血液的体积及组成.ppt

1,血液的體積及組成,70公斤重的成年男子含有5公升的血量。含紅血球、白血球及血小板。成年人血漿(plasma)佔全身血液總量的5060%。血漿的大部分是水，水主要作為溶劑。血漿呈淡黃色，其中含有數百種血漿蛋白，包括白蛋白(albumin)、球蛋白(globulins)及纖維蛋白原(fibrinogen)。,2,人類血漿之特異性,是一種非常豐富及複雜之生物來源物質。含超過100200種以上不同的（醣）蛋白（包括凝血因子，蛋白分解酵素抑制劑，蛋白分解酵素，免疫球蛋白），白蛋白，peptide，生長因子.。約1720種血漿成分已建立治療價值。是一人類治療所必需的兵工廠。,3,血漿來源,SourcePlasma(fromplasmapheresis)RecoveredPlasma(fromwholeblooddonations),4,血液的功能,運送細胞的產物及廢物，並將養分及氧氣送到細胞。血液內吞噬細胞的功用除了如清道夫外，並且能抵抗外來的感染。為運輸激素的途徑。平衡穩定體內的pH值。將體熱帶到皮膚發散以維持體溫恆定。,5,6,7,8,Takeabreak!,9,10,11,12,13,Virusestransmissibleviabloodandplasmaproducts,14,HumanVirusesofConcernWithRespecttoPlasmaDerivatives,EnvelopedVirusesHumanImmuneDeficiencyVirus(HIV)HepatitisB(HBV)HepatitisC(HCV)Non-EnvelopedVirusesHumanParvovirusB19(B19)HepatitisA(HAV),NotSignificientRisksHumanT-lymphotrophicvirus(HTLVITritonX-100)for4-6hoursat25to35oC.,23,Mostfrequentlyusedspecificviralinactivationtreatmentsofplasmaproducts,DryHeatTreatmentHeat-treatmentofalyophilisedproteinproductorfraction(drystate)fromseveralminutestoseveraldaysattemperaturesfrom60to100oC,24,Mostfrequentlyusedspecificviralinactivationtreatmentsofplasmaproducts,PasteurizationHeat-treatmentofanhomogeneousproteinsolution(liquidstate)for10hoursat60oC,generallyinthepresenceofstabilizers(sugars,amino-acids,polyols,.),25,ViralClearance,Clearance=Inactivationand/orRemovalIndividualmanufacturingsteps:-specificallydesignedforviralclearance-intendedprimarilyforpurificationEachclearancestepisseparatelyvalidatedProductionmethodsandpracticesmustconformtovalidatedmethods,26,ViralClearanceValidationI:Scale-down,Necessity:-Undesirabletointroducevirusesintoproductionfacilities;-Limitedabilitytoproducelargeamountsofhightiterviruspreparations;-Risktolaboratoryworkers.Requirements-Labprocessmimicsproductionscale(relativegeometries,volumes,flowrates,etc.)-Labprocessperformslikeproductionprocess(relativecapacity,yield,purification,etc.),27,ViralClearanceValidationII:Selectionofrelevantandmodelviruses,Typically,severalvirusesareselectedtoencompasstheanticipatedrisks.Relevant=avirusthatmaybefoundinthebloodorplasma.Model=alaboratorystrainofavirusnotnecessarilyfoundinthebloodorplasma.,28,Classificationforbiologicalproducts,ClassIProductsderivedfromhumantissuesorfluids:(plasmaderivatives,hormonesfromurine,placentalderivatives,etc.)Riskencountered:nospeciesbarrier,unknownviruses.Viralsafety:screeningofthedonorsandthecapacityoftheprocesstoeliminateand/orinactivateviruses.,29,Classificationforbiologicalproducts,ClassIIViralvaccines:killed(inactivated)andliveattenuatedvaccinesRiskencountered:Presenceofresidualactivevirusinkilledvaccines(Cutterincident-1953);reversiontovirulenceoftheattenuatedstrainsorafailureinGMP.Viralsafety:Controloftheinactivationprocedureandgeneticstabilityoftheattenuatedviruses.,30,Classificationforbiologicalproducts,ClassIIIProductsderivedfromanimaltissuesandfluids:collagen,heparins,animalimmunoglobulins,monoclonalantibodiesproducedinascites,etc.Riskencountered:Presenceofvirusesinthestartingmaterial;thescreeningforviralmarkersofthesourcematerialisnotfeasible.Viralsafety:Thereisthespeciesbarrier.Viralsafetyisbasedsolelyonthecapacityoftheprocesstoremoveand/orinactiveviruses.,31,Classificationforbiologicalproducts,ClassIVProductsderivedfromanimalcellcultures:proteinsobtainedbyrDNA,monoclonalantibodies,cytokines.Riskencountered:Presenceofvirusesinthecellsusedinproductionand/orcontaminationoftheproductbyvirusespresentinthereagentusedintheprocessorabreakthroughinSMP.Viralsafety:Characterizationandcontrolofthecellbanksandofthereagentsusedinproduction;processcapableofgeneratinghighlypurifiedproducts.,32,Classificationforbiologicalproducts,ClassVBacterialvaccines,toxoidesandrDNAp