Mab Characterization .pdf

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1、CharacterizationofMonoclonalAntibodyProductsVenkatR.Mukku,Ph.D.USPB&BExpertCommitteeMember,USAIgGStructureandFunctionalDomainsVH•AgbindingVariableC1HRegionVLCLC2•EffectorFunctionsHConstantADCC(FcgRI,II,III)RegionCDC(C1q)Fc•FcRnbindingC3HIgGIsoformsandVa

2、riants°N-terminalPyro-Glu°Aspisomerization°DeamidationVH°MethionineoxidationC1H°HeavyChainC-terminalLysineVL°DisulfideVariantsCL°FreeCysadductsC2H°Glycosylationvariants–Highmannose–G0C3H–G1–G2–FucosylationReleaseTestsvs.CharacterizationTests°Releasetest

3、s–Minimalnumberoftestsrequiredforevaluatingpurity,identity,safetyandpotency–Welldevelopedandvalidated–RobustmethodsforroutineuseinQClabs°Characterizationtests–Providedetailedinformationonthemolecule/product–RequirementforReferenceStandardcharacterizatio

4、n–Requiredforcomparabilitystudies–OftentechnicallychallengingforroutineuseMonoclonalAntibodyLotReleaseTestsTestExampleresultandspec.°ProteinConcentration-----------------------70.9mg/mL[63.0-77.0]°Potency-----------------------100%[80-125%]°ID(immunoass

5、ay)-----------------------Pass°SE-HLC-----------------------MP:99.8%,HMW:0.2%,LMW:0.0%[MP≥99%]°CE-SDS,reduced-----------------------HC+LC:98.9%,HC:66.8%LC:32.1%[LC+HC≥98%]°CEX-HPLC-----------------------MP:89.6%,Acidic:2.7%,Basic:7.7%[≥80%]°CEX-HPLCID--

6、---------------------Pass°Osmolality-----------------------314mOsm/kg[300±50]°pH-----------------------5.2at24.6°C[5.0–5.4]°Appearance-----------------------Report°Volume-----------------------1.2mL(average1.1525mL,n=5)[≥1mL]°Sub-visibleParticulate-----

7、-----------------29particles/container≥10μm[nomorethan6000]3particles/container≥25μm[nomorethan600]°Sterility-----------------------Pass°BacterialEndotoxin-----------------------<0.2EU/mL[≤5.0]°CHOPELISA-----------------------4.4ppm°Protein-AELISA------

8、-----------------<0.5ppm°DNAQPCR-----------------------<1pg/mgCharacterizationtestsforMabproducts°Others°PrimaryStructure–Non-reducedCE-SDS–LC/MSPeptideMaps–CEX-HPLC,lowpH–N-terminalSequencing–DSC–VerificationofC-terminus–AUC–SE-