用无菌工艺生产的无菌产品-现行GMP(FDA)

Pharmaceutical&EngineeringDesign2005,26(2)-GMP(:)ABA100(ISO5)BCD12(HEPA)E,ABCAB12A123456789BC12A1234BCDEABCDE:1:2:3:14©1995-2006TsinghuaTongfangOpticalDiscCo.,Ltd.Allrightsreserved.Pharmaceutical&EngineeringDesign2005,26(2),(21CFR210211)CGMP,FDA19871987(NDAAN2DA),1994,:1994,1994,CGMP,,,,FDA,,,FDA,,FDA(should),(CFR)210211,CGMPCFR,FDAA,CGMP(21CFR210211)21CFR600680,210.2(a)211.1(b)600-680210211:,,B,,,,,,,,,,,;;,,,,,,,,CGMP,,CGMP,1987,,,,,CGMP,,,,(),,,,CFR211.42(c),,,:333(10),:333(iii)333;(iv);333(vi)21CFR211.46(c),,,,24©1995-2006TsinghuaTongfangOpticalDiscCo.,Ltd.Allrightsreserved.Pharmaceutical&EngineeringDesign2005,26(2),(as2built),(,,)(1):1a(0.5m/ft3)ISOb0.5m/m3c(cfu/m3)c,d(90mm;cfu/4)10053,5201e1e1000635,2007310,0007352,000105100,00083,52000010050[]a,,/b,ISO14644-1ISO5100Ac,d,e,100(ISO5)A100(ISO5),(:,),,(:,),(2):0.53520,1,100(ISO5),,,,,,X.D.,,,,,,,,,,,(3),,,(:),,,,B,,,,,34©1995-2006TsinghuaTongfangOpticalDiscCo.,Ltd.Allrightsreserved.Pharmaceutical&EngineeringDesign2005,26(2)()100,000(ISO8)(),10,000(ISO7)(1),1,000(ISO6),100(ISO5)C,,12.5(Pa)(),,(.4),,100,000(ISO8),120,,,,(:),D1(:),,,,,,:,,,(),(),;2,,,,,1,,,,,(DOP)(PAO),,99.97%0.3,,,,0.3,,,DOP,,25-100/L,,1m3/min,1-2,0.01%,,,,(),()44©1995-2006TsinghuaTongfangOpticalDiscCo.,Ltd.Allrightsreserved.Pharmaceutical&EngineeringDesign2005,26(2)6,,,,E21CFR211.42(b),,,,21CFR211.42l,,:333(10),:(),,,,333(iii)333;(iv);(v);(vi)21CFR211.46(b),,,,,,,21CFR211.46(c),,,21CFR211.63,,,,,21CFR211.65(a),,,21CFR211.67(a),,,,21CFR211.113(b),,,,,100(ISO5),(4),,,,,,:,(SIP),,:,100(ISO5),,,(1),,(:),,54©1995-2006TsinghuaTongfangOpticalDiscCo.,Ltd.Allrightsreserved.Pharmaceutical&EngineeringDesign2005,26(2),,,,,(211.42),(211.63),,,()2005426228,,,,,,,,,,,,,,,;;;64©1995-2006TsinghuaTongfangOpticalDiscCo.,Ltd.Allrightsreserved.Pharmaceutical&EngineeringDesign2005,26(4)-GMP()V.,21CFR211.22(c),,21CFR211.25(a),,,CGMP(CGMP)CGMP,,CGMP21CFR211.25(c)21CFR211.28(a),21CFR211.28(b)21CFR211.28(c)21CFR211.28(d)(,),,,,,21CFR211.42(c),,:333(10):333(iv):33321CFR211.113(b),A,,,,,:(),,,,,,24©1995-2006TsinghuaTongfangOpticalDiscCo.,Ltd.Allrightsreserved.Pharmaceutical&EngineeringDesign2005,26(4),,,,,,,,,,,,,(,,,,,),(),(:,,,),,,,,,,B,,,C(.5)(:),,,,,,,,A21CFR210.3(b)(3),21CFR211.80(a),,,,,;21CFR211.80(b)21CFR211.84(d)(6),(,,),,,(IX),USP(WFI),,,34©1995-2006TsinghuaTongfangOpticalDiscCo.,Ltd.Allrightsreserved.Pharmaceutical&EngineeringDesign2005,26(4),(),,,,,,(SIP),,,,(EtO),,,,B/21CFR211.94(c),,21CFR211.94(d),,21CFR211.113(b),,1/,,,USP,,,99.9%(3)(.)(),,(),.C,,(,,,,,,),(:)USP,,,,(),,,,(.C),,,/GMP2/,:,44©1995-2006TsinghuaTongfangOpticalDiscCo.,Ltd.Allrightsreserved.Pharmaceutical&EngineeringDesign2005,26(4),(:,),211.19221CFR211.62,,21CFR211.65(a),,21CFR211.67(a),,,21CFR211.94l,,21CFR211.167(a)/,,CGMP(),,,(6,7)CGMP,,,,/,CIP/(:),321CFR211.111,,,,,,(:),,,21CFR211.63,211.65211.67,,,,21CFR211.84(c)(3)21CFR211.113(b),,,,,,,A,(211.113)(,,),54©1995-2006TsinghuaTongfangOpticalDiscCo.,Ltd.Allrightsreserved.Pharmaceutical&EngineeringDesign2005,26(4),,,,,,,,,,()1,,:,,(:),,(,)(,),,()(,,)SOP(:),,2,,,,,,,,,,,,,,:,,,,,,,,,,,,()3,,,,,,,,,,,,,,4,64©1995-2006TsinghuaTongfangOpticalDiscCo.,Ltd.Allrightsreserved.Pharmaceutical&EngineeringDesign2005,26(4),5000100005000,(.8)(:),,,,,(1),,,,,,,,5(:),,,,,,,6(),SOP,,7,,(:)[71],,100CFU,,,,(),,,,,,,8:,20-352.5142,,7,,,,(?),;,,,(),,,,(.B)(:,),,,74©1995-2006TsinghuaTongfangOpticalDiscCo.,Ltd.Allrightsreserved.Pharmaceutical&EngineeringDesign2005,26(4),,10,(),,,,,9,,,,,,,,,,(8,9),:5000,5000-10000:1,,2,,1000012,,,,,,FD&C[301(a)21U.S.C.331(a)]FDA,,,,B,0.2,,,;,(ATCC19146),,,(0.3),ATCC19146,,,(),107/cm2ATCC19146/(10,11,12)ATCC19146,,:,,84©1995-2006TsinghuaTongfangOpticalDiscCo.,Ltd.Allrightsreserved.Pharmaceutical&EngineeringDesign2005,26(4)(:),:(1)(2)pH(3),(4)(5)(6)(7)(8)(9),,:(.12),,,,,,,,(),,,,(),,C,,,(211.63211.113),,,,,,1,(specifiedloadconfiguration),,,,,,D-,(SIP):,(:,,,,,,),,:a:(:,),(:),b:,(BI),,,,,94©1995-2006TsinghuaTongfangOpticalDiscCo.,Ltd.Allrightsreserved.Pharmaceutical&EngineeringDesign2005,26(4),10-6FDA:2,,:,D-,(:),,:,,(),,,,,(comeup)()(41)10A,R0XCO{},:,,2.5PU,10A,,,:,610kV4.2,,,;,,1001000A,,:,(),,(1001000A),,:,I=1001000A,,,4.3,50100A,,5,,,,:200520221805©1995-2006TsinghuaTongfangOpticalDiscCo.,Ltd.Allrightsreserved.Pharmaceutical&EngineeringDesign2005,26(5)-GMP()X21CFR211.22(c)21CFR211.42(c),(10):(iv)21CFR211.56(b),,21CFR211.56(c),21CFR211.113(b)(),21CFR211.160(b),:(1),,(2)(3)(4),21CFR211.165(e)211.194(a)(2)21CFR211.192,,A1(),,(211.42211.113),,,(:,),,,,:,,,,,,,,,44©1995-2006TsinghuaTongfangOpticalDiscCo.,Ltd.Allrightsreserved.Pharmaceutical&EngineeringDesign2005,26(5),SOP,,SOP:(1);(2)(:);(3);(4)(:,);(5);(6);(7)2,,,,,,,,(:)(),,3,(),,,,,:70%Bacillus,spp.,,,(),,4:a,()b,:(),,,,,c(),(),,,(/),B,(,),,100,000(ISO8),,(,),54©1995-2006TsinghuaTongfangOpticalDiscCo.,Ltd.Allrightsreserved.Pharmaceutical&EngineeringDesign2005,26(5)(),,,,(),30-3548-7220-255-7,()C,,()D(:),,E(:),.A,21CFR210.3(b)(21),21CFR211.110(a)(),,,21CFR211.160(b),,:(1),(2)(3)(4)()21CFR211.165(a)()/,/,21CFR211.165(e)211.194(a)(2)21C