THORNTON

Dn u v phn tch nc tinh khit

m bo Tun th

Tun Th Quy nh V Nc
theo Yu Cu Dc in Quc T

mc lc
Trang 1. 2. 2.1 Tiu chun v tinh khit ca Nc USP l g? Tnh dn in v Tng lng Carbon Hu c (TOC) cho vic Gim st Mc tinh khit ca Nc: mc tiu cha USP <645> USP <645> Tnh dn in Li ch ca Kim tra trc tip trn h thng Nhit v USP <645> <645> Quy trnh Dn in Giai on 1 Giai on 2 & 3 Tm tt Yu cu Hiu chun i vi USP <645> Quy trnh Hiu chun c Khuyn ngh Hiu chun B hin th hoc Thit b o lng in t Hiu chun Cm bin Phng php Thng thng dng Kim th/Hiu chun Hng s Cm bin Phng php Thng thng dng Kim th/Hiu chun Nhit Cm bin (RTD) Hiu chun Hng s Vt l bng cch s dng Cm bin dn in K thut s Tn sut Hiu chun USP <643> Tng lng Carbon Hu c Th nghim Tnh ph hp ca H thng (SST) Quy trnh SST EP, JP, ChP, IP v Yu cu ca cc Dc in khc 3 3 Thornton c Tin s Richard Thornton (Gio s ti Hc vin Cng ngh Massachusetts, MIT) sng lp ra vo nm 1964 v tr thnh mt phn ca B phn Phn tch Quy trnh METTLER TOLEDO t nm 2001. V th dn u th trng ca cng ty c minh chng bng nhng cng c phn tch v cm bin ci tin chuyn dng trong cc ng dng Nc Siu tinh khit v Nc c tinh khit Cao nhiu ngnh khc nhau, bao gm: Dc, Cng ngh sinh hc, Vi in t v To in nng. Nhn vin ca METTLER TOLEDO Thornton hot ng trong nhiu t chc khoa hc khc nhau nh ASTM, ISPE, PDA, AIChE, SEMI v USP. Nghin cu chuyn su c tin hnh v: Tnh dn in ca Nc Siu tinh khit UPW Nhit Cao TOC v Ozon (O3) Ozone xy Ha tan v CO2 Hiu chun v Cn bng Nhit

3 4 4 4 5 5 5 6 6 7 7 8 8 9 9 9 10 10 10

3. 3.1 3.1.1 3.2 3.3 3.3.1 3.3.2 3.4 3.5 3.5.1 3.5.2 3.5.3 3.5.4 3.5.5 3.5.6 4. 4.1 4.1.1 5.

ISm khng ch l mt thc o

Qun l Cm bin Thng minh (ISM) l cng ngh c kim chng v cht lng v c tch hp vo trong cm bin. Cng ngh ny a ra tn hiu k thut s mnh, lu gi li cc d liu hiu chun hin ti v d liu hiu chun ca ring nh my, ng thi, tin on cc nhu cu bo dng, hiu chun hoc thay th cm bin.

11

6.

ng gp ca mETTLER TOLEDO Thornton cho vic Pht trin Cc Tiu chun 14

Tun th Quy nh v Nc dng trong Dc phm

Phn tch Quy trnh METTLER TOLEDO

Tiu chun v tinh khit ca Nc v USP

1. Tiu chun v tinh khit ca Nc

Nc Tinh khit (PW), Nc c tinh khit Cao (HPW), Nc ct pha tim (WFI) v Nc tinh khit Chng ct c s dng trong quy trnh sn xut Dc phm trn khp th gii. Cc c quan chc nng Hoa K v quc t thit lp ra cc tiu chun v cht lng nc i vi Nc Tinh khit v cc cp khc ca nc. Cc c quan chc nng chnh bao gm: Dc in Hoa K (USP) Dc in Chu u (EP) Dc in Nht Bn (JP) Dc in Trung Quc (ChP) Dc in n (IP)

2. USP l g?
Dc in Hoa K (USP) l mt c t chc quan phi chnh ph, chuyn thit lp cc tiu chun chnh thc chung cho thuc bn theo toa ca bc s v thuc bn t do ngoi quy (khng theo toa), m phm v cc sn phm chm sc sc khe khc c sn xut hoc bn Hoa K. USP cng thit lp cc tiu chun c cng nhn rng ri v thnh phn ca thc phm v cc thc phm n king b sung. C quan ny cng thit lp cc tiu chun v cht lng, tinh khit, bn v tnh ng nht ca nhng sn phm ny, l nhng yu t rt quan trng i vi sc khe cng ng. Cc tiu chun ca USP c cng nhn v s dng hn 130 quc gia trn ton cu. Nhng tiu chun ny gip m bo sc khe cng ng trn khp th gii trong gn 200 nm qua.

2.1 dn in v Tng lng Carbon Hu c (TOC) cho vic Gim st Mc tinh khit ca Nc
dn in v Tng lng Carbon Hu c (TOC) l cc s o cho vic kim sot hng lot tp cht hu c v ion Nc Tinh khit, Nc ct pha tim v sn phm ngng t ca qu trnh Chng ct Nc tinh khit. Chng <645> dn in ca nc v <643> Tng lng Carbon Hu c ca Dc in Hoa K cung cp cc phng php th nghim u tin cho vic kim th thit b, kim sot quy trnh trc tuyn v x nc cho sn xut. Cc thng s ca USP khng gii hn hay ngn cn vic s dng cc cng ngh thay th, m cung cp hng dn v cch kim nh nhng h thng phn tch ny, gii thch kt qu ca dng c o v thit lp tiu chun cho vic s dng dng c o lng i vi TOC v dn in, chng hn nh Kim Tra Tnh Tng Thch ca H Thng (SST), gii hn pht hin, yu cu v ha tan v hiu chun dng c o cho b hin th hoc thit b o lng in t.

Tun th Quy nh v Nc dng trong Dc phm

Phn tch Quy trnh METTLER TOLEDO

Mc tiu ca USP <645>

3. mc tiu ca USP <645>

1. m bo tnh ton vn ca cht lng nc hin c 2. Thay th cc th nghim ha cht t li thi 3. nh lng kt qu th nghim 4. Khuyn khch kim tra trc tip trn h thng 5. Gim thiu s lng th nghim cn thit 6. Tng mc tin cy ca th nghim

3.1 USP <645> dn in

Nc khi dng cho cc mc ch dc bao gm Nc ct pha tim, Nc c tinh khit Cao, Nc Tinh khit v Nc chng ct tinh khit. Hu ht cc dc in ton cu u a ra yu cu i vi vic sn xut nhng sn phm nc ny. Hoa K, cc quy nh v dn in c Dc in Hoa K nu r trong chng th nghim, <645> quy nh ny c kt hp hi ha vi cc dc in khc trn ton cu. Th nghim dn in l yu cu i vi Nc Tinh khit USP, Nc ct pha tim v sn phm ngng t ca qu trnh Chng ct Nc tinh khit. USP <645> l mt phng php th nghim gm 3 giai on i hi phi tin hnh kim tra trc tip trn h thng hoc ngoi tuyn. Th nghim dn in trc tuyn bao gm Giai on 1, trong khi Giai on 2 v 3 dnh cho th nghim ngoi tuyn. Trong thng 12 nm 2008, USP <645> c sa i nhm khuyn khch s dng phng php kim tra trc tip trn h thng:

kim dn in trc tip trn h thng (online) cung cp s o thi gian thc v c hi kim sot, quyt nh v can thip i vi quy trnh thi gian thc. Cn phi thn trng khi thu thp cc mu nc cho vic o lng dn in bn ngoi h thng (offline). mu c th b nh hng bi phng php ly mu, bnh cha mu v cc yu t mi trng chng hn nh nng CO2 trong mi trng xung quanh v hi nc hu c.
3.1.1 Li ch ca kim tra trc tip trn h thng C mt s li ch khi tin hnh kim tra trc tip trn h thng. Mt li ch chnh l vi kim tra trc tip trn h thng, cc li lin quan ti vic thu thp, x l v vn chuyn mu c gim thiu hoc loi b hon ton. Ngoi ra, v nc c n gin ha Vn sn xut v tiu dng lin tc, kim tra trc tip trn h Tun th thng cho php thu thp d liu thi gian thc, d liu ny c th c m ha v phn tch nhm cung cp ISM n gin ha vic tun th quy nh bng cch lu tr ni b cc thng tin quy trnh thi gian thc cng nh ton b lch d liu hiu chun ca cm bin v s ca nc. Th nghim ngoi tuyn cung cp gii php hn ch vic lu tr h s s sch. o lng thay th n gin, tit kim chi ph cho vic th nghim bn ngoi h thng.

Tun th Quy nh v Nc dng trong Dc phm

Phn tch Quy trnh METTLER TOLEDO

Mc tiu ca USP <645>

3.2 Nhit v USP <645>

Nhit l tham s chnh cho vic quan st thay i cht lng nc v c th c tc ng ng k ti cc s o dn in ca cc mu nc. USP <645> m t tm quan trng ca nhit theo cch ny:

V nhit c tc ng ng k ti kt qu o dn in ca cc mu nc nhit cao v thp, nhiu dng c o t ng chnh sa kt qu o thc t hin th gi tr c th c quan st v l thuyt 25C. Vic ny thng c thc hin thng qua s dng cm bin nhit c gn vo cm bin dn in v mt thut ton trong s mch ca dng c o. Thut ton b tr nhit ny c th khng chnh xc. Cc gi tr dn in phng php ny l nhng s o khng b tr nhit.
Ni cch khc, v cc thut ton b tr nhit gia cc nh sn xut thiu kh nng ti to, USP <645> yu cu cc s o dn in khng b tr nhit . Cc dng c o ca METTLER TOLEDO Thornton cho php bo co s o b tr v khng b tr nhit s dng b hin th v cm bin tng t.

3.3 <645> Quy trnh Dn in

3.3.1 Giai on 1 Giai on 1 dnh cho vic o lng trc tuyn. dn in b tr nhit v khng b tr nhit c o trc tuyn. Gi tr nhit o c c lm trn xung gi tr gn khong thp nht 5C v kt qu o nhit iu chnh c a vo bng bn di. Nu dn in o c khng ln hn gii hn trong bng ny, ngha l nc p ng yu cu i vi <645>. Giai on 1: Yu cu v Nhit v dn in Nhit (C) 0 5 10 15 20 25 30 35 40 45 50 dn in Ti a (S/cm) 0,6 0,8 0,9 1,0 1,1 1,3 1,4 1,5 1,7 1,8 1,9 Nhit (C) 55 60 65 70 75 80 85 90 95 100 dn in Ti a (S/cm) 2,1 2,2 2,4 2,5 2,7 2,7 2,7 2,7 2,9 3,1

Tun th Quy nh v Nc dng trong Dc phm

Phn tch Quy trnh METTLER TOLEDO

Mc tiu ca USP <645>

3.3.2

Giai on 2 & 3 kim tra trc tip trn h thng c cc yu cu khc v kt qu c th kh t c hn. c Giai on 2 v 3, mu c khuy ln ( lm cn bng mu nc vi CO2 trong khng kh) v nhit c iu chnh v 25 1C. Nu dn in nh hn 2,1 S/cm, ngha l nc p ng cc yu cu ca <645>. Tuy nhin, nu mu nc ln hn 2,1 S/cm, ngi dng chuyn sang Giai on 3. Giai on 3, nhit mu c duy tr 25C 1C. Mt dung dch kali clorua bo ha c pha thm vo mu nc v nng pH c xc nh n v gn nht 0,1 pH. Nu s o dn in t Giai on 2 khng ln hn dn in c tham chiu cho gi tr pH cho sn (xem Bng 2 trong USP <645>), ngha l nc p ng yu cu ca <645>. Nu dn in o c ln hn gi tr ny hoc pH nm ngoi khong 5,0 - 7,0, nc khng p ng yu cu ca, nc khng p ng yu cu ca of <645> v tnh dn in.

3.4 Tm tt Yu cu Hiu chun i vi USP <645>

dn in phi c o chnh xc bng dng c hiu chun. USP <645> c cc yu cu hiu chun i vi c b hin th v thit b o lng in t cng nh cm bin. Yu cu i vi b hin th hoc thit b o lng in t (cho cm bin k thut s) bao gm: Mch o nhit kim duyt. Bo co dn in hoc in tr khng b tr nhit. Hin th ha tan 0,1 S/cm. ha tan 1,0 S/cm khng c chp nhn. Xc minh hiu sut 0,1 S/cm bng cch thay th cm bin bng in tr c chnh xc c th truy nguyn (0,1%). V d: in tr 50 k c hng s vt l 0,1 cm-1 s hin th 2,0 0,1 S/cm.

Yu cu v B hin th v B hin th ca mETTLER TOLEDO Thornton Thng s ca USP in tr chnh xc ti 0,1% chnh xc theo quy nh, c th truy nguyn theo NIST hoc c quan quc gia tng ng chnh xc ca dng c khi khng c cm bin 1,3 S/cm l 0,1 S/cm Hin th dng c o ha tan ti 0,1 S/cm Phi bo co dn in hoc in tr khng b tr nhit m800 (ISM ) m300 (ISM) m300 (Analog)

C th truy nguyn 0,05% - 0,1% NIST

0,004 S/cm (0,3% kt qu o) 0,001 S/cm Bo co dn in hoc in tr b tr v khng b tr nhit

Tun th Quy nh v Nc dng trong Dc phm

Phn tch Quy trnh METTLER TOLEDO

Yu cu hiu chun ca USP <645> i vi cm bin dn in bao gm:

Mc tiu ca USP <645>

Nhit chnh xc ti 2C. Hng s vt l chnh xc v xc nh ti 2%. Hiu chun cm bin trong dung dch c dn in nu (ca NIST, nh cung cp ha cht, v.v..). Hiu chun cm bin trong dung dch c iu ch cho dn in c th (nc tiu chun hoc nc siu tinh khit ASTM D1125). Hiu chun cm bin vi mt cm bin hiu chun khc thng ca cng mt nh sn xut.

3.5 Quy trnh Hiu chun c Khuyn ngh

Ni chung, mt h thng o lng y gm c: thit b o lng in t hoc b hin th, thng c mch o lng, cm bin v cp lin kt cm bin vi b hin th. Cc tham s sau y phi c hiu chun y to ra mt h thng c hiu chun: 1. Thit b o lng in t hoc mch nhit 2. Mch in tr ca thit b o lng in t 3. Thnh phn nhit cm bin 4. Hng s vt l cm bin

Yu cu Cm bin v Cm bin ca mETTLER TOLEDO Thornton Thng s ca USP chnh xc hng s vt l: 2% s dng dung dch quy chiu (v d: ASTM D1125 hoc dung dch quy chiu khc) chnh xc nhit : 2C Cm bin UniCond Cm bin Analog chnh xc hng s vt l 1% Hiu chun c th truy nguyn theo ASTM D1125, D5391 v Nc Siu tinh khit 0,1C 25C Nhit c th truy nguyn theo NIST

3.5.1

Hiu chun B hin th hoc Thit b o lng in t Khi b hin th hoc thit b o lng in t c hiu chun, iu quan trng l phi xc minh v hiu chun in tr tt c cc khong v mch bn trong. Vic ny thng c thc hin bng cch s dng hp thp bin hoc thit b hiu chun ca mt nh sn xut bt k. nhng thit b ny, cc in tr c th truy nguyn c dng m phng nhit v dn in. Sau nhit v dn in o c s c so snh vi nhit v in tr c th truy nguyn. iu chnh s c thc hin nu cn hiu chun mch in t.

kh nng Truy nguyn ca B hin th

Tun th Quy nh v Nc dng trong Dc phm

Phn tch Quy trnh METTLER TOLEDO

Mc tiu ca USP <645>

3.5.2

Hiu chun Cm bin Hng s Vt l: Mc d hng s vt l cm bin c th c gi tr danh ngha, chng hn nh 0,1 cm-1, hng s vt l chnh xc thng c hiu chun ring nhm t c chnh xc cao hn. Vic ny c thc hin bng cch s dng mt dung dch xc nh khi so snh vi mt h thng o lng c hiu chun khc. Hiu chun hng s vt l ca nh my c chng nhn v truy nguyn theo tiu chun ASTM trong khi nhit c truy nguyn theo NIST. kh

nng Truy nguyn ca Cm bin

Cm bin Dn in Thornton 0,1 cm-1

Bn v Khi nim Hng s Vt l

1 cm

A d

Hng s Vt l = in cc nh hn bn trong 0,1 cm -1

Chiu di Din tch

0,1 cm 1 cm2

= 0,1 cm-1

1 cm

0.1 cm

Chiu di khong cch gia cc in cc Din tch thit din hiu qu ca cht lng gia cc in cc

3.5.3

Phng php Thng thng dng kim th/Hiu chun Hng s Cm bin
1 cm

Hiu chun hng s vt l ca cm bin c th t c bng cch s dng mt s phng d php. 1 cm

0.01 cm

1. Kim tra hoc hiu chun cm bin so vi cm bin hiu chunkhc. 2. Kim tra hoc hiu chun cm bin trong mt dung dch c dn in xc nh. Cc dung dch dn in cho mc ch ny c th c mua hoc c iu ch sn gi tr dn in c th s dng cc phng php tiu chun ASTM hoc Nc Siu tinh khit. Khi hiu chun hng s vt l cm bin, nn s dng mt b hin th c hiu chun v mt cp c chiu di tng t.

X l Cm bin D dng
Cm bin ISM c hiu chun sn mang li kh nng vn hnh khng c li vi tnh nng Cm v o n gin.

Tun th Quy nh v Nc dng trong Dc phm

Phn tch Quy trnh METTLER TOLEDO

Mc tiu ca USP <645>

3.5.4

Phng php Thng thng dng kim th/Hiu chun Nhit Cm bin (RTD) Hiu chun nhit thng lin quan ti vic so snh nhit o c vi mt nhit tham chiu. Khi kim tra v hiu chun nhit , nn s dng mt b hin th hiu chun hoc thit b o lng in t v mt dy cp c chiu di tng t ng thi nn gn h thng tham chiu nhit vo cng mt dung dch v bnh ng.

3.5.5

Hiu chun Hng s Vt l bng cch s dng Cm bin dn in k thut s Ci tin Cm bin Dn in/in tr ca UniCond tch hp mch o lng v cm bin vt l vo mt thit b. Cm bin v mch o lng khng tch ri nhau v chng c hiu chun ng thi ti nh my di dng mt h thng, dn n mt gii hn v li, ging vi cm bin analog thng thng. B hin th k thut s trong trng hp ny khng lin quan ti mch o lng v do khng cho li no. Vic tun th theo USP <645> yu cu phi hiu chun c hng s vt l cm bin v mch o lng. Mch o lng c th truy nguyn theo NIST v hng s vt l c th truy nguyn theo ASTM. Mch o lng ca cm bin UniCond c hiu chun trc khi lp rp. Trong trng hp Cm bin UniCond, mch o lng c lng ghp vo chnh bn trong cm bin ch khng phi b hin th, v M-un Hiu chun UniCond ph hp duy nht cho vic hiu chun mch o lng trong khi c lp t trong quy trnh.

3.5.6

Tn sut Hiu chun Nhm tun th nguyn tc th nghim v cc phng php thc hnh tt v o lng ca USP, phi thc hin hiu chun theo nh k. Hu ht cc dc in, k c USP, u khng ch nh tn sut hiu chun; iu ny ty thuc vo khuyn ngh ca tng nh sn xut. Quy chun ngnh thng xut thc hin hiu chun hng nm.

Cm bin V sinh UniCond

Tun th Quy nh v Nc dng trong Dc phm

Phn tch Quy trnh METTLER TOLEDO

USP <643> Tng lng Carbon Hu c

4. USP <643> Tng lng Carbon Hu c

Tng lng Carbon Hu c l s o cc tp cht hu c c trong nc dc phm c o di dng carbon. Cc phn t hu c c a vo nc t nc ngun, t cc nguyn vt liu ca h thng tinh lc v phn phi v t mng sinh hc pht trin trong h thng. C mt s phng php c chp nhn cho vic phn tch TOC. USP Chng <643> khng chng thc hay gii hn mt phng php no so vi mt phng php khc, m cung cp hng dn v cch thm nh nhng cng ngh ny v cch gii thch kt qu ca chng cho vic s dng lm th nghim gii hn. Tt c cc phng php u phi phn bit gia carbon v c, c trong nc t cc ngun nh CO2 ha tan v bicarbonate cng nh CO2 c to ra t qu trnh xy ha cc phn t hu c. USP <643> s dng cc tiu ch sau y nghim thu dng c o lng TOC: 1. Phi c Gii hn Pht hin l <0,05 mg carbon/L hoc 50 ppb TOC 2. Phi c hiu chun theo khuyn ngh ca nh sn xut 3. Phi phn bit c carbon v c, ngha l CO2, HCO3 vi CO2 c to ra t qu trnh xy ha cc phn t hu c 4. Phi c Th nghim Tnh ph hp ca H thng (SST) nh k

4.1 Th nghim Tnh ph hp ca H thng (SST)

V carbon hu c xut hin nhiu dng khc nhau trong t nhin v trong cc quy trnh x l nc, nhiu tnh trng xy ha v dng ha cht khc nhau c tm thy trong cc mu nc. Mc ch ca vic Th nghim Tnh ph hp ca H thng l nhm kim nghim dng c TOC bng cch kim chng rng dng c phn ng nh nhau i vi hai loi ha cht hu c dng th kh nng o lng ca n. USP <643> ch nh nhng ha cht ny gm ng ma Sucrose v 1, 4-Benzoquinone. Do cu trc ha hc khc nhau ca chng, Sucrose v 1, 4-Benzoquinone th nghim kh nng xy ha v ph v lin kt ca cng ngh o lng TOC. USP <643> yu cu phi tin hnh SST nh k trn mt dng c o hiu chun.

4.2 Quy trnh SST

1. o TOC ca nc dng iu ch nhng dung dch ny, Rw (Rw khng c vt qu 0,1 mg C/L (100 ppb)) 2. o TOC ca 0,50 mg C/L (500 ppb C sucrose), Rs 3. o TOC ca 0,50 mg C/L (500 ppb C p-benzoquinone), Rss 4. Phn ng phi trong khong 85 n 115%

Phn ng = 100 x

Rss - Rw Rs - Rw

10

Tun th Quy nh v Nc dng trong Dc phm

Phn tch Quy trnh METTLER TOLEDO

Yu cu ca Dc in Ton cu

5. EP, JP, ChP, IP v Yu cu ca cc Dc in khc

Mc ch ca dc in ti bt k quc gia no l cung cp mt bn trch yu hp php* v cc tiu chun c th thi hnh i vi c im nhn dng, tinh khit v bn ca sn phm, ng ngha vi cht lng sn phm. tip th sn phm mt quc gia c th, phi p ng cc tiu chun trong bn trch yu ca quc gia . C hn 40 bn trch yu trn ton cu, vi nhiu bn trch yu c th thi hnh bi nhiu quc gia. Do , nu bn l nh sn xut cc sn phm bn nhiu quc gia, bn cn phi tun th bn trch yu ca nhiu quc gia. Trong hai thp k qua, USP hp tc cht ch vi Dc in Chu u (EP) v Dc in Nht Bn (JP) thuc Nhm Tho lun v Dc in (PDG). Nhm ny theo ui l trnh Lm hi ha cc chuyn kho v cc chng chung. Lm hi ha c nh ngha l mt chng chung ca dc in hay ti liu dc in khc c cn i khi mt dc cht hoc dc phm c th nghim theo quy trnh c cn i ca ti liu cho kt qu ging nhau, v i ti quyt nh cht nhn/t chi nh nhau. Mc ch ca vic Lm hi ha l pht trin cc thng s, th nghim/quy trnh v tiu ch nghim thu nht qun cho cc dc cht v thuc. Li ch i vi ngnh dc l to ra mt b th nghim nht qun, khng phi nhng th nghim khc nhau, sao cho mt b th nghim p ng c cc yu cu v c im nhn dng, tinh khit v bn ca tng quc gia, nh gim thiu v n gin ha vic th nghim khng mang li gi tr gia tng. Lm hi ha l mt quy trnh lin tc v quy trnh ny c ng dng cho cc loi nc dc phm t nm 2000. N lc chnh nhm lm hi ha cc loi nc dc phm tp trung vo Nc Tinh khit v Nc ct pha tim, l nhng dng nc c s dng ph bin nht trong sn xut dc phm. V nhng loi nc ny c sn xut v s dng tt c cc nh my sn xut dc phm, c s u i rt ln trong ngnh nhm h tr mt b th nghim hi ha cho Nc Tinh khit v Nc ct pha tim. T nm 1996, USP n lc thay th cc th nghim ha cht t trc y bng th nghim dn in v gii hn TOC cng vi cc thng s dng c o thch hp. Trong nm 2000, EP bt u p dng cc th nghim dn in v TOC tng t, mc d khng hon ton ging vi USP, v cui nhng nm 2000, JP cng bt u p dng tng t nhng th nghim phn tch ny. Chi tit c th v tng dc in rt khc nhau, tuy nhin cc dc in Big 3 i t khng Hi ha trong nhng nm 1990 ln mt mc Hi ha rt cao. V d: cc th nghim v tinh khit ca ha cht ( dn in v TOC) v vi khun cho WFI c cn i hon ton, mc d cc phng php sn xut c cho php khc nhau. Mt khc, cc phng php sn xut c cho php i vi Nc Tinh khit cng nht qun c ba khu vc, tuy nhin gii hn dn in cho EP cao hn gii hn dn in USP v JP.
Tun th Quy nh v Nc dng trong Dc phm
Phn tch Quy trnh METTLER TOLEDO

11

Yu cu ca Dc in Ton cu

 V th gii ngy cng thu hp hn v sn xut ngnh mang tnh ton cu hn, cc dc in khc, in hnh l n (IP) v Trung Quc (ChP), cng ngy cng lin quan nhiu hn. Trong khi dc in ca nhng quc gia ny khng phi l thnh vin chnh thc ca PDG, chng cng tun th theo cc dc in khc. Nhng dc in ny v nhiu dc in khc s p dng cng mt loi tiu chun v tinh khit ca ha cht v ang c dn u bi USP. Trong khi mt s th nghim ha cht vn gi nguyn, dn in v TOC l cc ch bo chnh ca vic kim sot tinh khit ha cht v quy trnh h thng nc.
* Cc th nghim v thng s c m t trn c th thay i. Hy s dng dc in hin hnh v lin quan xc nh cc thng s hin ti.

Yu cu ca Dc in Ton cu
Thuc tnh
Nc Ngun cho PW v WFI

USP
Nc ung theo chun Hoa K, EU, Nht Bn, WHO Quy trnh ph hp

EP
Nc con ngi tiu th c

JP
Thng s nc ca JP

ChP
Nc ung hay Nc Tinh khit

IP
Nc ung hay Nc Tinh khit

Nc Tinh khit Phng php Sn xut Quy trnh ph hp Chng ct, trao i ion, UF hoc kt hp 100 1.3 trc tuyn hoc 2.1 ngoi tuyn 0,5 (0,3 cho kim sot) Chng ct, trao i ion hoc x l ph hp 100 5,1 (1 giai on) 0,5 0,2 0,2 Bt buc Chng ct hoc x l ph hp Chng ct Chng ct hoc RO vi UF, t Nc Tinh khit 10 1.3 trc tuyn hoc 2.1 ngoi tuyn 0,5 (0,3 cho kim sot) 0,25 Chng ct Chng ct Chng ct, trao i ion hoc x l ph hp 100 1,3 (3 giai on) 0,5 Bt buc Bt buc Bt buc

Tng mc a kh (cfu/mL) dn in (S/cm at 25C) TOC (mg/L) Nitrat (ppm) Tnh axit/Tnh kim Amoni (ppm) Cht c th xy ha Nc ct pha tim Phng php Sn xut

100 1,3 (3 giai on)

100 5,1 (1 giai on) 0,5 (ty chn) 0,2

0,5

Tng mc a kh (cfu/100 mL) dn in (S/cm at 25C) TOC (mg/L) Ni c t do Vi khun (EU/mL) Nitrat (ppm) Kim loi Nng Tnh axit/Tnh kim Amoni (ppm)

10 1,3 (3 giai on)

10 1,3 (3 giai on) 0,5 0,25 0,2

10 1,3 (3 giai on) 0,5 0,25 0,2 Bt buc Bt buc 0,2

10 1,3 (3 giai on) 0,5 0,25 Bt buc

0,5 0,25

* Hp bng khng yu cu th nghim

12
Tun th Quy nh v Nc dng trong Dc phm
Phn tch Quy trnh METTLERTOLEDO

Yu cu ca Dc in Ton cu

Yu cu Hiu chun v Th nghim ca Dc in i vi Tnh dn in

THIT B DN IN IN T (O IN TR) Yu cu hiu chun, tn sut khng c ch nh, do ngi s hu quyt nh, chp nhn hiu chun hng nm. Mch o nhit s c kim th. Dng c bo co dn in hoc in tr khng b tr nhit. Hin th ha tan ti thiu bng 0,1 S/cm. ha tan 1,0 S/cm khng c chp nhn. Kim tra hiu sut ti 0,1 S/cm bng cch thay th cm bin bng in tr c chnh xc c th truy nguyn (0,1%). V d: in tr 50 k c hng s vt l 0,1 cm-1 s hin th 2,0 0,1 S/cm. Cm BIN DN IN Hng s vt l xc nh 2%. Hiu chun cm bin trong dung dch c dn in nu (ca NIST hoc dung dch c chng nhn). Hiu chun cm bin trong dung dch c iu ch cho dn in c th (nc tiu chun hoc nc siu tinh khit ASTM D1125). Hiu chun cm bin vi mt cm bin c th truy nguyn c hiu chun khc c thc hin ni tuyn hoc trong phng th nghim hoc tr v cho nh sn xut. Nhit chnh xc ti 2C.

Hiu chun v Yu cu ca Dc in i vi TOC

YU CU V TOC Dng c o phi c Gii hn Pht hin bng 0,050 mg C/L (50 ppb TOC). Hiu chun theo khuyn ngh ca nh sn xut. Phi phn bit carbon v c, ngha l CO2, HCO3, vi carbon hu c. Phi c Th nghim Tnh ph hp ca H thng (SST) nh k. TH NGHIm TNH PH HP CA H THNG (SST) o TOC ca nc dng iu ch nhng dung dch ny, Rw. Khng vt qu 100 ppb. o TOC ca dung dch c iu ch nng 0,50 mg carbon/L (di dng sucrose), RS. o TOC ca dung dch c iu ch nng 0,50 mg carbon/L (di dng p-benzoquinone), RSS. Tn sut c chp nhn cho vic th nghim ty thuc vo vic thay i n UV. Phn ng phi trong khong 85 n 115%.

Phn ng = 100 x

Rss - Rw Rs - Rw

Tun th Quy nh v Nc dng trong Dc phm

Phn tch Quy trnh METTLER TOLEDO

13

ng gp ca METTLER TOLEDO Thornton

6. ng gp ca mETTLER TOLEDO Thornton cho vic Pht trin Tiu chun

Khi tnh dn in v TOC c xut thay th cc phng php th nghim ha cht t vo nm 1991, METTLER TOLEDO Thornton dn u ngnh v ang trong giai on pht trin cc tiu chun. Cc phng php ASTM cho tnh dn in c t lm tin trong cng trnh ca Dr. Thornton, ngi sng lp ca chng ti, vo nm 1989 v nhng nm trc . S dn u v k thut ca cng ty tip tc bng cc lun vn trong nm 1994 ca cc Tin s Morash v Bevilacqua, v trong nm 2004 ca cc Tin s Licht, Light, Bevilacqua v Morash c xut bn trong tp ch khoa hc c qua h thng bnh duyt, Electrochemical and Solid-State Letters. Nhng bi vit v k thut ny, kt hp vi s dn u ca Thornton v h thng o lng dn in/in tr cho ngnh vi in t, dn ng cho nhng ng gp vo USP. Nhng lun vn ny tp trung vo vic o dn in phc v cho nhu cu v nc c tinh khit cc cao ca ngnh vi in t. Nhu cu i vi lng ln nc khng c ion c th kim th ca ngnh ny c t lu, cng nh s dn u ca Thornton v khoa hc ha hc nc siu tinh khit. Sau , vic nh gi cc ti liu khoa hc ca Thornton khin ngnh dc v USP tm kim dng c phn tch v chuyn mn v tinh lc nc ca Thornton.

Tun Th d dng vi mETTLER TOLEDO

S t tin ca H thng
ISM gip m bo vic kim sot qu trnh sn xut t c cht lng sn phm ng u vi sn lng mong mun.

M800
B hin th a knh (2 hoc 4) c tnh linh hot v o lng nhiu tham s Qun l Cm bin Thng minh (ISM) Tnh n gin Cm v o iMonitor bo tr d phng Ch bo Thi hn s dng ng Biu xu hng cho tt c cc cm bin Bo m tun th cc quy nh ca dc in Thao tc trn menu n gin vi hiu nng v chnh xc v song.

M300
B hin th a knh (2) c tnh linh hot v o lng nhiu tham s Qun l Cm bin Thng minh (ISM) Tnh n gin Cm v o S o hin th sau vi giy kt ni p ng yu cu v hiu chun ca tt c cc dc in Ci t nhanh chng v d dng nh kh nng cm bin Cm v o.

14

Tun th Quy nh v Nc dng trong Dc phm

Phn tch Quy trnh METTLER TOLEDO

ng gp ca METTLER TOLEDO Thornton

Trong nm 1994, n lc ca chng ti bt u bng vic chuyn i cc th nghim ha cht sang mt th nghim v gii hn dn in lin quan, ngha l, nu bn vt qua c th nghim dn in, bn s cn phi vt qua c tt c 6 th nghim ha cht hin c. K t vic p dng th nghim dn in ny thay th 6 th nghim ha cht ny. Tng t, vi nhng thch thc v k thut ca vic cn bng nhit , Thornton pht trin mt phng php nhm to ra mt b gii hn dn in trc tuyn, ph thuc vo nhit , nh cho php thc hin o lng dn in nhit quy trnh m khng cn phi cn bng nhit . Trong nm 2000, USP thnh lp Ban Chuyn gia v Nc dng trong Dc phm, mt ban chuyn gia mi c hnh thnh c trch nhim pht trin v duy tr nh ngha php l cho cc chuyn kho v nc v cc chng th nghim lin quan. USP bu chn mt nhn vin ng chc ca METTLER TOLEDO Thornton lm Ch tch vi nhim k 5 nm, sau bu chn li ng ny thm mt nhim k 5 nm na t 2005-2010. Ban chuyn gia ny, l mt nhm c lp, gi y kt thc, nhng trch nhim gim st nc gi y thuc v Ban Chuyn gia Phn tch Ha cht ca USP vi nng lc chuyn mn tng t ca METTLER TOLEDO Thornton. Cng trnh do METTLER TOLEDO Thornton thc hin v s dn u ca USP dn ti vic m rng cc th nghim v dn in v TOC ca USP. Nhng th nghim ny, c tn l <643> Tng lng Carbon Hu c v <645> dn in ca Nc, dn ti vic p dng nhng th nghim v gii hn phn tch tng t ny trong EP, JP v cc dc in khc trn ton th gii. Ngy nay, nhng th nghim c th ny c thc hin cho cc dc in ton cu c t tin trong tc phm tin phong ca Tin s Thornton v nhng ngi k nhim ng trong hn 50 nm qua.

Qun l Cm bin Thng minh Thornton (ISm)

5000TOCi vi ISM
Kim sot ton b quy trnh v xu hng d liu chnh xc Chc nng Cm v o Thng bo sai lch tc th Lu gi d liu c n gin ha cho SST v CAL Bo tr khng c s c Thit k bn chc, tin cy hon ton khng c b phn chuyn ng Tun th tt c cc dc in Mang n sc mnh ca mt thit b phn tch vi s thun tin ca cm bin.

UniCond vi ISM
D liu Hiu chun dn in ti Nh my c lu tr trong cm bin Chc nng Cm v o Mch o lng hiu nng cao ton vn Tn hiu u ra k thut s mnh Hiu chun y nhm tun th v dc Hiu chun c theo di bi iMonitor (M800) nhm m bo tun th.

Ozon vi ISM
Phn ng nhanh, chnh xc D dng bo tr vi mng th xung Chc nng Cm v o Pht hin s 0 dng m bo tun th quy tc khng c cht b sung Gim st mt cch tin cy ton b quy trnh v sinh v xc nhn kh ozon.

Tun th Quy nh v Nc dng trong Dc phm

Phn tch Quy trnh METTLER TOLEDO

15

o lin tc, trc tip v thi gian thc nhm m bo s nht qun gia cc l v cht lng cho ngnh dc

Hy truy cp trang web ca chng ti khm ph cc sch trng, ghi ch ng dng, video hng dn v danh sch cc cuc hi tho trc tuyn ca chng ti.

www.mt.com/ism-pharma

bit thm thng tin

mETTLER TOLEDO Thornton, Inc. 36 Middlesex Turnpike Bedford MA 01730 in thoi: +1-781-301-8600 Fax: +1-781-301-8701 thornton.info@mt.com C th thay i v k thut METTLER TOLEDO Thornton, Inc. c in Hoa K 58 087 004 05/13