extractactables and leachables summit 2020ferent surface area to volume ratios (0.4 to 18 sq.cm./ml)...

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Extractables & Leachables Virtual Summit 2020Ensuring Quality, Safety, Suitability and Regulatory Compliance

for Drugs, Biologics and Medical DevicesJuly 30–31, 2020, Online EDT

Featuring Lessons Learned and Case Studies from Industry Experts:

With Representation From:

• CDRHScientificPerspectiveonChemicalAnalysisforMedicalDevices

• ISO10993-18:KeyConceptsandPracticesforEffectiveandCompliantChemicalCharacterizationSupportingtheBiologicalEvaluationofMedicalDevices

• UnderstandingtheMajorRevisionstoISO10993andtheNewEuropeanMedicalDeviceRegulations

• CaseStudy:MedicalDeviceToxicologicalRiskAssessmentFollowingNewPrinciplesofISO10993-17

• IdentificationandEvaluationofMaterialQualityAttributes(MQA)ofPolymerics

UsedinCellTherapyProductsManufacturing

• ChemicalInteractionsbetweenLeachablesandBiopharmaceuticals

• TheNeedtoIdentifyUnknownsfromaToxicologicalPerspective

• BPOGE&LforSingle-UseSystems– TheFinalChapter

• UtilizingBPOGdataforselectionandqualificationofSingleUseSystems

• Extractables/LeachablesStudies:AreYouCertainAboutthatUncertainty?

• ReducingResponseFactor(RF)VariationandtheneedforUncertainty

Factors(UFs)inExtractablesandLeachables Analysis

• ComparisonoftheSolubilizationPropertiesofPolysorbate80andIsopropanol/WaterSolventSystemsforOrganicCompoundsExtractedfromThreePharmaceuticalPackagingConfigurations

• ComprehensiveExtractablesStudyofAutoclavablePolyethersulfoneFilterCartridges

• Physics-basedModeltoPredictPatientExposuretoPolymerAdditivesinMedicalDeviceMaterials

• AndMuchMore!

MikeRubertoMaterial Needs

James HathcockPall Biotech

Cherry ShihPall Life Sciences

SteveZdravkovic

PPD

Eric HillBoston

Analytical

StephenDohertyToxikon

Daniel Norwood

Feinberg Norwood & Assoc.

Carsten Worsøe

Novo Nordisk A/S

MichelleKolodziejski

Eurofins BioPharma

Product Testing

MarkJordiJordi Labs

PietChristiaensNelson Labs

With Comprehensive Coverage On:

MikeEakinsEakins & Assoc.

DavidSaylorFDA

DennisJenkeTriad Scientific

SherryParkerWuXi AppTec

LisaOlsonNAMSA

PingWangJohnson &

Johnson

TedHeiseMED Institute

BerkOktemFDA

RonBrownFDA (retired)

CharlesFeliceJanssen R&D

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Extractables & Leachables Virtual Summit 2020

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Extractables & Leachables Virtual Summit 2020

identifiedandaccuratelyquantified.Afundamentalexpecta-tionthathasrarelybeenarticulateduntilrecentlyisthattheextractablesprofilebereproducible.Thatistosaythatifatestarticlewereprovidedtoseveralexperttestinglaborato-ries,theextractablesprofilesreportedbythoselaboratorieswouldbesimilar,ifnotequivalent,intheirimportantdetails,includingthenumberofextractablesreportedandtheiden-titiesandconcentrationsofthereportedextractables.

Recent, largely anecdotal, evidence suggests that thisexpectationofreproducibilitycouldbemoreawishthanarealityandthatextractablesprofilescanvary,insomecasesquitesubstantially,fromlabtolabandpossibilityevenwithinalab.Ifthislackofconsistencyistrueandreal,itcouldhaveasignificantbearingon,forexample,theuseofchemicalcharacterizationinthebiocompati-bilityassessmentofmedicaldevices.

In this presentation we will examine the published andavailableliteratureanddatathatisrelevanttothistopictoestablishwhethertheperceptionisrealityand,ifso,tocon-sideractionsthateitheramplifyorreduce/controlvariation.Furthermore,theavailableliteratureanddatawillbeusedtoquantifyreasonableexpectationsforreproducibility.

Q&A: Ask the Experts

10:35 ICHQ3E:ABriefOverviewCarsten Worsøe, Principal Scientist, Novo Nordisk A/S

The InternationalCommittee forHarmonisation (ICH)har approved the procurement of an ICH E&L guide-line.Althoughit isveryearly in the ICHprocessthis

shortpresentationwillgivebackgroundandhistory forthetopicapprovalinICHaswellasthecurrentlyknownprocessfortheICHguideline.

10:45 E&LRegulatoryPanelDiscussionModerator: Michael Eakins, Owner, Eakins & AssociatesPanel:

• DennisJenke,TriadScientificSolutions • RonaldBrown,Toxicologist,FDA(retired) • BerkOktem,Chemist,FDA

Discussants:TheAudience

11:20 ReducingResponseFactor(RF)Variation andtheneedforUncertaintyFactors(UFs) inExtractablesandLeachablesAnalysis

Dr. Mark Jordi, President, Jordi Labs

Chemical characterization per ISO 10993 has becomean important component of biocompatibility testing ofmedical devices. Similarly, pharmaceutical packagingischaracterizedforextractablesandleachablestover-

ifythesafetyofdrugproductsperUSP<1663>and<1664>.A majorconcernregardingtheaccuracyofextractablesandleachablesstudiesisquantitativeerrorduetoresponsefac-

Thursday,July30,2020, Eastern Daylight Time

8:00 Chairperson’s Welcome & Opening Remarks

Michael Eakins, Owner, Eakins & Associates

Regulatory Spotlight – Chemical Analysis for Medical Devices

8:10 CDRHScientificPerspectiveonChemicalAnalysisforMedicalDevices

Berk Oktem, Chemist, FDA

AbstractComingSoon

Critical Issues – Identifying Unknowns in E/L Studies

8:50 TheNeedtoIdentifyUnknownsfromaToxicologicalPerspective

Ron Brown, Toxicologist FDA (retired)

When conducting a toxicological risk assessment ofextractableand leachable (E&L) compounds, it is typ-ically assumed by the toxicologist that the extractedcompoundshavebeenidentifiedwithahighdegreeof

certainty.However,becauseofanalyticalchemistrychal-lenges,identificationofthecompoundstothislevelofcer-tainty isnotalwayspossible,especially fornon-targetedextractables. This talk with explore the implications ofconductingatoxicologicalriskassessmentofcompoundsthathavebeenonlytentativelyidentifiedandwillevaluaterecentproposalstoevaluatethesafetyofunidentifiedandpartially identifiedE&Lcompounds.Amongthestrategiesto be addressed in this presentation are the appropriateuseofThresholdofToxicologicalConcern(TTC)valuestoserveasdefaultTIorPDEvaluesforcompoundsthathavenotbeenconfidentlyidentifiedandneedtoidentifywhenacompoundisexpectedtobefoundinanextractbasedonknowledgeof thecompositionof thepolymericmaterialsofconstructionofthedeviceorpharmaceuticalpackaging.

9:30 Morning Break & Sponsor Presentations

9:55 Extractables/LeachablesStudies:AreYouCertainAboutthatUncertainty?

Dennis Jenke, President, Triad Scientific Solutions

There are many well-established and well-articulat-edexpectations forextractablesprofiles including thatallextractablesabovetheAETbediscovered,correctly

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Extractables & Leachables Virtual Summit 2020

Research Spotlight – Single Use Systems & BPOG

1:40 BPOGE/LforSingleUseSystems–TheFinalChapterJames Hathcock, Senior Director, Regulatory and Validation Consulting, Pall Biotech; Carsten Worsøe, Principal Scientist, Novo Nordisk A/S

Inthispresentation,wewillcoverthefollowingtopics:

• Supplierandend-usercollaboration• Extractablesecosystem• Datareviewprocess• Extractablesprotocolupdate• Communityofpractice

Case Studies – Utilizing BPOG data for selection and qualification of Single Use Systems

2:20 UtilizingBPOGDataforSelectionandQualificationofSingleUseSystems

Cherry Shih, Senior Scientist, Pall Life Sciences

The increasing availability of extractable datasetsaligned to standardized protocols (BPOG and USP<665>/<1665>)hasledtoadeeperunderstandingofex-

tractableprofilesindifferentsolvents.Wewillsharecaseswhere specific solvent profiles fromBPOGorUSP <665>canbeleveragedtobestsupportandsimplifytheriskas-sessmentprocess, forboth, thepurposeof initialmateri-alsselectionaswellasqualificationofamulticomponentsingleusesystem inadefinedmanufacturingprocess. Inapplyingstandardizeddatasets,weshareexamplesofhowextractablesprofilesperformedatdifferentsurfaceareatovolumeratios(0.4to18sq.cm./mL)comparetotheoretical-lyscaledvaluesbasedonsurfaceareaandvolumealone.Thegoalofthesecasestudiesistosimplifyandstrengthenapproachestoqualificationofsingleusematerials.

3:00 Afternoon Break & Sponsor Presentation

3:25 AssessingtheReactivityofLeachableswithBiopharmaceuticals,UsingINSULINasaMarkerCompoundCombinedIn-SilicoModelwithExperimental(Analytical)VerificationofProofofConcept,usingINSULINasaMarkerCompound

Piet Christiaens, Scientific Director, Nelson Labs Europe

In the EPREX case, leachable induced immuno-re-sponsescausedsevereadversereactionstoCKDpa-tients. Although the EPREX case is often referred to

by theE/Lcommunity tostress the importanceofan in-depth E/L evaluation of the C/C-system, it also showed

tor(RF)variation.Thiserroroccursbecausemanyextract-ables do not have commercially available standards andequalconcentrationsofdifferentextractablesgivedifferentsignalresponsesusingmassspectrometrydetectors.Recentpublicationshavehighlighted the risksposedbyRFvaria-tionforbothLCMSandGCM.Theimportanceof this issuehasbeenrecognizedbytheFDAresultingintheadditionofanuncertaintyfactor(UF)inthecalculationoftheanalyticalevaluationthreshold(AET).Whilethisaidsinmitigatingtherisksofunderreportingofextractables,theresultingrevisedAETcreatessignificantanalyticalchallengesoftenexceed-ing the limit of detection (LOD)of currentmass spectrom-etryinstrumentationandrequiringsampleconcentration.Italsocreatesquestionsastothevalidityofriskassessmentsbasedonrelativequantitationvaluesandisoneofthekeyissuesattherootofpoorreproducibilityinrecenthighpro-fileinterlaboratorystudies.Itisthereforestronglydesirabletodefineimprovedmethodsforquantitationwithmoreuni-versalRFswhichmitigatetheneedforUFs.Inthispresen-tation, alternative strategies for quantitation using tripledetectionliquidchromatographymassspectroscopy(LCMS)withultraviolet(UV)andchargedaerosoldetection(CAD)aswell as Gas ChromatographyMass Spectroscopy (GCMS)withsimultaneousFlameIonizationDetection(FID)willbepresented. Data comparing the response factors a varietyofextractablesbyUV,MS,FIDandCADwillbepresenteddemonstratinganapproach to reduceoverallRFvariation,the associatedneed forUFs and increasingconfidence intheresultingriskassessments.

12:00 Lunch Hour. Visit the Networking Chatroom

1:00 IdentificationandEvaluationofMaterialQualityAttributes(MQA)ofPolymericsUsedinCellTherapyProductsManufacturing

Ping Wang, Director, Johnson & Johnson, and Charles Felice, Principal Scientist, Janssen R&D

Cell therapy drug products such as CAR-T presentuniquechallengeswithrespect topolymericmaterialriskscomparedwithmorecommonbiologicprocesses.Themanufacturingprocessofcellproductshasfewerpurification steps, resulting in fewer opportunities toremovepolymeric-relatedimpuritiessuchasparticles,endotoxins,bioburden,andleachables&extractables.

These attributes are material quality attributes (MQAs)thatmustbeassessedand, if the risk ishigh,mitigated.Thispresentationwilldiscussthecorrelationofmanufac-turingprocessesandMQAs,andhowtheseprocesseswillimpacttherisklevelsoftheMQAstothefinaldrugproductqualityandpatientsafety.TheMQArisklevelsofthepoly-mericsateachstepwillbediscussed.

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Extractables & Leachables Virtual Summit 2020

Friday,July31, 2020, Eastern Daylight Time

8:25 Chairperson’s Welcome & Opening Remarks

Critical Issues—Exploring the Major Revisions to ISO 10993-1, -17, & -18: Methodological & Toxicological Considerations

8:30 ChemicalCharacterization&RiskAssessment ofMedicalDevices:Thoughts,Considerations& PointstoRemember

Stephen Doherty, Associate Director, Analytical Chemistry, Toxikon

Theconceptofchemicalcharacterizationofmedicalde-viceshascontinuedtoriseinimportanceaspartoftheevaluationofbiocompatibility.AspartofaRiskManage-

mentbasedsystemthechemicalcharacterization,togetherwiththeriskassessment,areessentialpartsofanyevalua-tion.Anunderstandingofthechemicalcharacterizationofmedicaldevicescanbeusedtoplanoverallbiocompatibil-itytestingstrategy,providedatatoassesscertainbiocom-patibilityendpointswithouttheneedoftesting,andallowonetobeabletobetterplanforandevaluatematerial/com-ponentchangesoverproduct lifecycle.Thispresentationwillreviewsomeofthegeneralconceptsofchemicalchar-acterizationasrelatedtobiocompatibility,whatitcanandcannotdo,provideanoverviewofsomeofthetechniquesused,andlookathowthechemicalcharacterizationgoeshand-in-handwiththeriskassessment.Inaddition,thepre-sentationwill discuss somepoints to consider as part ofplanningforandconductingachemicalcharacterizationtoprovidetheappropriatedatafortheriskassessmentbasedupontheparticularoutcomedesired.

9:05 ISO10993-18:KeyConceptsandPracticesforEffectiveandCompliantChemicalCharacterizationSupportingtheBiologicalEvaluationofMedicalDevices

Ted Heise, Vice President, Regulatory & Clinical Services, MED Institute

TheISO10993seriesofstandardsonbiologicaleval-uationofmedicaldeviceshasbeenevolvingovertheyears,workingtokeepupwithprogressinknowledge

of the subjectmatter. In keepingwith this progress, anupdateofISO10993-1(thetop-levelstandard)publishedin2018.Akeychangeinthisreviseddocumentwastheaddition of a more explicit requirement for chemicalcharacterization of all device types—regardless of thenatureanddurationofpatientcontact.

Tomeet the heightened focus on chemical characteriza-tion—and toupdate theexistingstandard—amajor revi-sionofISO10993-18“Chemicalcharacterizationofmedicaldevicematerialswithinariskmanagementprocess”wasundertaken.Thereviseddocumentshouldpublishinearly2020.Thisconferencesessionwillfocusonkeypartsofthenewdocument,bringinginexperienceandlessonslearnedfrommulti-stakeholderdevelopmentofthefinalstandard.

that the traditional E/L approach for container/closuresystems may not always be adequate in predictingleachables could chemically modify proteins, poten-tially causing immunogenicity through the formation of“anti-drug-antibodies.”

TheFDAGuidanceforIndustry:“ImmunogenicityAssess-mentforTherapeuticProteins”(2014)describesanaphy-laxis, cytokine release syndrome, infusion reactions,non-acutereactionsandcross-reactivitytoendogenousproteinsastheassociatedsafetyconcernswhenconsid-eringimmunogenicityasaresultofchemicalinteractionbetweenleachablesandproteins.

Thepresentationwilladdresstwowaysofpredictingifanyofthechemicalcompounds,foundintheextractionprofileofcontainer/closurecomponent,could lead toachemical interactionifanyof thoseextractableswouldbecomea leachable: (1)howtoperformanin-silicore-activityapproachofaverybroadsetofcommonlyknownextractablecompoundsand(2)achemicalreactivitytesttoactuallyscreenforresidualchemicalreactivity.

Inaddition,achemicalreactionmodel,basedonInsulinasamarkercompoundwasdevelopedtoactuallyverifythein-silicopredictedchemicalreactivityandcomparetheoutcomeof thein-silicoexercisewiththeobservedreactivitybetweenapredefinedsetofextractablesandinsulin.

4:05 StandardMethodsforExtractables/LeachablesProfiling:WhataretheImplications?Daniel Norwood, Principal Consultant, Feinberg Norwood & Associates

Modern analytical chemistry, in the form of GC/MSand LC/MS,hasbeenat center stage inextractable/leachable assessment since the late 1980s. Variousorganizations(PQRI,USP,etc.)haveattemptedtoes-tablishthebasicscientificprinciplesforaccomplish-ingextractables/leachablesassessmentsalongwith

the use of these highly sensitive and selective analyti-cal techniques.Overthepast tenyearsorso,ageneralconsensus has been established regarding the suite ofanalytical techniquesapplied toanyassessmentbasedon thevolatilityandchemicalnatureof theanticipatedanalytes.Thisconsensusincludes:Head-space(HS)GC/MSforvolatileanalytes,Directinjection(DI)GC/MSforsemi-volatileanalytescontainedinsolventextracts,Di-rectinjectionLC/MSfornon-volatileanalytescontainedin solvent extracts, and ICP/MS for elemental analytes.Theconsensusdoesnotincludeallofthedetailsoftheanalyticalmethods since the organizations that agreedon best practices did notwant to be proscriptive. Thispresentation will attempt to discuss the possibility ofestablishing standard methods for extractables/leach-ables. It will describe the requirements for standardmethodsalongwiththeimplicationsforthepharmaceu-ticalindustryoftheimplementationofstandardmethods.Theexperienceoftheenvironmentalindustrywithstan-dardmethodsinthe1970sand1980swillbeconsidered.

4:45 End of Day One

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Q&A: Ask the Experts

10:40 ISO10993PanelDiscussionModerator: Michael Eakins, Eakins & Associates

Panel:

• DennisJenke,TriadScientificSolutions• TedHeise,MEDInstitute• SherryParker,WuXiAppTec

Discussants:TheAudience

11:15 CommercialImplicationsofaProperlyPlannedBiologicalEvaluationStrategy,Including theUseofChemicalCharacterization

Lisa Olson, Vice President — North American Laboratory and Global Analytical Services, NAMSA

Since2009, theemphasisonariskmanagementpro-cess and characterization of materials continues to

shiftthebiologicalsafetyparadigm.Putsimply,thedaysof medical product manufacturers simply contractingwithatestinglaboratorytoperformahandfulofbiologi-calsafetytestsisnolongeranacceptedpracticebyanyglobal regulatory body. Medical device regulators arerequiringcarefullyplannedevaluationstrategiesbasedonriskandempiricaldata.

Join this session to learn howawell-planned strategyutilizing chemical characterization can have favorableandevencostsavingimplicationsforthecommercializa-tionofyourproduct.Thissessionwillbeastarttofinish,stepbystep instructiononwhentostartyourplanning,whatstepsto followtoexecutechemicalcharacteriza-tion testing and/or biological testing, and how to keepyourtimelinesasshortorshorterthanwhenperformingconventionalbiologicaltesting.

11:55 Lunch Hour. Visit the Networking Chatroom

12:55 Physics-basedModelstoPredictPatientExposuretoMedicalDeviceLeachables

David Saylor, Materials Scientist, FDA

Thematerialsthatcomprisemedicaldevicescontainsubstancesthatcanbetransferredtopatients.Patientexposure to thesesubstancesmaybedesirable,e.g.drug delivery, but more generally, there is concern

foradverseeffectsifachemicalisreleasedinsufficientquantities.Historically,thelikelihoodforadverseeffectshasbeenevaluatedusinganimal testing. Toxicologicalriskassessment(TRA)isanalternativeapproachthatcanobviatetheneedforextensiveanimaltesting.TRAreliesonexposureestimation,yetexposuredataarechalleng-ingtoobtainandinterpret.Physicsbasedmasstransportmodelsprovideapromisingalternativetoestablishclini-callyrelevantexposureestimates.Thispresentationwillprovideanoverviewofexposuremodelsandtheirusein

Topicstobecoveredwillinclude:

• Navigatingtheflowchart,includingfactorsthatcanhelpdeterminewhethercompositionalinformationmaybeadequateforchemicalcharacterization,oranalyticaltestingofextractsislikelytobenecessary;

• Considerationsfordeterminingextractionconditions;namely,solventselection,temperature,duration,andnatureofextraction(e.g.,simulateduse,exaggerated,orexhaustive);

• DistinctionsbetweenextractablesandleachablesintheapplicationofestablishedE&Lprinciplestomedicaldevices;

• Approachestoperforminganexhaustiveextraction,aswellasdiscussionofhowmultiplestepscanfacilitateuseofpracticalsafetythresholds;

• Qualificationofanalyticalmethods,includingdiscussionofparametersthatmaybecandidatesforuse;and,

• Additionalinsightsdrawnfromregulatorinputduringnumerousdiscussionsofvariouselementsofthestandard.

9:40 CaseStudy:MedicalDeviceToxicologicalRiskAssessmentFollowingNewPrinciplesofISO10993-17

Sherry Parker, Senior Director of Regulatory Toxicology, WuXi AppTec

ISO 10993-17,whichwas last revised is 2002, has un-dergoneasignificantrevisionandtheproposedtitleis“ToxicologicalRiskAssessmentofMedicalDeviceCon-

stituents”. The revised standardwill expand fromcurrentguidance on establishing allowable limits of leachablesubstances,toconductingatoxicologicalriskassessmentof medical device constituents. Proposed updates to thestandard and its current statuswill be presented. Topicswill include hazard identification, exposure assessment,dose-response assessment, and risk characterization.Therewillbeemphasisontheuseofexpertjudgementtodeterminewhether the toxicological risks of exposure toextractableorleachablechemicalsinmedicaldevicesareacceptable, what additional steps may be taken to miti-gaterisk, includingwhetherexposureestimatescouldbefurther refined through additional chemical characteriza-tionandwhentorecommendriskcontrol. Inaddition, thetechnical specification ISO/TS 21726:2019, Application oftheThresholdofToxicologicalConcern(TTC)forAssessingBiocompatibility of Medical Device Constituents, will bediscussed.Acasestudywillbepresentedtoprovideexam-ples todemonstrate theapplicationof thenewprinciplesproposedinISO10993-17andISO/TS21726tothetoxicolog-icalriskassessmentofmedicaldevices.

10:15 Morning Break & Sponsor Presentations

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Extractables & Leachables Virtual Summit 2020

creasethenumberand/oramountof impurities leachedfrom materials used during its manufacture, storage,and/or administration. However, it is uncertain if/howthe solubilization properties of this surfactant comparetonon-surfactantsolventsystems.Thegoalofthisstudyistoprovideinsightintothisareaofuncertaintybycom-paring thesolubilizationpropertiesofpolysorbate80 tothose of isopropanol/water solutions while in contactwithaplasticizedpolyvinylchlorideparenteraldeliverybag,asingle-usetypemanufacturingbag,andapolypro-pylene bottle. These properties were determined via abindingexperiment,inwhichasetofmodelcompoundswasintroducedintothesolutions,andviaanextractionexperiment, in which compounds were extracted fromthepackagingmaterial by the solutions. In both exper-iments, the amount of each compound present at equi-libriumwasassayed todetermine theextent theyweresolubilizedbythesolutionfromthepackagingmaterial.Results from these experiments illustrate differencesin the magnitude of solubilization obtained from solu-tions containing polysorbate 80 as compared to thosecomposed of isopropanol/water. However, it was alsodemonstratedthat theirsolubilizationpropertiescanbelinkedviaamathematicalmodel.

4:00 ChallengesofAssessingBreathingGasPathwaysperISO18562

Michelle Kolodziejski, Principal Chemist, Eurofins BioPharma Product Testing

Medicaldevicessuchasnebulizers,CPAPequipment,respirators, and the associated disposable accesso-riescanreleaseharmfulsubstances into thebreath-

inggasstream.Forexample,arangeofvolatileorganiccompounds may be released, including but not limitedto: siloxanes, phthalates, phenols, acrylates, alkanes,ketones,andalcohols.Toensurepatientsafety, theISO18562guidancefortheevaluationofbreathinggaspath-wayswas introduced in2017.Part3of thestandard fo-cuses on VOCs, although it does not provide specificsfortheanalyticalconsiderationsrelatedtosamplingandanalysis.Therefore, laboratoriesmustdetermineappro-priateequipmentanddevelopproceduresrelevanttothetesting,payingattentiontothefollowingconsiderations:sample collection, flow control valve selection, tubingtype, fittings, gas type, temperature control, flow rates,and sample dilution factors. ISO 18562-3 recommendsflow rates for different patient populations, while alsorecognizing actual flow rates of use. This presentationwillbeginwithanoverviewoftheISO18562setofstan-dards followed by a discussion of the considerations/difficultiesofperformingtheVOCstesting.Acasestudyfor a cPAP device componentwill be used to evaluatethereleaseprofilesofVOCsovertimeatadultandinfantflowrates.

4:40 Close of Program

biologicalriskevaluationofmedicaldevices,including:potentialbenefitsandcurrentuseinregulatoryapplica-tions, typesofmodelsthatcaninformTRAs,challengeswithuseinregulatorydecisionmaking,andstrategiestoovercomethesechallenges.

1:40 ManagingtheRiskofLeachablesthroughProactiveMaterialSelectionand

Michael Ruberto, President, Material Needs Consulting

Abstractcomingsoon

2:20 Afternoon Break & Sponsor Presentations

2:40 ExtractablesScreeningofSingleUseComponentsforQualification

Eric J. Hill, Director, Boston Analytical

SingleUseSystems(SUS)presentchallengeswithre-gards toextractablesand leachables, however theirease of use, quick change out capability, cost, andconfigurational flexibility provide significant advan-

tagesovertraditionalmanufacturingset-ups.WiththesechallengesregardingE&L,muchattentionhasbeenpaidto extractables data generation for use in vendor andmaterial selection.Ongoing discussions in the industryrevolvearoundtheBioPhorumOperationsGroup(BPOG)Standardized Extractables Testing Protocol for Sin-gle-UseSystems inBiomanufacturingand theproposedUSP<665>monographforsingleusesystems.Regardlessofhow thesediscussions resolveamongst the industry,after an SUS is selected there is still testing thatmustbeperformed.Thedatageneratedduringselectionisof-tennotrobustenoughforqualificationoftheSUSmate-rials for use in the manufacturing setting. It is criticalto perform extractables testing of the SUS formaterialcompatibilityusingthemanufacturingconditionsofuse,including timeand temperature. This extractables test-ingalsoshouldbeperformedusingtheactualsolutionscontacting each SUSmaterial. Case study examples ofextractablestestingformaterialcompatibilityandquali-ficationwillbepresented.

3:20 ComparisonoftheSolubilizationPropertiesofPolysorbate80andIsopropanol/WaterSolventSystemsforOrganicCompoundsExtractedfromThreePharmaceuticalPackagingConfigurations

Steve Zdravkovic, Senior Research Scientist, PPD

Ithasbeenreportedthatthepresenceofpolysorbate80inapharmaceuticalproduct’s formulationmayin-

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In the Age of COVID, the Show Must Go OnlineInresponsetooverwhelmingaudienceandspeakerfeedback,andinviewofthecurrenthealthandsafetyconcernsinvolvingthenovelcoronavirusCOVID-19,we’retakingour eventsonline(atleastfortheforeseeablefuture;wedohopetoseeyouagainsooninpersonwhenallthisisover!)Extractables & Leachables Virtual Summit 2020 is anentirelyonlineevent,completewithinsightfulpresentationsfromleadingresearchers,1:1networkingopportunities,livequestion&answersessions,andsponsoredinformationalpresentationsthathighlighthowvendorsaretacklingsomeofthekeyissuesfacingextractables&leachablestesting.Justsitbackandenjoythisonlinelearningexperiencefromthesafetyandcomfortofyourhomeoroffice.Missedasessionortwo?Noworries— thefullprogramwillbearchivedandavailableforpost-conferenceviewinganddownload.

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