceduresforelementalimpurities. 

2ndUSPExcipientWorkshop:FocusonExcipientQuality,CompendialTesting,andRegulatoryImpactNovember17‐18,2015,USPMeetingsCenter,Rockville,Maryland,USA

JiashengTu,Ph.D.USPAffiliation:Member,USPExcipientMonographs2ExpertCommitteeProfessorChinaPharmaceuticalUniversityNanjing,ChinaJiashengTuistheprofessorofpharmaceuticsofChinaPharmaceuticalUniversity,asupervisorofdoctoratestudents.Dr.TuhasalsoservedasthedeputychairofCHPpharmaceuticalexcipientcommittee,anexpertcommitteememberofCHP,anexpertcommitteememberofpharmaceuticalexcipientofUSP,consultantofCDEofCFDA,areviewerofnationalawardofChina,co‐editorofPharmaceuticalBiotechnologies.Dr.TugraduatedfromBeijingMedicalUniversity.HewasawardedPh.D.ofpharmaceuticsinChinaPharmaceuticalUniversityat1992anddidpostdoctoralresearchesinUniversityofthePacific,CA,during2001‐2003.Dr.Tualsoservedasjoint‐professorinUniversityoftheUniversityandJiangnanUnivesityinWuxi,China.SteeringCommitteeMemberModeratorRoundtableDiscussion/Q&A(30min)–ChallengesandOpportunitiesforHarmonization,UpdateandDevelopmentofExcipientSpecificationsTuesday,November17,2015,4:30–5:00p.m.ParallelBreakoutSessions:RationalizationofTerminologyusedinthemanufacturingofBiologics,includingDrugSubstance(upstream/downstreamprocessing)andDrugProduct(finalformulations)aspects.Todiscuss/understandwhencompendialgradematerialsarenecessaryinthemanufactureofBiologics.Parallelbreakoutsessionswillexploreandreportbackonlearningsrelatingtotheuseofthecurrentterminologyandproviderecommendations/pathforward.Wednesday,November18,2015,2:00–3:30p.m.

2ndUSPExcipientWorkshop:FocusonExcipientQuality,CompendialTesting,andRegulatoryImpactNovember17‐18,2015,USPMeetingsCenter,Rockville,Maryland,USA

KatherineUlmanAssociateScientistGlobalRegulatoryComplianceManagerDowCorningHealthcareMidland,MI,USAKatherineUlmanhasbeenemployedwithDowCorningCorporationfor40years.SheiscurrentlyaglobalregulatorycompliancemanagerforDowCorningHealthcare,aswellasaDowCorningassociatescientist.Shehasworkedinthedevelopmentandcharacterizationofpharmaceuticalexcipientandmedicaldevicerawmaterials/componentsfornearly27years.SheisamemberoftheACS,AAPS,andCRSandvicechairofScienceandRegulatoryPolicyforIPEC‐Americas.ShehaspublishedandpresentedseveralpapersinherfieldaswellasdevelopedandtaughtcoursesinOrganosiliconPolymerChemistryandTechnology.UlmanearnedherBachelorofSciencedegreeinchemistryfromtheSouthDakotaSchoolofMinesandTechnologyin1976.

PresentationAbstractPresentation1:FDA/OPQIIDIssuesandPotentialResolutionsTuesday,November17,2015,9:15–9:45a.m.TheInternationalPharmaceuticalExcipientsCounciloftheAmericas(IPEC‐Americas)isanindustryassociationthatdevelops,implements,andpromotesglobaluseofappropriatequality,safety,andfunctionalitystandardsforpharmaceuticalexcipientsanddeliverysystems.FDAcreatedaworkinggroupwithIPEC‐Americas,includingarepresentativefromGPhAtoaddressIIDissues.ThisgrouphasbeenmeetingquarterlywithmembersoftheFDAIIDExcipientWorkingGroup(EWG)sincetheyfirstformedinthefallof2011.AlthoughtheAgencyhasresolvedseveralhistoricalconcerns/issuesraisedbyIPEC‐AmericasandGPhA,includingbutnotlimitedtoIIDcontentanduse,theteamcontinuestoworkwiththeAgencyastheystrivetore‐designandmaintainIIDinformationwhileenhancingtheutilityandusabilityofthedatabase.Thistalkisintendedtoprovideanoverviewofdiscussiontopicscoveredbytheteam,aswellashighlighttheircurrentstatusandongoingactivities.

2ndUSPExcipientWorkshop:FocusonExcipientQuality,CompendialTesting,andRegulatoryImpactNovember17‐18,2015,USPMeetingsCenter,Rockville,Maryland,USA

HongWang,Ph.D.SeniorScientificLiaison,ExcipientsUSPRockville,MD,USADr.HongWangisaSeniorScientificLiaisoninScience—ExcipientsatU.S.PharmacopeialConvention.ShehasovertenyearsofexperienceindevelopingandupdatingUSP‐NFpublicstandards.ShereceivedherPh.D.inphysicalchemistryfromtheUniversityofBasel,Switzerland.PriortojoiningUSP,sheworkedatBioprocessandBioanalyticalResearchdepartmentinMerckResearchLaboratories,WestPoint,PAforsevenyears.BeforestartinganindustrialcareeratMerck,Dr.WangworkedasapostdoctoralresearchfellowatBrandeisUniversity,Waltham,MA,forabouttwoyears.

ModeratorSession2:ChallengesandOpportunitiesinExcipientMonographDevelopmentandUpdateTuesday,November17,2015,1:00–2:30p.m.

2ndUSPExcipientWorkshop:FocusonExcipientQuality,CompendialTesting,andRegulatoryImpactNovember17‐18,2015,USPMeetingsCenter,Rockville,Maryland,USA

Y.JohnWang,Ph.D.PrincipalScientistGenentechSanFrancisco,CA,USADr.Y.JohnWangisaFellowofAmericanAssociationofPharmaceuticalScientists(AAPS).Hehasbeenworkingover11yearsintheLateStagePharmaceuticalDevelopmentatGenentech,amemberoftheRocheGroup.HereceivedhisB.S.Pharmacyand,fromtheUniversityofMichigan,Ph.D.inPharmaceuticalChemistry.PriortoGenentech,heworkedintheformulationdepartmentatSquibb,Ortho,SciosandBayer.Hisareasofexpertisearestabilityofdrugproduct,autoclavecycledevelopment,proteinformulationandstabilizers,deamidation,oxidationofpeptidesandproteins.Heauthoredorcoauthoredover60peer‐reviewedarticles,anumberofbookchaptersandtwoPDATechnicalReportsandco‐editedtwobookstitledFormulation,CharacterizationandStabilityofProteinDrugs.HewasamemberoftheBoardofDirectorsoftheParenteralDrugAssociationand,in1992,ChairofAAPSBiotecSection.PresentationAbstractPresentation5:DrugProductManufacturer’sPerspectiveontheUseofPharmaceuticalExcipientsinBiologicsFinishedFinalProduct/Formulation;FocusingontheCharacterizationofSurfactantsWednesday,November18,2015,1:00–1:30p.m.Polysorbate20and80,andpoloxamber188areusedextensivelyindrugproductsofbiologics.Recentlytheinstabilityofpolysorbatehasbeennoticedindevelopmentormarketproducts.Insomeoccasions,insolubleparticleswereobserved.ThecompositionsofpolysorbatearemuchmorecomplexthanwhataredefinedbypharmacopeiawhichincludesonlyhydrocarbonchainlengthandnumberofPOE.Variationinheadgroup,sorbitol,sorbitan,orisosorbide,inorderofesterification,mono,di‐,tri‐,ortetra‐esters,andthepresenceofun‐esterifiedheadgroup(non‐surfactant),werenotdescribednorcontrolled.Forpolysorbate,newassaymethodmaybedeveloped.Byusinglipasetogeneratehydrolyzedpolysorbate,alllauratepolysorbate20wasfoundnottoproduceinsolubleparticles.Basedonthisobservation,compositionoffattyacidsinpolysorbate20mayberevised.Wealsoproposetoreducetheunsaturationspecificationtozeroforpoloxamer.

2ndUSPExcipientWorkshop:FocusonExcipientQuality,CompendialTesting,andRegulatoryImpactNovember17‐18,2015,USPMeetingsCenter,Rockville,Maryland,USA

StevenWolfgang,Ph.D.USPAffiliation:GovernmentLiaison,USPExcipientMonographs1ExpertCommitteeChemistU.S.FoodandDrugAdministration(FDA)SilverSpring,MD,USADr.WolfgangreceivedhisPh.D.inInorganicChemistryfromtheCityUniversityofNewYorkin1983.HejoinedFDAin2005afterspending15yearsasatechnicalsupportchemistforamanufacturerofAPIsandexcipients.Dr.WolfgangstartedasaCMCreviewerfornewdrugsandmovedovertotheOfficeofCompliancein2007.Dr.WolfgangisanFDAliaisontotheUSPExcipientExpertCommitteeandtoexpertpanelsforthemodernizationofthePovidoneandTalcmonographsandremainsactiveinresearchatFDA.

SteeringCommitteeMemberPresentationAbstractPresentation5:FDAPerspectiveonExcipientMonographUp‐to‐DateTuesday,November17,2015,1:00–1:30p.m.Abstractforthcoming.

2ndUSPExcipientWorkshop:FocusonExcipientQuality,CompendialTesting,andRegulatoryImpactNovember17‐18,2015,USPMeetingsCenter,Rockville,Maryland,USA

SusanZuk,M.S.LeadChemistU.S.FoodandDrugAdministration(FDA)SilverSpring,MD,USASusanholdsaBSinChemistryfromSyracuseUniversityandaMSinBiotechnologyfromJohnsHopkinsUniversity.Duringher15yearswiththeFDA,shehasservedasChemistryReviewer,TeamLeaderandActingDeputyDirectorintheOfficeofGenericDrugsandasActingBranchChiefoftheDivisionofInternalPoliciesandProcedures(DIPAP)intheOPQOfficeofPolicyforPharmaceuticalQuality(OPPQ).SheisthecurrentleaderoftheFDACDERExcipientWorkingGroup.Inthisrole,sheisresponsibleforoverseeingtheIIDproject.SusanhasservedonmanyFDAcommitteesandworkinggroupsrelatedtoproductsafetyandquality.

PresentationAbstractPresentation3:FDACDERInactiveIngredientDatabase:GoalsandProgressTuesday,November17,2015,10:40–11:10a.m.TheFDAInactiveIngredientDatabase(IID)playsacentralroleindailydecisionsmadebyFDAandthepharmaceuticalindustry.ForFDA,theIIDisreferencedduringallstagesoftheapplicationprocess,fromfilingthroughchemistry,bioequivalence,toxicology,andclinicalreviewsofbothgenericandnewdrugproductapplications.Itisusedasthebasisforacceptanceofinactiveingredientsingenericdrugproductformulations.Forindustry,theIIDguidesmanyproductdevelopmentdecisions.Thislist,whichprovidesthemaximumapprovedlevelofeachinactiveingredientperunitdose,dosageformandrouteofadministration,isperiodicallyupdatedastheFDAapprovesproductscontainingnewingredientsandhigherlevelsofexistingingredients.ButtheIIDinitspresentformhaslimitations.Inthispresentation,theprogressofFDA’seffortstodevelopabetter,morefunctionalIIDwillbediscussed.ThepresentationwillalsodescribeFDA’svisionforthefutureoftheIID.