层析介质寿命及验证

1、GE Healthcare20-3099101002000cGMP109970 A70 AFHiniiramiiimnnnnnnrammiinrnn210 A10099CIPCHO-20001.Protein AProtein ACHONaOHStreamline91.4STREAMLINE rProtein AA: 1.0m M NaOH 2M Nacl 20%2100cm 巾B:5%20m M EDTA0.1M NaCI 20mM NaH2PO4 pH 7.51.5C:50mMHAC 20%Mabselect SuReProtein AProtein A0.1 -0.5MNaOH4 Mab

2、selectSuRe 0.1-0.5MNaOH200#1.4#1.4st> tUm?sum3. Mabselect protein AMTHI#1.421DEAE sepharose Fast FLow36000.52CM sepharose Fast FLow3120013Sephacryl &200 HR58001DEAE Sepharose Fast FlowCM Sepharose Fast Flow3CIPDEAESepharose Fast FlowCM3A: 40mln6MGuHCI3B: 3h6M GuHCI3C:40 min 0.1 M3D: 40mln0.1M

3、NaoH3E:3h0.1 M NaoH3F:MabselectMabselectMabselectMabselectMabselectMabselectGuHCINaOHwoSepharose Fast Flow dsXr叶><- L3 RSKU-tXlttlWiO &1 R bMRf“” urne«fwi»t L3”yWw IUH#1.41.3r 20 W r M IM >X.160 曲 OT) 330liCuMl lff(4Kto£4 Mabselect SuRe 0.1-0.5M NaOH 20010%CIPDNAc.DNAO.OI

4、MNaOHProtein A20%NaOHNaOHNaOH1.5NaOHNaOH1124-57 AF1.4.2GE Healthcare18-NaOH1.5.1GE HealthcareAKTApilota.2.2CV1M NaO I EX3-4CVUV/pH/condCIP1-10CIP0.5-1.0NaOH30-60minO.OIMnaOH 20%DNAb.1 MNaOH + 1MNaCIDNAc.DNA2Md.NaOH3 M NaCIDNADNADNADNAa.NaOH3. AKTApilotEscherichia coliATCC8739Pseudomonas ase

5、ruginosaATCC 9027Staphlococcus aureusATCC6538Pichia pastorisGS115USPXXV#IM NaOHPHNaOH250 ml10s/ml16-20nN1 M554GE Healthcare BPGAKTApilot BPGFast FlowTCSP Sepharose15 cm WMPHIMNaOH1 h106/ml16-20PH5655.AKTApilot1#2#3#6#7#10# 11#4# A/B5#8# pH9#4. AKTApilotU/mlEcoliRaeruginosaS.aureusPichia past

6、oris1.S102002.00004. A/B00005.02006.00007.0000&pH00009.000010.UV000011.00006. BPG1# 2#5#1g 6#10»11#3#O-ring 4#7#8#9#12#13#1.4#1.45. BPGS.aureus1.3x103org/mlE.coli1.1x10 org/mlRaeruginosa85x104 org/mlCilbicans1.0x10* org/mlAfiiger1.0x104 org/ml10000020000030000004000005ig00000600000700000800

7、0009000001000000110000012000001300000#1.6251.62SOPSOPGE HealthcareGE HealthcareAxichrom1.2.3.HCP DNA98%4.UV/pH/Cond5.mmcmHETPAsCapto Q502069001.15Gapto Q702066001.23Capto Q4002075001.17Capto Q10001075001.3SP Fast Flow501066001.32SP Fast Flow701071001.32SP Fast Flow4001055001.35SP Fast Flow1000105500

8、1.356. AxichromScale-downScale-dow nNlh + 17. AxichromScale-down2000NaCINaOH3.1Scale-down0.45 pm#7.CIP2M NaCI0.510-15minCIP30%2-32-310-15min10-15minCIPa. IMNaOHb.C2MNaCI HICIMNaOH + IMNaCI4CV1.5CV1CV4CV2h2h2hCIP0.5-1M NaOH41-2hCIPa. 0.5-2MNaOHb. 0.5%441-2h1-2h70%30%3.1.270%NaOH4-6 hCIP15-30 min1CV3.

9、1.1.4a. 0.5%3-4 CV30%NaOH0.5-1.0 M0.b0.5MNaOH8NaOHBPGQ Sepharose Fast Flow1200EU/ml23h1 M NaOHPHTOCLAL1M NaOH1100 ng/mlBioprocessa.0.5-1 CVb.10-15 minc.2-3 CVd.0.1-0.5M NaOH1-2 CV2M NaCI 0.5 CV30%2-3 CV3.1.3+ 1 M NaCIa.3-4b3.1.4GF/IEX/HICCV0.5-1 M NaOHPH1-2 CV57 AFa. GF/IEX/HIC3

10、-4 CVb.0.5-1 M NaOHPH1-2 CV8.NaOHNaOHGE HealthcareNaOHNaOHCIPCIP1 M NaOH18-1124-70ct*n u?7l 晞机Oi WiTWWr悯 IMItaCi. I*、：Qf 冲scale-downAxichrom9.AKTAAKTAUSPVIUnicorndown3.2.2PHAKTAexplorerCIPscale 叩scale-Uricor nAxichromCFD Computational Fluid Dynamics3.1.5CIPa. CIPCIPb. CIPc. CIPCIPTOCTOC9#sca

11、le-up scale-dow n#10. AKTA explorer#6.A KTA explorera.A11/A2 B1/B2PH7.8.c. AA14d. Frac 950Blanke. AKTA explorerA12CIPA13CIPAmgen.5.UnicornCIPUnicornCIP blankCIP blank11. UnicornCcAf Arifllytia13.10-20MflbAS 曲。GO ortea12. Mabselect Sure 50GE Healthcarescale-downReadyToProcessReadyToProcessWave

12、11fh n斗厂UIUIULJ口口口口口UUU UUU#14. Ready To ProcessRead/ToProcessReadyToProcess.1. GE Healthcare Application note 18-1 124-75 AF Use of sodium hydroxide for cleaning and sanitizing chromatography media and systems .2. Gail Sofer, Bioprocess Technical, November 2007 Cleaning and Cleaning Validati

13、on in Process Chromatography- Curre nt Industry Practices a nd Future Prospects 3. GE healthcare poster Novel high capacity and alkaline stable protein A media.4. Anurag Singh Rthore and Gail Sofer Validation in manufacturing of biopharmaceuticals-Guidelines, Current Practices, and Industrial Case S

14、tudies 2005.5. Biorpharmacuetical Process Validation Gail Sofer 2000.6. Lars Hagel,Gunter Jagschies and Gail Sofer Han dbook of Process Chromatography-Development, manufacturing. Validation and Economics second Edition 20077. GE Healthcare Poster,The use of NaOH for CIP of rProtein Amedia:a 300 cycl

15、e study.& Gail Sofer; January 2003 Biorprocess; Establishing Resin lifetime.9. GE Healthcare application note 18-1171-11 AA Sanitization of AKTApilot with sodium hydroxide 10. GE Healthcare application note 18-1020-86 AB Sanitization of BPG column with sodium hydroxide .11. 200412. Jane Turton a

16、nd Zain Moola; Biopharm April 2002;Storing an Ion-Exchange Chromatography Gel in Dilute Alkali During Recycling Improves Cleaning.GE HealthcareCIP5Sephadex G-252-132-132-13O.OIMNaOHSephacryl High Resolution3-112-133-1120% NaOHSuperdex prep grade3-122-143-12O.OIMNaOHSepharose Fast Flow3-132-143-13O.O

17、IMNaOHSTREAMLINETMSP4-133-144-13O.OIMNaOHSTREAMLINE DEAE2-912-142-13O.OIMNaOHSP Sepharose Big Beads4-133-144-13O.OIMNaOHQ Sepharose Big Beads2-122-142-12O.OIMNaOHANXSepharose 4 Fast Flow(h/lsub)2-912-143-13O.OIMNaOHCapto wQ2-122-142-12O.OIMNaOHCapto S4-123-144-13O.OIMNaOHMacroCap SP3-122-134-11O.OIM

18、NaOHDEAESepharose Fast Flow2-912-142-12O.OIMNaOHCM Sepharose Fast Flow6-1012-144-13O.OIMNaOHSP Sepharose Fast Row4-133-144-130.01 M NaOHQ Sepharose Fast Flow2-122-142-12O.OIMNaOHSP Sepharose High Performance4-133-144-13O.OIMNaOHQ Sepharose High Performance2-122-142-12O.OIMNaOHSOURCETM15/30S2-131-142

19、-13O.OIMNaOHSOURCE 1 引 30Q2-121-142-12O.OIMNaOHQ Sepharose XL2-122-142-12O.OIMNaOHSP Sepharose XL4-133-144-13O.OIMNaOHSTREAMLINE Q XL2-122-142-12O.OIMNaOHSTREAMLINE SP XL4-133-144-130.01 M NaOHCapto MMC3-122-142-12O.OIMNaOHSTREAMLINE Direct HST3-122-133-13O.OIMNaOHPhenyl Sepharose Fast Flowh/I sub)3

20、-132-143-13O.OIMNaOHPhenyl Sepharose High Performance3-132-143-13O.OIMNaOHButyl-SSepharose 6 Fast Flow3-132-143-13O.OIMNaOHButyl Sepharose Fast Flow3-132-143-13O.OIMNaOHOctyl Sepharose Fast Flow3-132-143-13O.OIMNaOHSOURCE 15 RPC1-121-141-12O.OIMNaOHSOURCE30 RPC1-121-141-12O.OIMNaOHCIPpHpHpHpHpH90-40

21、01-3pHBlue Sepharose 6 Fast Flow4-123-134-120.01 MNaOHChelating Sepharose Fast Flow4-8.522-143-130.01 MNaOHIMAC Sepharose 6 Fast Flow4-8.522-143-120.01 MNaOHNi Sepharose 6 Fast Flow4-8.522-143-120.01 MNaOHSTREAMLINE Chelating48.523-143-130.01 MNaOHSTREAMLINE Heparin4-124-134-120.01 MNaOHHeparin Seph

22、arose 6 Fast Flow4-124-134-120.01 MNaOHnProtein A Sepharose 4 Fast Flow24-932F03-920%MabSelect2924-113-1020%MabSelect SuRe24-930.1-0.5M NaOH3-1220%MabSelect Xtra24-932-123-1020%2%rProtein A Sepharose Fast Flow24-9324-113-1020%STREAMLINErProtein A2<9324-113-1020%Protein G Sepharose 4 Fast Flow24-932503-920%rmp Protein A Sepharose Fast Flow2<9324-113-1020%PlasmidSelect Xtra3-112-133-1120%15#4 pH 3920%02 MigPHSPNaOH 20%50 mMpH 722%GE Healthcare # lifesciences800-810-911883312111212(852)2100 6314(010)5806 9403(021)3877-/808(U20)0363 3828-6/96