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USP Workshop on Glycosylation Analysis for Biopharmaceuticals Workshop August 25-26, 2015 USP Meetings Center, Rockville, Maryland USA
USP WORKSHOP ON GLYCOSYLATION ANALYSIS FOR BIOPHARMACEUTICALS
August 25-26, 2015 USP Meetings Center, Rockville, MD USA
Final Agenda
DAY ONE: Tuesday, August 25, 2015 8:00 – 8:30 a.m.
Registration
8:30 – 8:40 a.m.
USP Welcome & Workshop Introduction Tina Morris
Senior VP, Science Global Biologics, USP
SESSION 1 Opening Keynote Presentation Introduction: Chris Jones, Ph.D.
8:40 – 9:20 a.m.
The Critical Features of Glycosylation for the Therapeutic Products
Pauline M. Rudd, Ph.D. National Institute for BioProcessing Research and Training in Ireland (NIBRT), University College, Dublin (Ireland)
SESSION 2
The Role of Glycosylation for Therapeutic Proteins Moderator: Michael DeFelippis, Ph.D.
9:20 – 9:45 a.m.
The Use of Alternative Methods as Surrogate Measures of Biological Activity
Guoying Jiang, Ph.D. Genentech
9:45 – 10:10 a.m.
Break
10:10 – 10:35 a.m.
Characterization and Impact of Glycosylation in an IgG fusion protein
Christopher Barton, Ph.D. MedImmune
10:35 – 11:00 a.m.
Case Study: Influence of Fab Glycosylation on The Pharmacological Properties of a Monoclonal Antibody
Bryan Harmon, Ph.D. Eli Lilly and Company
USP Workshop on Glycosylation Analysis for Biopharmaceuticals Workshop August 25-26, 2015 USP Meetings Center, Rockville, Maryland USA
11:00 a.m. – 11:30 a.m.
Panel Discussion
11:30 a.m. – 12:30 p.m.
Lunch & Poster Session
SESSION 3 Current Technologies Moderator: Trish Li, Ph.D.
12:30 – 12:55 p.m.
Common Analytical Methods for Oligosaccharide and Monosaccharide Analysis
Parastoo Azadi, Ph.D. Member, USP Glycoproteins and Glycan Analysis Expert Panel
12:55 – 1:20 p.m.
The Common Challenges Faced Today When Performing Glycosylation Analysis
Jeffrey S. Rohrer, Ph.D. Member, USP Glycoproteins and Glycan Analysis Expert Panel
1:20 – 1:45 p.m.
Practical Glycoprofiling Approach for Measurement and Control of Glycosylation
Tapan Das, Ph.D. Bristol-Myers Squibb
1:45 – 2:15 p.m.
Panel discussion
2:15 – 2:35 p.m.
Break
SESSION 4 Standardization Moderator: Chris Jones, Ph.D.
2:35 – 2:55 p.m.
Standard procedures: USP <1084>, <212> , <210>, and <129> Chris Jones, Ph.D.
Chair, USP Glycoproteins and Glycan Analysis Expert Panel
2:55 – 3:05 p.m.
USP Reference Standards Edith Chang, Ph.D.
USP
3:05 – 3:30 p.m.
The NIST mAb: A Reference Material to Supplement Biopharmaceutical Characterization
John Schiel, Ph.D. National Institute of Standards and Technology (NIST)
3:30 – 4:00 p.m.
Panel discussion
4:00 – 5:00 p.m.
Networking Reception & Poster Session
USP Workshop on Glycosylation Analysis for Biopharmaceuticals Workshop August 25-26, 2015 USP Meetings Center, Rockville, Maryland USA
DAY TWO: Wednesday, August 26, 2015 8:00 – 8:30 a.m.
Registration
8:30 – 9:10 a.m.
SESSION 5 Plenary Session: Regulatory Expectations
Christopher Downey, Ph.D. U.S. Food and Drug Administration (FDA)
SESSION 6
Emerging Technologies Moderator: Parastoo Azadi, Ph.D.
9:10 – 9:35 a.m.
In Vitro Glycoengineering – A Useful Tool for Protein Characterization and Optimization
Marco Thomann Roche Diagnostics GmbH
9:35 – 10:00 a.m.
Bacterial Glycoengineering: from enzymes and pathways to human therapeutics and vaccines
Matt DeLisa, Ph.D. Department of Chemical and Biomolecular Engineering, Cornell University
10:00 – 10:25 a.m.
Break
10:25 – 10:50 a.m.
Relative and Absolute Quantitation of Glycoprotein Glycans Using Isotopically Labeled Standard Glycoproteins
Ron Orlando, Ph.D. Complex Carbohydrate Research Center, University of Georgia
10:50 11:15 a.m. MAb Glycan Profiling by LC/MS Peptide Mapping Bhavana Shah, Ph.D.
Amgen 11:15 11:45 a.m. Panel discussion
11:45 a.m. – 12:45 p.m.
Lunch & Poster Session
SESSION 7 Regulatory Approaches on Glycosylation Moderator: John Cipollo, Ph.D.
12:45 – 1:10 p.m.
What are the Expectations from the Regulatory Agencies John Mark, Ph.D.
Health Canada
USP Workshop on Glycosylation Analysis for Biopharmaceuticals Workshop August 25-26, 2015 USP Meetings Center, Rockville, Maryland USA
1:10 – 1:35 p.m.
Expectations for Glycosylated Biosimilars (manufacturer perspective)
Catherine Srebalus Barnes, Ph.D. Hospira
1:35 – 2:00 p.m.
Expectations for Glycosylated Biosimilars (regulatory perspective) Birgit Schmauser, Ph.D.
Federal Institute for Drugs and Medical Devices (BfArM) (Germany)
2:00 – 2:30 p.m.
Break
SESSION 8 Post-approval changes registration Moderator: John Schiel, Ph.D.
2:30 – 2:55 p.m.
Modulation of Glycosylation Patterns by Bioprocess Techniques José M. Gomes, Ph.D.
Pfizer
2:55 – 3:20 p.m.
Post-approval Changes – Regulatory Perspective Maria-Teresa Gutierrez-Lugo, Ph.D.
OBP/CDER/U.S. Food and Drug Administration
3:20 – 3:50 p.m.
Panel discussion
3:50 – 4:10 p.m.
What Was Said & Next Steps Trish Li, Ph.D.
USP
4:10 – 4:30 p.m.
Closing Remarks Chris Jones, Ph.D.
Chair, USP Glycoproteins and Glycan Analysis Expert Panel
4:30 p.m. Workshop Adjourns
USP Workshop on Glycosylation Analysis for Biopharmaceuticals Workshop August 25-26, 2015 USP Meetings Center, Rockville, Maryland USA
USP WORKSHOP ON GLYCOSYLATION ANALYSIS FOR BIOPHARMACEUTICALS
August 25-26, 2015 USP Meetings Center, Rockville, MD USA
Poster Presentations
1. Tomasz Baginski et al. Genetech
End-to-End HILIC UHPLC Glycoprofiling Method for Development, Process Characterization/Validation and Quality Control of Therapeutic Monoclonal Antibodies
2. Kudrat Goswami et al. Merck
Advanced analytical Technologies for N-Glycan Profiling: Assessment of InstantABTM AssayMap® Automation and GlycoworksTM Rapifluor-MSTM
3. András Guttman et al. Sciex Separations
Multi-Site N-Glycan Mapping by Capillary Electrophoresis
4. Akira Harazono National Institute of Health Sciences
New Japanese Pharmacopoeia General Test and General Information for Glycosylation Analysis of Glycoprotein
5. Jenifer L. Hendel et al. Ludger Ltd
A Fluorescent Labeling and Enrichment System for Glycopeptides Generated from Proteolytic Digestion of IgG mAbs; A System That Can Be Used as Part of the Peptide Mapping Workflow
6. Anne Kroll Kristensen et al. Novo Nordisk
Implementation of QbD Principles in Designing a Fast, Robust Method for Profiling of N-linked Carbohydrates in Antibodies
7. Jeremy Kunkel et al. Health Canada
Comparison of Orthogonal Chromatographic and Lectin-Affinity Microarray Methods for Glycan Profiling of a Therapeutic Monoclonal Antibody
8. Matthew A. Lauber et al. Waters Corporation
Wide-Pore Amide HILIC Separations for Assaying the Domain-Specific Glycosylation of mAbs
9. Matthew A. Lauber et al. Waters Corporation
Rapid Preparation of N-Glycans Using a Novel Fluorescence and MS Active Labeling Reagent
10. Leitão, O.L. et al. National Institute for Health Quality
New methods for Oligosaccharide Analysis from Recombinant Human Erythropoietin by UPLC/ESI/QTOF/MS in Brazil
11. Mark Lies et al. Sciex Separations
Rapid Level-3 Characterization of Glycoprotein Therapeutics BY CESI-MS
12. Paula Magnelli et al. New England Biolabs
Improving Sample Workflow: Rapid PNGase F for Accurate Antibody Characterization
13. Loretta Yang et al Glycosensors and Diagnostics
Development of a Glycoprofiling Method Using Multiplex Flow Cytometry
14. Jia Zhao et al. Merck
An effective LC-MS Based Method for On-line Characterization of N-linked Glycans in Biological Therapeutics
USP WORKSHOP ON GLYCOSYLATION ANALYSIS
FOR BIOPHARMACEUTICALS
Speaker / Moderator / Planning Committee Information (alpha order)
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
ParastooAzadi,Ph.D.USPAffiliation:Member,USPGlycoproteinsandGlycanAnalysisExpertPanelTechnicalDirectorUniversityofGeorgiaAthens,GA,USADr.AzadireceivedherB.Sc.inChemistryin1987fromUniversityofNorthLondon,UKandherPh.D.degreeinbiochemistryin1991fromImperialCollegeofScienceandTechnology,UniversityofLondon,studyingstructuralcharacterizationofcarbohydratesandglycoproteinsbymassspectrometryunderthesupervisionofProfs.A.DellandH.R.Morris.In1990throughto1994shewastheseniorscientistandthestudydirectoratM‐Scanlimited,anAnalyticalMassSpectrometryConsultancyinUKwhereshewasresponsibleforcompletestructuralcharacterizationofnativeandrecombinantproteinsandglycoproteinsusingmassspectrometryasaservicetothepharmaceuticalindustry.In1994shejoinedtheComplexCarbohydrateResearchCenterasapostdoctoralfellowandstudiedtheeffectoftheenzymesendohyrolaseandendolyaseonrhamnogalacturonanI,andcharacterizationofthefragmentsproducedbytheseenzymesbyESI‐MSandESIMS/MS.In1996shebecametheAssociateTechnicalDirectorofplantandmicrobialAnalyticalServicesattheComplexCarbohydrateResearchCenterwhereshewasresponsibleforplantandmicrobialserviceprogramwherepolysaccharidesandlipopolysaccharideswereanalyzedforotherinstitutes.Since2001,Dr.AzadihasbeentheTechnicalDirectorofAnalyticalServiceandTrainingattheComplexCarbohydrateResearchCenter.AstheTechnicalDirector,thesheoverseesandmanagesallanalyticalservicesandtrainingconductedattheCCRC,whicharesupportedbythreefederalresourcecentersofexcellencethatCCRChasbeenawarded:TheDepartmentofEnergy‐fundedCenterforPlantandMicrobialComplexCarbohydrates,theNationalInstitutesofHealthResourcesCenterforIntegratedGlycotechnology,andtheNationalInstitutesofHealthforBiomedicalGlycomics.Theanalyticalserviceprogramofferstwomainareasofservice:standardanalysesandcontractanalyses.Thesamplessubmittedforthesetypesofanalysescomefromacademic,government,non‐profitorganizationsandprivatecompanies,throughouttheUnitedStatesandinternationally.Dr.Azadiworkscloselywiththeresearchscientistsinindustryondevelopingcarbohydratebaseddrugsandtheneedforout‐sourcingpriortophaseIandphaseIIclinicaltrials.
USPWorkshoponGlycosylationAnalysisforBiopharmaceuticalsWorkshopAugust25‐26,2015,USPMeetingsCenter,Rockville,Maryland,USA
Herlaboratoryalsoconductsresearchinareasofstructuralcharacterizationofplant,bacterialandanimalpolysaccharides,glycoproteinsandglycolipidsusingMSandNMRtechniques.
PlanningCommitteeMemberModeratorSession6:EmergingTechnologiesWednesday,August26,2015,9:10a.m.–11:45a.m.PresentationAbstractCommonAnalyticalMethodsforOligosaccharideandMonosaccharideAnalysisTuesday,August25,2015,12:30p.m.–12:55p.m.Productionofhigh‐qualitypharmaceuticalrecombinanttherapeuticglycoproteinwithconsistencyinglycanqualityisstillchallenging.Sinceglycansareresponsibleforbioactivity,solubility,immunogenicity,andclearanceratefromcirculation,itisvitaltohavedetailedmapofglycansinrecombinanttherapeuticglycoprotein.However,duetotheenormousdiversityofcarbohydratestructuresandtheirheterogeneity,thisstillremainsoneofthebottlenecksoffullstructuralcharacterization.Detailedglycoproteinstructuralanalysishastobeabletoidentifythepeptidesequencewheretheglycansareattached,aswellasthestructureoftheglycanportion,includingoligosaccharidesequenceandglycosyllinkages.Wewilldetailmethodsformassspectrometry(MS)experimentsonbothreleasedglycans(“glycomics”),aswellasonintactglycopeptides(“glycoproteomics”)usingEDT,HCDandCIDfragmentationpathwaysthatareneededtofullyelucidatethestructureofglycoproteins.Additionalprotocolswillbeshownwhereacombinationofglycosylcompositionandglycosyllinkageanalysisusingacombinationofmethylationanalysis,MSnandexoglycosidasedigestionwillprovideinformationontheglycantopologyaswellasdetectionmethodsforpotentialnon‐humanmodificationsthatcouldarisefrommammalianexpressionsystemssuchasGalα1‐3GalandN‐glycolylneuraminicacid(NeuGc).Ourconsolidatedexperimentswilloutlineallthenecessaryinformationpertainingtotheglycoprotein,includingglycanfinestructure,attachmentsite,andglycosylationdegreetobeobtainedpharmaceuticalrecombinantglycoproteins.
USPWorkshoponGlycosylationAnalysisforBiopharmaceuticalsWorkshopAugust25‐26,2015,USPMeetingsCenter,Rockville,Maryland,USA
ChristopherBarton,Ph.D.SeniorScientistMedImmuneWashington,DC,USAChrisisaSeniorScientistatMedImmune,leadingthenovelmoleculesgroupwithinanalyticalbiotechnology.HestartedworkingoncarbohydrateanalyticsduringaPhDonpolysaccharidesandglycoproteinsynthesisattheUniversityofCambridge.Hecompletedpost‐doctoraltrainingworkinginaUKanti‐dopinglaboratory,anddevelopedexpertiseinmassspectrometryinthecontractresearchsector.HisroleatMedImmuneisfocusedonthedevelopmentofanalyticalapproachesforthetestingandcharacterizationofnon‐monoclonalantibodyproducts.Hisresearchinterestsincludedevelopingtoolsfortheanalysisandunderstandingofproteinglycosylationandpost‐translationalmodificationincellculture.
PresentationAbstractCaseStudy:CharacterizationandImpactofGlycosylationonPKofanIgGfusionproteinTuesday,August25,2015,10:10a.m.–10:35a.m.Non‐monocloncalantibodybiotherapeuticsoftenhavemultipleglycosylationsitesoccupiedwitharangeofgalactosylatedandsialylatedglycans.Thenatureandextentofthesespeciescanimpacttheprotein’spharmacokineticandpharmacodynamicprofile,andisanimportantfeaturetomonitorduringbiotherapeuticdevelopment.WepresentacasestudyofthecharacterizationofN‐glycosylationinadimericIgGfusionproteinwithtwoFcglycosylationsitesandfournon‐Fcsites.Theglycosylationoftheproteinwascharacterizedbyaseriesoftoolsofincreasingdetail.Thefirststagewascompositionalanalysisofthelevelofcomponentneutralmonosaccharidesandsialicacidspecies.Oligosaccharideprofilingofenzymaticallyreleasedglycanswasthenundertakentocharacterizetheglobalglycosylationprofileoftheprotein.Finallyanalysisbypeptidemappingwasusedtodeterminethesite‐specificglycosylationpattern.ThemodelproteinwasdeterminedtobedecoratedwithdistinctglycansateachoftheN‐glycosylationsites.TheFcwasoccupiedprimarilybyagalactosylatedbi‐antennaryglycans.Thenon‐Fcglycanswereoccupiedbyabroaderrangeofspecies,withbi‐antennaryandtri‐antennarycoresbeingobserved,decoratedwithvariablelevelsofgalactosylationandsialylation.Wefurtherpresentanapproachtounderstandtheimpactofglycosylationonproteinfunctionatanearlystageindevelopment,byproducingsamplesofproteinwithspecificglycosylationpatternsandstudyingtheseininvitroandinvivomodelsystems,includinganon‐humanprimatemodeltostudytheimpactof
USPWorkshoponGlycosylationAnalysisforBiopharmaceuticalsWorkshopAugust25‐26,2015,USPMeetingsCenter,Rockville,Maryland,USA
glycosylationonPK.Thisinformationcanbecombinedwiththeglycosylationanalysistoolsdescribedabovetotargetprocessdevelopmentonaproteinwiththemostdesirableglycosylationstate.
USPWorkshoponGlycosylationAnalysisforBiopharmaceuticalsWorkshopAugust25‐26,2015,USPMeetingsCenter,Rockville,Maryland,USA
EdithChang,Ph.D.ScientificLiaison,Global BiologicsU.S. Pharmacopeia (USP)Rockville,MD,USADr.ChangisaScientificLiaisonofGlobalBiologicswithUSP.SheservesasaleadliaisonforUSPProteinsExpertCommittee.Dr.ChangreceivedherM.S.andPh.D.inBiochemistrywithaminorinMolecularGeneticsfromUniversityofCalifornia,Riverside.PriortojoiningUSP,sheworkedmostrecentlyatKansasCityUniversityofMedicineandBiosciences,KansasCity,MO,whereshewasAssistantProfessorofBiochemistryandPrincipleInvestigatorforresearchprojectstoinvestigatetheroleofcyclooxygenase2inmalignanttransformationandcancerinvasion.EarlieremploymentwasatThermoFisherPiercewhereshewasaResearchScientistatR&Ddepartment.Dr.Changistheauthororco‐authorofmanypeer‐reviewedpublicationsinthefieldsofbiochemistry,molecularbiologyandcancer,andhasservedasanad‐hockreviewerforseveralpeer‐reviewedjournalsincludingCancerResearch,MolecularCancerTherapeutics,ClinicalCancerResearch,andTheInternationalJournalofBiochemistry&CellBiology.
PlanningCommitteeMemberPresentationAbstractUSPReferenceStandardsTuesday,August25,2015,2:55p.m.–3:05p.m.USP Reference Standards (RSs) are highly-characterized physical specimens used in testing by pharmaceutical and related industries, and are closely tied with the documentary standards published in the USP–NF, Food Chemicals Codex, and Dietary Supplements Compendium. This presentation will provide an overview of USP reference standards, and discuss the biologics RSs that are associated with compendial procedures for analysis of protein glycosylation.
USPWorkshoponGlycosylationAnalysisforBiopharmaceuticalsWorkshopAugust25‐26,2015,USPMeetingsCenter,Rockville,Maryland,USA
JohnCipollo,Ph.D.USPAffiliation:GovernmentLiaison,VaccinesforHumanUse–ViralVaccinesSeniorStaffFellowU.S.FoodandDrugAdministrationBethesda,MD,USADr.CipolloreceivedhisPh.D.in2000fromtheStateUniversityofNewYorkatAlbany.Heperformedhispost‐doctoralworkatBostonUniversitySchoolofDentalMedicineunderProfessorsCatherineCostelloinmassspectrometryandCarlosHirschberginbiochemistry.Hehaspublishedoverthirtyscientificarticlesintheareasofcarbohydratestructuralanalysisandglycomicswithstrongemphasisincarbohydratemassspectrometry.Dr.Cipollohasworkedextensivelyintheglycomicsofaseriesoforganismsincludinghuman,Caenorhabditiselegans,Entamoebainvadens,Entamoebahistolytica,andseveralyeastspecies.Hiscurrentinterestsincludethefunctionofglycosylationinproteincarbohydrateinteractionsinadaptiveandinnateimmunityandtheimpactofthosefunctionsinvaccinedevelopmentandperformance.Otherinterestsincludenovelchemistriesforimprovementofpolysaccharideconjugateandotherglycoconjugatebasedvaccines.AstherearefewbroadlyacceptedinformaticsplatformsforglycomicsanalysistheCipollogrouphas,andiscurrentlydeveloping,inhouseglycomicssoftwareforprocessingofmassspectrometryandglycanarrayglycomicsdataDr.CipolloservesasaProductSpecialistforCBERFDAprimarilyasaproductreviewerforbacterialpolysaccharidesandpolysaccharideconjugatevaccines.PlanningCommitteeMemberModeratorSession7:RegulatoryApproachesonGlycosylationWednesday,August26,2015,12:45p.m.–2:00p.m.
USPWorkshoponGlycosylationAnalysisforBiopharmaceuticalsWorkshopAugust25‐26,2015,USPMeetingsCenter,Rockville,Maryland,USA
TapanDas,Ph.D.Director,BiologicsDevelopmentBristol‐MyersSquibbNewYork,USATapanisaDirectorintheAnalyticalDevelopmentgroupofBristol‐MyersSquibb.HeleadstheMassSpectrometryandBiophysicsCenterofExcellenceengagedinadvancedcharacterizationandanalyticsforbiologicsdevelopment.PriortojoiningBMS,hewasatPfizerBiotherapeuticsR&Dandbuiltaworldclassstate‐of‐the‐artfacilityforBiophysicalCenterofExcellence.TapanisamemberofAAPS(AmercianAssociationofPharmaceuticalScientists)andservedAAPSinvariousroles,mostrecentlyservedastheChairoftheBiotechnologySection.
PresentationAbstractPracticalGlycoprofilingApproachforMeasurementandControlofGlycosylation)Tuesday,August25,2015,1:20p.m.–1:45p.m.Glycancompositionisakeyqualityattributeformanyproteintherapeutics.Glycanscaninfluencethemodeofaction,pharmacokinetics,andsafety.Robustanalyticalmethodsarecriticalformeasurementandcontrolofglycansduringprocessdevelopmentandforprocesscontrolinmanufacturing.Choiceofglycanassaymaydependondevelopmentphase,neededthroughput,andcharacterizationdatasought.Thispresentationwillincludebiotherapeuticcasestudiesfor(a)applicationinprocessdevelopmentand(b)forextendedcharacterization.
USPWorkshoponGlycosylationAnalysisforBiopharmaceuticalsWorkshopAugust25‐26,2015,USPMeetingsCenter,Rockville,Maryland,USA
MichaelDeFelippis,PhDUSPAffiliation:Member,Monographs–BiologicsandBiotechnology1ExpertCommittee;Member,GlycoproteinsandGlycanAnalysisExpertPanel;andChair,TherapeuticPeptidesSeniorResearchFellowEliLilly&CompanyIndianapolis,IN,USAMichaelR.DeFelippis,PhDjoinedtheLillyResearchLaboratoriesofEliLillyandCompanyin1990aftercompletinghisdoctorateinbiochemistry.HeiscurrentlyaSeniorResearchFellowworkingintheBioproductResearchandDevelopmentdivision.Hisworkisfocusedondevelopmentofproteinandpeptidebiopharmaceuticalproductswithparticularemphasisoncharacterizingphysicochemicalproperties,definingdeliveryoptions,developingcontrolstrategies,executingtechnologytransfersandpreparingdatapackagestosupportworldwideregulatorysubmissionsandpost‐launchregistrations.Dr.DeFelippishaspublishedmanuscripts,reviewarticlesandbookchaptersonthesubjectsofproteinandpeptidestructuralcharacterizationandformulationdesign/deliverystrategies.Hehasgivennumerouspresentationsonthesetopicsandisanamedinventoronseveralpatentsrelatedtotheseareas.
PlanningCommitteeMemberModeratorSession2:TheRoleofGlycosylationforTherapeuticProteinsTuesday,August25,2015,9:20a.m.–11:30a.m.
USPWorkshoponGlycosylationAnalysisforBiopharmaceuticalsWorkshopAugust25‐26,2015,USPMeetingsCenter,Rockville,Maryland,USA
MattDeLisa,Ph.D.WilliamL.LewisProfessorofEngineeringDepartmentofChemicalandBiomolecularEngineering,CornellUniversityIthaca,NewYork,USAProfessorDeLisareceivedaB.S.inChemicalEngineering fromtheUniversityofConnecticut in1996;aPh.D.inChemicalEngineering fromtheUniversityofMarylandin2001;anddidpostdoctoralworkattheUniversityofTexas‐Austin,DepartmentofChemicalEngineering.DeLisajoinedtheDepartmentofChemicalandBiomolecularEngineeringatCornellUniversityasanassistantprofessorin2003.Hewaspromotedtoassociateprofessorin2009andtofullprofessorin2013.Inaddition,herecentlyservedasaGastprofessur attheSwissFederalInstituteofTechnology (ETHZürich)intheInstitutfürMikrobiologie.DeLisahasreceivedseveralawardsforhisworkincludinganNSFCAREERaward(2005),aNYSTARWatsonYoungInvestigatoraward(2004),aBeckmanFoundationYoungInvestigatoraward(2005),anOfficeofNavalResearchYoungInvestigatoraward(2006),aNYSTARDistinguishedFacultyAward(2007),aCornellProvost'sAwardforDistinguishedScholarship(2009),andtheAmericanChemicalSocietyBIOTdivisionYoungInvestigatoraward(2010).Hewasalsonamedasoneofthetop35younginnovators(TR35)byMIT'sTechnologyReview(2005),wasselectedastheAllanP.ColburnMemorialLecturerattheUniversityofDelaware(2009),andwaschosenastheinauguralrecipientoftheWiley‐Blackwell Biotechnology andBioengineeringDanielI.C.Wangaward(2008),whichhonorsadistinguishedyoungresearcherinthisfield.Mostrecently,hewasselectedtotheIDA/DARPADefenseScienceStudyGroup(2014‐15)andelectedtotheAmericanInstituteforMedicalandBiologicalEngineering (2014).ProfessorDeLisa'sresearchfocusesonunderstanding andcontrollingthemolecularmechanismsunderlyingproteinbiogenesis ‐‐foldingandassembly,membranetranslocationandpost‐translationalmodifications ‐‐inthecomplexenvironmentofalivingcell.Hiscontributions toscienceandengineeringincludetheinventionofnumerouscommerciallyimportanttechnologies forfacilitatingthediscovery,designandmanufacturing ofhumandrugsandseminaldiscoveries intheareasofcellularproteinfoldingandproteintranslocation. PresentationAbstractInterestinusingnon‐MammaliancellsWednesday,August26,2015,9:35a.m.–10:00a.m.Carbohydratesaddalevelofdiversityacrossallformsoflifethatisunparalleledbytheinformationcontentofnucleicacidsandproteins.Thelackofasimpletemplatetotranslateaglycancodeintodefinedsugarstructurescontributestothis
USPWorkshoponGlycosylationAnalysisforBiopharmaceuticalsWorkshopAugust25‐26,2015,USPMeetingsCenter,Rockville,Maryland,USA
complexityandimpedeseffortsaimedattheproductionofbiologicallyimportantglycansandglycoconjugates.Withthediscoveryofglycoproteinsynthesisinbacteriaandfunctionaltransferofglycosylationpathwaysbetweenspecies,Escherichiacolicellshavebecomeatractablehostforunderstandingglycosylationandtheunderlyingglycancodeoflivingcells.Moreover,effortstomanipulatethepathwaysfromsugarnucleotidestoglycolipidstoglycoproteinshavetransformedE.coliintoalivingfactoryforscalable,bottom‐upproductionofcomplexglycoconjugatesbydesign.Here,IwilldiscussoureffortstodevelopE.coliforthebiosynthesisofadiversearrayofglycanstructures,whichcanbeusedtotailortheactivity,stability,half‐life,andimmunogenicityofanarrayofproteintargetsrangingfrombiopharmaceuticalstoindustrialenzymes.IwillalsodiscussoureffortstounifyproteinglycosylationinE.coliwiththeadvancedtoolsofproteinengineeringsuchascellsurfaceandphagedisplaytechnologies.Theresultisapowerfulnewwaytoengineertheenzymes,pathways,end‐products,andgenomesofglycoengineeredbacteriaforcreatingthenextgenerationofproteintherapeuticsandvaccines.
USPWorkshoponGlycosylationAnalysisforBiopharmaceuticalsWorkshopAugust25‐26,2015,USPMeetingsCenter,Rockville,Maryland,USA
ChrisopherD.Downey,Ph.D.LeadChemistU.S.FoodandDrugAdministration(FDA)/CDEROfficeofBiotechnologyProductsDr.DowneyreceivedhisPhDin2006fromtheUniversityofColoradoatBoulder,wherehestudiedtheconformationaldynamicsofRNAtertiarystructures.From2007to2011,heperformedhispostdoctoralworkattheUniversityofColoradoatBoulder,studyingthemolecularmechanismsofgenomicDNAreplication.Dr.DowneyservedasaProductQualityreviewerinFDA/CDER’sOfficeofBiotechnologyProducts(OBP)beginningin2012.Hehasextensiveexperienceinthereviewofenzymereplacementtherapies,hematologicgrowthfactors,anddigestiveenzymesandintheinspectionoffacilitiesmanufacturingtherapeuticbiotechnologyproducts.Since2014,Dr.DowneyhasservedasaLeadChemistinOBP’sDivisionofBiotechnologyReviewandResearch‐II,providingtraining,technicalandregulatoryguidance,andsecondaryreviewforhisteamofproductqualityreviewers.
PresentationAbstractPlenarySession:RegulatoryExpectationsWednesday,August26,2015,8:30a.m.–9:10a.m.Proteinglycosylationaffectsawide‐rangeofattributesthatcontributetothesafetyandefficacyofproteintherapeutics.Theseattributesincludephysicochemicalstability,immunogenicity,bioavailability,andbiodistribution.Thecomplexityofthebiologicalfunctionstowhichglycosylationcontributesandtheheterogeneousnatureofglycoformsrepresentadistinctchallengeinproductdevelopmentandinregulatoryreview.Thispresentationwillprovideageneraloverview,fromareviewer’sperspective,ofregulatoryexpectationsforcharacterizingglycosylation,linkingglycosylationattributestofunction,anddevelopingacontrolstrategy.Thetalkwillalsodiscussgeneralconceptsandexpectationsforestablishingcomparabilitybeforeandaftermanufacturingchangesandforanalyzinganalyticalsimilaritydataforglycosylationinthecontextofbiosimilars.
USPWorkshoponGlycosylationAnalysisforBiopharmaceuticalsWorkshopAugust25‐26,2015,USPMeetingsCenter,Rockville,Maryland,USA
JoséM.GomesPrincipalScientist,CultureProcessDevelopmentPfizer,Inc.Andover,MA,USAJoséisabiochemist&biophysicistwithconsiderableexperienceincellculture,chemicalengineering,andmolecularbiologyincluding18yearsofindustryexperience.HejoinedPfizerthroughtheacquisitionofWyethandcurrentlyholdsthepositionofPrincipalScientistwithintheCultureProcessDevelopmentgroupinBiotherapeuticsR&D.Hisworkfocusesondevelopmentandsupportofupstreamprocessesforawidegamutofprojectsfromearly‐stagetolate‐stageclinicalproducts,biosimilars,commercialproducts,andnext‐generationproducts.HeiscurrentlyleadingtheupstreamprocessteamforPfizer’s1stbiosimilarprogram.Hisparticularareasofinterestincludeunderstandingeffectsofprocessparametersonproductquality,utilizationofdesignofexperiments&qualityriskmanagement,applicationofQbD,andunderstandingfactorsaffectingprocesstechtransfer&scale‐up(includingagitationandaerationeffects).Priortojoiningindustry,JoséwasinvolvedinstudyinglipidandhormonemetabolismatTuftsMedicalSchoolandtheU.S.D.A.
PresentationAbstractModulationofGlycosylationPatternsbyBioprocessTechniquesWednesday,August26,2015,2:30p.m.–2:55p.m.Theglycosylationofrecombinantproteinsmaybeacriticalqualityattributedependentonmodeofaction.Variabilityinglycosylationpatternsmayalteranantibody’seffectorfunctionsinpatients,suchasantibody‐dependentcellmediatedcytotoxicity(ADCC),complement‐dependentcytotoxicity(CDC),andFc‐receptorbinding.Therefore,theabilitytomodulateglycosylationpatternscanenablestructure/functionstudiestofurtherproductunderstandingandenablethedevelopmentofoptimizedmanufacturingprocessescapableofconsistentlydeliveringmaterialofdesiredquality.Thispresentationwilldiscusstheapproachesandstrategiesofmodulatingglycosylationpatternsthroughuseofvariousbioprocesstechniquessuchasprocessparametercontrol,cellculturemediasupplements,enzymaticinhibitors,andcelllineselection.
USPWorkshoponGlycosylationAnalysisforBiopharmaceuticalsWorkshopAugust25‐26,2015,USPMeetingsCenter,Rockville,Maryland,USA
Maria‐TeresaGutierrez‐Lugo,Ph.D.U.S.FoodandDrugAdministrationSilverSpring,MD,USADr.Gutierrez‐LugoisaProductQualityTeamLeaderintheOfficeofBiotechnologyProducts(OBP),CDER,FDA.PriortojoiningtheFDAin2008,Dr.Gutierrez‐LugoconductedpostdoctoralresearchattheNIHandattheUniversityofArizona.SheholdsaPh.D.inChemicalSciences(Pharmacy)fromtheNationalAutonomousUniversityofMexico
PresentationAbstractRegulatoryPerspectiveWednesday,August26,2015,2:55p.m.–3:20p.m.Post‐approvalmanufacturingchangesofbiopharmaceuticalscouldresultinchangesinproductqualityattributeswhichcouldimpactsafetyandefficacyofthedrugproduct.Comparabilityofpre‐changeandpost‐changeproductisneededtodemonstratethatthemanufacturingchangedidnotadverselyimpactthesafetyandefficacyofthedrugproduct.Thispresentationwillprovideageneralbackgroundontheexpectationsofcomparabilityandwillpresentcasestudiesofpost‐approvalmanufacturingchangesofglycosylatedproducts.
USPWorkshoponGlycosylationAnalysisforBiopharmaceuticalsWorkshopAugust25‐26,2015,USPMeetingsCenter,Rockville,Maryland,USA
BryanHarmon,Ph.D.ResearchFellowEliLillyandCompanyIndianapolis,IN,USAResearchFellow,EliLillyandCompany,Dr.HarmonreceivedhisB.S.inChemistryfromRose‐HulmanInstituteofTechnologyandhisPh.D.inAnalyticalChemistryfromPurdueUniversityunderProf.FredRegnier.Followingapost‐doctoralpositionunderProf.DanielI.C.WangattheBiotechnologyProcessEngineeringCenteratMIT,heworkedinthevaccinedivisionofMerckResearchLaboratoriesfor3years.SincejoiningLillyin1999,Dr.HarmonhasservedasagroupleaderfortheBioproductStructuralCharacterizationTeam.Histeamisresponsiblefordetailedstructuralcharacterizationofallpeptide,protein,andmonoclonalantibodycandidatesinLilly'sdevelopmentpipeline,includingtheelucidationofpost‐translationalmodifications,suchasglycosylation,aswellasdegradationproductsandmechanisms.AtLilly,Dr.HarmonhasalsoplayedaleadingroleinestablishingcomparabilitystrategiesandinthedevelopmentandapplicationofQualitybyDesignprinciplesforbioproducts.Hehasalsoservedastheleaddevelopmentscientistforseverallatephaseprojects.
PresentationAbstractCaseStudy:InfluenceofFabGlycosylationonThePharmacologicalPropertiesofaMonoclonalAntibodyTuesday,August25,2015,10:35a.m.–11:00a.m.Recombinantmonoclonalantibodies(mAbs)intendedforuseastherapeuticagentstypicallycontainaconservedN‐linkedglycosylationsiteintheFcregionthatcanplayanimportantroleinthepharmacologicalpropertiesofthemAb,includingmediatingeffectorfunctionsforIgG1mAbs.ThiscasestudyinvolvesamAbthatcontainsanadditionalN‐linkedglycosylationsiteinitsFabregion.InordertounderstandtheimpactoftheFabglycosylationonthepharmacokineticsofthemAb,themAbwasisolatedfromtimepointsamplesobtainedfromahumanclinicalstudy,andLC‐MSglycosylationanalysiswasperformedinordertoidentifytheoligosaccharidestructuresthatareclearedmorerapidly.ThisinformationwasfurtherutilizedtoestablishacontrolstrategyforensuringconsistentFabglycosylationprofilesand,thus,consistentpharmacokinetics,includingthevalidationoftheLC‐MSmethodasaGMPspecificationtest.
USPWorkshoponGlycosylationAnalysisforBiopharmaceuticalsWorkshopAugust25‐26,2015,USPMeetingsCenter,Rockville,Maryland,USA
GuoyingJiang,Ph.D.SeniorScientist|BiologicalTechnologiesGenentechSanFrancisco,CA,USAGuoyingJiang,Ph.D.,isaSeniorScientistandGroupLeaderintheBiologicalTechnologiesgroupwithintheAnalyticalDepartment&QualityControlDepartmentatGenentech,aMemberoftheRocheGroup.Guoyingisleadingateamofscientistsandresearchassociatesfocusingonpotencyassaydevelopment,optimizationandvalidationinsupportofGMPlotreleaseandstabilitytesting.HergroupisalsosupportingpotencymethodstransferanddevelopingcharacterizationmethodsforFceffectorfunction.GuoyingobtainedherB.SdegreefromPekingUniversityinChina,andPh.D.degreefromColumbiaUniversityinNewYork.ShewasapostdoctoralscientistinMountSinaischoolofMedicineinNewYorkbeforejoininginGenentechin2008.
PresentationAbstractTheUseofAlternativeMethodsasSurrogateMeasuresofBiologicalActivityTuesday,August25,2015,9:20a.m.–9:45a.m.Antibodiesrecognizingcellsurfaceexpressedantigens,areabletoengageFcγreceptorsoneffectorcellssuchasmonocytes,macrophages,naturalkillercells,neutrophils,orbindtoC1q,andelicitimmuneeffectorfunctionssuchasADCP,ADCC,andCDC.Glycosylationrepresentsoneofthemainsourcesofheterogeneityofantibodyglycoformsandcangreatlyinfluenceeffectorfunctionwithpotentialimpacttosafetyorefficacy.Casestudieswillbepresenteddescribingthecorrelationbetweenglycosylationandbioactivity,andthepotentialuseofphysicochemicalorbindingassaysasasurrogatemeasuresofCDCandADCCactivity.
USPWorkshoponGlycosylationAnalysisforBiopharmaceuticalsWorkshopAugust25‐26,2015,USPMeetingsCenter,Rockville,Maryland,USA
ChrisJones,Ph.D.USPAffiliation:Chair,USPGlycoproteinsandGlycanAnalysisExpertPanelHeadofDivision,LaboratoryofMolecularStructureNationalInstituteforBiologicalStandardsandControlPottersBar,Hertfordshire,UnitedKingdom
Dr. Chris Jones has worked at NIBSC since 1982, with 23 years as a Head of Division responsible for developing, implementing and validating sophisticated physico-chemical methods for the characterisation of complex biological products. He uses Nuclear Magnetic Resonance (NMR) spectroscopy, circular dichroism and other optical spectroscopy approaches, mass spectrometry and specialised HPLC approaches for glycan and peptide mapping.
Dr. Jones is a world expert on the physico-chemical characterisation of polysaccharide and glycoconjugate vaccines, widely used in infants to protect against meningitis, acute respiratory infections and invasive pneumococcal infections, and typhoid. He is also closely involved in writing regulatory guidance for these products and teaches courses.
PlanningCommitteeMemberModeratorSession4:StandardizationTuesday,August25,2015,2:35p.m.–4:00p.m.PresentationAbstractStandardprocedures:USP<1084>,<212>,<210>,and<129>Tuesday,August25,2015,2:35p.m.–2:55p.m.TheUnitedStatesPharmacopeiaaredevelopingaseriesofgeneralchaptersandreferencestandardstosupporttheroutinetestingofglycoproteins,called<1084>Glycoproteinandglycananalysis–generalconsiderations,<210>MonosaccharideAnalysisand<212>OligosaccharideAnalysis.Thistalkwilldescribetheaims,scope,structureandevolutionofthesechapters,theassociatedreferencestandardsandrelationshiptoproductmonographsandtheproductclasschapter<129>AnalyticalProceduresforRecombinantTherapeuticMonoclonalAntibodies.ClosingRemarksWednesday,August26,2015,4:10p.m.–4:30p.m.
USPWorkshoponGlycosylationAnalysisforBiopharmaceuticalsWorkshopAugust25‐26,2015,USPMeetingsCenter,Rockville,Maryland,USA
TrishLi,Ph.D.SeniorScienceandStandardsLiaisonU.S. Pharmacopeia (USP)Rockville,MD,USATrishLi,Ph.D.joinedUSPin2006.SheiscurrentlyaSr.ScienceandStandardsLiaisonworkingatBiologics&BiotechnologyDepartment.Shemanagesaportfolioofreferencestandardsandmonographs.PriortoUSP,Dr.LiworkedforPfizer’sGlobalManufacturingDivision,QualityOperationDepartmentatGroton,Connecticut.SheobtainedBScinChemistryfromPekingUniversity,andPh.D.inOrganicChemistryfromUniversityofMiami.
PlanningCommitteeMemberModeratorSession3:CurrentTechnologiesTuesday,August25,2015,12:30p.m.–2:15p.m.PresentationAbstractWhatWasSaid&NextStepsWednesday,August26,2015,3:50p.m.–4:10p.m.Thissessionwillbeasummaryoftheworkshop’sdiscussions.
USPWorkshoponGlycosylationAnalysisforBiopharmaceuticalsWorkshopAugust25‐26,2015,USPMeetingsCenter,Rockville,Maryland,USA
JohnMark, MSc,PhDHealthCanadaJohnMarkreceivedhisMScinPhysiologyattheUniversityofManitobadevelopingmagneticresonance‐based,non‐invasivediagnosticmethodsattheNationalResearchCouncilCanada‐InstituteforBiodiagnostics.Subsequently,hecompletedaPhDinBiochemistryattheUniversityofOttawawherehestudiedproteinstructure‐functionrelationshipsintherapeutictargetproteins.JohneventuallyjoinedHealthCanadain2008asaResearchChemistintheCenterforVaccinesEvaluation’sProteinChemistrylaboratorywherehisworkfocusedonthedevelopmentofnovelin‐vitromethodstoassessproteincomparability,withaspecificfocusonSubsequentEntryBiologics.Currently,JohnisaSeniorBiologist/EvaluatorwiththeCMCQualitygroupinHealthCanada’sCenterfortheEvaluationofRadiopharmaceuticalsandBiologics,MonoclonalAntibodiesDivision.
PresentationAbstractWhataretheExpectationsfromtheRegulatoryAgenciesWednesday,August26,2015,12:45p.m.–1:10p.m.Proteinglycosylationisoneofnature’smostwidespreadpost‐translationalmodifications.Itisalsooneofthemoredifficultattributestocharacterizebytraditionalanalyticalmethods.Nevertheless,duetothepotentialeffectsthatglycosylationcanhaveonabiologic’spotency,immunogenicity,andcirculatoryhalf‐life;acomprehensivedeterminationoftheglycosylationisrequiredinmajorregulatoryfilings.Butwhataretheexpectations?TherecanbesomeconfusionsincetherequirementsdescribedinICHQ5EandQ6Baregeneral,butthedetailsrequestedbyregulatorsareoftenmuchmorespecificandvaryfromregiontoregionorevenreviewertoreviewer.Toprovidesomeinsightintowhatisexpected,thistalkwillfocusontheCMCQualityreviewprocessatHealthCanadaandtheexpectationsfromaCanadianperspective.Topicswillincludethetheoreticalrisksrelatedtochangesinglycosylation,thechallengesassociatedwithproducingproductwithacceptableglycanvariability,anddiscussionoftheregulatoryexpectationsforglycancharacterizationandanalysis.
USPWorkshoponGlycosylationAnalysisforBiopharmaceuticalsWorkshopAugust25‐26,2015,USPMeetingsCenter,Rockville,Maryland,USA
RonOrlando,Ph.D.ProfessorofBiochemistryandMolecularBiologyComplexCarbohydrateResearchCenter,UniversityofGeorgiaAthens,GA,USADr.RonOrlandoreceivedhisB.S.innaturalsciencein1983fromSt.Mary'sCollegeofMaryland,hisPh.D.inchemistryin1988fromtheUniversityofDelaware,andservedasapost‐doctoralfellowattheUniversityofMarylandBaltimoreCountyfrom1988until1990.AfterservingfortwoyearsasaseniorscientistattheSuntoryInstituteofBioOrganicResearch(Osaka,Japan),hejoinedthefacultyoftheComplexCarbohydrateResearchCenterattheUniversityofGeorgiainJanuary1993,whereheiscurrentlyaProfessorofBiochemistry&MolecularBiologyandChemistry.RonOrlandohasover27yearsofexperiencewithmassspectrometry,23oftheseyearsfocusedontheidentification,characterization,andquantitationofproteinsandtheirpost‐translationalmodifications.Hehasco‐authoredover120publicationsinpeerreviewedjournals,hasgivenover100invitedlecturesatvariousconferences,andhasservedonover40NIHreviewpanels.Dr.OrlandoisthecurrentEditor‐in‐ChieffortheJournalofBiomolecularTechniques(JBT),andservesonanumberofeditorialboards.Hehasorganizedandtaughtshort‐coursesontheAnalysisofGlycoproteinsbyMassSpectrometryatmeetingsoftheAmericanSocietyforMassSpectrometry(ASMS),theAssociationofBiomolecularResourceFacilities(ABRF)andtheInternationalSymposiumandExhibitontheSeparationofProteins,Peptides&Polynucleotides(ISPPP),andisthefounderandpast‐chairoftheABRFGlycoproteinResearchGroup.Dr.Orlandoisalsoaserialentrepreneurhavingfounded3spin‐off/start‐upcompanies:BioInquirein2007,GlycoScientificin2009andPhotochemTechnologiesin2012.Hewasgiventheawardof"EntrepreneuroftheYear"fromtheGeorgiaBioBusinessCenter,andwasnamedaleaderoftomorrowbySpectroscopymagazine.PresentationAbstractRelativeandAbsoluteQuantitationofGlycoproteinGlycansUsingIsotopicallyLabeledStandardGlycoproteinsWednesday,August26,2015,10:25a.m.–10:50a.m.Theabilitytoaccuratelyquantitatetheglycanchainsattachedtoglycoproteinshaswide‐rangingimplications.Numerousstudiesoverthepast40yearshavedemonstratedthatabnormalglycosylationoccursinvirtuallyalltypesofhumancancers,anddemonstratethepotentialofusingglycanmarkersineitheradiagnosticoraprognosticmanner.Theglycosylationonrecombinantproteintherapeuticsisalsoknowntohaveprofoundeffects,withoneofthebetterknownexamplesbeingtheincreasedserumhalf‐lifeoferythropoietin(EPO)resultingfromglycoengineering.Hence,thequantificationofglycoproteinglycansplayimportantrolesfromthediscoveryofnewdiagnostic/prognosticmarkerstothedevelopmentoftherapeuticagents.
USPWorkshoponGlycosylationAnalysisforBiopharmaceuticalsWorkshopAugust25‐26,2015,USPMeetingsCenter,Rockville,Maryland,USA
Acurrentimpedimentforperformingquantitativeglycomicsistheshortageofstandardglycoproteinsandisotopicallylabeledreagentstoenableaccuratequantitation.Thedifficultywithglycanquantitationhasbeenhighlightedbyinter‐laboratorystudiesconductedbytheHumanProteomeOrganization(HUPO)andtheAssociationofBiomolecularResourceFacilities(ABRF),whichdemonstratedthatquantitativemeasurementoftheglycansinasinglesampledeviatedbymorethan100%acrossparticipatinglaboratories.ThefocusofthispresentationistheevaluationofanIgGwithisotopicallylabeledglycansasaninternalstandardforboththerelativeandabsolutequantitationofN‐linkedglycansreleasedfrombothhumanserumIgGsandwholehumanserum.Thesestudiesdemonstratedthattheuseoftheinternalstandardleadtoasignificantlyimprovedaccuracy,reducedthecoefficientsofvariation(CVs)byover10fold,droppingthestandarddeviationtolessthan10%fromtheover100%deviationobtainedwithoutthelabeledstandard,andgreatlyreducedtheinter‐laboratoryvariabilitydespiteexperimentsbeingperformedbydifferentresearchersindifferentlocations.TheimprovementsassociatedwiththeisotopicallylabeledIgGleadustopredictthatthiswillbeavaluablestandardfortheanalysisofglycoproteinglycans.
USPWorkshoponGlycosylationAnalysisforBiopharmaceuticalsWorkshopAugust25‐26,2015,USPMeetingsCenter,Rockville,Maryland,USA
JeffRohrer,Ph.D.DirectorofApplicationsDevelopmentDionexProductsforThermoFisherScientific,Inc.Sunnyvale,CADr.RohreristheDirectorofApplicationsDevelopment,DionexProductsforThermoFisherScientific,.InthispositionhedirectstheworkofthecorporateapplicationslaboratoryinSunnyvaleCalifornia.HealsoadvisesandreviewstheworkofotherchromatographylabsatThermoFisherScientific.TheselabsdevelopHPLC,IC,HPAE‐PAD,andotherLC‐basedassays.Dr.Rohrerisanauthorof69peer‐reviewedpublicationsandisamemberoftheUnitedStatesPharmacopeia(USP)ExpertCommitteeonMonographDevelopmentforSmallMolecules#1,amemberoftheUSPExpertPanelonModernizationofIdentificationTests,andamemberoftheUSPExpertPanelonGlycoproteinandGlycanAnalysis.Between2005and2010hewasamemberoftheUSPExpertCommitteeforantibioticsmonographdevelopment.Heisalsotheco‐editorofabooktitledApplicationofIonChromatographyforPharmaceuticalandBiologicalProductsthatwaspublishedin2012.Dr.RohrerjoinedThermoFisher(thenDionex)in1989andhasheldpositionsthatinclude,MarketingFieldChemist,SeniorBiochemistinR&D,andApplicationsLabManager.PriortojoiningThermoFisherhespenttwoyearsasapost‐doctoralassociateinDr.ElizabethTheil'slabatNorthCarolinaStateUniversitystudyingthemechanismofirondepositionintotheproteinferritin.JeffreceivedhisBSinChemistryfromFranklinandMarshallCollegein1981andhisPh.D.inChemistryfromtheUniversityofDelawareworkingwithDr.HaroldWhiteIIIstudyingtheroleofglycosylationinthetransportofchickenserumriboflavin‐bindingproteinacrosstheoocytemembrane.
PresentationAbstractTheCommonChallengesFacedTodayWhenPerformingGlycosylationAnalysisTuesday,August25,2015,12:55p.m.–1:20p.m.Whiletherearenumerousmethods/techniquesforcharacterizingaprotein’sglycosylation,nosingleonecanprovidealltheinformationdesired,andnomethodiswithoutitsliabilities.Forthesereasons,fewifanylabsrelyonjustonemethodofglycosylationanalysis.Threecommonglycosylationassaysaremonosaccharidecomposition,sialicacidcomposition,andoligosaccharideprofiling.Thispresentationwilllookatsomeofthechallengesfacedforeachofthesethreeassays,withafocusonliquidchromatographictechniques.Thechemicalandenzymaticsamplepreparationrequiredforeachassaywillbeamajorpartofthediscussion.Forexample,whataretheproblems/challengesofacidhydrolysisformonosaccharideanalysis,shouldIchooseacidhydrolysisorneuraminidasetreatmentforsialicacidanalysis,andshouldIanalyzenativeorlabeledoligosaccharides?Accuracy,reproducibility,sensitivity,analysistime,andotherfactorswillbediscussedastheypertaintoeachmethodandtypicalanalysisneeds.
USPWorkshoponGlycosylationAnalysisforBiopharmaceuticalsWorkshopAugust25‐26,2015,USPMeetingsCenter,Rockville,Maryland,USA
PaulineRudd,Ph.D.ResearchProfessorofGlycobiologyNationalInstituteforBioProcessingResearchandTraining(NIBRT),UniversityCollege,DublinDublin,IrelandProfessorPaulineM.RuddBSc,LRIC,MA(Oxon),PhDistheResearchProfessorofGlycobiologyatUniversityCollege,Dublin.SheheadstheGlycoSciencesResearchGroupattheNationalInstituteforBioProcessingResearchandTraininginIreland(NIBRT)wheresheisaPIandconsultant.Inadditiontoherbasicresearchinterests,shehasmanylinkswithpharmaceuticalcompaniesacrosstheworldbecauseGlycoScienceisamajorareaofspecialisedexpertiserequiredtoensurethesafetyandefficacyofbiotherapeuticdrugs,suchasmonoclonalantibodiesforcancerandautoimmunedisorders.TheopenaccessdatabasesandbioinformaticsprogrammesdevelopedinherlabhaverecentlybeenincorporatedintotheWatersUNIFIsoftwarewheretheyaretailoredtowardstheneedofBioPharma.ProfessorRuddobtainedaBScinChemistryattheUniversityofLondonandaPhDinGlycobiologyattheOpenUniversity,UK.ShewasaFoundingScientistofWessexBiochemicals(laterSigmaLondon),VisitingResearchAssociateatTheScrippsResearchInstitute,CA,VisitingProfessorofBiochemistryatShanghaiMedicalUniversityPRC,VisitingScientistatBenGurionUniversityoftheNegev,IsraelandanErskineVisitingFellow,CanterburyUniversity,Christchurch,NewZealand.SheisaFellowoftheRoyalSocietyofMedicine,London,visitingProfessoratSt.George’sHospital,LondonandanAdjunctProfessoratNorthEasternUniversity,Boston,NUIGalway,TrinityCollegeDublinandatUniversityCollege,Dublin.SheisaVIatBTI,AStar,Singapore.In2010shewasawardedtheJamesGregoryMedalandanAgilentThoughtLeaderawardandin2012shereceivedaWatersGlobalInnovationaward.In2014shewasawardedanHonoraryDoctorateatGothenburgUniversity,Sweden.ProfessorRuddhasmorethan280scientificpublicationsandhasgivenover350lecturesandseminarsatinternationalmeetings.BeforemovinghergrouptoDublinin2006,ProfessorRuddwasamemberoftheOxfordGlycobiologyInstitutefor25years,whereshewasaSeniorResearchFellowandaUniversityReaderinGlycobiologyattheUniversityofOxford.PresentationAbstractTheCriticalFeaturesofGlycosylationfortheTherapeuticProductsTuesday,August25,2015,8:40a.m.–9:20a.m.AlterationsinglycosylationarecommoninphysiologicalandpathologicalprocessesaswellasinthebioprocessingofproductssuchasMAbsandEtanercept..GlycansgiverisetocriticalfeaturesorGCQAs(GlycosylatedCriticalQualityAttributes)thatcanaffectsafetyandefficacy,suchashalf‐life,Fc
USPWorkshoponGlycosylationAnalysisforBiopharmaceuticalsWorkshopAugust25‐26,2015,USPMeetingsCenter,Rockville,Maryland,USA
dependentdownstreamfunctionandimmunogenicity.Glycanstructuresare,inthefirstinstance,controlledbygenes,howevertheprocessingpathwaysalsodependonthebioprocessingconditionsandcellspecificpathways.Theseregulateglycoproteinexpressionandprovidefurthermechanismsforfinetuninganddiversifyingtheglycansandthefunctionsoftheproteinstowhichtheyareattached.Theprofiling,characterisation,anddetailedanalysisofreleasedN‐andO‐glycansandglycopeptidesischallenging,thereforeaplatformhasbeendesignedtosimplifythetechnologywhilepreservingtheintegrityofthedata.Aroboticplatformtoreleaseandlabelglycansfromglycoproteinsina96/384wellplateformathasbeendevelopedasafrontendtoglycanseparationstechnologiesincludingonline‐HILIC/MS/MSandcapillaryelectrophoresis.DatabasesforthesetechnologiesareopensourceandalsoincorporatedintoWatersUNIFIsoftwareaswllasbeingavailableontheNIBRTwebsite(http://glycobase.nibrt.ie/tools.html).Asensitivelabel(ADC)hasrecentlybeendevelopedbyNIBRTandWatersalsohavedevelopedRapifluor.Theplatformhasbeenoptimisedfortherigorous,detailedandquantitativeanalysisofbiopharmaceuticalsateachstageofthemanufacturingprocessandisalsoapplicabletobasicresearch.Theplateformatmakesitconvenientforlargesamplesets;itisrelativelycheap,robustandquantitative.Thebioinformaticsprogrammesenablethelessexperiencedresearchertohandlethedataandthepossibilityofintegratingtheprogrammeswithother–omicsdataisnowonthehorizon.ReferencesAutomated,high‐throughputIgG‐antibodyglycoprofilingplatform.StöckmannH,AdamczykB,HayesJ,RuddPM.AnalChem.2013Sep17;85(18):8841‐9.Genomicsmeetsglycomics‐thefirstGWASstudyofhumanN‐GlycomeidentifiesHNF1αasamasterregulatorofplasmaproteinfucosylation.LaucG,EssafiA,HuffmanJE,RuddPM,RudanI.etal.,PLoSGenet.2010;6(12).Automated,high‐throughputserumglycoprofilingplatform.StöckmannH,O'FlahertyR,AdamczykB,SaldovaR,RuddPM.IntegrBiol(Camb).2015Jul20.[Epubaheadofprint]UltrahighThroughput,Ultrafiltration‐BasedN‐GlycomicsPlatformforUltraperformanceLiquidChromatography(ULTRA3).StöckmannH,DukeRM,MillánMartínS,RuddPM.AnalChem.2015Jul31.[Epubaheadofprint]Inpress:JustinM.Prien,HenningStöckmann,SimoneAlbrecht,SilviaM.Martin,M.Varatta,M.Furtado,S.Hosselet,MeiyaoWang3TrinaFormolo,PaulineM.Rudd,and,JohnE.SchielACSpublicationsCh8.TheElucidationofCoandPost‐TranslationalModificationsOrthogonalTechnologiesforNISTmAbN‐GlycanStructureElucidationandQuantitation
USPWorkshoponGlycosylationAnalysisforBiopharmaceuticalsWorkshopAugust25‐26,2015,USPMeetingsCenter,Rockville,Maryland,USA
JohnSchiel,Ph.D.ResearchChemistNationalInstituteofStandardsandTechnology(NIST)Gaithersburg,MD,USADr.SchielreceivedhisBS(2004)andPh.D.(2009)inchemistryfromtheUniversityofNebraska‐Lincoln.Dr.SchieljoinedtheNationalInstituteofStandardsandTechnologyin2009tobeginworkonglycoanalyticalmethoddevelopment,andiscurrentlyaresearchchemistintheNISTBiomolecularMeasurementDivisionwithanappointmentattheInstituteforBioscienceandBiotechnologyResearch.HeisleadingLC‐andMS‐basedbiomanufacturingresearcheffortsatNIST/IBBR;developingasuiteoffundamentalmeasurementscience,standards,andreferencedatatoenablemoreaccurateandconfidentcharacterizationofproductqualityattributes.Dr.SchielisalsotheprojectcoordinatorfortherecombinantIgG1κNISTmonoclonalantibodyReferenceMaterial(NISTmAb)programandaco‐editoroftheassociatedACSbookseries“State‐of‐the‐ArtandEmergingTechnologiesforTherapeuticMonoclonalAntibodyCharacterization”.Heisanauthorofover20peerreviewedpublications,4bookchapters,andrecipientofnumerousAwards,includingtheACSDivisionofAnalyticalChemistryFellowship,BioanalysisYoungInvestigatorAward,andUNLEarlyAchieverAward.
ModeratorSession8:Post‐approvalchangesregistrationWednesday,August26,2015,2:30p.m.–3:50p.m.PresentationAbstractProvidingWell‐characterizationStandards(NIST)Tuesday,August25,2015,3:05p.m.–3:30p.m.Monoclonalantibodies(mAbs)arethefastedgrowingclassoftherapeutics,whosesafetyandefficacyhavebeendirectlylinkedtoglycoprofilecontent.Thecomplex,multi‐antennarynatureofglycanshasresultedindevelopmentofatiered,lifecyclestage‐appropriatetoolboxofanalyticalapproachesforglycoanalysis.Asaruleofthumb,moreinformation‐richmethodsrequiremorecomplexsamplehandlingandanalysis.Evaluationofevolvingglycoanalyticalmethodshasbeensupplementedbyawidelyavailablerepresentativetestmaterial.ThispresentationwilldiscusstheestablishmentofanIgG1kReferenceMaterialexpectedtomorefirmlyunderpinregulatorydecisionsandfacilitatethedevelopmentoforiginatorandfollow‐onbiologics.TheRMisintendedforavarietyofusesincluding,butnotnecessarilylimitedto:systemsuitabilitytests,establishingmethodorinstrumentperformanceandvariability,comparingchanginganalyticalmethods,assistinginmethodqualification,etc.TheNISTmAbglycoanalyticalcharacterizationandcertificationwillbediscussed.Conclusionsdrawnfromtheunprecedentedindustry‐widebookcollaboration“State‐of‐the‐ArtandEmergingTechnologiesforTherapeuticMonoclonalAntibodyCharacterization”willalsobepresented.
USPWorkshoponGlycosylationAnalysisforBiopharmaceuticalsWorkshopAugust25‐26,2015,USPMeetingsCenter,Rockville,Maryland,USA
BirgitSchmauser,Ph.D.FederalInstituteforDrugsandMedicalDevices(BfarM)Bonn,GermanyDr.BirgitSchmauserisaseniorassessorofpharmaceuticalqualityattheGermanRegulatoryAuthority(BfArM)intheUnit“PharmaceuticalBiotechnology,Biologicals,Inspections”.ShestudiedpharmacyattheUniversityofMunichandholdsaPhDfromBerlinFreeUniversity.Shehasscientificandregulatoryexperienceofmanyyears.Herexpertiseandprofoundknowledgeinglycobiologyoptimallyapplyinevaluationofbiotechnology‐derivedmedicinalproductsincludinginvestigationalmedicinalproducts.ForseveralyearsshehasbeenatemporaryadviserfortheWorldHealthOrganisation(WHO)inaprequalificationprogramme.
PresentationAbstractExpectationsforGlycosylatedBiosimilars(regulatoryperspective)Wednesday,August26,2015,1:35p.m.–2:00p.m.Asimilarbiologicalmedicinalproductisdevelopedbaseditsown,uniquemanufacturingprocess.Atthesametimetheclaimtobebiosimilartoanexistingbiologicalmedicinalproductrequiresadaptationsofprocessdesignandperformanceinsuchawaythatthebiosimilar´squalitytargetproductprofileaswellasitsqualityattributesandcharacteristicsarehighlysimilartothereferencemedicinalproduct.Glycosylationofabiologicalsubstancemayexhibitahighlevelofcomplexityandinherentmolecularvariabilityperseincludingdiversityintypeandsiteofglycosidiclinkages,intypeofmonosaccharideswithsite‐specificmodificationsandintheextentofbranchingandbranchelongation.Themanufacturerofabiosimilarisconsequentlychallengedtodemonstratethatthereareconsistentrangesofsimilaritybetweentheglycostructuresofthebiosimilarandreferenceproducttoasufficientextentandthattheseconsistentsimilarityrangesallowreducingthepanelofnon‐clinicalandclinicalstudiestobeperformedwiththebiosimilar.Thelevelofdetailthatcanbeachieveduponanalysisofglycosylationprofileshastremendouslyincreasedinthepastyears.Thusitisoneofthemainregulatoryexpectationsthatmanufacturersofbiosimilarsprovideathorough,comprehensivecomparisonofbiosimilarandreferenceproductwiththenecessarylevelofstructuraldetailtopicturetheglycosylationprofilesofbothproductsandderivethesimilarityclaimthereof.Evaluationofsimilarityshouldincludeathoroughdiscussionofallstructuralresultsobtainedaswellasasoundjustificationfortherepresentativenessofresultsbasedonnumberandchoiceofbatchesforcomparison.Itisconsideredessentialtodistinguishacceptableandunacceptabledifferencestakingintoaccountthecriticalqualityattributesdefined.Neverthelessaregulatorydecisionwillalwaysincludethequalityofdataprovidedaswellasinterpretationandjustificationprovidedtoexcludethatpotentialdifferencesobservedmayhaveanunexpectedimpactonsafetyandefficacy.
USPWorkshoponGlycosylationAnalysisforBiopharmaceuticalsWorkshopAugust25‐26,2015,USPMeetingsCenter,Rockville,Maryland,USA
BhavanaShahSeniorScientistAmgenInc.,ThousandOaks,CA,USABhavanaisaseniorscientistintheproductattributedsciencegroupoftheprocessdevelopmentdepartmentatAmgenInc.ShehasworkedasananalyticalchemistinvariousAmgendepartmentsincludingresearch,quality,andprocessdevelopmentformorethan25years.ShehasdevelopedamethodofglycanprofilingforglycoproteinandantibodyproductsbyLC‐MSMSpeptidemapping.Shehasextensiveexperienceinsite‐specificglycancharacterizationaswellasreferencestandardcharacterizationsofglycoproteinandmonoclonalantibodies,usingvariousLCandmassspectrometrytechniques.Asapartofqualitydepartment,shedeveloped,validated,andimplementedroutinelotreleasemethods,suchasglycanprofilingandsialicacidestimationforglycoproteins.Sheisalsoinvolvedinmethoddevelopmentfortheestimationofpost‐translationmodificationsandmisincorporationofproteins,aswellasmonoclonalantibodies.BhavanahasanM.S.inAnalyticalandMedicinalChemistryfromtheUniversityofBombay,India.Shehasauthoredseveraltechnicalresearcharticlesinpeer‐reviewedpublications.PresentationAbstractMAbGlycanProfilingbyLC/MSPeptiteMappingWednesday,August26,2015,10:50a.m.–11:15a.m.TraditionallyN‐glycananalysisofaglycoproteinisdonebyhighpHanionexchangechromatography(HPAEC),reversedphaseliquidchromatography(RPLC)orrecentlydevelopedhydrophilicinteractionliquidchromatography(HILIC).ThesemethodsrequirereleaseofN‐glycansbyenzymefollowedbyfluorescentlabelingofN‐glycans.Theprotocolislaborintensiveandtimeconsuming,anddoesnotprovidesite‐specificglycosylationinformation.Liquidchromatography‐tandemmassspectrometry(LC‐MS/MS)peptidemappingisroutinelyusedforproteinstructuralcharacterizationand,asabonus,canpotentiallyprovideglycanprofileoneachindividualglycosylationsite.Inthiswork,arecentlydevelopedglycopeptidefragmentationmodelisusedforautomatedidentificationofglycan,basedontheirMS/MS(fragmentationpattern)ofN‐glycopeptidesfromproteolyticdigestionofmonoclonalantibodies(mAbs).LC‐MSconditionswereoptimizedforaccurateglycanprofiling.GlycanprofilesobtainedfromLC‐MS/MSwerecomparedwiththeprofilesobtainedbyconventionalmethodslikeHPAEC,RPLCandHILIC.RobustnessoftheLC‐MS/MSmethodisalsoevaluatedforaccuracy,reproducibility,andlinearity.Basedonthesameconceptafullyautomatedfasthighthroughputmethodisalsodevelopedforat‐lineprofilingofmAbglycansdirectlyfromcellculturemedia.TheLC‐MS/MSpeptidemappingmethodwithfullyautomateddataanalysisrequireslesssample
USPWorkshoponGlycosylationAnalysisforBiopharmaceuticalsWorkshopAugust25‐26,2015,USPMeetingsCenter,Rockville,Maryland,USA
preparationandalsoprovidessite‐specificinformation.ItcanserveasanalternativemethodforroutineprofilingofN‐glycansonimmunoglobulinsaswellasotherglycoproteinswithsimpleN‐glycans.
USPWorkshoponGlycosylationAnalysisforBiopharmaceuticalsWorkshopAugust25‐26,2015,USPMeetingsCenter,Rockville,Maryland,USA
CatherineSrebalusBarnes,Ph.D.SeniorDirector,GlobalBiologics–AnalyticalSciencesHospiraGlobalBiologicsR&DLakeForest,IL,USADr.SrebalusBarnesiscurrentlytheSeniorDirectorforHospiraGlobalBiologics,BioanalyticalSciences.HercurrentresponsibilitiesincludemanagementofHospira’sGlobalBioanalyticalSciencesgroupslocatedintheU.S,AsiaandAustralia.Thesegroupsareresponsibleforbioanalyticalandbioassaymethoddevelopmentandvalidation,characterizationofHospiraandoriginatorbiologicproductsaspartofanalyticalbiosimilarityassessments,bioanalyticalsupportforcelllineandprocessdevelopment/optimizationandtestingoroversightforoutsourcedrelease/stabilitytestingofproductsforuseinclinicaltrials.Inherrole,CathyisresponsiblefordefinitionandimplementationofstrategiesfordemonstrationofanalyticalbiosimilaritybetweenHospiraandoriginatorproductsandprovidingoversightfordevelopmentandimplementationofanalyticalcontrolstrategiesforHospira’sbiologicproducts.Sheactivelyparticipatesinauthoring/reviewofRegulatorysubmissionsandmeetingswithRegulatoryagenciesinsupportofHospira’sbiologicsprograms.PriortojoiningHospirain2012,CathyheldanumberofleadershiproleswithincreasinglevelsofresponsibilityintheBioproductDevelopmentorganizationatEliLillyandCompany,includingDirector,BioproductAnalyticalDevelopmentandDirector,BioprocessPurificationDevelopmentandViralSafety.CathyhasaB.S.inChemistry(WestVirginiaUniversity,U.S.A.)andaPh.D.inAnalyticalChemistry(IndianaUniversity,U.S.A).PresentationAbstractExpectationsforGlycosylatedBiosimilars(manufacturerperspective)Wednesday,August26,2015,1:10p.m.–1:35p.m.FDAguidelinesforbiosimilarproductsrequirethatsponsorsdemonstratetherearenoclinicallymeaningfuldifferencesinthesafety,purityandpotencyoftheproposedbiosimilarproductandreferenceproducttosupportapproval.Thedevelopmentofglycoproteinbiosimilarproductsrequiresacomprehensivecomparisonofglycosylationattributesfortheproposedbiosimilarproductandthereferenceproduct.Theanalyticalbiosimilarityassessmentshouldstartwithanassessmentoftheproductattributesthatarepotentiallyclinicallymeaningful(i.e.,CriticalQualityAttributesorCQAs).Thecriticalityofspecificglycosylationsitesandglycanstructuresdependsonthemechanismofactionforthespecificglycoprotein.TheglycosylationCQAsshouldbeconsideredtodefinetheanalyticalmethodsandglycosylationattributesthatarethefocusofthebiosimilarityassessment.
USPWorkshoponGlycosylationAnalysisforBiopharmaceuticalsWorkshopAugust25‐26,2015,USPMeetingsCenter,Rockville,Maryland,USA
AproposedframeworkfordefiningtheglycosylationCQAsforbiosimilarglycoproteinproductsandtheapplicationoftheproposedCQAstodefinetheanalyticalmethodsandstrategyfortheanalyticalbiosimilarityassessmentwillbediscussed.Casestudiesfortherapeuticmonoclonalantibodiesanderythropoietinbiosimilarproductswillbeusedtodemonstratetheapproach.Inaddition,theuseofsupportiveinvitroandinvivostudiestorefinepreliminaryCQAassignmentsformonoclonalantibodiesanderythropoietinbiosimilarproductswillbediscussed.
USPWorkshoponGlycosylationAnalysisforBiopharmaceuticalsWorkshopAugust25‐26,2015,USPMeetingsCenter,Rockville,Maryland,USA
MarcoThomannGroupleaderDevelopmentAnalyticsRocheDiagnosticsGmbHMunich,GERMANYMarcoThomannhasbeenworkingwithRocheDiagnosticsinPenzberg,Germany,forelevenyearsnow.HefinishedhisstudyofBiotechnology/BioinformaticsatUniversityofAppliedSciencesinWeihenstephan,Germany,withaGerman“DiplomaEngineer”degree.HestartedatRochewithhisdiplomathesisinthefieldofBioinformatics,continuedasananalyticspecialist,whereheworkedonthecharacterizationofproteinsusingdifferentHPLC,spectroscopicandmassspectrometrytechniquesinaGMPenvironment.In2008,Marcobecamegroupleaderinthesamedepartment,responsibleforthecharacterizationoftherapeuticproteinsduringclinicalphaseIIandIIIincludingpreparationofregulatoryfilings.Recently,hegotalsoinvolvedinCQAassessmentforalatestageproject.Hisgroupalsofocusesonoligosaccharideanalyticsaswellasglycoenzymecharacterizationforinvitroglycoengineeringandtheirapplicationontherapeuticproteins.
PresentationAbstractInVitroGlycoengineering–AUsefulToolforGlycanStructure‐FunctionCharacterizationandMoleculeOptimizationWednesday,August26,2015,9:10a.m.–9:35a.m.Glycosylationoftherapeuticproteinsisofspecialinterestsinceitcansignificantlyimpactbiologicalactivity.Glycosylationisheterogeneousandsubjecttobatch‐to‐batchvariability,thusitsimpactonproteinfunctionisnoteasytoinvestigate.However,assessmentofe.g.antibodyFcglycanstructure–functionrelationshipbecomesmoreandmoreofinterest.Inthistalktheinvitroglycoengineering(IVGE)technologyanditsapplicationwillbeintroduced.MultipleexampleswillbeshownwhereIVGEaddsaclearbenefittoglycancharacterizationaswellasinvitrostructure‐functionanalysis.SamplepreparationworkflowsforinvitrogalactosylationandsialylationofIgG1Fcglycanswillbeexplained.AnditseffectontheMode‐of‐Action,FcreceptorbindingandADCCactivity,aswellastheimpactonpharmacokineticpropertieswillbeaddressed.AlsoIVGEhasbeenusedtosupportCQAassessmentofalatestageproject.Insummary,thetechnologycanbeappliedtoincreasespecificmoleculeknowledgeaswellastooptimizemolecularpropertiesofclinicalcandidates.
USPWorkshoponGlycosylationAnalysisforBiopharmaceuticalsWorkshopAugust25‐26,2015,USPMeetingsCenter,Rockville,Maryland,USA
EarlZablackis,Ph.D.USPAffiliation:Member,Monographs–BiologicsandBiotechnology2ExpertCommitteePanel;Member,VaccinePolysaccharideNMRIdentityTestingExpertPanel;Member,VaccinesforHumanUse–ViralVaccinesExpertPanel;Member,1041BiologicsRevisionExpertSubcommittee;andMember,210MonosaccharideAnalysisSubcommitteeDirector,MethodValidationSanofiPasteurSwiftwater,PA,USAIamabiologist/botanistwhodevelopedakeeninterestincellwallpolysaccharidesandthusbecamecarbohydratebiochemist.MyeducationtookmethroughprogramsattheUniversityofCalifornia,BerkeleytotheUniversityofHawai’iandfinallytheUniversityofCalifornia,SantaBarbara,followedbyapost‐doctoralfellowshipattheComplexCarbohydrateResearchCenterattheUniv.ofGeorgia.Mycareerspans30yearsworkingasacarbohydratechemistinacademiaandthebiopharmaceutalindustry.Mycarbohydrateworkwasfocusedontheisolation,purificationandcharacterizationoffinestructureofpolysaccharidesusingmultipletechniquesemployingvariousseparationtechnologiestovariousanalyticaltoolssuchasmassspectroscopyandNMR.Myindustrialexperiencecoversglycananalysisfromrecombinantglycoproteins,monoclonalantibodiesandbacterialpolysaccharidesforvaccines.Ihaveadditionalexpertiseinvalidationofanalyticalmethods.InmycurrentpositionatSanofiPasteur(vaccines)intheManufacturingTechnologydepartment,IamtheDirector‐PrincipalScientistintheAnalyticalProcessandTechnologyplatformresponsibleformethodqualification,validationandtransferprogramsaswellascompliancewithqualitysystems.IamcurrentlyamemberoftheBiotechnologyAdvisoryBoard(BioAB)ofthePDAaswellasamemberoftheUSPBiologicsandBiotechnology2ExpertCommittee.IhavecontributedtoPDATechnicalReports57and57‐2coveringanalyticalmethoddevelopment,qualification,validationandtransfer;andtoUSPchapter<1238>BacterialVaccines.IamalsocurrentlyactiveonUSPexpertpanelsdevelopingchapters<210>MonosaccharideAnalysis,and<198>IdentificationofBacterialPolysaccharidesUsingNuclearMagneticResonanceSpectroscopyPlanningCommitteeMemberNotPresenting
USPWorkshoponGlycosylationAnalysisforBiopharmaceuticalsWorkshopAugust25‐26,2015,USPMeetingsCenter,Rockville,Maryland,USA
RebeccaZangmeister,Ph.D.USPAffiliation:Member,USPGlycoproteinsandGlycanAnalysisExpertPanelScienceAdvisorBiomolecularMeasurementDivisionNationalInstituteofStandardsandTechnologyGaithersburg,MD,USARebeccaA.ZangmeisteristheScienceAdvisorfortheBiomolecularMeasurementDivisionoftheMaterialMeasurementLaboratoryattheNationalInstituteofStandardsandTechnology(NIST)inGaithersburg,MD.RebeccagraduatedfromtheUniversityofArizona,Tucson,AZ,in2001withaPh.D.inAnalyticalChemistry,specializinginorganicthinfilmsandsurfacecharacterization.ThecommonthemeofhersubsequentresearchprojectsatNISThaveinvolvedthedepositionandanalyticalcharacterizationofbiomoleculesatsurfaces(planarornanomaterialbased).Hermostrecentresearcheffortshavefocusedonthedevelopmentofmeasurementmethodsforbiologicswithanemphasisonrapidglycosylationassaysforuseinthebiomanufacturingoftherapeuticproteins.PlanningCommitteeMemberNotPresenting