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WBDVVNJOUIFDBCJOFUXBTCSPLFOXJUIQVSFOJUSPHFOPODFUIFFOUJSF ESZJOHDZDMFXBTDPNQMFUFE*OBGJSTUTUFQUIFQSFTTVSFXBTSBJTFEVQ UP NCBS BOE UIF TIFMWFT XFSF NPWFE VQ JO PSEFS UP QVTI UIF TUPQQFSTJOUPUIFCPUUMFOFDLBOEDMPTFUIFWJBMTDPNQMFUFMZ5IFOUIF DBCJOFU QSFTTVSF XBT CBMBODFE UP BUNPTQIFSJD QSFTTVSF %VF UP UIF QSFTTVSFHSBEJFOUGSPNUIFPVUTJEFUPUIFJOTJEFUIFWJBMTXFSFTFBMFE WFSZ UJHIUMZ 5IF USBZT XFSF VOMPBEFE GSPN UIF ESZFST BOE DSJNQFE
EJSFDUMZ "T B MBTU TUFQ UIF WJBMT XFSF FJUIFS DPOUSPMMFE WJTVBMMZ CZ PQFSBUPST PS BGUFS CFJOHXBTIFEJOTQFDUFEPQUJDBMMZCZBOBVUPNBUFEDBNFSBTZTUFNUPEFUFDUEFGFDUTPG UIFDSJNQJOHUIFHMBTTPSUIFDBLFBQQFBSBODF
" 2VBMJUZDPOUSPM
6OEFSSPVUJOFDPOEJUJPOTUISFFTBNQMFTQFSESZFSXFSFESBXOBOETFOUUPUIF2VBMJUZ
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)JHI DPTUT JODVSSFE BT UIJT NFUIPE XBT UJNF DPOTVNJOH TBNQMF EFTUSVDUJWF BOE SFRVJSFE FOWJSPONFOU QPMMVUJOH SFBHFOUT %FQFOEJOH PO UIF QSPEVDU UIF 2$
EFQBSUNFOUJOWPJDFEQFSCBUDISFMFBTFCFUXFFOUPNJOVUFT"MSFBEZTPNFZFBST BHP UIJT GBDU JOEVDFE B DIBOHF SFRVFTU GPS UIF NPTU GSFRVFOU QSPEVDU BU UIBU UJNF 'VSUIFSNPSF B OPOEFTUSVDUJWF OFBSJOGSBSFE /*3 EFUFSNJOBUJPO XJUI B MBCPSBUPSZ
HSBUJOH TQFDUSPNFUFS XBT SFHJTUFSFE BT PGGJDJBM SFMFBTF NFUIPE &YDMVEJOH BOZ QSFQBSBUJWF TUFQ POF NFBTVSFNFOU UPPL OP NPSF UIBO POF NJOVUF BOE SFEVDFE UIF DPTUTCZUXPUIJSET
0DDBTJPOBMMZ PVU PG TQFDJGJDBUJPO 004 WJBMT XFSF EFUFDUFE "QQBSFOUMZ TPNF PG UIF UIPVTBOETPGWJBMTJOFBDIESZFSMPBEHPUTIVUCFUXFFOUIFJSOFJHICPSTMFBEJOHUPBO JOTVGGJDJFOU TIFMG DPOUBDU BOE UIFSFCZ B XPSTF UIFSNBM DPOEVDUJWJUZ 5IJT DBVTFE VOTBUJTGBDUPSZESZJOHSFTVMUTGPSSBSFFYDFQUJPOTJODPNQBSJTPOUPUIFUPUBMOVNCFSPG WJBMT 4PNF VOTVDDFTTGVM TUVEJFT XFSF DPOEVDUFE UP SFQSPEVDF TVDI TVQQPTFE QIFOPNFOB%VFUPOBUVSBMQSPDFTTWBSJBUJPOTEJGGFSFODFTJOXBUFSDPOUFOUPGUIFFOE QSPEVDUTFFNFEUP CF VOBWPJEBCMF 5XP SFTVMUJOH TDFOBSJPT XFSF QPTTJCMF &JUIFSUIF PVUMJFSTXFSFOPUEFUFDUFECVUEFMJWFSFEXJUIUIFSFTUPGUIFDPNQMJBOUQSPEVDUCFBSJOH QPUFOUJBM IFBMUI SJTLT BOE FYQFOTJWF QSPEVDU SFDBMMT 0S UIF XIPMF CBUDI IBE UP CF EFTUSPZFE EVF UP UIF CBE SFTVMUT PG UIF PVUMJFST CFJOH SBOEPNMZ TBNQMFE 5IF MBUUFS DBVTFEFRVBMMZBIJHIMPTTPGNPOFZBEFDSFBTFPGUIFTFSWJDFMFWFMBOEBOJODSFBTFPG UIFXPSLMPBEGPSUIFQSPEVDUJPOTUBGG
5IF BJN XBT UP QSFWFOU CPUI TDFOBSJPT UIF EFMJWFSZ PG BOZ 004 WJBM BOE UIF EFTUSVDUJPO PG BO FOUJSF CBUDI 0CWJPVTMZ UIF OBSSPX SBOEPN TBNQMJOH EJE OPU SFBMMZ BMMPXBWBMVBCMFFWBMVBUJPOGPSBSFQSFTFOUBUJWFCBUDIBWFSBHF
"UPUBMJOMJOFJOTQFDUJPOPGUIFDSJNQFEQSPEVDUJOTUFBEXPVMEPGGFSUIFPQQPSUVOJUZUP DIFDLUIFCBUDIGPS004WJBMTBOEUPSFKFDUUIFNTJNVMUBOFPVTMZ#ZUIJTXBZJUDPVME CFHVBSBOUFFEUIBUUIFSFNBJOJOHBOEGJOBMMZEFMJWFSFEDIBSHFNFFUTUIFTQFDJGJDBUJPOT 5IJTDPVMEPOMZCFQFSGPSNFECZBOPOJOWBTJWFOPOEFTUSVDUJWFBOEUIFSFCZQSFDJTF BOESFMJBCMFNFUIPE
/FBSJOGSBSFEBOBMZTJT /*3"GVMGJMMTUIFTFSFRVJSFNFOUTTJODF/*3SBEJBUJPOQFOFUSBUFT HMBTTBOEOPGVSUIFSTBNQMFQSFQBSBUJPOMJLFEJMVUJPOJTOFDFTTBSZ5IFGFBTJCJMJUZPGUIJT EFUFSNJOBUJPOPOBMBCPSBUPSZTDBMFDPODFSOJOHPOFQSPEVDUXBTBMSFBEZQSPWFO 8JUISFHBSE UPB QSPDFTTBOBMZUJDBMUFDIOPMPHZ 1"5 JUIBE UP CF EFNPOTUSBUFE UIBU UIF /*3 NFBTVSFNFOU XBT BMTP GFBTJCMF GPS UIF PUIFS QSPEVDUT PG UIF EFQBSUNFOU BT XFMM*OUIFGPMMPXJOHDIBQUFSTPOMZUIFTZOPOZNTPGUIFQSPEVDUTkOBNFTHJWFOJO5BCMF
"XFSFVTFE5PBMMPXBOJOMJOFNFBTVSFNFOUXJUIPVUTMPXJOHEPXOUIFQSPEVDUJPO
MJOFT TQFFE NVDI IJHIFS NFBTVSFNFOU WFMPDJUJFT XPVME CF SFRVJSFE UIBO JO UIF MBCPSBUPSZBQQMJDBUJPO(JWFOUIBUUIFMJOFTNBYJNVNTQFFEXBTWJBMTQFSNJOVUF BOE UIF BVUPNBUFE BOBMZ[FS TIPVME CF JOUFHSBUFE EJSFDUMZ CFIJOE UIF DSJNQJOH NBDIJOF UIF QFSGPSNBODF JO TQFFE BOE BDDVSBDZ PG /*3" IBE UP CF FWBMVBUFE 'PS TFDVSJUZSFBTPOTBGVSUIFSNBSHJOPGBCPVUXBTBEEFEUPUIFNBYJNVNWFMPDJUZ
"DDPSEJOHMZ B TQFDUSPNFUFS BCMF UP QFSGPSN BDDVSBUF TBNQMF BOBMZTFT QFS TFDPOE IBEUPCFJEFOUJGJFE
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%FTDSJQUJPO OPOTUFSPJEBM BOBMHFTJDBOUJ JOGMBNNBUPSZ BHFOU
BOUJWJSBMGVTJPO JOIJCJUPS
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7JBMEJBNFUFS<NN>
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<PCKFDUTNJO>
-PUTJ[F
Table A-1: Attributes and registered values of the freeze-dried products in question.
Product C 400 mg and Product D were either under development or revalidation and were just mentioned for completeness.
5PDBMJCSBUFBRVBOUJUBUJWFPSRVBMJUBUJWF/*3NPEFMNVDIQSFQBSBUPSZXPSLIBEUPCF DPOEVDUFE"SFGFSFODFNFUIPEXBTOFFEFEUPQSPWJEFUIFBDUVBMWBMVFTJOSFMBUJPOUP UIF BDRVJSFE TQFDUSB 0CWJPVTMZ UIJT XPSL DPVME OPU CF EPOF JO BO PQFSBUJWF BSFB PUIFSXJTFUIFXIPMFQSPEVDUJPOXPVMECFJOUFSSVQUFE4VCTFRVFOUMZTVDIBOBQQBSBUVT IBEUPCFNBJOUBJOFEJOBMBCPSBUPSZBOEUIFOUSBOTGFSSFEUPUIFJOMJOFBQQMJDBUJPO 5IFGJOBMEFDJTJPOBCPVUUIFSFBMJ[BUJPOPGUIF1"5QSPKFDUTIPVMECFDPOTJEFSFEXJUI SFHBSEUPGJOBODJBMBTQFDUT
&KDSWHU%7KHRUHWLFDOEDFNJURXQG
# 3FHVMBUPSZDPOUFYU
1IBSNBDFVUJDBMTBSF QSPEVDUT UIBU OFFE UP DPNQMZXJUI IJHIFTU EFNBOETJO UFSNT PG RVBMJUZ FGGJDBDZ BOE TBGFUZ *O UIF MBTU EFDBEFT UIF QIBSNBDFVUJDBM RVBMJUZ TZTUFNT XFOUUISPVHIBHSFBUEFWFMPQNFOU5IFESJWFSPGUIJTQSPDFTTXBTUPBIJHIFYUFOEUIF CPEZPGD(Y1SVMFTBOESFHVMBUJPOTBDPMMFDUJWFUFSNGPSDVSSFOU(PPE.BOVGBDUVSJOH -BCPSBUPSZBOE$MJOJDBM1SBDUJDFT
"T UIFTF SFHVMBUJPOT BSF CJOEJOH SFRVJSFNFOUT GPS BOZ OFX JOTUBMMBUJPO JO B QIBSNBDFVUJDBM QSPEVDUJPO FTQFDJBMMZ UIF (.1 TIPVME CF QSFTFOUFE TUSVDUVSBMMZ BOE UFYUVBMMZDPODFSOJOH/*3TQFDUSPTDPQZ
5IF BQQMJDBUJPO PG UIFTF SVMFT JT SFHVMBSMZ WFSJGJFE CZ UIF BENJOJTUSBUJWF BVUIPSJUJFT 'SPNUIFQPJOUPGWJFXPGBOJOUFSOBUJPOBMMZPQFSBUJOH4XJTTQIBSNBDFVUJDBMTDPNQBOZ FTQFDJBMMZ UIF 4XJTTNFEJD UIF 64 "NFSJDBO 'PPE BOE %SVH "ENJOJTUSBUJPO '%"
BOEUIF&VSPQFBO.FEJDJOFT&WBMVBUJPO"HFODZ &.&"BSFPGSFMFWBODF5IFBQQMJFE TUBOEBSET GPS UIF JOTQFDUJPOT BSF PSJFOUFE BU UIF CFTU QSBDUJDFT PG UIF DPNQFUJUPST BOEUIFUFDIOPMPHJDBMQSPHSFTT
# $VSSFOU(PPE.BOVGBDUVSJOH1SBDUJDF D(.1
*OPSEFSUPFOTVSFUIFRVBMJUZPGNFEJDJOFTWBSJPVTQIBSNBDPQPFJBTQSPWJEFHVJEFMJOFT DPODFSOJOH UIF EFWFMPQNFOU QSPEVDUJPO TUPSBHF BOE BOBMZUJDT PG NFEJDBM QSPEVDUT 5IFTFHVJEFMJOFTBSFPGBTUBUVUPSZOBUVSFBOEFOTVSFVOJGPSNRVBMJUZPG NFEJDJOFTBOEUFTUNFUIPET
*O UIF 8PSME )FBMUI 0SHBOJ[BUJPO 8)0 QVCMJTIFE GPS UIF GJSTU UJNF CBTJD QSJODJQMFT PG BO BEWJTPSZ OBUVSF GPS HPPE QSBDUJDF JO UIF NBOVGBDUVSF BOE RVBMJUZ DPOUSPMPGESVHTXJUIUIFBJNPGJNQSPWJOHUIFRVBMJUZPGNFEJDJOFT4JODFUIFOWBSJPVT PSHBOJ[BUJPOT IBWFQVCMJTIFEBEEJUJPOBMJOTPNFDBTFTFYQBOEFEQSJODJQMFT5IFTF
D(Y1 HVJEFMJOFT BSF OPX NBOEBUPSZ GPS QIBSNBDFVUJDBMT NBOVGBDUVSFST 'JHVSF # JMMVTUSBUFTUIFHFPHSBQIJDTDPQFPG(.1HVJEFMJOFT
Europe:
USA:
GMP
Japan:
GMP EC-GMP
National GMP PIC(S)-GMP
Figure B-1: Overview of relevant GMP guidelines. GMP = Good Manufacturing Practices, EC = European Community, PIC = Pharmaceutical Inspection Convention, and its successor organization PICS = Pharmaceutical Inspection Cooperation Scheme.
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
EFWFMPQNFOU PG OFX NFEJDJOFT 5IF PCKFDUJWF PG TVDI IBSNPOJ[BUJPO JT B NPSF FDPOPNJDBM VTF PG IVNBO BOJNBM BOE NBUFSJBM SFTPVSDFT BOE UIF FMJNJOBUJPO PG VOOFDFTTBSZ EFMBZ JO UIF HMPCBM EFWFMPQNFOU BOE BWBJMBCJMJUZ PG OFX NFEJDJOFT *O NFBOUJNF TBGFHVBSET PO RVBMJUZ TBGFUZ BOE FGGJDBDZ BOE SFHVMBUPSZ PCMJHBUJPOT UP QSPUFDUQVCMJDIFBMUITIPVMECFNBJOUBJOFE
#7BMJEBUJPOPGBOBMZUJDBMNFUIPET
5IF WBMJEBUJPO PG BOBMZUJDBM NFUIPET JT B DPNQMFY UFDIOJDBM NBUUFS PG DPOGJSNJOH UIF USVTUXPSUIJOFTT PG UIF NFUIPE 7BMJEBUJPO FOTVSFT UIBU VOEFS SPVUJOF DPOEJUJPOT UIF NFUIPE ZJFMET QSFEJDUJWF SFQSPEVDJCMF BOE BDDVSBUF SFTVMUT %FQFOEJOH PO UIF BQQMJDBUJPO PG UIF BOBMZUJDBM NFUIPE UIF QBSBNFUFST JOEJDBUFE JO UIF GPMMPXJOH UBCMF NVTUCFUBLFOJOUPBDDPVOU
1BSBNFUFS %FGJOJUJPO
"DDVSBDZ %FUFSNJOBUJPOPGUIFEFWJBUJPOGSPNUIFUSVFWBMVF
1SFDJTJPO "NFBTVSFPGUIFEFHSFFPGSFQSPEVDJCJMJUZ.BUIFNBUJDBMMZQSFDJTJPOJT FYQSFTTFECZUIFTUBOEBSEEFWJBUJPOPGBOVNCFSPGNFBTVSFNFOUT -JOFBSJUZ 1SPQPSUJPOBMJUZCFUXFFONFBTVSFNFOUSFTVMUBOERVBOUJUZPGTVCTUBODF 3PCVTUOFTT 4VTDFQUJCJMJUZPGGBJMVSFPSSFTJTUBODFUPPVUTJEFJOGMVFODFTBOEDIBOHFTUP
NFBTVSFNFOUQBSBNFUFST
4QFDJGJDJUZ "OJOEJDBUJPOPGUIFFYUFOEUPXIJDIUIFNFUIPEVTFEJTDBQBCMFUPEJTUJOHVJTI UIFDPNQPVOEUPCFEFUFDUFEBOEPUIFSDPOTUJUVFOUT
%FUFDUJPOMJNJU 5IFTNBMMFTUTJHOBMUIBUDBOTUJMMCFEFUFDUFEXJUIBEFRVBUFSFMJBCJMJUZ -JNJUPGRVBOUJGJDBUJPO 5IFTNBMMFTURVBOUJUZPGUIFTVCTUBODFUPCFEFUFSNJOFEUIBUDBOTUJMMCF
RVBOUJUBUJWFMZEFUFDUFEXJUIBEFRVBUFBDDVSBDZBOEQSFDJTJPO Table B-1: Parameters used to evaluate analytical methods.
5IF BDDFQUBODF DSJUFSJB GPS WBMJEBUJPO PG B NFUIPE TIPVME CF TQFDJGJFE JO BEWBODF JO BDDPSEBODFXJUIDVSSFOUQSBDUJDF%FUBJMTPGBDUVBMJOUFSOBUJPOBMDSJUFSJBBSFHJWFOJOUIF SFGFSFODFT
#2VBMJGJDBUJPOPGBOBMZUJDBMBQQBSBUVT
2VBMJGJFE MBCPSBUPSZ BQQBSBUVT NVTU CF VTFE UP WBMJEBUF BOBMZUJDBM NFUIPET 5IF QVSQPTF PG RVBMJGZJOH BOBMZUJDBM BQQBSBUVT JT UP UFTU BOE HVBSBOUFF UIF QSPQFS GVODUJPOJOH PG UIF BQQBSBUVT CZ NFBOT PG BQQSPQSJBUF UFTUJOH %FQFOEJOH PO UIF QSJODJQMFPGNFBTVSFNFOU FH677*4UIFQIBSNBDPQPFJBTTUBUFMJNJUTXIJDINVTU CFBDIJFWFE
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
requirementsUser
Performance qualification
PQ
System specifications
Technical design
Development
Installation qualification
IQ
Operational qualification
OQ
Design qualification
DQ Accord
ing to According to According to
According to According to
Figure B-2: V-model for the purchase and development of analytical devices. The terms are defined in the accompanying text.
#$PNQVUFSJ[FETZTUFNWBMJEBUJPO
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&TQFDJBMMZJOOFXMZEFWFMPQFEQSPHSBNTWBMJEBUJPOTIPVMECFTFFOBTBOBMMFNCSBDJOH RVBMJUZ BTTVSBODF BQQSPBDI BOE JT BMTP QFSGPSNFE JO BDDPSEBODF XJUI UIF 7 NPEFM TIPXOJO'JHVSF#
# 1SPDFTTBOBMZUJDBMUFDIOPMPHZ
"T EFNPOTUSBUFE BCPWF UIF QIBSNBDFVUJDBM JOEVTUSZ NBOVGBDUVSJOH TFDUPS JT IJHIMZ SFHVMBUFE BOE UIF SFTQPOTJCMF BVUIPSJUJFT EFNBOE SFWJFX BOE BQQSPWBM PG QSPDFTT EPDVNFOUBUJPO BOE GBDJMJUZ QSJPS UP PGGJDJBM BQQSPWBM PG BOZ GBDJMJUZ PS QSPEVDU 4VCTFRVFOU QSPDFTT DIBOHFT PGUFO SFRVJSF B OFX SFWJFX BOE BQQSPWBM CFGPSF JOTUJUVUJPO 5IVT FWFO UIF POHPJOH NBOVGBDUVSJOH QSPDFTT JT DPOUJOVPVTMZ TVCKFDU UP JOTQFDUJPO BOE (.1 TUBOEBSET DPOGPSNBODF 0O UIF PUIFS IBOE (.1 TUBOEBSET BSF NPTUMZFNQJSJDBMBOEOPUTDJFODFCBTFE5IJTTZTUFNFWPMWFEBCPVUZFBSTBHP XIFOUIFEJGGFSFOUTFDUPSTPGJOEVTUSZMBDLFESJHPSPVT401T
/FWFSUIFMFTT NBOVGBDUVSFST PCTFSWF BO JODSFBTJOH USFOE UPXBSE NBOVGBDUVSJOH SFMBUFEQSPCMFNT3FDBMMTEJTSVQUJPOPGNBOVGBDUVSJOHPQFSBUJPOTMPTTPGBWBJMBCJMJUZPG FTTFOUJBM ESVHT OFHBUJWFJNQBDU POOFX ESVH BQQSPWBMT BOE MPX NBOVGBDUVSJOH BOE 2VBMJUZ "TTVSBODF 2" QSPDFTT FGGJDJFODZ BSF UIF DPOTFRVFODFT *O DPNCJOBUJPO BMM UIJT FOET VQ JO B MPTT PG JNBHF BOE UP JODSFBTFE DPTU JNQMJDBUJPOT 5IF QFSGPSNBODF FYQFDUBUJPOTLFFQPOCFJOHVONFU8IJMFVUJMJ[BUJPOMFWFMTEFDSFBTFUPPSMFTT PGUIFQSPEVDUTBSFTDSBQQFEBOEOFFEUPCFSFXPSLFEBOEUIFDPTUTPGRVBMJUZJT JOFYDFTTPG
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Figure B-3: Illustration of the ’DMAIC’ procedure according to the Six Sigma concept.
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Figure B-4: Higher sigma indicates better processes. The pharmaceutical industry is typically located between two and three V which is a sign for poor productivity.
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Systems for design, analysis and control
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of raw and in-process materials and processes to assure final product quality.
Figure B-5: Definition of PAT proposed by the CDER.
Figure B-6: Paradigm shift to the process control philosophy considering tablet manufacturing as an example: (a) end of phase testing of quality, to reduce the risk in moving to the next stage, (b) continuously or more frequently quality testing during each phase, to recognize deviations right in time to take measures. The amount of classical laboratory control can be reduced.
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Figure B-7: Options for introducing PAT. *A step-by-step approach, one unit operation at a time similar to option B, is also an option.
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Figure B-8: Illustration of the meaning of the terms in-line, on-line, at-line, and off-line.
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Figure B-9: Example of overall cycle times: without respect to the product, QC testing times are significant.
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Temperature [°C]100 Pressure1
[mbar]
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6.13
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