LI TANhm tng bc thc hin l trnh hi nhp trong lnh vc sn xut dc phm, ngy 9/9/1996, B trng B Y t ban hnh Quyt nh s 1516/BYT Q v vic chnh thc p dng tiu chun Thc hnh tt sn xut thuc ca Hip hi cc nc ng Nam (GMP ASEAN) i vi cc c s sn xut thuc tn dc Vit Nam. to tin cho vic Vit Nam gia nhp T chc Thng mi th gii (WTO), ngy 03/11/2004, B trng B Y t ban hnh quyt nh s 3886/2004/Q - BYT v vic trin khai p dng cc nguyn tc tiu chun Thc hnh tt sn xut thuc (GMP) theo khuyn co ca T chc Y t th gii (WHO). Ban hnh km theo Quyt nh ny c bn hng dn trin khai thc hin v a ra l trnh trin khai cc doanh nghip sn xut dc phm trong nc thc hin. Trong qu trnh hi nhp ton cu lnh vc dc phm, bn cnh Thc hnh tt sn xut thuc (GMP) ca T chc Y t th gii (WHO) cn c hng dn Thc hnh tt sn xut thuc ca Chu u (EU), Thc hnh tt sn xut thuc ca H thng hp tc thanh tra dc phm (PIC/S). trin khai cc hot ng hi nhp lnh vc dc phm trong khu vc (ACCSQ/PPWG), cc nc ASEAN d kin p dng chung hng dn Thc hnh tt sn xut thuc (GMP) ca H thng hp tc thanh tra dc phm (PIC/S) tin ti tha nhn v cng nhn ln nhau. Nhm h tr doanh nghip sn xut dc phm trong nc i tt, n u, nng cao nng lc cnh tranh khi hi nhp, B Y t n hnh ti liu Hng dn thc hnh tt sn xut thuc ca H thng hp tc thanh tra dc phm (PIC/S) ban hnh ngy 01/6/2006 di hnh thc song ng Vit- Anh. y l mt trong nhng ti liu c bn gip cc doanh nghip sn xut dc phm Vit Nam nng cp h thng m bo cht lng, h thng h s ti liu, thm nh quy trnh sn xut, thm nh h thng my mc v.v. B Y t hy vng rng ti liu ny s hu ch cho cho cc doanh nghip sn xut dc phm ca Vit Nam trong vic xy dng v trin khai hot ng sn xut thuc, gip cc doanh nghip sn xut dc phm trin khai p dng nguyn tc, tiu chun Thc hnh tt sn xut thuc Vit Nam ngy cng tt hn, c nng lc v kinh nghim, to ra nhiu c hi trong qu trnh Vit Nam gia nhp t chc thng mi Quc t (WTO).B trng B Y t

PGS.TS. Trn Th Trung Chin 1

MC LC GII THIU Trang CHNG 1 QUN L CHT LNG Nguyn tc . m bo cht lng ... Thc hnh tt sn xut thuc (GMP) . Kim tra cht lng Xem xt li cht lng sn phm CHNG 2 NHN VIN Nguyn tc . Qui nh chung .. Nhn vin ch cht . o to .. V sinh c nhn . CHNG 3 NH XNG V THIT B Nguyn tc . Nh xng . Qui nh chung . Khu vc sn xut .. Khu vc bo qun Khu vc kim tra cht lng Khu ph .. CHNG 4 H S TI LIU Nguyn tc Qui nh chung . Nhng h s ti liu cn thit .. Tiu chun . Tiu chun i vi nguyn liu ban u v nguyn liu bao gi Tiu chun cht lng i vi sn phm trung gian v bn thnh phm ... Tiu chun thnh phm .. Cng thc sn xut v hng dn ch bin . Hng dn ng gi . H s ch bin l .. H s ng gi l . Qui trnh v h s ghi chp .. Tip nhn Ly mu . Th nghim Cc vn khc . CHNG 5 SN XUT Nguyn tc Qui nh chung . 2

phng nhim cho trong sn xut Thm nh Nguyn liu ban u Thao tc ch bin sn phm trung gian v bn thnh phm.. Nguyn liu ng gi .. Hng dn ng gi Thnh phm . Nguyn vt liu b loi, phc hi v nguyn liu b tr v .. CHNG 6 KIM TRA CHT LNG . Nguyn tc . Qui nh chung .. Thc hnh tt phng kim tra cht lng .. H s ti liu . Ly mu . Th nghim Chng trnh nghin cu n nh . CHNG 7 - SN XUT V KIM NGHIM THEO HP NG Nguyn tc .. Qui nh chung .. Bn hp ng . Bn nhn hp ng Bn hp ng . CHNG 8 . KHIU NI V THU HI SN PHM Nguyn tc . Khiu ni Thu hi sn phm CHNG 9 T THANH TRA Nguyn tc . Ph lc 1 Sn xut cc dc phm v trng .. Nguyn tc . Qui nh chung .. Cng ngh c lp .. Cng ngh thi, ng thuc v hn .. Cc sn phm tit trng cng on cui Pha ch v trng Nhn s Nh xng Thit b V sinh . Ch bin Tit trng .. Tit trng bng nhit 3

Tit trng bng nhit m Tit trng bng nht kh Tit trng bng bc x . Tit trng bng Ethylen Oxid Lc nhng sn phm m khng tit trng c trong bao gi cui cng Hon thnh sn phm v trng . Kim tra cht lng . Ph lc 2 Sn xut cc sn phm thuc sinh hc Phm vi . Nguyn tc Nhn s .. . Nh xng v thit b Khu vc nui sc vt v vic nui sc vt H s ti liu Sn xut. Nguyn liu ban u .. H thng m chng v ngn hng t bo Cc nguyn tc hot ng Kim tra cht lng . Ph lc 3 Sn xut thuc phng x . Nguyn tc Nhn vin Nh xng v thit b . Sn xut .. Kim tra cht lng Phn phi v thu hi Ph lc 6 Sn xut cc kh y hc Nguyn tc Nhn vin Nh xng v thit b . H s ti liu .. Sn xut .. Kim tra cht lng Bo qun v phn phi nh ngha Ph lc 7 Sn xut thuc tho dc .. Nguyn tc Nh xng Khu vc bo qun Khu vc sn xut . H s ti liu .. .. 4

Tiu chun cht lng v nguyn liu ban u . Hng dn qui trnh sn xut . Ly mu . Kim tra cht lng Ph lc 8 Ly mu nguyn liu ban u v nguyn liu ng gi Nguyn tc Nhn s . Nguyn liu ban u Nguyn liu bao gi . Ph lc 9 Sn xut ch phm lng, kem v thuc m Nguyn tc Nh xng v thit b . Sn xut .. Ph lc 10 Sn xut ch phm kh dung p sut phn liu xng Nguyn tc Qui nh chung Nh xng v thit b . Sn xut v kim tra cht lng .... Ph lc 11 H thng vi tnh ho Nguyn tc Nhn s Thm nh . H thng . Ph lc 12 S dng bc x ion ho trong sn xut.. .. Gii thiu . Trch nhim .. Do c liu bc x . Thm nh qui trnh nh gi c s chiu x . Nguyn tc chung Thit b chiu x tia Gamma Thit b chiu x chm tia electron . Ti nh gi Nh xng . Ch bin Thit b chiu x tia Gamma Thit b chiu x chm tia electron . H s ti liu . Theo di nhim khun . Ph lc 13 Sn xut thuc nghin cu Nguyn tc 5

Gii thch thut ng . Qun l cht lng .. Nhn vin Nh xng v thit b H s ti liu ... Tiu chun cht lng v hng dn n t hng . H s tiu chun cht lng ca sn phm.. Cng thc gc v hng dn ch bin gc . Hng dn ng gi H s ch bin, kim tra v ng gi l Sn xut Nguyn liu ng gi .. Cc hot ng sn xut Nguyn tc p dng i vi sn phm so snh Cc hot ng sn xut sn phm m . nh m ngu nhin .. ng gi Dn nhn Kim tra cht lng . Xut l . Chuyn hng Khiu ni . Thu hi v tr li sn phm . Thu hi ... Tr li sn phm Hu sn phm . Ph lc 15 nh gi v thm nh Nguyn tc K hoch v thm nh .. H s ti liu nh gi .. nh gi thit k nh gi lp t . nh gi vn hnh . nh gi hiu nng nh gi nh xng, h thng v thit b ang s dng ... Thm nh qui trnh Qui nh chung . Thm nh tin lng Thm nh ng thi . Thm nh hi cu Thm nh v sinh Kim sot thay i 6

Ti thm nh .. Gii thch thut ng Ph lc 17 Xut xng theo thng s sn xut . Nguyn tc . Xut xng theo thng s sn xut Xut xng theo thng s sn xut i vi sn phm v trng . Gii thch thut ng HNG DN THC HNH TT SN XUT THUC I VI SN XUT DC PHM GII THIU tip tc thun li trong vic xo b cc ro cn thng mi i vi cc sn phm dc, tng cng tnh thng nht ca cc quyt nh cp php v m bo duy tr cc tiu chun m bo cht lng cao trong vic pht trin, sn xut v kim sot cc sn phm dc ca cc quc gia Chu u, ngi ta tho thun nhm hi ho cc nguyn tc ca GMP c p dng theo Cng c v thanh tra dc phm ( PIC) v H thng hp tc v thanh tra Dc phm ( PIC/ S) vi cc nguyn tc ca bn hng dn thc hnh tt sn xut thuc v cc Ph lc ca cc quc gia EU. Tuy nhin, cc thay i ti thiu trong vic bin tp tr nn cn thit p dng vn bn hng dn EU cho cc mc ch v yu cu ca Cng c. Cc thay i nh sau: Khi nim v sn phm dc ( cp l sn phm thuc trong hng dn ny) c trong iu 1 ca Cng c v thanh tra dc phm c gi li. Cc tham kho ca Hng dn EU c xo b; Thut ng Ngi c trnh chuyn mn khng tn ti trong PIC hay PIC/S , v c thay bng Ngi c u quyn (xem Bng ch gii thut ng) Do tt c cc nc k kt Cng c PIC hay cc c quan tham gia trong khun kh h thng PIC khng tham gia trong Hip nh v Dc th cc quc gia Chu u nn thut ng cp Dc th cc nc Chu u trong hng dn c sa i v c l Dc Th cc nc Chu u hoc cc nc c lin quan Cc tiu chun v nguyn tc c trong bn hng dn ny c xem nh l mt bn tham kho c nhng chun b thng tin v vic tin hnh sn xut theo yu cu ca Cng c v thanh tra dc phm ( PIC) v H thng hp tc v thanh tra Dc phm ( PIC/ S). Cc bin php hnh chnh ca cc c quan y t cp quc gia nn c trc tip hng ti vic p dng cc tiu chun trong thc t, v bt k cc 7

quy nh mi hoc sa i cp quc gia no v phc v thc tin sn xut cht lng tt phi t nht p ng mc ca h. Cc tiu chun cng nhm cho cc nh sn xut ly lm c s cho vic hon thin cc nguyn tc c th thch ng vi cc nhu cu ring ca nh sn xut . Bn cnh nhng vn chung ca Thc hnh tt sn xut thuc cp trong cc chng ca bn Hng dn ny, cc hng dn b sung c tch hp. Mc ch ca cc hng dn b sung ny trn cc phng din khc l nhm cung cp cc chi tit v lnh vc hot ng c th l cc lnh vc c th khng cn thit p dng cho tt c cc nh sn xut. Cc tiu chun t ra y c p dng vi thuc v cc sn phm tng t phc v nhu cu s dng ca con ngi. Tuy nhin, vic ch nh vy cng c khuyn co dnh cho vic sn xut cc sn phm thuc th y. Cn nhn ra rng c cc phng php c th chp nhn, ngoi nhng g phng php c m t trong hng dn ny, c kh nng p ng cc nguyn tc ca Hng dn. Hng dn ny khng c p t bt k cn tr no i vi s pht trin ca cc khi nim hoc nhng cng ngh mi c thm nh v a ra mc m bo cht lng tng ng t nht vi nhng tiu chun t ra trong Hng dn ny.Lch s sa cha Bn hng dn

Ngy S phin bn 21 thng 12 nm 2000 PH 1/97( Rev.)

10 thng 8 nm 2001

PH 1/97 ( Rev.2)

15 thng 1 nm 2002

PH 1/97 ( Rev.3)

1 thng 9 nm 2003 1 thng 7 nm 2004

PE 009-1 PE 009-2

L do sa li Sa ph lc 14 nh s li tt c cc ph lc Thay i a ch nh bin tp v thm tuyn b bn quyn Thm vo phn s ln sa. Sa i on th 42 ca ph lc 1 Sa ph lc 6 Ph lc mi 15 Ph luc mi 17 Sa i bng tra cu thut ng Ph lc mi 4 Ph lc mi 5 Tham kho cho Ph lc 18 ca Hng dn EC GMP Sa i Ph lc 1( ch yu phn 3) Sa Ph lc 13 Thay i trong phn phi hp ca nh bin tp. 8

1 thng 1 nm 2006 1 thng 6 nm 2006

PE 009- 3 PE 009-4

Sa Chng 1 Sa chng 6

9

CHNG 1: Nguyn tc

QUN L CHT LNG

Ngi nm gi ca mt giy php sn xut cc dc phm nhm m bo rng chng thch hp cho mc ch s dng, tun theo cc yu cu cp php ca th trng v khng t bnh nhn vo nguy c do khng tng xng v tnh an ton, cht lng hoc hiu qu. Mc tiu cht lng t c l trch nhim ca qun l cp cao v i hi s tham gia v cam kt ca i ng nhn vin trong cc ban ngnh khc nhau v tt c cc cp thuc cng ty, cc nh cung cp ca cng ty v cc nh phn phi. t c mc tiu cht lng ng tin cy phi c mt h thng thit k sng to v kh thi trong vic hp nht, m bo cht lng qu trnh thc hnh tt sn xut thuc cng nh kim sot cht lng. N nn c dn chng hon ton bng ti liu v gim st mt cch c hiu qu. Tt c cc phn ca h thng m bo cht lng nn c nhng sng kin tng ng t nhng nhn vin u t, v cc gi thit, trang thit b v tin nghi y , thch hp. Mt s trch nhim php l dnh cho ngi nm quyn sn xut v ngi c u quyn. 1.1. Cc khi nim c bn ca m bo cht lng, thc hnh tt sn xut thuc v qun l cht lng lun mang tnh tng h. Cc yu t ny c nu ra y nhm nhn mnh mi quan h ca chng v tm quan trng ch yu i vi sn xut v kim sot dc phm

m bo cht lng 1.2. m bo cht lng l mt khi nim rng bao trm tt c nhng vn c nh hng chung hoc ring bit ti cht lng mt sn phm. l ton b cc k hoch c xp t vi mc ch m bo cc dc phm c cht lng p ng c mc ch s dng ca chng. V th m bo cht lng kt hp c GMP vi cc yu t khc, k c cc yu t nm ngoi phm vi ca hng dn ny H thng m bo cht lng ph hp cho sn xut dc phm phi m bo l: i. Sn phm c thit k v pht trin theo cch thc sao cho c th m bo p ng c cc yu cu ca GMP v Thc hnh tt phng kim nghim (GLP); Cc thao tc sn xut v kim tra cht lng c nu r rng v cc nguyn tc GMP c vn dng; Trch nhim qun l c nu r rng; C cc b tr cho sn xut, cung ng v cho vic s dng ng loi nguyn liu ban u v nguyn liu bao gi; Thc hin tt c cc bc kim tra cn thit i vi sn phm trung gian, cc bc kim tra trong qu trnh sn xut v thm nh; 10

ii. iii. iv. v.

vi. vii.

Thnh phm c ch bin v kim tra ng theo cc quy trnh nh; Sn phm khng c bn hay cung cp trc khi ngi c u quyn chng nhn mi l sn phm c sn xut v kim nghim theo ng cc quy nh nu trong giy php lu hnh v cc quy ch c lin quan n vic sn xut, kim tra cht lng v xut l dc phm; C cc bin php m bo ti mc ti a l sn phm c bo qun, phn phi v sau l bo qun sao cho duy tr c cht lng trong sut tui th ca sn phm; C mt quy trnh t thanh tra v/hoc kim tra v cht lng thng xuyn nh gi hiu qu v tnh ph hp ca h thng m bo cht lng.

viii.

ix.

Thc hnh tt sn xut dc phm (GMP) 1.3. Thc hnh tt sn xut l mt phn ca m bo cht lng, gip m bo rng sn phm c sn xut mt cch ng nht v c kim sot theo ng cc tiu chun cht lng ph hp vi mc ch s dng ca chng cng nh theo ng cc quy nh ca giy php lu hnh hay ch r sn phm. Thc hnh tt sn xut thuc c lin quan n hai qu trnh sn xut v kim tra cht lng. Thc hin theo GMP i hi: i. Tt c cc quy trnh sn xut u c xc nh r rng, c r sot mt cch c h thng theo kinh nghim, v c chng minh l kh nng sn xut ra cc sn phm t yu cu v cht lng theo cc tiu chun nh; S nh gi cc bc ca quy trnh sn xut v thay i c ngha n qu trnh thm nh; C tt c cc iu kin thun li cn thit i vi GMP, bao gm: a. nhn vin c trnh chuyn mn ph hp v qua o to; b. nh xng v khng gian; c. my mc thit b v dch v ph hp; d. ng nguyn vt liu, bao b v nhn mc; e. cc quy trnh v hng dn c duyt; f. bo qun v vn chuyn ph hp; iv. Cc hng dn v quy trnh c vit dng hng bng ngn ng d hiu, r ngha, p dng c c th cho tng phng tin, my mc; Cng nhn vn hnh c o to thc hin quy trnh mt cch chnh xc; 11

ii. iii.

v.

vi.

C ghi chp li bng tay hoc bng thit b ghi chp trong khi sn xut cho thy trong thc t mi cng on nu trong quy trnh v hng dn u c thc hin v s lng cng nh cht lng sn phm t yu cu. Bt c sai lch ng k no cng phi c ghi li y v phi c iu tra; H s ghi li vic sn xut v phn phi gip cho c th tra cu li ton b lch s ca mt l sn phm, phi c lu gi theo mu m bo d hiu v d tip cn; Phn phi sn phm (bn bun/quy m ln) ph hp hn ch ti a bt c nguy c no i vi cht lng; Cn c mt h thng thu hi bt k l sn phm no ang c bn hay cung cp; Nhng khiu ni v cc sn phm ang lu hnh phi c kim tra, tm ra nguyn nhn thiu st v cht lng, v c bin php ph hp i vi sn phm c sai hng v ngn chn vic lp li cc sai hng ny.

vii.

viii. ix. x.

Kim tra cht lng 1.4. Kim tra cht lng l mt phn ca GMP lin quan n vic ly mu, tiu chun v kim nghim, cng ng thi lin quan n vn t chc, h s ti liu v quy trnh duyt xut m bo tin hnh cc php th ph hp v cn thit, v nguyn vt liu khng c xut cho s dng hoc sn phm khng c xut em bn hay cung cp, nu nh chng cha c nh gi l t cht lng. Cc yu cu c bn i vi kim tra cht lng nh sau: i. Phi c c s trang thit b, nhn vin c o to v quy trnh c ph duyt thc hin vic ly mu, kim tra v kim nghim nguyn liu ban u, nguyn vt liu bao gi, sn phm trung gian, bn thnh phm v thnh phm, v nu cn theo di iu kin mi trng v mc ch tun th nguyn tc GMP; Vic ly mu nguyn liu ban u, nguyn vt liu bao gi, sn phm trung gian, bn thnh phm v thnh phm phi c thc hin bng cc phng php v do nhng nhn vin c b phn kim tra cht lng ph duyt; Phi lp h s, bng tay v/hoc bng thit b ghi chp, chng minh rng tt c cc quy trnh ly mu, kim tra v kim nghim cn thit u thc s c tin hnh, v bt k sai lch no so vi quy trnh u c ghi y vo h s v c iu tra; Thnh phm phi c cha cc hot cht theo ng thnh phn nh tnh v nh lng ca sn phm nh c m t trong giy php 12

ii.

iii. Phi thc hin vic thm nh cc phng php kim nghim; iv.

v.

lu hnh; cc thnh phn phi t mc tinh khit quy nh, c ng trong bao b ph hp v dn nhn ng; vi. Phi ghi li kt qu kim tra v kim nghim theo tiu chun i vi cc nguyn vt liu v sn phm trung gian, bn thnh phm v thnh phm. Vic nh gi sn phm phi bao gm c vic r sot v nh gi cc h s ti liu v sn xut c lin quan v vic nh gi nhng sai lch so vi quy trnh nh;

vii. Khng c xut mt l sn phm no ra bn hay cung cp trc khi ngi c u quyn chng nhn rng l sn phm theo ng cc yu cu trong giy php lu hnh. viii. Cn lu gi lng mu i chiu ca nguyn liu ban u v thnh phm c th kim nghim sn phm sau ny nu cn thit; mu lu phi c gi trong bao b ngoi tr khi bao b ngoi c kch c c bit ln. Xem xt cht lng sn phm 1.5. Cc t xem xt cht lng thng k hoc lin tc i vi sn phm y t c cp php, bao gm cc sn phm ch dnh cho xut khu, phi c tin hnh vi mc ch kim nh tnh n nh ca quy trnh hin ti, tnh hp l cc tiu chun hin hnh ca nguyn liu ban u v thnh phm lm r cc xu hng v xc nh cc ci tin i vi sn phm v quy trnh sn xut. Nhng t xem xt nh vy phi c thc hin bnh thng v phi ghi li thnh ti liu hng nm, v c xem xt cc t kim tra trc v cn phi c t nht: i. ii. iii. iv. Mt t xem xt nguyn liu ban u v nguyn liu ng gi s dng cho sn phm c bit l nguyn liu t cc ngun mi; Mt t xem xt vic kim sot trong qu trnh sn xut v cc kt qu v thnh phm; Mt t xem xt tt c cc m khng t quy cch theo quy nh v iu tra tt c cc sn phm ny; Mt t xem xt v cc mc sai lch ln hoc khng tun th v cc iu tra lin quan v tnh hiu qu ca hot ng sa cha v ngn nga thc hin; Mt t xem xt v tt c cc thay i din ra i vi qu trnh x l hoc phng php phn tch; Mt t xem xt v tt c cc dng giy php lu hnh sn phm c trnh/cp/t chi, bao gm ca h s nc th ba (ch xut khu); Mt t xem xt v kt qu ca chng trnh theo di tnh n nh v bt k khuynh hng c hi no; 13

v. vi.

vii.

viii.

Mt t xem xt v cc v tr li hng, khiu ni v thu hi lin quan n cht lng v cc cuc iu tra thc hin vo thi gian ; Mt t xem xt v mc y ca qu trnh sn phm hoc cc hot ng sa cha thit b khc trc ; Mt t xem xt cc cam kt hu mi i vi cc giy php lu hnh mi v cc thay i v giy lu hnh; Trng thi phm cht ca cc thit b v cc vt dng lin quan, v d HVAC, nc, kh nn Mt t xem xt cc hp ng k thut m bo rng cc hp ng ny cp nht vi thc t;

ix. x. xi. xii.

Trng hp nh sn xut v ngi c quyn lu hnh sn phm l khc nhau, phi nh gi kt qu kim tra ny, v nu ra nh gi c nn tin hnh sa cha, phng nga hoc thm nh li khng. L do v cc hot ng sa cha cn ghi chp li. Cc hnh ng sa cha hoc ngn nga theo tho thun phi c hon thnh mt cch c hiu qu v ng gi. Phi c nhng qui trnh qun l cho qun l hot ng thng xuyn v tin hnh kim tra cc hot ng ny, kim tra tnh hiu qu ca nhng qui trnh c thm nh trong sut thi gian t kim tra. Xem xt cht lng c th c phn nhm theo sn phm, v d dng bo ch rn, dng bo ch lng, sn phm v trngvi nhng gii trnh khoa hc. Trng hp ngi c quyn lu hnh sn phm khng phi l nh sn xut, phi c mt tho thun v k thut gia cc bn khc nhau, trong ch r cc trch nhim tng ng ca tng ngi trong vic thc hin xem xt cht lng. Ngi c u quyn c trch nhim v xc nhn m cui, v cng vi ngi c lu hnh sn phm m bo vic xem xt cht lng c thc hin ng thi gian v chnh xc.

14

CHNG 2: Nguyn tc

NHN S

Vic thit lp v duy tr mt h thng m bo cht lng t yu cu v tnh chnh xc ca vic sn xut ph thuc vo yu t con ngi. V vy, phi c nhn vin c trnh thc hin tt c cc cng vic thuc phm vi trch nhim ca nh sn xut. Cn xc nh r trch nhim c nhn, trch nhim ny phi c c nhn c lin quan hiu r v c ghi li. Tt c cc nhn vin phi c hiu bit v cc nguyn tc ca GMP nh hng n h nh th no v cn c o to mi v thng xuyn ph hp vi nhu cu ca h; k c cc hng dn v v sinh. Quy nh chung 2.1. Nh sn xut cn c nhn vin c trnh chuyn mn cng nh kinh nghim thc t cn thit. Trch nhim giao cho mi c nhn khng nn qu nhiu khin c th dn n nguy c i vi cht lng sn phm. Nh sn xut phi c mt s t chc. Tt c cc cn b c trch nhim u phi c bn m t cng vic c th v phi c giao quyn thch hp thc hin cc trch nhim . Nhim v ca h c th c u quyn cho cc cn b cp ph c trnh t yu cu. Khng nn c nhng thiu ht cng nh s chng cho thiu l gii trong trch nhim ca cc nhn vin lin quan n vic p dng GMP. Nhn vin ch cht bao gm trng b phn sn xut, trng b phn kim tra cht lng v ngi c u quyn, nu t nht mt trong s nhng ngi ny khng chu trch nhim v xut cc sn phm. Nhng v tr ch cht thng do nhn vin chnh thc m nhim. Cc v tr trng b phn sn xut v trng b phn kim tra cht lng cn c lp vi nhau. Trong cc cng ty ln, c th cn phi u quyn mt s chc nng c cp trong cc im 2.5, 2.6, 2.7. .... Trng b phn sn xut nhn chung c nhng trch nhim sau: i) ii) m bo sn phm c sn xut v bo qun theo ng h s ti liu ph hp c c cht lng yu cu; ph duyt cc hng dn lin quan n thao tc sn xut v m bo chng c thc hin mt cch nghim ngt;

2.2.

Nhn vin ch cht 2.3.

2.4. 2.5.

iii) m bo h s sn xut c nh gi v k bi mt ngi c giao nhim v ny trc khi chng c gi ti b phn kim tra cht lng; iv) kim tra vic bo tr nh xng v my mc thit b lin quan n sn xut; v) m bo rng vic thm nh ph hp c thc hin; 15

vi) m bo rng vic o to ban u v o to lin tc cho nhn vin c thc hin v vic o to c iu chnh ph hp vi nhu cu. 2.6. Trng b phn kim tra cht lng nhn chung c nhng trch nhim sau: i) duyt hoc loi b nu thy ph hp, nguyn liu ban u, nguyn vt liu bao gi, sn phm trung gian, bn thnh phm v thnh phm; nh gi h s l;

ii)

iii) m bo tt c cc php th cn thit u c thc hin; iv) ph duyt cc tiu chun, hng dn ly mu, phng php th, v cc quy trnh kim tra cht lng khc; v) ph duyt v theo di vic kim nghim theo hp ng; vi) kim tra vic bo dng c s, nh xng v my mc thit b; vii) m bo cc thm nh ph hp c thc hin; viii) m bo vic o to ban u v o to lin tc cho nhn vin b phn kim tra cht lng c thc hin v vic o to c iu chnh cho ph hp vi nhu cu. Trch nhim khc ca b phn kim tra cht lng c tm tt trong chng 6. 2.7. Ni chung, cc v tr trng b phn sn xut v trng b phn kim tra cht lng c mt s trch nhim chung, hoc cng thc hin mt s cng vic lin quan n cht lng. Tu thuc vo lut php quc gia, nhng trch nhim ny c th bao gm: ph duyt quy trnh thao tc bng vn bn v cc ti liu khc, k c cc sa i; theo di v kim sot mi trng sn xut; bo m vn v sinh trong nh my; thm nh quy trnh; o to; ph duyt v theo di nh cung cp nguyn vt liu; ph duyt v theo di nh sn xut theo hp ng; quy nh v theo di iu kin bo qun ca nguyn vt liu v sn phm; thc hin v nh gi cc kim sot trong qu trnh; lu gi h s; theo di vic tun th quy nh v GMP; 16

kim tra, iu tra v ly mu, nhm theo di cc yu t c th c nh hng ti cht lng sn phm. o to 2.8. Nh sn xut cn t chc o to cho tt c nhn vin c nhim v trong khu vc sn xut v phng kim tra cht lng (k c nhn vin k thut, bo dng v lm v sinh), v nhng nhn vin khc c nh hng n cht lng sn phm.

2.9. Bn cnh vic o to c bn v l thuyt v thc hnh GMP, nhn vin mi tuyn cn c o to v nhng vn ph hp vi nhim v c giao. Vic o to phi lin tc, v hiu qu o to phi c nh gi nh k. Chng trnh o to cn phi ph hp, c ph duyt chnh thc bi trng b phn sn xut hay trng b phn m bo cht lng. H s o to cn phi c lu gi. 2.10. Nhn vin lm vic trong nhng khu vc c nguy c b tp nhim, v d khu vc sch hoc nhng khu vc x l cc nguyn vt liu c hot tnh cao, c, ly nhim hoc d gy d ng, cn c o to chuyn su. 2.11. Khch tham quan v nhn vin cha qua o to tt nht l khng nn cho vo khu vc sn xut v kim tra cht lng. Nu khng trnh c vic ny h phi c thng bo trc nhng thng tin c lin quan, c bit l v v sinh c nhn v c trang b cc trang phc bo h cn thit. Cn gim st h cht ch. 2.12. Khi nim m bo cht lng v tt c cc bin php c kh nng nng cao nhn thc v vic thc hin m bo cht lng cn c bn lun thu o trong cc kho o to. V sinh c nhn 2.13. Chng trnh v sinh c th cn c thit lp v ph hp vi cc yu cu khc nhau trong phm vi nh my. Chng trnh cn bao gm quy trnh lin quan ti sc kho, cc thc hnh v sinh, v trang phc ca nhn vin. Nhng quy trnh ny phi c tt c nhn vin trong khu vc sn xut v khu kim tra hiu v lm theo mt cch nghim ngt. Chng trnh v sinh phi c nh qun l khuyn khch c v v cn c bn lun thu o trong cc kho o to. 2.14. Tt c nhn vin c tuyn u phi kim tra sc khe. Vic tuyn m theo v tr sn xut, iu kin sc kho c lin quan n cht lng sn phm v trnh sn xut. Sau ln kim tra sc khe ln u, cc ln khm khc c thc hin khi cn thit. 2.15. Thc hin tng bc nhm m bo ph hp vi thc t l nhng ngi mc bnh truyn nhim v ngi c vt thng h trn b mt c th khng c php tham gia sn xut dc phm. 2.16. Mi nhn vin vo khu vc sn xut cn mc qun o bo h ph hp vi thao tc sn xut s thc hin. 17

2.17. Khng c php n, ung, nhai, ht thuc, hay tr thc phm, ung v thuc ht cng nh thuc cha bnh ca c nhn trong khu vc sn xut v khu vc bo qun. Nhn chung, cc hnh vi khng v sinh trong khu sn xut hay cc khu vc khc c th gy nh hng bt li ti cht lng sn phm u b ngn cm. 2.18. Nhn vin vn hnh cn trnh tip xc trc tip bng tay vi sn phm h v bt k phn thit b no c tip xc vi sn phm. 2.19. Nhn vin phi c hng dn s dng cc phng tin v sinh tay. 2.20. Tt c yu cu c th i vi sn xut nhng nhm sn phm c bit c cp trong hng dn b sung, v d nh sn phm v trng.

18

CHNG 3: Nguyn tc.

NH XNG V THIT B

Nh xng v thit b phi c v tr, c thit k, xy dng, sa cha v bo dng ph hp vi cc thao tc sn xut s din ra. B tr mt bng v thit k ca nh xng phi nhm mc ch gim ti a nguy c sai st v m bo lm v sinh cng nh bo dng c hiu qu trnh nhim cho, tch t bi hoc rc, v ni chung l bt k nh hng bt li no ti cht lng sn phm. Nh xng Quy nh chung 3.1. Nh xng phi c t trong mt mi trng cng vi cc bin php bo v qu trnh sn xut gim ti a nguy c tp nhim i vi nguyn liu hoc sn phm.

3.2. Nh xng cn c bo dng cn thn, phi m bo cc hot ng bo dng v sa cha khng l nguy c cho cht lng sn phm. Nh xng phi c lm v sinh v ty trng nu cn theo cc quy trnh chi tit bng vn bn. 3.3. nh sng, nhit , m v vic thng gi phi ph hp sao cho chng khng c nh hng bt li trc tip hoc gin tip ti dc phm trong khi sn xut v bo qun, hoc nh hng n vic vn hnh chnh xc ca my mc thit b. 3.4. 3.5. Nh xng phi c thit k v trang b sao cho c th bo v ti a khi s xm nhp ca cn trng hoc cc ng vt khc. Cn thc hin cc bc trnh s ra vo ca nhng ngi khng c u quyn. Khu vc sn xut, bo qun v kim tra cht lng khng phi l ng i ca nhng ngi khng lm vic .

Khu vc sn xut 3.6. hn ch ti a nguy c gy nguy him nghim trng cho sc khe do sn phm b nhim cho, cn c nh xng chuyn bit v khp kn cho vic sn xut nhng dc phm c bit, v d nhng nguyn vt liu d gy d ng (v d penicillin), hoc sinh phm (v d cc sinh vt sng). Vic sn xut thm mt s sn phm khc, v d mt s khng sinh, hc mn, cht c t bo v nhng sn phm khng phi dc phm, khng nn tin hnh trong cng mt nh xng. i vi cc sn phm ny, trong nhng trng hp ngoi l, c th chp nhn nguyn tc sn xut theo chin dch trong cng nh xng vi iu kin l phi c bit thn trng v c tin hnh cc thm nh cn thit. Vic sn xut cc thuc c chuyn ngnh, v d nh thuc dit cn trng hoc thuc dit c, khng c php tin hnh nh xng dnh cho sn xut dc phm.

19

3.7. Mt bng nh xng phi c b tr sao cho vic sn xut c thc hin trong nhng khu vc tip ni nhau, theo mt trt t hp l tng ng vi trnh t ca cc hot ng sn xut v tng ng vi mc sch cn thit. 3.8 Phi c din tch lm vic v bo qun trong qu trnh sn xut c th t my mc thit b v nguyn vt liu mt cch c trt t v hp l, sao cho hn ch ti a nguy c ln ln gia cc sn phm hoc cc thnh phn ca sn phm, trnh nhim cho, v gim ti a nguy c b st hoc p dng sai bt k mt bc sn xut hay kim tra no.

3.9. nhng ni nguyn liu ban u, nguyn vt liu bao gi trc tip v sn phm trung gian, bn thnh phm tip xc vi mi trng, b mt bn trong (ca tng, sn v trn nh) phi nhn v khng c k nt cng nh ch ni h, khng c sinh ra cc ht tiu phn, cho php lm v sinh, v ty trng nu cn, d dng v c hiu qu. 3.10. Cc ng dn, mng n, cc im thng gi v cc dch v khc phi c thit k v lp t sao cho trnh to ra cc hc kh lm v sinh. Khi bo dng, cn tip cn nhng dch v ny t bn ngoi khu vc sn xut, nu c. 3.11. Cc ng thot nc phi ln, v c rnh ng xi phng trnh tro ngc. Nu c th, cn trnh ng thot nc h. Nhng nu cn thit phi c th nn xy nng d lm v sinh v ty trng. 3.12. Khu vc sn xut phi c thng gi tt, c thit b kim sot khng kh (bao gm nhit v, nu cn m v thit b lc) ph hp vi cc sn phm ang c sn xut, ph hp vi hot ng sn xut v vi mi trng bn ngoi. 3.13. Vic cn nguyn vt liu ban u cn c thc hin khu cn ring bit c thit k cho mc ch ny. 3.14. Trong trng hp bi pht sinh (v d khi ly mu, cn, trn v cc thao tc ch bin ng gi sn phm kh), phi thc hin cc qui nh c bit ngn nga tp nhim v d dng lm v sinh. 3.15. Khu vc xng ng gi dc phm phi c thit k v b tr c bit trnh ln ln v nhim cho. 3.16. Khu vc sn xut phi sng, c bit nhng ni thc hin vic kim tra bng mt thng trong qu trnh sn xut. 3.17. Cc kim tra trong qu trnh c th c thc hin trong khu vc sn xut nu chng khng gy ra bt k nguy c no i vi sn xut. Khu vc bo qun 3.18. Khu vc bo qun phi rng, cho php bo qun c trt t nhiu loi nguyn vt liu v sn phm: nguyn liu ban u v nguyn vt liu bao 20

gi, sn phm trung gian, bn thnh phm v thnh phm, sn phm bit tr, sn phm c php xut, b loi, b tr v hay sn phm thu hi. 3.19. Khu vc bo qun phi c thit k hoc iu chnh m bo iu kin bo qun tt. c bit l phi sch s, kh ro, nh sng v duy tr nhit chp nhn c. Trong khu vc cn iu kin bo qun c bit (v d nh v nhit , m) th phi m bo cc iu kin ny, c kim tra, theo di v ghi chp li mt cch thch hp. 3.20. Khu vc nhn v xut hng phi b tr ring bit v bo v c nguyn vt liu v sn phm trc thi tit. Khu vc nhn phi c thit k v trang b cho php cc thng nguyn liu c lm sch nu cn trc khi bo qun. 3.21. Khi bit tr c bo m bng cch bo qun nhng khu vc ring bit, nhng khu vc ny phi c bin hiu r rng v ch nhng ngi c thm quyn mi c php ra vo. Nu s dng mt h thng khc thay th bit tr c hc h thng phi m bo an ton mc tng ng. 3.22. Thng cn phi c khu vc ring ly mu nguyn liu ban u. Nu ly mu ngay khu vc bo qun, phi tin hnh sao cho c th trnh c tp nhim hay nhim cho. 3.23. Cn c khu vc bo qun tch ring nguyn vt liu v sn phm b loi, thu hi hoc b tr v. 3.24. Nhng nguyn vt liu hoc sn phm c hot tnh cao phi c bo qun khu vc an ton v c bo v. 3.25. Nguyn vt liu bao gi in sn c coi l rt quan trng trong vic m bo dc phm ng vi ni dung trn nhn, cn c bit ch n vic bo qun an ton nhng nguyn vt liu ny. Khu vc kim tra cht lng 3.26. Thng thng, phng kim nghim phi c tch bit khi khu vc sn xut. iu ny c bit quan trng i vi phng kim nghim kim sot sinh hc, vi sinh, hoc th ng v phng x, chng cng phi cch bit nhau. 3.27. Phng kim nghim phi c thit k ph hp vi cc hot ng s tin hnh ti . Cn c din tch trnh ln ln v nhim cho. Cn c din tch ph hp bo qun mu v h s. 3.28. C th cn c phng ring cho dng c th nghim nhy cm bo v chng khi b rung ng, nhiu in t, m. 3.29. C yu cu c bit cn thit cho cc phng kim nghim x l cc cht c bit nh mu sinh hc hay mu phng x Khu ph 3.30. Cc phng v sinh v ngh gii lao phi tch bit khi cc khu khc. 21

3.31. Phng thay v gi qun o, khu vc tm ra v v sinh phi d dng tip cn v ph hp vi s ngi s dng. Nh v sinh khng c thng trc tip vi khu vc sn xut v bo qun. 3.32. Nu iu kin cho php, xng bo dng nn tch khi khu vc sn xut. Trng hp c ph tng v dng c trong khu vc sn xut, phi trong phng hoc t c kho dnh ring cho mc ch . 3.33. Nh nui ng vt phi cch ly tt khi cc khu vc khc, vi li ra vo ring (li vo ch ring cho ng vt) v thit b x l khng kh ring. My mc thit b 3.34. My mc thit b sn xut phi c thit k, b tr v bo dng ph hp vi mc ch s dng. 3.35. Thao tc bo dng v sa cha khng c gy ra bt k mi nguy him no i vi cht lng ca sn phm 3.36. My mc thit b sn xut phi c thit k sao cho lm v sinh d dng v cn thn. Chng cn c lm sch theo quy trnh chi tit v ch c bo qun iu kin sch s v kh ro. 3.37. My mc thit b ra v lm v sinh phi c la chn v s dng sao cho khng tr thnh ngun gy tp nhim. 3.38. My mc thit b phi c lp t sao cho hn ch c nguy c sai st hoc tp nhim. 3.39. My mc thit b sn xut khng c gy c hi cho sn phm. Nhng b phn ca my mc thit b sn xut c tip xc vi sn phm khng c gy phn ng, to ra thm cht hay hp thu cht mc c th nh hng ti cht lng sn phm v khng gy bt k nguy him no. 3.40. Phi c cn v thit b o lng c khong v chnh xc ph hp cho hot ng sn xut v kim tra cht lng. 3.41. o lng, cn, ghi h s v thit b kim tra phi c hiu chun v kim tra nh k u n bng phng php thch hp. Phi duy tr vic ghi chp y cc th nghim. 3.42. Cc ng ng c nh cn c dn nhn r rng ch r ni dung bn trong, hng dng chy, nu thch hp. 3.43. ng ng vn chuyn nc ct, kh ion ho c thc hin, v nu thch hp, cc ng ng nc khc cn lm v sinh theo quy trnh ni chi tit cc gii hn hnh ng i vi nhim vi sinh v cc bin php cn thc hin. 3.44. My mc b hng cn c a ra khi khu vc sn xut v kim tra cht lng. Hoc t nht thit b cng phi c dn nhn ghi r l hng.

22

CHNG 4: Nguyn tc.

H S TI LIU

H s ti liu tt l mt phn thit yu ca h thng m bo cht lng. H s ti liu vit r rng ngn nga sai st do truyn t bng li ni v cho php truy sot lch s ca l. Tiu chun, cng thc nh sn xut v cc hng dn, quy trnh v ti liu khng b sai st, v phi c thnh vn bn. Tnh r rng ca h s l ht sc quan trng. Quy nh chung 4.1. Tiu chun m t chi tit cc yu cu m sn phm hoc nguyn vt liu c s dng hoc thu c trong qu trnh sn xut phi t c. Tiu chun c dng lm c s nh gi cht lng. Cng thc nh sn xut, quy trnh v hng dn ng gi cp n tt c nguyn vt liu ban u s dng v trnh by tt c quy trnh ch bin v cc thao tc ng gi Cc quy trnh a ra cc ch dn cho vic thc hin cc thao tc v d nh lm v sinh, qun o, kim sot mi trng, ly mu, cc th nghim, vn hnh thit b. Ti liu h s cp lch s ca mi l sn phm, bao gm c phn phi v nhng bi cnh khc c lin quan n cht lng ca sn phm cui. 4.2. H s ti liu cn c thit k, son tho, r sot v phn pht mt cch thn trng. H s ti liu phi tun th cc phn c lin quan ca giy php sn xut v h s lu hnh. 4.3. 4.4. H s ti liu phi c ngi c thm quyn ph hp ph duyt, k v ghi ngy thng. H s ti liu phi c ni dung r rng: nu r tiu , bn cht v mc ch ca h s. Phi trnh by c trt t v d kim tra. Nhng ti liu sao chp phi r rng v d c. Khi sao chp cc ti liu gc c ti liu lm vic khng c c sai st trong qu trnh sao chp. H s ti liu phi thng xuyn c r sot v cp nht. Khi mt ti liu c sa i, cn phi c h thng ngn nga vic v s dng nhng phin bn c. H s ti liu khng c vit bng tay; nhng nhng h s ti liu i hi phi nhp s liu, th s liu nhp phi r rng, d c v khng ty xo c. Cn c khong trng cho vic nhp s liu .

4.5.

4.6.

4.7. Bt k thay i no i vi mt ti liu cng phi c k v ghi ngy; vic thay i phi bo m c th c c thng tin c. Khi cn phi ghi li c l do thay i. 4.8. Cn lp h s hoc hon tt h s khi tin hnh bt k hot ng no sao cho mi hot ng quan trng lin quan n sn xut dc phm u c 23

th truy ngc li c. H s s sch phi c lu gi cho n t nht mt nm sau khi thnh phm lin quan ht hn. 4.9. S liu c th c ghi li bng h thng x l s liu in t hoc cch ghi hnh hoc cc phng tin ng tin cy khc. Cn phi c quy trnh chi tit lin quan n h thng s dng v phi kim tra chnh xc ca s liu ghi chp. Nu h s ti liu c x l bng phng php x l s liu in t, ch c ngi c u quyn mi c php nhp hoc thay i s liu trong my tnh, v lun phi c mt h s ghi li cc thay i hay xo b . Phi hn ch truy cp bng cch s dng mt khu hoc cc bin php khc v vic nhp cc s liu quan trng cn c kim tra mt cch c lp. H s l c lu trn my tnh phi c bo v bng cch sao li sang bng t, vi phim, in ra giy, hoc cc bin php khc. iu c bit quan trng l trong thi gian lu gi, s liu phi lun sn sng khi cn truy cp. Nhng h s ti liu cn thit Tiu chun 4.10. Cn c cc tiu chun c ph duyt ph hp v ghi ngy thng i vi nguyn liu ban u, nguyn liu bao gi v thnh phm; nu c cn c tiu chun cho c sn phm trung gian v bn thnh phm. Tiu chun i vi nguyn liu ban u v nguyn liu bao gi 4.11. Tiu chun i vi nguyn liu ban u, bao b s cp v bao b c in n bao gm, nu thch hp: a. m t i vi nguyn vt liu, trong c: tn c t v m s ni b; tham chiu n chuyn lun ca dc in, nu c nh cung cp c ph chun v nu c th nh sn xut gc ca sn phm; mt mu bao b c in n; b. hng dn ly mu v kim nghim, hoc tham chiu n quy trnh thc hin; c. cc yu cu v nh tnh v nh lng, vi gii hn cho php. d. iu kin bo qun v cc thn trng; e. thi hn bo qun ti a trc khi kim nghim li. Tiu chun i vi sn phm trung gian v bn thnh phm 4.12. Cn c tiu chun i vi sn phm trung gian v bn thnh phm. Nu sn phm c mua hay gi i, hoc nu s liu thu c t sn phm trung gian c dng nh gi thnh phm. Cc tiu chun phi tng

24

t nh tiu chun i vi nguyn liu ban u hoc thnh phm, nu ph hp. Tiu chun thnh phm 4.13. Tiu chun thnh phm cn c: tn sn phm v m tham kho nu c; cng thc hoc tham chiu cng thc; m t dng bo ch v chi tit ng gi; hng dn ly mu v kim nghim, hoc tham chiu n quy trnh thc hin; yu cu v nh tnh v nh lng, vi gii hn cho php; iu kin bo qun v cc thn trng c bit trong x l nu c; tui th. Cng thc sn xut v hng dn ch bin 4.14. Cn c cng thc nh sn xut v hng dn qu trnh c ph duyt chnh thc cho mi sn phm v mi c l sn xut; Chng c kt hp trong mt h s. Cng thc nh sn xut cn c: a. b. c. tn sn phm, c m tham kho ca sn phm lin quan n tiu chun ca n; m t dng bo ch, hm lng, v c l; danh mc cc nguyn liu ban u c s dng, lng ca mi cht, c m t bng tn v k hiu tham kho thng nht cho loi nguyn liu ; cn nu r cht no s b mt i trong qu trnh ch bin; cng b sn lng thnh phm d kin v gii hn cho php, v sn lng sn phm trung gian, nu c. nu a im ch bin v thit b s dng ch yu; cc phng php, hoc tham chiu phng php, c s dng chun b v vn hnh cc my mc thit b quan trng (v d nh lm v sinh, lp t, hiu chun, v trng); hng dn ch bin chi tit ln lt tng bc (v d: kim tra nguyn vt liu, x l s b, trnh t thm cc nguyn vt liu, thi gian trn, nhit ); hng dn i vi cc kim tra trong qu trnh sn xut v cc gii hn tng ng; 25

d.

4.15. Hng dn qu trnh cn c: a) b)

c)

d)

e) f)

nu cn, quy nh v bo qun sn phm, k c bao b, nhn v cc iu kin bo qun c bit; nhng iu cn c bit thn trng.

Hng dn ng gi 4.16. Cn c cc hng dn ng gi chnh thc c ph duyt cho mi sn phm, quy cch ng gi v dng ng gi. Cc hng dn thng bao gm, hoc c tham chiu, nhng ni dung sau: a) b) c) d) tn sn phm; m t dng bo ch, hm lng, v ng s dng nu c; quy cch ng gi c nu bng s lng, trng lng, hoc th tch sn phm trong bao b ngoi cng; danh mc y tt c cc nguyn vt liu bao gi cn cho mt c l chun, bao gm s lng, c, v dng, c m hoc s tham kho lin quan n tiu chun cho mi loi nguyn vt liu bao gi; nu ph hp, c v d hoc bn sao ca nguyn vt liu c in n c lin quan v mu ca chng, trn ch r ch no ghi s l v ngy ht hn; cc thn trng c bit cn c thc hin, k c phi kim tra k khu vc v thit b ng gi nhm m bo dn quang dy chuyn trc v sau khi thc hin hot ng ng gi; m t thao tc ng gi, bao gm c nhng thao tc ph tr quan trng, v my mc thit b s dng; chi tit nhng ln kim tra trong qu trnh ng gi, c hng dn ly mu v gii hn cho php.

e)

f)

g) h)

H s ch bin l 4.17. Cn lu gi h s ch bin l cho mi mt l sn xut. H s cn da trn nhng phn lin quan trong cng thc nh sn xut v quy trnh hng dn c duyt hin s dng. Phng php chun b h s cn c thit k sao cho trnh c nhng sai st trong sao chp. H s cn c s ca l ang c sn xut. Trc khi bt u ch bin, cn kim tra m bo my mc thit b v ni sn xut khng cn nhng sn phm, h s ti liu hoc nguyn vt liu t l trc khng cn thit cho quy trnh ch bin hin ti, v my mc thit b sch v ph hp cho mc ch s dng. Trong khi pha ch, cn ghi li nhng thng tin sau vo thi im tin hnh mi thao tc, v sau khi hon thnh h s ghi chp phi c ngy thng v do ngi chu trch nhim pha ch k tn: a. tn sn phm; 26

b. c. d. e.

ngy v gi bt u, ngy gi thc hin cc cng on trung gian chnh, v ngy gi hon thnh vic sn xut; tn ngi chu trch nhim mi cng on sn xut; ch k tt ca nhn vin vn hnh mi bc sn xut chnh v, nu ph hp, ca ngi kim tra mi thao tc (v d khi cn); s l v/hoc s kim sot phn tch v khi lng thc t ca mi nguyn liu ban u (k c s l v khi lng ca nguyn liu phc hi hoc ti ch cho thm vo); bt k thao tc ch bin lin quan no, v nhng my mc thit b chnh c s dng; bn ghi cc kim tra trong qu trnh sn xut thc hin, ch k tt ca ngi thc hin, v kt qu; lng sn phm c c mi cng on sn xut trng tm ghi ch v nhng s c c bit, nu r chi tit, c ch k duyt nhng sai lch so vi cng thc sn xut v qu trnh hng dn.

f. g. h. i.

H s ng gi l 4.18. Cn lu gi h s ng gi l cho mi l hoc mt phn ca l ch bin. H s ny cn da trn cc phn lin quan ca hng dn ng gi, v cn c phng php chun b cc h s ny trnh nhng sai st trong sao chp. Cc bn ghi nn km theo s l, lng bn thnh phm ch ng gi cng nh s l v lng thnh phm d kin s thu c. Trc khi bt u bt k thao tc ng gi no, cn kim tra m bo my mc thit b v ni ng gi khng cn sn phm ng gi trc , ti liu, hoc nguyn vt liu khng cn thit cho thao tc ng gi hin ti, v my mc thit b sch v ph hp cho mc ch s dng. Cn ghi chp li nhng thng tin sau y vo thi im thc hin mi thao tc, cn ghi r ngy v ch k ca ngi chu trch nhim vi thao tc ng gi: a. tn sn phm b. ngy v gi thc hin thao tc ng gi; c. tn ngi chu trch nhim tin hnh cc thao tc ng gi; d. ch k tt ca nhn vin vn hnh cc bc chnh; e. cc bn ghi kim tra nhn dng v kim tra vic tun th theo hng dn ng gi, k c cc kt qu kim tra trong qu trnh ng gi; f. chi tit cc thao tc ng gi thc hin, c nu c my mc thit b v dy chuyn ng gi s dng; g. bt c khi no c th, lu li mu bao b in sn, k c mu c duyt em in i vi s l, ngy ht hn v bt k thng tin in thm no; 27

h. ghi ch v bt k s c c bit no, bao gm chi tit nhng sai lch so vi hng dn ng gi, c vn bn ph duyt ca ngi c thm quyn; i. s lng v s tham kho hay nhn dng ca tt c bao b in sn v bn thnh phm xut ra ng gi, ng gi, hu hoc tr v kho, v s lng sn phm c c c th i chiu y . Quy trnh v h s ghi chp Tip nhn 4.19. Cn c quy trnh thao tc chun v h s v vic tip nhn tng chuyn hng nguyn liu ban u, nguyn vt liu bao gi s cp hoc bao b c in n. 4.20. H s nhn hng cn c: a. b. c. d. e. f. g. h. tn nguyn vt liu trn phiu giao hng v trn thng hng; tn ni b v/hoc m nguyn vt liu (nu khc so vi tn mc a); ngy nhn; tn nh cung cp, v nu c th, tn nh sn xut; s l hoc s tham kho ca nh sn xut; tng khi lng, v s thng hng nhn; s l quy nh sau khi nhn; bt k nhn xt c lin quan no khc (v d tnh trng thng hng, v.v.)

4.21. Cn c cc quy trnh bng vn bn cho vic dn nhn, bit tr, v bo qun nguyn liu ban u, nguyn vt liu bao gi v cc nguyn vt liu khc, nu ph hp. Ly mu 4.22. Cn c quy trnh bng vn bn cho vic ly mu, trong ch r ngi c u quyn ly mu, phng php v thit b ly mu, s lng mu ly v cc thn trng cn tun th trnh tp nhim cho nguyn vt liu hoc lm mt phm cht nguyn vt liu (xem chng 6, mc 13) Th nghim 4.23. Cn c quy trnh bng vn bn cho vic kim nghim nguyn vt liu v sn phm mi cng on khc nhau trong qu trnh sn xut, trong m t phng php v thit b s dng. Phi ghi li c cc th nghim tin hnh (xem chng 6, mc 17) Khc 4.24. Cc qui trnh bng bng vn bn v vic cho xut xng hoc loi b cn c i vi cc nguyn liu v sn phm, c bit trng hp xut xng 28

thnh phm bn th phi c ch k ca ngi c u quyn c ch nh lm vic ny. 4.25. Nu cn thit h s phn phi l sn phm c lu gi d dng thu hi l (xem chng 8) 4.26. Cn c quy trnh bng vn bn v h s ghi chp li mi hot ng tin hnh hoc, cc kt lun c i vi: Thm nh; Vic lp t v hiu chun my mc thit b; Vic bo dng, lm v sinh v kh trng; Nhng vn nhn s bao gm o to, trang phc v v sinh; Vic theo di mi trng; Vic kim sot cn trng; Khiu ni; Thu hi; Nhng trng hp b tr li. 4.27. Qui trnh thao tc r rng cn c cho cc phn/cng on sn xut chnh v thit b th nghim. 4.28. Cn lu gi s sch c ghi chp v vic thm nh, hiu chun, bo dng, lm v sinh, hoc sa cha cc my mc thit b chnh v quan trng, nu ph hp c ghi ngy thng v tn ngi thc hin nhng cng vic . 4.29. Cn lu gi s sch ghi chp theo th t thi gian vic s dng cc my mc thit b chnh v quan trng cng nh khu vc tin hnh ch bin sn phm.

29

CHNG 5: Nguyn Tc

SN XUT

Cc thao tc sn xut phi c thc hin theo quy trnh nh r rng; Chng phi p ng vi cc nguyn tc Thc hnh tt sn xut thuc nhm thu c nhng sn phm c cht lng yu cu v ph hp vi giy php sn xut v lu hnh Quy nh chung 5.1. 5.2. Sn xut phi c thc hin v gim st bi ngi c thm quyn. Tt c cc thao tc x l nguyn vt liu v sn phm, nh tip nhn v bit tr, ly mu, bo qun, dn nhn, cp pht, ch bin, ng gi, v phn phi u phi thc hin theo ng cc quy trnh hoc hng dn bng vn bn v c ghi chp li nu cn thit. Tt c nguyn liu u vo phi c kim tra m bo chuyn hng ph hp vi n t hng. Bao b phi c lm sch, nu cn, v c dn nhn vi cc d liu c qui nh. Bao b hng v bt k vn no c nh hng n cht lng nguyn liu phi c iu tra, ghi chp v bo co vi phng kim tra cht lng. Ngay sau khi tip nhn hoc ch bin, nguyn liu u vo v thnh phm phi c bit tr bng cc bin php vt l hoc bin php hnh chnh, cho n khi chng c xut s dng hoc phn phi. Sn phm trung gian v bn thnh phm c mua phi c x l ti ni tip nhn nh x l nguyn liu ban u . Tt c nguyn liu v sn phm phi c bo qun theo iu kin thch hp do nh sn xut qui nh v theo trt t c th phn tch l v quay vng hng bo qun trong kho. Phi tin hnh kim tra v sn lng v cn i s lng, khi cn, m bo khng c s khc bit nm ngoi gii hn cho php. Khng c tin hnh ng thi hoc lin tc cc thao tc trn cc sn phm khc nhau trong cng phng, tr khi khng c nguy c ln ln hoc nhim cho.

5.3.

5.4.

5.5.

5.6. 5.7.

5.8. 5.9.

5.10. tt c cc giai on sn xut, phi bo v sn phm v nguyn liu khi nguy c nhim khun v cc nhim khc. 5.11. Khi lm vic vi nguyn liu v sn phm khan, phi c bit thn trng trnh pht sinh v phn tn bi. Nhng bin php ny phi c bit c p dng khi x l cc nguyn liu c hot tnh cao v d gy d ng. 5.12. Trong sut thi gian ch bin, tt c nguyn vt liu, bao b ng bn thnh phm, nhng my mc thit b chnh, v nu c c cc phng 30

c s dng, u phi c dn nhn hoc nu khng phi c k hiu nhn dng ghi tn sn phm hoc nguyn vt liu ang c ch bin, nng (nu thch hp), v s l. Nu c nn nu c cng on sn xut. 5.13. Nhn c dn trn bao b, thit b hoc nh xng phi r rng, khng kh hiu, v theo mu qui nh ca cng ty. S rt hu ch khi trn nhn, c s dng cc t c mu sc th hin tnh trng ca bao b, thit b hoc nh xng (v d: tnh trng bit tr, chp nhn, b loi, sch, ) 5.14. Phi tin hnh kim tra m bo rng cc ng ng v cc b phn khc ca my mc thit b s dng chuyn sn phm t khu vc ny sang khu vc khc c tip ni ng cch. 5.15. Phi trnh bt k sai khc no so vi hng dn hoc qui trnh. Nu c s sai lch, n phi c chp thun bng vn bn ca ngi c thm quyn, vi s tham gia kin ca phng kim tra cht lng, khi thch hp. 5.16. Vic ra vo nh xng sn xut cn hn ch, ch cho ngi c trch nhim mi c ra vo. 5.17. Thng thng, nhng sn phm khng phi l thuc khng c sn xut cng khu vc hoc trn cng my mc thit b dng sn xut dc phm. phng nhim cho v nhim khun trong sn xut 5.18. Cn trnh mt nguyn liu ban u hoc mt sn phm b nhim do mt nguyn liu hay sn phm khc. Nguy c nhim cho v tnh ny c th xy ra do thiu kim sot s phn tn bi, kh, hi, bi nc, hoc vi sinh vt t cc nguyn vt liu v sn phm trong qu trnh sn xut, t d cht bm li trn my mc thit b, t trang phc v da ca nhn vin vn hnh, v.v. Mc nghim trng ca nguy c ny thay i tu thuc vo loi yu t gy nhim v loi sn phm b nhim. Trong s nhng yu t gy nhim nguy him nht c cc nguyn liu gy d ng, cc ch phm sinh hc c cha cc vi sinh vt sng, mt s loi hc mn, cc cht c t bo, v cc nguyn vt liu c hot tnh cao khc. Nhng sn phm khi b tp nhim d gy nguy him nht l nhng sn phm dng ng tim truyn v nhng sn phm dng vi liu ln v/hoc lu di. 5.19. Cn trnh nhim cho bng cc bin php k thut v t chc ph hp, v d: a) Sn xut cc khu vc ring bit (yu cu cho nhng sn phm nh penicillin, vaccine sng, cc ch phm vi khun sng v mt s sinh phm khc), hoc tin hnh sn xut theo t (tch bit bng thi gian) sau c lm v sinh thch ng; b) Cung cp cc cht gi, h thng thi khng kh ph hp; c) Hn ch ti a nguy c tp nhim gy ra do s ti tun hon hoc ti lu ca khng kh khng qua x l hoc x l cha m bo; 31

d) Gi trang phc bo h trong khu vc ch bin cc sn phm c nguy c nhim cho c bit cao; e) S dng cc quy trnh v sinh v kh nhim c nh gi v hiu qu, v lm v sinh my mc khng sch s l ngun gy nghim cho ph bin; f) S dng h thng khp kn trong sn xut; g) Kim tra d cht v s dng nhn ghi tnh trng v sinh trn my mc. 5.20. Cn kim tra nh k cc bin php ngn nga nhim cho v hiu qu ca chng theo cc quy trnh thao tc thit lp. Thm nh 5.21. Cc nghin cu thm nh s b sung cho thc hnh tt sn xut thuc v phi c tin hnh theo qui trnh xc nh. Kt qu v kt lun phi c ghi li. 5.22. Khi bt k mt cng thc sn xut hoc phng php ch bin mi c chp nhn, phi tin hnh cc bc chng minh tnh ph hp ca chng trong (cho) sn xut thng quy. Mt qui trnh xc nh, c s dng nguyn liu v thit b c th, s sn xut ra nhng sn phm c cht lng n nh theo yu cu. 5.23. Bt k s thay i c ngha i vi qu trnh sn xut, bao gm c bt k thay i v thit b hoc nguyn liu c nh hng n cht lng v/hoc lp li ca quy trnh u phi c thm nh. 5.24. Cc quy trnh v th tc cn nh k nh gi li m bo chng vn c kh nng t c kt qu mong mun. Nguyn liu ban u 5.25. Vic mua nguyn liu ban u l mt hot ng quan trng cn c s tham gia ca nhng nhn vin c hiu bit su v ton din v sn phm ca cc nh cung cp. 5.26. Ch nn mua nguyn liu ban u ca nhng nh cung cp c duyt, c tn trong tiu chun tng ng, v nu c th, mua trc tip ca hng sn xut. Khuyn ngh rng cc tiu chun do nh sn xut thit lp cho nguyn liu ban u nn c tho lun vi nh cung cp. S c li nu tt c nhng kha cnh quan trng trong sn xut v kim tra cht lng nguyn liu ban u, k c cc yu cu v x l, dn nhn, v ng gi, cng nh quy trnh khiu ni v loi b, u c tho lun vi nh sn xut v nh cung cp. 5.27. Vi mi chuyn hng, cc thng hng t nht phi c kim tra v tnh ton vn ca bao b v nim phong, v s tng ng gia phiu giao hng v nhn ca nh cung cp.

32

5.28. Nu mt t giao hng nguyn liu bao gm nhiu l khc nhau, mi l phi c xem xt mt cch ring r ly mu, kim nghim v xut cho s dng. 5.29. Nguyn liu ban u khu vc bo qun phi c dn nhn ph hp (xem phn 5, mc 13). Nhn t nht phi c nhng thng tin sau: tn sn phm v m ni b khi cn, nu p dng; s l c t lc tip nhn; nu thch hp, tnh trng ca hng ho (v d: ang bit tr, ang kim nghim, xut, b loi); nu thch hp, ngy ht hn hoc ngy cn phi tin hnh kim nghim li. Khi s dng h thng bo qun hon ton bng my tnh, khng nht thit phi c tt c cc thng tin ny ghi r rng trn nhn. 5.30. Phi c cc quy trnh hoc bin php ph hp m bo nhn dng c nguyn liu ng bn trong mi thng nguyn liu ban u. Cn phn bit r cc thng nguyn liu c ly mu.(xem phn 6, mc 13) 5.31. Ch c s dng nhng nguyn liu ban u c b phn kim tra cht lng duyt cho xut s dng v vn cn trong hn dng. 5.32. Ch ngi c giao nhim v mi c php cp pht nguyn liu ban u theo mt quy trnh bng vn bn, m bo ng loi nguyn liu c cn hoc o lng chnh xc vo cc thng ng sch c dn nhn ng. 5.33. Mi nguyn liu c cp pht, trng lng hay th tch ca chng phi c kim tra li mt cch c lp. Vic kim tra ny phi c ghi chp li. 5.34. Nguyn liu cp pht sn xut mi l thnh phm phi c gi cng vi nhau v dn nhn r rng nhn bit iu . Thao tc ch bin - Sn phm trung gian v bn thnh phm 5.35. Trc khi bt u bt k thao tc ch bin no, phi tin hnh cc bc m bo l khu vc lm vic v my mc thit b l sch v khng c bt k nguyn liu ban u, sn phm, d phm hoc cc ti liu khng cn thit cho thao tc sp din ra. 5.36. Sn phm trung gian v bn thnh phm phi c bo qun trong iu kin ph hp. 5.37. Qui trnh sn xut phi c thm nh (xem phn thm nh trong chng ny). 5.38. Phi tin hnh v ghi li tt c cc kim tra trong qu trnh v kim tra mi trng. 33

5.39. Phi ghi chp li v iu tra bt k sai lch ng k no i vi sn lng d kin. Nguyn liu bao gi 5.40. Vic mua, qun l, kim tra cc nguyn liu bao gi trc tip v bao b in sn u phi thc hin nh i vi nguyn liu ban u. 5.41. Phi c bit ch n bao b in sn. Bao b in sn phi c bo qun trong iu kin an ton loi tr kh nng b tip cn tri php. Cc loi nhn ct ri v bao b in sn khc phi c bo qun v vn chuyn trong cc thng ring ng kn trnh ln ln. Ch c ngi c giao nhim v mi c php cp pht nguyn liu bao gi theo mt quy trnh bng vn bn c duyt. 5.42. Mi ln giao hng hoc mi l bao b in sn hoc bao b trc tip phi c cp mt m s c bit hoc mt k hiu nhn dng ring. 5.43. Bao b ng gi trc tip hoc bao b in sn ht hn hoc khng cn dng c phi em hu v vic hu b ny phi c lu h s. Hng dn ng gi 5.44. Khi xy dng mt chng trnh ng gi, phi c cc ch c bit nhm gim n mc ti thiu nguy c nhim cho, ln ln hoc b tro i. Khng c ng gi cc sn phm khc nhau trong cc khu vc gn nhau, tr khi c s phn cch vt l. 5.45. Trc khi bt u thao tc ng gi, phi thc hin cc bc kim tra m bo khu vc lm vic, dy chuyn ng gi, my in v my mc thit b khc sch v khng cn bt k sn phm, nguyn vt liu hoc ti liu s dng trc , nu nhng sn phm, nguyn vt liu hoc ti liu khng cn cho thao tc ng gi hin ti. Vic dn quang dy chuyn phi c thc hin theo ng danh mc kim tra thch hp. 5.46. Tn v s l ca sn phm ang c ng gi phi c treo trong mi im ng gi hoc mi dy chuyn ng gi. 5.47. Khi cp pht cho b phn ng gi, tt c sn phm v bao b ng gi s dng phi c kim tra v s lng, nhn dng v s ph hp vi Hng dn ng gi. 5.48. Bao b ng thuc phi sch trc khi ng thuc. Cn phi ch trnh v loi b bt k cc tc nhn nhim no, nh mnh v thu tinh hoc mnh kim loi. 5.49. Thng thng, vic dn nhn phi c thc hin cng nhanh cng tt tip ngay sau vic ng gi v nim phong. Nu cha dn nhn ngay c, phi thc hin qui trnh ph hp m bo khng xy ra ln ln hoc dn nhm nhn.

34

5.50. Phi kim tra v ghi li tnh chnh xc ca bt k hot ng in n no (vd: m s, hn dng) c thc hin ring r hoc trong qu trnh ng gi. Phi ch vic in bng tay, v phi nh k kim tra li. 5.51. Phi quan tm c bit khi s dng nhn ct ri v khi thc hin in ngoi dy chuyn. Thng thng, nn s dng nhn cun ct thnh nhn ri nhm trnh ln ln. 5.52. Phi tin hnh kim tra m bo rng bt k my c m, my m nhn in t hoc cc thit b tng t khc hot ng mt cch chnh xc. 5.53. Nhng thng tin c in v dp trn bao b ng gi phi r rng v kh phai hoc kh ty xo. 5.54. Kim tra sn phm trong qu trnh ng gi cn phi bao gm t nht nhng ni dung sau: a) Hnh thc chung ca bao gi; b) Vic ng gi c hon thin khng ; c) Vic c dng ng sn phm v bao b ng gi khng; d) Vic in c chnh xc khng ; e) My gim st trn dy chuyn c hot ng ng chc nng khng; Mu ly ra khi bng ti ng gi khng c tr li; 5.55. Nhng sn phm c lin quan n mt s c bt thng trong ng gi ch c a tr li qu trnh ng gi sau khi qua thanh tra, iu tra c bit v c ngi c thm quyn cho php. Phi lu h s chi tit v hot ng ny. 5.56. Bt k khc bit c ngha hoc bt thng trong vic i chiu s lng sn phm ch ng gi v bao b ng gi in sn, vi s lng n v thnh phm cn phi c iu tra, cn nhc tho ng trc khi xut xng. 5.57. Khi hon thnh thao tc ng gi, bt k bao b ng gi in s l m khng s dng, phi c hu v vic hu b phi c ghi trong h s. Nu bao b in sn cha c s l c tr v kho, th phi tun th theo quy trnh bng vn bn. Thnh phm 5.58. Thnh phm phi c bit tr cho ti khi c php xut xng trong nhng iu kin do nh sn xut thit lp. 5.59. Vic nh gi thnh phm v h s ti liu trc khi xut xng sn phm ra th trng l cn thit v c m t trong chng 6: Kim tra cht lng.

35

5.60. Sau khi xut xng, thnh phm phi c bo qun nh hng ho s dng c, trong nhng iu kin do nh sn xut quy nh. Nguyn vt liu b loi, phc hi v nguyn liu b tr v 5.61. Nguyn vt liu v sn phm b loi phi c dn nhn r rng ch r tnh trng v c bo qun ring trong khu vc hn ch ra vo. Chng c th c tr li cho nh cung cp hoc c ti ch hoc hu b, tu trng hp. Bt c bin php no c tin hnh, cng phi c chp nhn ca ngi c u quyn v phi c ghi trong h s. 5.62. Vic ti ch sn phm b loi ch c php trong trng hp ngoi l. Vic ny ch c chp nhn nu cht lng ca thnh phm khng b nh hng, nu cc ch tiu cht lng vn t, v nu c thc hin theo ng cc quy trnh xc nh c ph duyt, sau khi nh gi nhng nguy c c th xy ra. Cn lp h s theo di vic ti ch. 5.63. Vic phc hi mt phn hoc ton b nhng l trc t cht lng yu cu bng cch a vo mt l ca cng sn phm mt cng on sn xut nht nh u phi c ph duyt trc. Vic phc hi ny phi c thc hin theo ng quy trnh nh sau khi nh gi nhng nguy c c th xy ra, k c nh hng c th c i vi tui th sn phm. Vic phc hi phi c ghi vo h s. 5.64. B phn kim tra cht lng cn cn nhc s cn thit phi tin hnh cc php th b sung i vi bt k thnh phm no c ti ch hoc c s dng sn phm phc hi t l trc. 5.65. Nhng sn phm b tr v t th trng v khng nm trong s kim sot ca nh sn xut phi c hu, tr khi chc chn c l cht lng ca chng vn t yu cu; chng c th c cn nhc cho bn li, dn nhn li, hoc phc hi trong l sau ch sau khi c b phn kim tra cht lng nh gi mt cch nghim ngt theo mt quy trnh bng vn bn. Cn nh gi tt c cc yu t nh tnh cht ca sn phm, iu kin bo qun c bit nu c yu cu, iu kin v lch s ca sn phm, v khong thi gian tri qua k t khi sn phm c bn ra. Khi c bt k nghi ng no v cht lng sn phm, khng c cn nhc cho xut bn li hoc s dng li mc d c th ti ch ho cht c bn phc hi hot cht. Bt k bin php p dng no cng phi c ghi vo h s.

36

CHNG 6: Nguyn tc

KIM TRA CHT LNG

Kim tra cht lng lin quan n vic ly mu, tiu chun v th nghim, cng ng thi lin quan n vn t chc, h s ti liu v quy trnh duyt xut m bo tin hnh cc php th ph hp v cn thit, v nguyn vt liu khng c xut cho s dng hoc sn phm khng c xut em bn hay cung cp, nu nh chng cha c nh gi l t cht lng. Kim tra cht lng khng ch b hp trong cc hot ng ca phng th nghim, m bao gm mi quyt nh lin quan n cht lng sn phm tnh c lp ca b phn kim tra cht lng so vi b phn sn xut c coi l yu cu c bn i vi hot ng hiu qu ca b phn kim tra cht lng. Tnh c lp ca b phn kim tra cht lng so vi b phn sn xut c coi l yu cu c bn i vi hot ng hiu qu ca b phn kim tra cht lng (xem chng 1). Quy nh chung 6.1. Mi ch s hu giy php sn xut u phi c phng kim tra cht lng. Phng kim tra cht lng cn phi c lp vi cc phng khc v thuc quyn qun l ca mt ngi c trnh v kinh nghim ph hp, ngi ny c th iu hnh mt hoc nhiu phng th nghim. Cn c ngun lc m bo rng mi bin php v kim tra cht lng u c thc hin c hiu qu v ng tin cy. 6.2. Nhim v chnh ca trng phng kim tra cht lng c tm tt chng 2. Phng kim tra cht lng ni chung cng cn c nhng nhim v khc, v d nh xy dng, thm nh v thc hin tt c cc quy trnh kim tra cht lng, gi mu i chng ca nguyn liu v sn phm, m bo vic ghi nhn chnh xc cho bao b cha nguyn vt liu v sn phm, m bo vic theo di n nh ca hot cht v sn phm, tham gia iu tra nhng khiu ni lin quan n cht lng sn phm vv.. Tt c cc hot ng ny u cn phi c thc hin theo cc quy trnh bng vn bn v ghi vo h s nu cn thit. Vic nh gi thnh phm phi tnh n mi yu t c lin quan, k c iu kin sn xut, kt qu kim tra trong qu trnh, xem xt h s sn xut (k c h s ng gi), vic tun th cc tiu chun ca thnh phm, v vic kim tra thnh phm sau cng. Nhn vin b phn kim tra cht lng phi tip cn c khu vc sn xut ly mu v iu tra, nu cn. Nh xng v thit b ca phng kim tra cht lng phi t nhng yu cu chung v yu cu ring cho khu vc kim tra cht lng c cp trong chng 3.

6.3.

6.4.

Thc hnh tt phng kim tra cht lng 6.5.

37

6.6.

Nhn s, nh xng, v thit b trong phng th nghim cn phi ph hp vi nhim v c giao tu theo bn cht v qui m hot ng sn xut. V cc l do c bit, c th chp nhn s dng phng th nghim bn ngoi, theo ng chi tit nguyn tc cp trong chng 7. Phn tch theo hp ng, nhng iu ny phi c th hin trong h s kim tra cht lng. H s ti liu phng th nghim cn phi tun th theo nguyn tc nu trong chng 4. Mt phn quan trng ca h s ti liu ny lin quan n kim tra cht lng v cc chi tit sau y phi c sn sng cho phng kim tra cht lng : - Tiu chun cht lng; - Qui trnh ly mu; - Qu trnh th nghim v ghi chp (bao gm h s phn tch v/hoc s ghi chp ca kim nghim vin) - Bo co phn tch v/hoc phiu phn tch; - S liu gim st mi trng, nu yu cu; - Ghi chp thm nh phng php phn tch, nu ph hp; - Quy trnh v h s ghi chp hiu chun ca thit b o v bo tr thit b my mc.

H s ti liu 6.7.

6.8. Bt k h s ti liu kim tra cht lng lin quan n h s l sn xut phi c lu gi 01 nm sau ngy ht hn ca l. 6.9. i vi mt vi loi d liu (kt qu th nghim phn tch, sn lng, kim tra mi trng ) cn lu gi cc h s ti liu c th nh gi c xu hng. 6.10. Ngoi nhng thng tin c a vo h s l, cc d liu gc nh s tay ghi chp ca kim nghim vin v/hoc h s lu ca phng th nghim cn c lu gi v lun sn sng s dng. Ly mu 6.11. Ly mu phi c tin hnh theo qui trnh bng vn bn duyt vi cc chi tit sau: - Phng php ly mu; - Dng c dng ly mu; - Lng mu c ly; - Hng dn cho vic chia mu c yu cu; - Loi v iu kin ca bao b ng mu ly s s dng; - nh du bao b ly mu; 38

- Nhng ch c bit khi ly mu, c bit i vi vic ly mu nguyn liu v trng hoc nguyn liu c c tnh; - iu kin bo qun; - Hng dn v sinh v bo qun dng c ly mu. 6.12. Mu i chng phi i din cho l ca nguyn liu hoc sn phm m n c ly ra t . Nhng mu khc cng c th c ly gim st nhng thi im quan trng nht ca qu trnh sn xut (nh: lc bt u v kt thc ca qu trnh) 6.13. Mi bao b ng mu phi c dn nhn vi cc thng tin v: S lng, s l sn xut, ngy ly mu v nhng thng m mu c ly ra. 6.14. Mu i chng t l ca thnh phm cn lu gi mt nm na sau khi ht hn dng. Thnh phm nn gi trong bao gi cui cng v bo qun iu kin c khuyn co. Mu nguyn liu ban u (khng phi l dung mi, kh, nc) cn lu gi t nht 02 nm sau khi xut xng sn phm nu n nh cho php. Thi gian ny c th rt ngn hn nu n nh ca nguyn liu ngn c cp trong tiu chun lin quan. Mu i chng ca nguyn liu v sn phm c ly va , ti thiu l cho php tin hnh ti kim tra vi y cc bc. Th nghim 6.15. Phi thm nh cc phng php phn tch. Tt c cc thao tc th nghim c m t trong giy php lu hnh phi c tin hnh theo ng cc phng php c ph duyt. 6.16. Kt qu thu c phi c ghi chp v kim tra m bo rng chng ph hp vi cc kt qu khc. Cc tnh ton phi c kim tra theo tiu chun cht ch. 6.17. Cc php th thc hin phi c ghi chp li v nhng h s bao gm t nht nhng d liu sau: a) Tn ca nguyn liu hoc sn phm, v nu ph hp, dng bo ch; b) S l sn xut v nu ph hp, tn ca nh sn xut v/hoc nh cung cp; c) Tham chiu n tiu chun v qui trnh th nghim lin quan; d) Kt qu th nghim bao gm c nhng quan st c v tnh ton, v tham chiu n cc phiu phn tch. e) Ngy th nghim; f) Ch k nhng ngui thc hin th nghim ; g) Ch k ca nhng ngi xc nhn th nghim v tnh ton, nu ph hp. 39

h) Kt lun r rng cho xut hay t chi (hoc nhng quyt nh khc) v ch k km theo ngy thng ca ngi c trch nhim c ch nh. 6.18. Tt c kim tra trong qu trnh, bao gm c nhng kim tra ca ngi sn xut trong khu vc sn xut, phi thc hin theo phng php ph chun ca phng kim tra cht lng v kt qu phi c ghi vo h s. 6.19. Phi lu c bit i vi cht lng thuc th, bnh o th tch v cc dung dch, cc cht chun v mi trng nui cy. Chng phi c chun b theo qui trnh bng vn bn 6.20. Thuc th phng th nghim d kin s dng ko di phi c ghi trn nhn ngy pha ch, v c ch k ca ngi pha ch. Ngy ht hn ca nhng thuc th khng bn vng v mi trng nui cy phi ch r trn nhn cng vi iu kin bo qun ring. Ngoi ra, i vi dung dch chun th tch, ngy chun cui cng v ch s F hin ti cng phi ch r. 6.21. Nu cn thit, ngy tip nhn ho cht cho qu trnh th nghim (v d: thuc th, cht chun) phi c ch r trn bao b ng. Cc hng dn s dng v bo qun phi c tun th. Trong mt s trng hp, c th l cn thit tin hnh th nh tnh v/hoc php th khc ca nguyn liu thuc th trc khi tip nhn hoc s dng. 6.22. ng vt s dng cho th nghim cc thnh phn, nguyn liu hoc sn phm nu thch hp nn bit tr trc khi dng. Chng phi c gi v kim tra m bo tnh ph tnh ph hp vi mc ch s dng, Chng cn c nh du, c y h s lu gi cho bit lch s s dng ca chng. Chng trnh nghin cu n nh 6.23. Sau khi a ra th trng, n nh ca sn phm thuc phi c theo di theo mt chng trnh lin tc thch hp c th cho php pht hin bt k s thay i v n nh (mc thay i v tp cht, hoc kh nng ho tan hot cht) lin quan n cng thc ca sn phm trong dng ng gi em bn. 6.24. Mc ch ca chng trnh theo di n nh thng xuyn l theo di sn phm cho ti khi ht hn dng v xc nh rng sn phm ang duy tr, v c th c d kin vn duy tr trong tiu chun cho php iu kin bo qun ghi trn nhn. 6.25. Chng trnh theo di n nh ny p dng ch yu i vi sn phm thuc ng trong bao gi m n c bn, nhng cn xem xt vic a bn thnh phm vo chng trnh theo di. V d, khi bn thnh phm c gi trong thi gian di trc khi c ng gi v/hoc c vn chuyn t nh my sn xut n nh my ng gi, s tc ng n n nh ca sn phm ng gi phi c nghin cu nh gi di iu 40

kin mi trng xung quanh. Ngoi ra cn xem xt n sn phm trung gian c bo qun v s dng trong thi gian di. Nghin cu n nh ca cc sn phm ti t hp c thc hin trong qu trnh nghin cu pht trin sn phm v khng cn phi theo di thng xuyn. Tuy nhin khi cn thit n nh sn phm ti t hp cng cn phi theo di. 6.26. Chng trnh nghin cu n nh thng xuyn phi c m t trong vn bn cng theo cc qui nh chung trong chng 4 v c bo co kt qu. Thit b s dng cho chng trnh nghin cu n nh thng xuyn (bung theo di n nh) phi c thm nh v bo tr theo qui nh chung trong chng 3 v ph lc 15. 6.27. cng cho chng trnh nghin cu n nh thng xuyn phi c ko di n ht hn dng v phi bao gm, nhng khng gii hn trong nhng thng s sau: - S lng l cho mi hm lng v c l khc nhau, nu thch hp - Cc phng php th vt l, ho hc, vi sinh hc v sinh hc lin quan - Cc ch tiu chp nhn - Tham chiu n phng php th - M t h thng np l cha - Khong cch thi gian th nghim (cc im mc thi gian) - M t iu kin bo qun (s dng cc iu kin bo qun chun ho ca ICH i vi th nghim di hn, nht qun vi iu kin ghi trn nhn) - Cc thng s khc dnh ring cho sn phm thuc. 6.28. cng cho chng trnh nghin cu n nh thng xuyn c th khc so vi cng cho nghin cu n nh di hn ban u c trnh trong h s ti liu ng k thuc vi iu kin s khc bit c gii trnh v ghi chp trong quy trnh (v d tn s th hoc khi cp nht theo hng dn ca ICH) 6.29. S lng l v tn s th nghim phi m bo cung cp s lng d liu cho php phn tch xu hng. Tr khi c l do chnh ng no khc, t nht mt l/mt nm ca mi sn phm c sn xut mi cc hm lng v mi loi bao b ng gi s cp, nu ph hp, phi c a vo chng trnh nghin cu n nh (tr khi khng c l sn phm no c sn xut trong nm ). i vi nhng sn phm cn theo di n nh thng xuyn c yu cu th nghim dng ng vt v khng c k thut thay th ph hp c thm nh no khc th tn sut th c th tnh n phng php tin cn nh gi nguy c - hiu qu. Trong cng, nguyn tc thit k v t du v ma trn c th c p dng nu c nh gi l m bo tnh khoa hc. 41

6.30. Trong vi trng hp, cn b sung thm cc l vo chng trnh nghin cu n nh thng xuyn. V d, mt nghin cu n nh thng xuyn cn c tin hnh sau bt k mt thay i ng k no hoc sai lch ng k no i vi quy trnh sn xut hoc ng gi. Bt k hot ng sn xut li, ti ch hoc phc hi cng phi c xem xt a vo nh gi n nh. 6.31. Kt qu ca chng trnh nghin cu n nh thng xuyn cn c cung cp cho ngi c trch nhim v c bit l ngi c u quyn. Khi nghin cu n nh thng xuyn c tin hnh ni khc vi ni sn xut bn thnh phm hoc thnh phm, th cn c mt tho thun bng vn bn gia cc bn c lin quan. Kt qu ca cc nghin cu n nh thng xuyn cn phi c sn ni sn xut c quan c thm quyn xem xt. 6.32. Cc trng hp khng t tiu chun hoc c xu hng bt thng ng k phi c iu tra. Bt k kt qu khng t no c khng nh hoc c khuynh hng khng t phi c bo co cho c quan c thm quyn lin quan. Nhng nh hng c th c i vi cc l lu hnh trn th trng cn c xem xt ph hp vi cc quy nh ti chng 8 ca hng dn GMP v tham kho vi c quan c thm quyn lin quan. 6.33. Mt tm tt d liu chung, bao gm c bt c kt lun tm thi no v chng trnh phi c ghi li v lu gi. Bn tm tt cn c xem xt nh k.

42

CHNG 7: Nguyn tc

SN XUT V KIM NGHIM THEO HP NG

Vic sn xut v kim nghim theo hp ng phi c xc nh r rng, c thng nht v c kim sot nhm trnh nhng hiu lm c th dn ti vic sn phm hoc cng vic khng t cht lng mong mun. Phi c hp ng bng vn bn gia bn hp ng v bn nhn hp ng, trong quy nh r rng nhim v ca mi bn. Hp ng phi ch r cch thc m ngi c thm quyn xut xng tng l sn phm ra th trng thc hin trch nhim y ca h Ghi ch: Chng ny cp trch nhim ca nh sn xut i vi cc c quan c thm quyn ca cc nc thnh vin v vic cp giy php lu hnh v giy php sn xut. D th no, khng gy nh hng ti trch nhim ring ca bn nhn hp ng v bn hp ng i vi khch hng. Quy nh chung 7.1. Phi c hp ng bng vn bn quy nh cc vn v sn xut v/hoc kim nghim c tho thun v bt k tho thun k thut no khc c lin quan. 7.2. Tt c cc tho thun v sn xut v kim nghim theo hp ng, bao gm c nhng thay i c d kin trong cc tho thun k thut hoc tho thun khc phi ph hp vi giy php lu hnh ca sn phm c lin quan. Bn hp ng 7.3. Bn hp ng phi chu trch nhim nh gi nng lc ca bn nhn hp ng v kh nng thc hin thnh cng cc cng vic theo yu cu v m bo thng qua hp ng rng cc nguyn tc v hng dn GMP nh c gii thch trong hng dn ny, c tun th. 7.4. Bn hp ng phi cung cp cho bn nhn hp ng tt c cc thng tin cn thit tin hnh cc hot ng theo hp ng mt cch chnh xc theo ng giy php lu hnh v cc quy nh lut php khc. Bn hp ng phi m bo rng bn nhn hp ng nhn thc y v mi vn lin quan n sn phm hay cng vic c th gy hi cho nh xng, my mc thit b, nhn vin, cc nguyn vt liu hoc cc sn phm khc ca h. 7.5. Bn hp ng phi m bo rng mi sn phm v nguyn vt liu ch bin do bn nhn hp ng giao li u t tiu chun, hoc sn phm c ngi c thm quyn ra quyt nh xut xng. Bn nhn hp ng 7.6. Bn nhn hp ng phi c nh xng, my mc thit b, kin thc v kinh nghim cng nh nhn vin nng lc thc hin tho ng cng 43

vic do bn hp ng t ra. Ch nhng c s c giy php sn xut mi c thc hin sn xut theo hp ng. 7.7. Bn nhn hp ng phi m bo tt c sn phm hoc nguyn liu c giao cho h phi thch hp cho mc ch d kin ca chng. 7.8. Bn nhn hp ng khng c chuyn cho bn th ba cng vic c giao cho mnh theo hp ng k khi cha c bn hp ng nh gi v chp nhn tho thun . Cc tho thun t ra gia bn nhn hp ng v bn th ba phi m bo sao cho cc thng tin v sn xut v kim nghim cung cp cho bn th ba tng t nh thc hin gia bn hp ng v bn nhn hp ng. 7.9. Bn nhn hp ng phi trnh nhng hot ng c th c nh hng xu n cht lng ca sn phm c sn xut v/hoc kim nghim cho bn hp ng. Bn hp ng 7.10. Cn xy dng bn hp ng gia bn hp ng v bn nhn hp ng trong nu r trch nhim ca mi bn v sn xut v kim tra sn phm. Nhng kha cnh k thut ca hp ng phi do nhng ngi c thm quyn vi kin thc ph hp v cng ngh dc, kim nghim dc phm v v GMP son tho. Tt c cc tho thun v sn xut v kim nghim phi theo ng giy php lu hnh sn phm v c thng nht gia hai bn. 7.11. Bn hp ng phi nu r cch ngi c u quyn xut xng l thnh phm ra th trng m bo rng mi l c sn xut v kim tra t theo cc yu cu ca giy php lu hnh. 7.12. Bn hp ng phi ch r ai l ngi chu trch nhim mua, kim nghim v xut nguyn vt liu, tin hnh vic sn xut v kim tra cht lng, k c kim tra trong qu trnh sn xut, v ai c trch nhim ly mu v phn tch. Trong trng hp kim nghim theo hp ng, bn hp ng phi nu r vic bn nhn hp ng c ly mu ti c s ca nh sn xut hay khng. 7.13. H s sn xut, kim nghim, phn phi v mu i chiu phi c lu tr bi hoc phi c sn i vi bn hp ng. Bt c h s no c lin quan ti vic nh gi cht lng ca mt sn phm b khiu ni hoc nghi ng c sai hng phi c truy cp v cp n trong quy trnh x l sai hng/thu hi ca bn hp ng. 7.14. Hp ng phi cho php bn hp ng c kim tra c s ca bn nhn hp ng. 7.15. Trong trng hp kim nghim theo hp ng, bn nhn hp ng phi hiu rng h chu s thanh tra ca cc cc c quan c thm quyn.

44

CHNG 8: Nguyn tc

KHIU NI V THU HI SN PHM

Tt c cc khiu ni v cc thng tin khc lin quan n sn phm c kh nng b sai hng u phi c xem xt cn thn theo cc quy trnh bng vn bn. Phi xy dng mt h thng thu hi, nu cn thit, cc sn phm c bit hoc nghi ng l c h hng t th trng mt cch nhanh chng v hiu qu. Khiu ni 8.1. Cn c mt ngi chu trch nhim x l cc khiu ni v quyt nh bin php x l, bn cnh phi c nhn vin h tr ngi ny. Nu ngi ny khng phi l ngi c u quyn, th ngi c u quyn phi c thng bo v bt k khiu ni, iu tra hay thu hi no. Cn c mt quy trnh bng vn bn m t bin php tin hnh, k c vic cn cn nhc n bin php thu hi, trong trng hp khiu ni lin quan n mt sn phm sai hng . Bt k khiu ni no lin quan n sn phm b sai hng phi c lp thnh h s vi y cc chi tit v giy t gc, v phi c iu tra thu o. Ngi chu trch nhim v kim tra cht lng thng s phi tham gia vo vic iu tra cc vn ny. Nu sn phm b sai hng c pht hin hoc nghi ng mt l, cn tnh n vic kim tra cc l khc nhm xc nh xem chng c b sai hng tng t khng. c bit phi kim tra cc l c s dng sn phm ti ch t l c sai st. Tt c cc quyt nh v bin php thc hin lin quan n khiu ni u phi c ghi vo h s v tham chiu ti h s l tng ng. H s v khiu ni cn c r sot mt cch thng xuyn tm ra du hiu ca nhng vn c bit hoc vic lp li cc sai st c th dn n vic thu hi nhng sn phm lu hnh. Cn thng bo cho c quan c thm quyn trong trng hp nh sn xut ang tnh n bin php x l cc trng hp c th do li ca sn xut, sn phm mt phm cht, hoc bt k vn cht lng nghim trng no ca mt sn phm. Phi ch nh mt ngi chu trch nhim thc hin v phi hp vic thu hi v cn phi c nhn vin h tr x l tt c cc kha cnh trong thu hi mc khn cp thch hp. Ngi chu trch nhim thu hi thng c lp khi b phn tip th v bn hng. Nu ngi ny khng phi l ngi c u quyn, th ngi c u quyn phi c thng bo v bt k vic thu hi no. 45

8.2.

8.3.

8.4.

8.5. 8.6.

8.7.

Thu hi sn phm 8.8.

8.9. 8.9.

Cn c cc quy trnh bng vn bn c kim tra v cp nht thng xuyn, khi cn thit, nhm gip cho vic t chc cc hot ng thu hi. Cc hot ng thu hi phi c kh nng trin khai nhanh chng ti bt k thi gian no.

8.10. Tt c cc c quan c thm quyn ca tt c cc nc ni sn phm c th c phn phi, phi c thng bo ngay lp tc v sn phm d kin c thu hi v n b sai hng hoc nghi ng l c sai hng. 8.11. H s phn phi phi m bo sn sng cho ngi c trch nhim thu hi, v phi c y thng tin v nhng i l bn bun v nhng khch hng c cung cp trc tip (a ch, in thoi v/hoc fax trong v ngoi gi lm vic, l v s lng phn phi) k c nhng mu cho xut khu v mu cho y t. 8.12. Cc sn phm thu hi v cn c xc nh v bo qun ring r ti mt khu vc an ton trong khi ch quyt nh x l. 8.13. Phi ghi li vo h s din tin ca qu trnh thu hi v phi c mt bn bo co cui cng, bao gm c s liu i chiu gia lng sn phm phn phi v lng sn phm thu hi v. 8.14. Cn thng xuyn kim tra v nh gi hiu qu ca k hoch thu hi.

46

CHNG 9: Nguyn tc

T THANH TRA

T thanh tra c tin hnh nhm theo di vic p dng v tun th cc nguyn tc thc hnh tt sn xut v xut cc bin php khc phc cn thit. 9.1. Vn nhn s, nh xng, thit b, ti liu, sn xut, kim tra cht lng, phn phi cc sn phm thuc, thu xp gii quyt v khiu ni v thu hi, t thanh tra, phi c nh k kim tra theo mt chng trnh c chun b trc nhm kim tra s ph hp ca chng vi cc nguyn tc m bo cht lng. T thanh tra phi c tin hnh mt cch c lp v chi tit bi ngi c thm quyn c cng ty ch nh. Thanh tra c lp ca chuyn gia bn ngoi cng c th rt hu ch. Tt c cc hot ng t thanh tra phi c ghi chp li. Bo co thanh tra cn bao gm tt c nhng quan st c thc hin trong qu trnh thanh tra, v nu thch hp, c nhng xut v bin php khc phc. Nhng tuyn b v cc hnh ng c thc hin tip theo cng phi c ghi chp li.

9.2.

9.3.

47

PH LC 1 Nguyn tc:

SN XUT CC DC PHM V TRNG

Sn xut cc dc phm v trng tun theo nhng yu cu c bit nhm lm gim n mc ti thiu nguy c b nhim vi sinh vt , nhim cc tiu phn v ch nhit t. Cc iu ph thuc ng k vo k nng, s o to v quan im ca nhng ngi lin quan. m bo cht lng c tm quan trng c bit v vic sn xut sn phm ny phi tun th nghim ngt theo nhng phng php pha ch v quy trnh c thit lp v thm nh cn thn. Khng c t s tin cy n thun i vi s v trng v cc kha cnh khc ca cht lng vo bt c qu trnh x l cui cng no hoc th nghim trn thnh phm. Ch : Hng dn ny khng a ra nhng phng php chi tit xc nh sch v mt vi sinh vt v tiu phn ca khng kh, b mt, v. vCn tham kho cc ti liu khc nh: Cc b tiu chun EN / ISO Nhng quy nh chung: 1. Qu trnh sn xut cc sn phm v trng phi c tin hnh trong khu vc sch, m ngi v /hoc thit b my mc, v nguyn liu ra vo khu vc phi i qua cc cht gi (airlock). Khu vc sch phi c duy tr mt tiu chun thch hp v sch, v c cung cp khng kh c lc qua mng lc c hiu nng lc thch hp. Cc thao tc khc nhau trong chun b nguyn vt liu, pha ch, ng l phi c tin hnh cc phng ring bit nm trong khu sch. Cc hot ng sn xut c chia thnh 2 loi; loi 1, cc sn phm c tit trng cng on cui cng, v loi 2 cc sn phm c sn xut trong iu kin v trng mt vi hoc tt c cc cng on sn xut. Khu vc sch sn xut sn phm v trng c phn loi theo cc yu cu c trng v mi trng. trng thi hot ng, mi thao tc sn xut i hi mt mi trng c mc sch thch hp nhm hn ch ti a nguy c nhim tiu phn hoc nhim vi sinh vt vo sn phm hoc nguyn liu ang c ch bin. p ng cc iu kin trong trng thi hot ng, nhng khu vc sch ny phi c thit k sao cho khng kh t c mc sch nht nh trng thi ngh. Trng thi ngh l iu kin khi nh xng hon thnh vic xy dng, lp t, cc thit b sn xut c lp t v ang hot ng, nhng khng c mt nhn vin vn hnh. Trng thi hot ng l iu kin khi my mc ang c vn hnh theo phng thc hot ng xc nh v vi s c mt ca mt s lng nhn vin xc nh. Trng thi hot ng v Trng thi ngh phi c xc nh cho tng phng sch hoc dy cc phng sch.

2.

3.

48

i vi vic sn xut cc ch phm v trng, c 4 cp c phn bit nh sau: Cp A: Khu vc cc b cho cc thao tc c nguy c cao, nh ng thuc, y nt, ng thuc v cc l h, v lm kn v trng. Thng thng, nhng iu kin ny c to ra bi cc laminar. Cc laminar phi cung cp khng kh ng nht vi tc khong 0,36 0,54m/s (gi tr hng dn) ti v tr lm vic ca cc laminar s dng trong phng sch m . Vic duy tr c tnh ca laminar phi c chng minh v c thm nh. Dng khng kh mt chiu v tc nh hn c th c s dng trong nhng thit b c lp kn v nhng hp chuyn dng c sn gng tay gim tip xc vi cc cht c x l (glove box) Cp B: i vi vic pha ch v ng l v trng, cp ny l mi trng ph cn cho khu vc c cp A. Cp C v D: Khu vc sch thc hin cc cng on t quan trng hn trong qu trnh sn xut sn phm v trng. Phn loi mc s lng tiu phn trong khng kh i vi cc cp sch trn c trnh by trong bng sau y. Trng thi ngh(b) Cp sch Trng thi hot ng(b)

S lng ti a cc tiu phn cho php/m3 tng ng hoc ln hn (a) 0,5 m(d) 5,0 m 1(e) 1(e) 2000 20 000 0,5 m(d) 3500 350 000 3 500 000 Khng qui nh (f) 5,0 m 1(e) 2000 20 000 Khng qui nh (f)

A B (c) C(c) D(c) Ch :(a)

3500 3500 350 000 3 500 000

o m tiu phn da trn vic dng mt thit b m tiu phn khng kh ring bit o c s lng cc tiu phn c cc kch thc nh tng ng vi hoc trn ngng c tuyn b. Cn s dng mt h thng o lin tc theo di s lng cc tiu phn vng sch cp A v c khuyn co cho vng ph cn c cp sch B. kim tra theo 49

thng quy, tng th tch mu khng c nh hn 1 m3 cho khu vc sch cp A v B v tt nht cng c p dng cho khu vc sch cp C.(b)

Cc yu cu v tiu phn nu trong bng i vi trng thi ngh phi t c sau mt thi gian lm sch ngn khong 15-20 pht (gi tr ny mang tnh hng dn) tnh trng khng vn hnh sau khi kt thc thao tc sn xut. Cc yu cu v tiu phn i vi khu vc sch cp A trong trng thi hot ng c nu trong bng cn c duy tr ti khu vc cha sn phm bt c khi no sn phm hoc bao b cha sn phm m tip xc trc tip vi mi trng. C th chp nhn c l khng phi lc no cng c th chng minh vic t yu cu v tiu phn ti v tr ng l khi qu trnh ng l ang c thc hin, do s to ra cc tiu phn hoc ht nh t bn thn sn phm. t c khng kh sch cp B, C v D, s ln trao i khng kh cn ph hp vi kch thc phng, vi thit b v s nhn vin c mt ti . H thng khng kh phi c lp t lc cui thch hp chng hn nh lc HEPA cho cp sch A,B v C.

(c)

Gi tr hng dn a ra i vi s lng ti a cc tiu phn cho php trng thi ngh v trng thi hot ng tng ng vi cp sch trong EN/ISO14644 -1 vi kch thc tiu phn 0,5 m(e)

(d)

Nhng khu vc ny c d kin l hon ton khng c cc tiu phn c kch thc ln hn 5 m. Bi v khng th chng minh c s khng c cc tiu phn cng vi bt k ngha thng k no, nn gii hn c t ra l 1 tiu phn/m3 . Trong qu trnh nh gi-thm nh phng sch, phi chng minh rng khu vc vn duy tr trong cc gii hn c xc nh

(f)

Nhng yu cu v gii hn s ph thuc nhiu vo tnh cht ca cc hot ng c thc hin. Nhng v d ca cc hot ng c thc hin trong cc cp sch khc nhau c a ra trong bng di y (cn tham kho cc mc 11 v 12):

Cp sch A C D

V d cc hot ng cho nhng sn phm tit trng cui cng (xem mc 11) ng sn phm, khi c nhng ri ro bt thng Pha ch dung dch, khi c nhng ri ro bt thng. ng sn phm Pha ch dung dch v cc thnh phn cho vic ng sn phm tip theo sau V d cc hot ng cho sn xut thuc trong iu kin v trng (xem mc 12) 50

Cp sch

A C D 4. 5.

Pha ch v ng sn phm trong iu kin v trng Pha ch dung dch c lc v trng khi ng ng. X l cc thnh phn bao b sau khi ra

Cc khu vc phi c theo di trong qu trnh thao tc kim sot mc sch v tiu phn ca cc cp sch khc nhau. Ti cc khu vc ang tin hnh thao tc v trng phi tin hnh gim st thng xuyn bng cch s dng cc phng php nh t a thch, ly mu khng kh v ly mu b mt (v d phng php lau bng bng swabs v a thch tip xc). Phng php ly mu trong qu trnh thao tc khng c gy nh hng cho vic bo v khu vc. Cc kt qu kim tra phi c xem xt khi nh gi h s l cho php xut xng thnh phm. Cc b mt v nhn vin u phi c theo di sau cc thao tc quan trng. Vic theo di thm nhim vi sinh vt cng c yu cu ngoi hot ng sn xut, v d sau khi thm nh h thng, thm nh v sinh v lm v sinh. Cc gii hn khuyn co trong vic theo di mc nhim vi sinh vt ti khu vc sch trong qu trnh thao tc: Cc gii hn khuyn co mc nhim vi sinh vt (a) Cp sch Ly mu In gng tay t a thch a thch tip khng kh xc (ng (5 ngn tay) (ng knh 3 (CFU/m ) knh 55mm) (CFU/gng) 90mm) (b) (CFU/a) (CFU/4h) A