QualitybyDesign(QbD)BasedProcessDevelopmentforCell-FreeTherapeuticsUsingExosomeandExtracellularMatrix(ECMs)-DerivedfromAdiposeTissue

Abstract

Biopharmaceuticalsareadrugthatusescells,proteins,geneticmaterials,andcomplexesfrombiologicaltissuesasatreatmentfordiseases.Andbiopharmaceuticalshavebeeninthespotlightasatherapeutictoolforincurablediseasestoreplaceexistingchemicaldrugs.Comparedtoconventionalchemicaldrugs,biopharmaceuticalshavedistinguishedcharacteristicssuchaslargermolecularweight(morethan150kDa),complexmolecularstructureandformulation.Complicatedandheterogeneousbiopharmaceuticalformulationrequirescomplexandrepetitiverefiningproceduresforproductbiopharmaceuticals,resultinginsignificantdifficultyandcostincreaseinproduction.Besides,understandingthecorrelationbetweenproductqualityandprocessparametersisstillbeingleaked.However,therearemanycasesinwhichclinicaltrialsforbiopharmaceuticalshavereportedtheamazingefficacyofvariousdiseases,thereforebiopharmaceuticalsareinthespotlightasanewtreatmentplatformforovercomingincurablediseases. Herein,theisolationandfunctionalizationofstemcellexosomesandextracellularmatrix(ECM)derivedfromadiposetissueswerestudiedandevaluatedonabasisofqualitybydesign(QbD)conception.Asarawmaterial,humanandporcineadiposetissuescaneasilybeobtainedthroughahugeamountofbiologicalwastes.thestemcellexosomes,whichareoneofthemainfactorsintheparacrineactionofstemcelltherapy,wereextractedfromhumanadipose-derivedstemcells(hASCs),andstemcellexosomeswereeffectivelyproducedthroughthetangentialflowfiltration(TFF)andsize-exclusionchromatographyprocess,wherearecompatibletomass-productionandgoodmanufacturingpractice(GMP).Ievaluatedthecorrelationbetweenprocessparametersandthequalityofstemcellexosomes,andthisallowedthemanufactureofhigh-purifiedstemcellexosomeswithanti-inflammatoryeffects.ECMwasisolatedfromhumanandporcineadiposetissueandtheECMwasmodifiedbymechanicalandbiochemicalprocessestoenhancetheirsafetyandfunctionality.ThesefunctionalECMcouldbeappliedtohemostatandadiposetissueregeneration.Moreover,themanufacturingprocessofbiopharmaceuticalsderivedfrombiologicalresourcescouldbeoptimizedandtheprocessoptimizationwasachievedbyunderstandingthecorrelationbetweenproductperformancesandprocessconditions.Moreover,thesestudiesofprocessdevelopmentforbiopharmaceuticalscouldbeusedasapracticalexampleoftheQbDbasedprocessdevelopmentforbiopharmaceuticals.