cong-nghe-bao-che-duoc-pham.pdf

B Y T

CNG NGH BO CH DC PHM

(DNG CHO O TO DC S I HC)

M S: .20.Z.09

NH XUT BN GIO DC H NI 2007

Ch o bin son: V KHOA HC V O TO B Y T

Ch bin: PGS.TS. HONG MINH CHU

Page 1 of 255Bo Y te - Cong nghe bao che duoc p

30/09/2009file://C:\Windows\Temp\kgtcqomwpi\cong_nghe_bao_che_duoc_pham.htm

Tham gia bin son: PGS. TS. HONG MINH CHU PGS.TS. L QUAN NGHIM TS. L HU ThS. NGUYN NHT THNH

Tham gia t chc bn tho: ThS. PH VN THM TS. NGUYN MNH PHA

Li gii thiu

Thc hin mt s iu ca Lut Gio dc, B Gio dc v o to v B Y t ban hnh chng trnh khung o to Dc s i hc. B Y t t chc bin son ti liu dy hc cc mn c s v chuyn mn theo chng trnh trn nhm tng bc xy dng b sch t chun chuyn mn trong cng tc o to nhn lc y t.

Sch CNG NGH BO CH DC PHM c bin son da trn chng trnh gio dc ca Trng i hc Y Dc Thnh ph H Ch Minh trn c s chng trnh khung c ph duyt. Sch c PGS.TS. Hong Minh Chu (Ch bin) v cc tc gi PGS.TS. L Quan Nghim, TS. L Hu, ThS. Nguyn Nht Thnh bin son theo phng chm: Kin thc c bn, h thng; ni dung chnh xc, khoa hc; cp nht cc tin b khoa hc, k thut hin i v thc tin Vit Nam.

Sch CNG NGH BO CH DC PHM c Hi ng chuyn mn thm nh sch v ti liu dy hc chuyn ngnh o to Dc s i hc ca B Y t thm nh nm 2007. B Y t quyt nh ban hnh ti liu dy hc t chun chuyn mn ca ngnh trong giai on hin nay. Trong thi gian t 3 n 5 nm, sch phi c chnh l, b sung v cp nht.

B Y t chn thnh cm n cc tc gi v Hi ng chuyn mn thm nh gip hon thnh cun

Bn quyn thuc B Y t (V Khoa hc v o to) 874 2007/CXB/7 1918/GD M s: 7K727M7 DAI



sch; Cm n GS. L Quang Ton, PGS.TS. Hu Ngh c v phn bin, cun sch sm hon thnh kp thi phc v cho cng tc o to nhn lc y t.

Ln u xut bn, chng ti mong nhn c kin ng gp ca ng nghip, cc bn sinh vin v cc c gi ln xut bn sau sch c hon thin hn.

V KHOA HC V O TO B Y T

LI NI U

Thc hin ng li cng nghip ho v hin i ho t nc, cc ngnh cng ngh nc ta v ang c nhiu tin b v cng hin ng k. Trong , cng ngh dc phm t s ng dng nhng tin b khoa hc k thut ca nhiu ngnh nh cng ngh ho hc, cng ngh sinh hc, cng ngh c kh, in, in t, tin hc... nghin cu pht trin, v ang c nhng ng gp nht nh. Tuy nhin, cng ngh dc phm vn cn tn ti nhiu bt cp, cha p ng kp yu cu i hi ca kinh t x hi hin nay v cho tng lai.

tin kp v ho nhp vi cc nc trong khu vc, ngoi mt quyt tm cao, i hi i ng khoa hc c chuyn mn su, l thuyt i i vi thc t, mun vy phi ch trng cng tc o to. Chnh v th, gp phn nh b vo s nghip cng nghip ho v hin i ho ngnh dc nc nh ni chung v trong cng tc o to nhn lc dc ni ring, B mn Cng nghip Dc, Trng i hc Y Dc Thnh ph H Ch Minh bin son cun Gio trnh cng ngh bo ch dc phm nhm cung cp cho hc vin nhng thng tin, kin thc c s l thuyt chuyn khoa ct li nht, kt hp vi thc t i hi ca ngnh dc.

Trong khun kh chng trnh khung ca B Y t, c s trao i, hi tho v chng trnh vi Trng i hc Dc H Ni v tham kho chng trnh ca mt s trng nc ngoi c quan h hp tc o to v nghin cu nh Trng i hc Mahidol Thi Lan, Trng i hc Paris Sud v Trng i hc Bordeaux II CH Php, ni dung chnh ca gio trnh ny l cng ngh sn xut cc dng thuc. Trc ht, dng thuc rn phn liu v dng thuc v (tit) trng c bin son.

Hy vng cun sch gp phn hu ch cho vic hc tp v nghin cu ca sinh vin dc, cng nh bn c c nhu cu quan tm, tham kho khc.

Ln u tin xut bn, chc chn cun sch cn nhiu khim khuyt, cc tc gi mong nhn c s gp ca bn ng nghip cng nh c gi ln ti bn sau c hon thin hn. Xin chn thnh cm n.

TM. Cc tc gi



HNG DN S DNG SCH Cun sch gm ba phn chnh, tng ng vi ba chng:

Chng 1: i cng v cng ngh bo ch dc phm cung cp cc thng tin, kin thc ti thiu cn thit cho hc vin v nhng vn i cng chung i vi cng ngh bo ch dc phm, to c s nng cao hiu bit, m rng tm nhn bao qut v l thuyt v thc t ca ngnh dc nc ta ni ring v ca khu vc cng nh trn th gii ni chung. T , hc vin c th xc nh vai tr v nhim v cho mnh trong hin ti v tng lai.

Chng 2: Cc qu trnh cng ngh c bn trong cng ngh bo ch dc phm gip cho hc vin hiu bit v nhng qu trnh v thit b thng gp trong cng ngh bo ch thuc. Chng ny trnh by cc nguyn l hot ng cng nh phm vi ng dng ca nhng trang thit b, my mc . Ngoi ra, trong chng ny cng trnh by s lc v c l lm c s cho s tnh ton, la chn. T , cng c hiu bit ca hc vin o to con ngi lm ch nhng trang thit b, my mc c s vt cht hin i.

Chng 3: Cng ngh bo ch mt s dng thuc vi cng ngh mi kt hp ng dng nhng ph gia truyn thng v hin i vo cc dng thuc vin nh vin nn, vin bao, vin nang. Bn cnh , dng thuc tim cng c trnh by trong chng ny.

Gio trnh ny c bin son theo khun mu chung ca Trng i hc Y Dc TP. H Ch Minh, l s la chn, thng nht sau nhiu cuc hi tho v tp hun v chng trnh v vit gio trnh trong d n nng cao cht lng dy v hc ca nh trng.

Trong mi chng cc bi c nh s th t tip theo bi ca chng trc. Trc khi nghin cu hc tp hoc tham kho vo ni dung chnh ca bi, hc vin cn c mt ci nhn tng quan v xc nh c mc tiu ca mnh vi mc tiu ca bi. thc hin mc tiu , cn phi c nhng ni dung chnh vit trong sch, bng cch bm st mc lc v dn bi, hc vin s nhn ra c ni dung ca bi cn c hay tham kho.

Sau qu trnh hc tp, nghin cu, hc vin c th t kim tra nh gi (lng gi) kt qu tip thu nh phn cu hi lng gi c ghi cui mi bi.

Vi cch lm vic, hc tp, nghin cu nghim tc, hy vng s em li hiu qu xng ng cho hc vin lm nn tng cho s vn dng sng to vo thc tin ngnh ngh.

CC TC GI

Ch bin Hong Minh Chu



BNG NHNG CH VIT TT

Bi 1 S LC V S RA I V PHT TRIN

CNG NGH BO CH DC PHM

CND SXT CNBC SXDP CNHH CNHD CNSH CNKS HTCL KTCL HTBCL THTSXT CNBCDP GPs/GxP GMP GLP GSP ISO SOP WHO ASEAN

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Cng ngh dc Sn xut thuc Cng ngh bo ch Sn xut dc phm Cng ngh ho hc Cng ngh ho dc Cng ngh sinh hc Cng ngh khng sinh H thng cht lng Kim tra cht lng H thng m bo cht lng Thc hnh tt sn xut thuc Cng ngh bo ch dc phm Good Practices Nhng thc hnh tt (GMP, GLP, GSP, v.v) Good Manufacturing Practices Thc hnh tt sn xut thuc Good Laboratory Practices Thc hnh tt phng kim nghim Good Storage Practices Thc hnh tt bo qun thuc International Standard Organization T chc tiu chun quc t Standard Operational Procedures Quy trnh thao tc chun World Health Organization T chc Y t Th gii Hip hi cc nc ng Nam

CHNG 1

I CNG V CNG NGH BO CH DC PHM



1.1. S ra i ca cng ngh bo ch dc

Thuc lun l mt nhu cu khng th thiu c trong i sng con ngi. Cng nh mi ngnh khc, thuc i hi mt nn sn xut ngy cng cao v pht trin theo s pht trin v tin b ca loi ngi.

Thi tin s, loi ngi bit dng thuc t thin nhin nh cy, c, l, thn, r, v cy cha bnh, chng li bnh tt v sinh tn. Khi , ngi ta dng nhng nguyn liu cn ti, hoc c th phi kh dnh. Dn dn, ngi ta bit dng nc thm t, ri bit un vi nc (sc) ly nc sc dng l dng bo ch th s u tin ca dc phm.

Khi loi ngi bit ln men mt s thc vt cha bt, ng, ri bit ct ra ru (khong 1000 nm trc cng nguyn), th cng t mt dng thuc th hai xut hin. l ru thuc, Ngnh bo ch thuc cng ngh bo ch dc phm xut hin nh vy, t nhng dng th s n gin ban u nh nc sc, ru thuc, cao thuc,

Tri qua my ngn nm lch s pht trin, tin b ca loi ngi, cng vi nhng cuc Cch mng khoa hc k thut cng nh nhu cu ngy cng gia tng ca con ngi v phng v cha bnh, k thut sn xut thuc cng ngy cng pht trin vi nhng dng thuc tinh t hn, phc tp hn. C th l cc dng thuc vin, vin nn, vin bao, vin nang, thuc tc dng ko di, thuc tim, dch truyn,

l lch s ra i, tn ti v pht trin ca cng ngh bo ch cc dng thuc ni ring v ca nn sn xut thuc ni chung.

MC TIU 1. Trnh by c s cn thit ca cng ngh bo ch dc phm. 2. K ra v phn tch c nhng yu t quan trng thc y s pht trin nn cng ngh bo

ch dc phm (yu t dn s, yu t bnh tt, yu t KHKTCN). 3. Trnh by c hai vai tr quan trng ca cng ngh dc phm sn xut thuc. 4. Phc ha c mt khung cnh sn xut thuc cha bnh Vit Nam trong cc thi k lch s

trc v sau nm 1975.



S 1.1. V tr, vai tr ca cng ngh bo ch dc phm i vi sc khe con ngi

1.2. S pht trin tt yu ca cng ngh bo ch dc phm

S pht trin ca cng ngh bo ch dc phm i lin vi s pht trin v tin b chung ca nhn loi, n p ng nhu cu v thuc phng, chn on v cha bnh ngy cng gia tng ca ton cu. Nhng yu t quan trng thc y cng ngh bo ch pht trin l:

* S gia tng dn s

Theo qu dn s Lin Hip Quc (UNFPA) cng b trong nhng nm gn y dn s th gii c s tng vt, mang tnh cht bng n.

Mt khi dn s tng, nhu cu v thuc cng phi tng theo. Mc s dng thuc bnh qun u ngi, c 10 nm li tng gp i. Vit Nam, ch trong 5 nm, t 1990 1995 mc s dng thuc tng gp 10 ln. (Tuy nhin, trn th gii, mc tiu th ang c s chnh lch ln gia cc nc pht trin v cc nc ang pht trin. Ngi dn cc nc cng nghip s dng dc phm bnh qun gp 30 ln nc ang pht trin. tng quc gia cng c tnh trng tng t v thc trng ngi dng thuc thnh th v nng thn).

* S gia tng v bnh tt

Chng loi bnh tng, bnh ngy cng nguy him hn do vi trng khng thuc, do iu tr khng ng phc hoc khng thuc, do thin tai v nhng l do khc V d bnh st rt, bnh lao vn cn l cn bnh e do hng triu ngi trn th gii. Cn bnh th k AIDS, mi him ho ca ton cu v cc bnh do virus khc.

* S pht trin ca cc ngnh KHCN khc: Cng nghip dc da trn s pht trin ca cng nghip ho dc (bao trm l cng nghip ho hc), sn xut nguyn liu cung cp cho cng ngh bo ch cc dng thuc. Cng nghip ho dc c th i t tng hp ho hc ra cc cht hoc chit tch cc cht tinh khit t nguyn liu thin nhin, cy, con (thc vt, ng vt). S pht trin ca cng ngh bo ch thuc cn c b tr bi s cung cp nguyn liu ngy cng phong ph ca cng nghip thuc khng sinh v cng nghip sinh hc. Bn cnh , Cng ngh bo ch cc dng thuc cn c s h tr tch cc ca tin b khoa hc k thut t nhiu ngnh, nh in t, c kh, ho hc



* Li nhun cng l mt ng c thc y cng ngh bo ch thuc pht trin, ng thi ng gp tch cc cho nn kinh t x hi

i i vi vai tr sn xut, cung ng thuc cho y t phc v cng tc chm sc v bo v sc khe con ngi, cng ngh bo ch thuc cn ng gp mt phn khng nh v tch cc cho nn kinh t x hi.

1.3. Vi nt v tnh hnh bo ch thuc Vit Nam

Trc Cch mng thng Tm nm 1945: Cha c sn xut cng nghip, ch yu l ngun t Php quc, c chng l pha ch theo n, c gng bo ch mt vi dng thuc m, thuc nc, vi phng tin hon ton th cng cc bnh vin hoc hiu thuc t nhn, tnh cht hon ton l thuc.

Sau Cch mng thng Tm nm 1945, thi k khng chin chng thc dn Php (19451954): p ng yu cu ca chin tranh v quc, cng ngh bo ch thuc lm ra nhng loi thuc phc v chin trng, cc loi thuc thng thng cho nhn dn nh thuc cm, st, ho, tiu chy,, mt vi vaccin c bn, thuc st rt, Nhng xng bo ch mang tnh chuyn nghip nh Xng Qun dc XF14, LK10, LK34, LK5, ln lt ra i. Tuy c s trang thit b vn cn rt th s, t to, sn xut tiu th cng, nhng y chnh l tin cho nn sn xut thuc mang tnh cng nghip sau ny. Thi gian ny nc ta sn xut ra c mt s thuc nh Calci chlorid dc dng pha tim, Ether m, Chloroform m, chit c Long no, Morphin, Strychnin, Cafein pha tim,

Thi k 19551975: Sau hip nh Geneve 1954, t nc tm chia lm hai min:

Min Bc hon ton gii phng, yu cu t ra cho ton ngnh l bo m nhng thuc ch yu cho nhn dn, phn u sn xut trong nc nhng th thuc thng thng nht, thng nht tn dc v ng dc. C s tp trung u tin c quy m ln, c kh ho, thit b tng i hin i lc by gi l X nghip Dc phm Trung ng 1 (XNDPTW1), X nghip Dc phm Trung ng 2 (XNDPTW2), v bt u xy dng x nghip a phng cc tnh, phn u cc tnh thnh u c x nghip dc phm (XNDP) xy dng b mn Cng nghip Dc ti Trng i hc Dc H Ni.

Min Nam cn nm trong ch thc dn kiu mi, cng nghip dc pht trin theo li t bn, c nhng c s bo ch sn xut ln, c thit b hin i, nhng cng c nhiu c s sn xut th cng, thit b chp v, Vo giai on ny, c khong trn 120 vin bo ch ln nh, nhng nguyn vt liu hon ton ph thuc nc ngoi.

T sau 1975: Nc nh thng nht, ngnh Dc thng nht ch o, phng hng t Nam ti Bc, tn dng mi c s vt cht, trang thit b bo ch sn xut tt c nhng thuc no c th sn xut c vi mi ngun nguyn liu c th c c. Pha Nam tp hp v thnh lp XNDPTW 21, 22, 23, 24, 25, 26 v Lin vin bo ch 7. Sau sp xp li nh sau: XNDPTW 24, 25, 26 mt s x nghip thuc a phng qun l nh XNDP 29, XNDP 32, XN Mebiphar, Pha Bc, cc XNDPTW1, XNDPTW2, XNDPTW3, v mi tnh, thnh hu ht u c cc c s sn xut thuc ln, nh, Ch trng xy dng ngnh dc tin ln chnh quy hin i cng nh Chnh sch quc gia v thuc Vit Nam (1996) ch ra: M rng ging dy cc Trng i hc, xy dng v cng c i ng cn b, c i hc nc ngoi, B Y t cng quyt nh thnh lp B mn Cng nghip Dc ti trng i hc Y Dc TP. H Ch Minh (Quyt nh s 1899/BYTQ).

GMP c cp ti t 1984, bng nhiu cuc hi tho, tp hun v GMP.

Chnh sch quc gia v thuc c Chnh ph ban hnh t 2061996, theo c yu cu Cng



nghip Dc phi cung ng 70% nhu cu thuc cho nhn dn trong nc, phi phn u t tiu chun GMP, ban hnh Quyt nh ca B Y t s 1516 ngy 991996 v vic trin khai p dng cc nguyn tc tiu chun GMP ca Hip hi cc nc ng Nam , gi tt l ASEAN GMP, v Thng t hng dn thc hin vic trin khai p dng cc nguyn tc ASEAN GMP ca B Y t s 12/BYTTT ngy 1291996. Tt c cc doanh nghip sn xut dc phm phi GMP ho chm nht l vo nm 2005. T 2005 p dng WHO GMP.

T nhng nh hng ln v c bn ca chnh sch thuc quc gia, vi nhng i hi bc xc ca ngnh Dc, nc ta xy dng quy hoch tng th u t pht trin ngnh Dc Vit Nam thi k 1996 2010, bao gm:

1. Nghin cu quy hoch pht trin cng nghip ho dc giai on 1996 2010 2. Nghin cu quy hoch u t pht trin cng nghip khng sinh 3. Quy hoch sn xut, pht trin dc liu v cc vng dc liu Vit Nam 4. Quy hoch sn xut, pht trin cng nghip bao b dc giai on 1996 2010 5. Quy hoch sn xut, pht trin cng nghip bo ch giai on 1996 2010 6. Quy hoch sn xut, pht trin v phn b cng nghip dc giai on 1996 2010 7. .

Nhn chung, trong mt thi gian kh di, t c ch bao cp chuyn sang c ch th trng, cng ngh bo ch dc phm ni ring v cng nghip dc Vit Nam ni chung cn nhiu lng tng, mc d cng c nhng ng gp nht nh, nhng hu nh khng c mt chin lc lu di. n nay, ngnh Dc c nhng nh hng chin lc pht trin, m ra l trnh pht trin ca cng ngh bo ch dc phm, phc v c lc nhu cu v thuc trong nc v xut khu.

TI LIU THAM KHO 1. L Quang Ton, KT ho dc, NXB Y hc H Ni, 1971. 2. Hong nh Cu, Y X hi hc Bi ging CK2 H Dc H Ni, 1985. 3. B Y t, Chnh sch Quc gia v thuc, H Ni, 1996. 4. B Y t, Chin lc pht trin KHCN ngnh Y t n nm 2020, H Ni, 1998.

CU HI LNG GI * TR LI NGN: 1. Yu t thc y s pht trin cng ngh bo ch dc phm

a) S gia tng dn s b) c) S pht trin ca KH CN d)

2. S biu din vai tr CND trong s nghip Y t, bo v v chm sc sc kho con ngi:



a) b) c) d) ...

3. Vi nt v tnh hnh sn xut thuc Vit Nam (ghi ngn gn mt n hai dng) a) Trc Cch mng thng Tm 1945: b) Sau Cch mng thng Tm 1945 (Khng chin chng thc dn Php): c) Thi k 1955 1975: d) T sau 1975:

Bi 2 QU TRNH NGHIN CU,

BO CH SN XUT THUC RA TH TRNG

2.1. Qu trnh nghin cu, bo ch sn xut thuc mi

MC TIU 1. V li c v gii thch s tng qut qu trnh nghin cu mt thuc mi ra th trng. 2. Nu c mc tiu ca giai on nghin cu, bo ch v giai on sn xut. 3. Trnh by c nhng yu cu cn thit xy dng mt cng thc bo ch thuc. 4. K c 4 ni dung chnh ca mt h s xin php sn xut thuc v cc ni dung chnh trong

h s dc phm. 5. Trnh by c nhng bc c bn nghin cu, bo ch sn xut mt thuc generic ra th

trng. 6. K c tm tt cc bc tin hnh xy dng tiu chun mt thuc generic.



2.1.1. S tng qut

C th tng qut ho qu trnh nghin cu, bo ch sn xut mt thuc mi ra th trng nh sau:

S 2.1. S tng qut qu trnh nghin cu sn xut mt thuc mi. Ghi ch: NVL: Nguyn vt liu: CPT: Ch phm thuc ; SXTNM: Sn xut thuc nguyn mu;

NC(CT,QT): Nghin cu (Cng thc, Quy trnh); SXCN: Sn xut cng nghip.

2.1.2. Giai on nghin cu, bo ch thuc nguyn mu

Mc tiu ca giai on ny l tm ra c mt cng thc bo ch sn xut tt nht, ph hp vi nhng iu kin kinh t k thut, t bo ch thuc nguyn mu th lm sng v xin php sn xut a ra th trng.

Ngi sn xut ni chung, ngi dc s ni ring lun lun c gng nghin cu sn xut ra nhng thuc c cht lng, hiu qu, an ton. Mun vy, phi xem xt rt k lng nhng thnh t ca cht lng. Nhng thnh t c rt nhiu. i vi mt thuc mi, a ra c th trng, cn phi c s nghin cu, la chn:

ng a thuc vo c th (ng s dng). Dng bo ch thch hp. T dc v cht ph gia. Nguyn liu bao b ng gi. Quy trnh sn xut. Kim tra. Quy trnh ng gi, bo qun...

S la chn khng th thc hin c nu thiu s hiu bit v hot cht cng nh ton b nhng g v kh nng, lin quan n hot cht. Trong sn xut thuc, vic xy dng cng thc cho mt dng bo ch ca mt thuc mi cha hot cht c hot tnh tr liu l rt quan trng. xy dng cng thc ny phi c s kt hp cht ch gia nhng c s nghin cu v pht trin sn xut vi nhng phng th nghim kim tra. Trc ht phi hiu bit v hot cht, tip l xy dng c cng thc cho dng bo ch sn xut sau ny.

2.1.2.1. Nhng hiu bit v hot cht



Mun xy dng c cng thc cho mt thuc mi vi hot cht c tnh tr liu, iu quan tm u tin, nh l im xut pht tin hnh nhng cng vic v sau, l hot cht (dc cht). Hot cht l i tng nghin cu ca nhiu nh khoa hc: ho hc, c cht hc v dc l hc,... Nh nghin cu bo ch sn xut thuc phi xem xt rt ra nhng nhn nh, nhng mc tiu quan st c c th s dng vo cng vic nghin cu ca mnh. Nhng tnh cht ho l ca hot cht cn c bit r nh trnh by trong bng 2.1.

Bng 2.1. Nhng tnh cht ca hot cht cn bit chc chn trc khi cp nghin cu mt dng ch phm

a) Tnh cht vt l

Tnh tan ca hot cht l mt thuc tnh rt quan trng. Phi hiu bit chc chn v s ho tan trong nc ca hot cht, bi v n s cho hng la chn dng thuc s dng (dng a vo c th) v n ng vai tr ln trong tnh sinh kh dng. Quan trng hn na l nhng s hiu bit v kh nng ho tan ca hot cht trong nc nhng pH khc nhau v phi bit n phn phi nh th no ty thuc vo pH hay ty thuc vo s tham gia ca hai pha: nc v du.

b) Tnh cht ho hc

Tnh cht ho hc rt quan trng trong nghin cu n nh ca thuc.

Phi bit hot cht chu nh hng ca nhit khc nhau nh th no. Phi bit nh hng ca m ra sao. nh hng ca oxy khng kh. nh hng ca nh sng,...

V phi bit c sn phm phn hy cui cng c th xc nh sau nhng th nghim v s n nh, xc nh tui th hay thi hn dng thuc.

bit c nhng iu phi tin hnh th nghim trong nhng iu kin nhit , m, nh sng v c oxy, t d on c gii hn s dng thuc (tui th ca thuc) trong iu kin bo qun bnh thng trn th trng.

Mt cng vic nghin cu rt phc tp khc na l nhng nghin cu nhn bit nhng tng k ca

Tnh cht ho l S phn ca hot cht trong c th

Tnh cht cm quan Tnh cht vt l: Kh nng ho tan Tnh cht ho hc:

Thuc v dc + S phn phi + Sinh chuyn ho + Thi tr Hot tnh tr liu (tc dng iu tr) + Ni tc dng + C ch + Tc dng ph Sinh kh dng

Tnh n nh v

Tng k

Nhit m

Oxy khng kh nh sng Cc tc nhn khc



hot cht vi nhng thnh phn khc trong thuc v hot tnh ca n trong mi trng sinh hc.

c) S phn ca hot cht trong c th

Nhng yu t lin quan ti s phn ca hot cht trong c th thng c kho st bi cc nh nghin cu dc l v hon tt bi cc thy thuc lm sng.

Nghin cu dc ng hc, trc tin ch ra cho chng ta v s phn phi ca hot cht, sinh chuyn ho trong c th, ri s thi tr (thanh thi) ca n.

gip cho tc dng iu tr mt cch hu hiu, chng ta phi c gng tm hiu, bit nhiu v kh nng v ni tc dng, c ch tc dng ca hot cht.

Mt nghin cu khng th thiu l gii hn tr liu, ngha l tm ra c khong cch gia liu iu tr v liu m xut hin tc dng ph hay c hi.

Nh bo ch, sn xut phi nghin cu bit hot cht xm nhp vo c th nh th no, trc ht phi nghin cu sinh kh dng ca n.

Trc khi nghin cu cng thc, cn c mt d kin v cch thc thc hin, nhm mc tiu t c mt m hnh ti u sinh kh dng xc nh. Nhng yu t mong mun l:

S thm ko di trong c th.

Xc nh nhng nh (hp thu) nng trong mu.

2.1.2.2. Cng thc

Nghin cu xy dng (thit lp) cng thc cho mt thuc mi, nh bo ch sn xut thuc thng phi quan tm ti: hot cht, ng a thuc vo c th, dng ch phm, nhng t dc, bao b ng gi, quy trnh sn xut v kim tra.

a) Hot cht c th tn ti nhiu dng khc nhau. S la chn ty thuc vo cch dng v nhng nghin cu v s n nh, ho tan v sinh kh dng ca thuc.

b) ng a thuc vo c th

La chn ng a thuc vo c th ph thuc:

Sinh kh dng ca hot cht. Tc tc dng mong mun, thi gian iu tr v s liu trong ngy. Loi bnh nhn nhng la tui v th trng khc nhau (s sinh, tr em, ngi ln, ngi gi,...)

cng nh tnh trng, bt u hay ti pht, nh hay bnh vin, iu tr lu ng hay khng,... ng ung l ng thng dng nht, p dng c cho nhiu hot cht.

c) Dng thuc, la chn dng ch phm ty thuc vo ng dng thuc. Mt s dng ch phm thng c nghin cu, s dng nh tm tt bng 2.2.

Bng 2.2. Dng ch phm thng dng



* ng ung:

Vin nn v vin nang l dng thuc rn phn liu thun tin cho bo qun, vn chuyn v iu tr lu ng, thun tin cho sn xut cng nghip vi s lng ln.

Dng dung dch, hn dch nc cng l dng thuc thng dng. Di dng a liu, thun tin dng cho mt s chng loi bnh nht nh.

* ng dng ngoi ung: Khng nhiu, thng l dng ng tim di dng dung dch nc. Nu l bt tim, a phn c ng trong l, nhng c mt cu hi t ra cho vn bo qun.

d) Nhng cht t dc v nhng cht ph gia

i vi nhng cht ny, yu cu quan trng nht l tr v mt ho hc, khng c tc dng ph. bit c ti a s m bo v mt cht t dc hoc cht ph gia no , ngi ta s phi nghin cu thnh phn ho hc, tinh khit,...

S la chn ngy nay rt d dng nh da vo Dc in, hoc nhng ti liu nghin cu ca cc nh nghin cu cng nghip dc tng hp, gm c: Tn, tn khoa hc, cng thc ho hc (cng thc nguyn, cng thc cu to), trng lng phn t, tnh cht vt l,... V khng th thiu nhng kt qu nghin cu ca nh bo ch sn xut thuc, chng hn nh trn chy ca n,...

Nh bo ch sn xut quan tm ti yu t nh hng n sinh kh dng ca thuc, la chn t dc vi c tnh cho php, iu khin c tc gii phng hot cht. T , nh hng s dng t dc vo nhng mc tiu nghin cu khc nhau hay vo nhng i tng c th khc nhau.

e) Bao b ng gi l mt thnh phn khng th thiu c ca mt dng thuc, c vai tr:

Bo v dc phm (Trnh cc s thay i ca kh hu, nh sng, cc ngun gy nhim v cc va chm khi vn chuyn).

To gi tr thng mi cho mt hng (hp dn khch hng, tin s dng, xc nh v cung cp nhng thng tin cn thit sm nht,...)

Cn ch nhng nguyn liu bao b ng gi tip xc trc tip vi thuc (bao b ng gi u tin), cn la chn theo hng nhng nguyn liu c ghi trong danh mc ca cc Dc in.

Nhng th nghim quan trng cho php xc nh thi gian ko di s dng (hn dng) mt thuc

ng dng Dng thuc sn xut chnh Ung Vin nn, nang, dung dch hay nh dch nc Ngoi ng tiu ho Dung dch nc ng trc trng n ng sinh dc Vin nn, dung dch, trng,... Mt Dung dch nc,... O.R.L (Tai mi hng) Dung dch nc, bt,... Ngoi da M, dung dch, thuc dn,



phi thc hin trong iu kin c bao b xc nh.

2.1.3. Giai on xin giy php sn xut thuc a ra th trng

H s hon chnh xin giy php sn xut thuc a ra th trng, yu cu c 4 phn chnh: 1. Phn thuc v dc (bo ch, phn tch, kim nghim,...) 2. Phn thuc v c tnh. 3. Phn thuc v dc l. 4. Phn thuc v lm sng.

H s dc thng gm c: Thnh phn, s lng v cht lng. M t quy trnh sn xut. Kim tra nguyn liu u vo v bao b. Kim tra trn sn phm trung gian, bn thnh phm v thnh phm. M t nhng iu kin bo qun v cch dng.

Trng hp c bit cn c gii thch ngi dng c s la chn ng v chnh xc. Km theo h s phi c nhng nghin cu v tnh n nh, v dc ng hc, sinh kh dng, phm vi iu tr cng nh nhng iu lut bt buc v k thut v kinh t.

Mt im rt quan trng cn lu l nhng th nghim lm sng khng th lm li c theo li c. Nhng th nghim trn ngi l hiu lc mt ln cho tt c vi nhng n v ca l thuc nguyn mu. Theo thi quen (li c), mi l sn xut, nhng th nghim thay th bng nhng th nghim ho l cho php xc nhn cht lng ca thuc.

H s lm theo Quy ch ng k thuc, ban hnh km theo quyt nh B Y t.

2.1.4. Giai on sn xut v kim tra

Mc tiu ca giai on ny l ti sn xut quy m cng nghip ra nhng thuc c cht lng ph hp vi cht lng ca l nguyn mu (l ng k sn xut).

Ngoi ra, t c mc tiu trn, quy trnh sn xut cn phi la chn theo nhng mc tiu nh, cng cn ty thuc vo c nguyn liu s dng.

Mi mt cng on phi c nhng thng s k thut quyt nh, thuc sn xut ra m bo cht lng ton din. Mun vy cn phi kim tra cht ch, t nguyn liu u, sn phm trung gian, n sn phm cui cng bng nhng thit b chnh xc c tin cy cao, c s thm nh,... (kim tra cht lng).

Kim tra s ng nht gia cc l sn xut da trn tnh n nh ca thuc v trn tnh sinh kh dng ca hot cht,...

Tm li giai on ny cn phi thc hin nghim ngt mi tiu chun, mi yu cu ca GMP nhm m bo cht lng thuc n nh a ra th trng.



Qu trnh nghin cu mt thuc mi ra th trng i hi nhiu thi gian v kinh ph kh ln. Trc y, k t khi bt u nghin cu tm ra c hot cht c tc dng n khi sn xut c thnh phm bn ra th trng, thng phi mt 10 15 nm v tiu tn khong hng trm triu USD. Ngy nay, thi gian ny c th rt ngn li.

2.2. Qu trnh nghin cu, bo ch sn xut mt thuc generic ra th trng

Thuc generic l mt thuc c cng thc ging nh thuc nguyn thy c quyn c mt hay nhiu hng bo ch khc nhau sn xut khi tnh c quyn khai thc khng cn na.

Thc t, khi mt hng bo ch nghin cu thnh cng mt hot cht mi, cng hiu cao i vi mt bnh no , th ch nhn xin ng k bn quyn sng ch trnh b sao chp, v c khi h phi b ra c trm triu USD M trong nghin cu, nht l vi nhng khng sinh. Nhng sau mt thi gian sn xut c quyn (v d nh 17 nm Php, 15 nm M), thuc y tr thnh cng cng v tt c cc hng bo ch trn th gii u c th sn xut m khng phi tr bn quyn sng ch.

Qu trnh nghin cu sn xut mt thuc generic ra th trng khng mt nhiu thi gian v tn km bng nghin cu sn xut mt thuc mi, c th qua nhng bc nh sau.

2.2.1. Nghin cu tm kim, la chn cng thc ti u

Trc ht, nh nghin cu phi c mt tng, a ra mt d kin mc tiu t ti: dng ch phm, hnh thc, mu m, tiu chun, v.v

Thc hin tng , cn phi: Thu thp ti liu xung quanh mc tiu: ti liu trong nc, nc ngoi, v hot cht, v dng ch

phm cha hot cht , v cc cht ph gia, v cc bao b ch phm ,... tt c cc ti liu c th phc v c nhiu nht cho mc tiu nghin cu ca mnh.

Tm hiu th trng, quan st thc t, nhng ch phm c,... trnh nhi li, t hc tp, cng c tng v d kin,...

Tm kim ngun nguyn vt liu cho sn xut c cht lng, s lng n nh, gi c ph hp,... v ph hp vi iu kin kinh t k thut hin c.

D kin cng thc da trn nhng cng thc truyn thng/kinh in hoc nhng ti liu mi nht. Th nghim trn cc cng thc la chn ra mt cng thc tt nht, cc thng s k thut ti u

nhm m bo cht lng thuc ph hp vi cc iu kin: + K thut: Cht lng n nh vi ngun nguyn vt liu hin c, c th sn xut c lu di. + V y hc: Gii p c nhng cu hi: 1) Thuc c tc dng khng? 2) C tc dng ph khng? 3) Dung np tt khng? 4) Thuc c tnh

sinh kh dng,... Ch yu phi kim tra kh nng gii phng hot cht ( ho tan) ca thuc sn xut ra theo cng thc , v an ton ca thuc.

+ V th trng: Ngi tiu dng chp nhn dng ch phm, s dng thun tin, d dng, khng nhm ln,...

+ V kinh t: Gi c thch hp, hiu qu kinh t,...

2.2.2. Th nghim v xy dng tiu chun ch phm



Sau khi la chn c mt cng thc tt nht ph hp vi nhng iu kin kinh t k thut, s sn xut th nghim t n s n nh v cht lng v sn xut ra thuc nguyn mu (thuc ny s gi km theo h s xin giy php ng k sn xut), v ng thi, tin hnh xy dng tiu chun.

Xy dng tiu chun ch phm: Yu cu k thut Cng thc: phi ghi y tn hot cht, t dc,... s lng v cht lng (theo tiu chun no,...). Nguyn vt liu: s lng, cht lng,... (ghi theo hng dn GMP). Phng php th: Nhn xt cm quan. + nh tnh. + nh lng. Thuyt minh tiu chun + nh tnh: phng php, tiu chun, cch tin hnh,... + nh lng: phng php, m t cch tin hnh, kt qu,... Ch : chnh xc, tin cy ca phng php n nh ca thuc: Phng php xc nh n nh. M t cch tin hnh. Kt qu, x l v bin lun,

Kt lun: Phi khng nh nhng cng vic thc hin l c tnh khoa hc v chnh xc vi tin cy cao, c x l thng k hay theo phn mm no ca my tnh,... Ch km theo nhng ti liu gc (photo), cc bn tnh ton c th...

2.2.3. Gi mu n c quan kim nghim

Gi mu thuc n c quan kim nghim, km theo cc ti liu lin quan n dc phm , bao gm:

Nhng tiu chun xy dng v ngh.

Nhng h s ti liu cn thit km theo (theo yu cu ca mt hng).

2.2.4. Xy dng quy trnh sn xut (son tho)

Thc hin theo mu hng dn ca c quan qun l (Cc Dc B Y t).

2.2.5. Tp hp, son tho h s xin ng k sn xut

Theo iu khon quy nh i vi thuc sn xut trong nc, trong bn Quy ch ng k thuc ban hnh km theo quyt nh ca B Y t.

2.2.6. Sn xut v kim tra cht lng

Sn xut v kim tra cht lng thc hin theo GMP.



TI LIU THAM KHO 1. Hong Minh Chu, Sn xut Thuc Cng nghip Dc, Bi ging cho Dc s v CT3, i hc

Y Dc, TP.HCM, 1997). 2. LE HIR, Abrgs de Pharmacie galenique, R.F.Paris, 2000. 3. Quy ch ng k thuc ban hnh km theo quyt nh ca B Y t.

CU HI LNG GI * TR LI NGN: 1. Qu trnh nghin cu sn xut thuc mi ra th trng:

S tng qut: (V li s xng c)

2. Mc tiu ca giai on nghin cu v sn xut th ra thuc nguyn mu: Mc tiu ca giai on ny l nghin cu tm ra c (a) tt nht (ph hp iu kin kinh t x hi), t (b) a th lm sng

3. giai on nghin cu v sn xut th thuc nguyn mu, nhng thnh t quan trng cn nghin cu la chn:

a) b) ng a thuc vo c th (ng s dng) c) d) Nhng cht ph gia (t dc) d) f) Quy trnh sn xut g) h) Quy trnh ng gi i)

4. Nhng hiu bit v hot cht (3 ghi nh quan trng) a) Tnh cht (a) b) Tnh cht (b) c) Tnh cht (c)

5. Trong tnh cht vt l ca hot cht phi bit chc chn: a) Tnh (a) b) Hiu bit v kh nng (b) nhng pH khc nhau

6. Cc hiu bit v nhng nh hng ln hot cht gip cho s nghin cu n nh thuc l: nh hng ca nhit khc nhau a) nh hng ca (a) nh hng ca oxy khng kh



b) nh hng ca (b)

7. Gip cho nghin cu n nh thuc cn: a) Phi bit sn phm (a)........ cui cng b) Bit nhng (b) ca hot cht vi nhng thnh phn

khc trong thuc

8. S phn ca thuc trong c th Nhng nghin cu lin quan: a) Nghin cu (a) b) Ni tc dng,(b)... tc dng c) Gii hn (c), ngha l tm ra c khong cch gia liu iu tr v liu m xut hin tc dng ph hay c hi.

9. Nh bo ch sn xut phi nghin cu bit hot cht Xm nhp (a) nh th no, trc ht phi nghin cu....... (b) ca thuc.

10. Nghin cu thit lp mt cng thc cho thuc mi, nh bo ch sn xut thng quan tm n: a) Hot cht b) vo c th c) Dng bo ch ch phm d) Nhng cht e) Bao b ng gi f) g) Kim tra

Bi 3 H THNG QUN L CHT LNG

CC GxP P DNG TRONG SN XUT DC PHM MC TIU

1. Trnh by c mt s khi nim c bn v cc GxP (GMP, GLP, GSP), ISO; s cn thit, mc tiu v vai tr trong cc c s sn xut thuc.

2. Gii thch c mi quan h m bo cht lng (BCL), GMP v kim tra cht lng (KTCL).

3. Phn tch c 5 yu t, 3 nguyn tc v 10 yu cu c bn ca GxP. 4. K c 17 chuyn mc ca WHO GMP v phn tch tm tt theo 5 yu t v cc nguyn tc



CC KHI NIM C BN 1. CHT LNG

1.1. Khi nim v sn phm v cht lng ni chung

* Sn phm l kt qu ca cc hot ng v ca cc qu trnh ch nh v khng ch nh, gm sn phm vt cht thun tu, phi vt cht, gm c dch v, phn cng v phn mm.

* Cht lng l mt tp hp cc c tnh vn c p ng cc yu cu (nhu cu hay mong i c cng b, ngm hiu hay bt buc).

1.2. Cht lng thuc

L tng hp cc tnh cht c trng ca thuc, th hin mc ph hp nhng yu cu nh trc trong iu kin xc nh v kinh t k thut x hi, c th hin bi cc yu cu sau y:

C hiu lc phng bnh, cha bnh. Khng c hoc t c tc dng ph c hi. n nh v cht lng trong thi gian xc nh. Tin dng, d bo qun. Hnh thc hp dn.

1.3. c im v yu cu v thuc

Thuc l hng ho c bit lun c hai mt li v hi. Thuc l nhng dng bo ch c nhiu thnh phn to nn, c tc dng dc lc. Thuc l mt loi sn phm c hm lng cht xm v cng ngh cao. Cht lng thuc khng d dng nhn bit c bng cm quan. Thuc phi gn lin vi thng tin v sn phm.

Yu cu: cht lng, hiu qu, an ton v kinh t.

2. QUN L CHT LNG l cc hot ng c phi hp nh hng v kim sot mt t chc v cht lng. Vic nh hng v kim sot cht lng ni chung bao gm lp chnh sch cht lng v mc tiu cht lng, hoch nh cht lng, kim sot cht lng, m bo cht lng v ci tin cht lng

3. KIM SOT CHT LNG (QC) l s dng cc k thut phn tch v tin hnh cc hot ng

c bn ca cc GxP. 5. Lin h v k ra c mt s c s sn xut thuc Vit Nam vn dng cc GxP v t tiu

chun GMP (hoc c ba: GMP, GLP v GSP).



tho mn cc yu cu ca cht lng.

Kim sot cht lng nhm vo vic gim st qu trnh v loi tr cc nguyn nhn khng ph hp tt c cc giai on thng qua vic nh gi cht lng so vi yu cu ra. Mt s hot ng ca kim sot cht lng v m bo cht lng c mi quan h tng tc.

4. M BO CHT LNG (QA) l mt khi nim rng bao gm ton b cc vn ring l hay tng hp nh hng n cht lng sn phm, k c cc nguyn liu. m bo cht lng l tng th cc k hoch c thc hin nhm mc tiu m bo cc nguyn liu v cc dc phm t cht lng yu cu s dng.

Ni cch khc, m bo cht lng l ton b k hoch, bao gm c GMP, c tin hnh theo trnh t, m bo dc phm ph hp cng dng ca n.

5. MI TNG QUAN GIA M BO CHT LNG, GMP V KIM TRA CHT LNG THUC

H thng m bo cht lng thuc l mt h thng bao trm tt c nhng yu t, nhng bin php c thc hin nhm m bo cc thuc sn xut ra u t cht lng ng k. Nh vy h thng ny c lin quan n tt c cc khu, cc giai on, t c nhn n tp th c nh hng n cht lng thuc. H thng m bo cht lng thuc phi m bo rng:

* Sn phm c thit k phi m bo cc yu cu GMP, GLP, GSP. * Cc thao tc v kim tra cht lng phi tun theo GMP (cc SOP). * Trch nhim qun l phi c nu r trong phn m t cng vic (phn nh). * Cn b tr cung ng v s dng ng nguyn liu, bao b. * Kim tra nguyn liu u vo, sn phm trung gian, bn thnh phm, quy trnh sn xut. * Thnh phm c pha ch ng cch v kim tra theo cc quy trnh nh (bo m sn xut v

kim tra cht lng trc khi xut xng). * Sn phm ch c xut xng/bn khi c chng nhn ca ngi c thm quyn theo quy nh

trong giy php. * C k hoch bo qun, phn phi v qun l sn phm duy tr cht lng trong thi gian hn

dng ca thuc. * C mt quy trnh thanh tra/t thanh tra v cht lng thng xuyn nh gi c hiu qu v

tnh kh dng ca h thng m bo cht lng (t chc thc hin t thanh tra v gim st cht lng)

Tm li: H thng m bo cht lng c th c hnh dung biu din theo s 3.1 sau:



S 3.1. Mi quan h gia H thng m bo cht lng, GMP v kim tra cht lng

CC NGUYN TC THC HNH TT (GxP) P DNG TRONG CC C S SN XUT THUC (CNDP SXT) Thc hnh tt sn xut thuc GMP (Good Manufacturing Practice)

Thc hnh tt phng kim nghim thuc GLP (Good Laloratory Practice)

Thc hnh tt bo qun thuc GSP (Good Storage Practice)

1. NM YU T C BN CA CC GxP (CN GI 5 M) Con ngi (Man M1) Nguyn vt liu (Material M2) Mi trng, c s sn xut (Millieu M3) Trang thit b (Machine M4) Ti liu quy trnh, phng php,... (Method M5)



S 3.2. Nm yu t c bn ca GxP

1.1. Con ngi (M1)

L mt trong nhng yu t quan trng hng u, i hi:

v s lng, tiu chun C thc v thi quyt tm thc hin GMP

m bo c nhng yu t trn i vi con ngi, cn c s o to, c hun luyn thng xuyn, c k hoch v chng trnh c th.

1.2. Nguyn vt liu (M2)

Ch c nguyn liu tt mi cho sn phm tt. Nguyn vt liu bao gm:

Hot cht, cc cht ph gia, t dc, nguyn vt liu bao b ng gi (ng gi trong, ng gi ngoi),...

1.3. Mi trng, c s vt cht (M3)

a im, mi trng, thit k, xy dng ng chc nng,... m bo cp v sinh theo yu cu.

1.4. Trang thit b (M4)

Phi c trang b ph hp thc hnh tt theo yu cu: v s lng, chng loi, ng b,... ng v vt liu, thit k, ch to, cht lng tt. t ng v tr, s dng thun tin, d v sinh, an ton,...

1.5. Ti liu (quy trnh, phng php tin hnh,) (M5)

H thng ti liu ph hp theo tinh thn Vit ra nhng g lm, lm theo nhng g vit v cc kt qu ghi vo h s, phi c y quy trnh, phng php tin hnh, kim tra, ni chung phi c



y cc ti liu thc hnh.

2. BA NGUYN TC C BN CA CC GxP 1. Vit nhng g cn lm (cc hng dn, quy trnh, thao tc chunSOP,) 2. Lm theo nhng g vit 3. Ghi kt qu vo h s (h s ho)

3. MI YU CU C BN CA CC GxP 1. Vit cc quy trnh (cc SOP) 2. Thc hin theo cc quy trnh 3. H s ho cng vic lm 4. Thm nh 5. S dng trang thit b thch hp 6. Bo tr trang thit b 7. Hun luyn, o to 8. Sch s, trt t, v sinh, ngn np 9. Cnh gic cht lng 10. T thanh tra.

4. SN PHM CA CC GxP Sn phm ca GMP l thuc (dc phm) vi nhng yu cu: cht lng, hiu qu, an ton v

kinh t. Sn phm ca GLP l nhng phiu kim nghim vi nhng yu cu: trung thc, khch quan, chnh

xc v tin cy. Sn phm ca GSP l nhng hng ho vi 4 yu cu c bn: bo qun ng iu kin (yu cu ca

thuc), phn loi sp xp hp l (theo ng cc nguyn tc ba d, FIFO, FEFO), qun l cht ch h thng (HSTL) v cht lng m bo (khng b bin i).

Sn phm ca c ba GPs l sn phm thuc tho mn ngi tiu dng.

5. NI DUNG C TH CA CC GxP Vit Nam ang p dng WHO GMP, GLP v GSP do B Y t ban hnh.

THC HNH TT SN XUT THUC (GOOD MANUFACTURING PRACTICE GMP)



1. M U

1.1. Yu cu khch quan v ch quan

* Nhu cu v thuc cng ngy cng tng:

V s lng:

+ Dn s ngy cng tng (theo qu dn s Lin hip quc UNFPA cng b nhng nm gn y dn s th gii tng vt mang tnh cht bng n) nm 1987 th gii c 5 t ngi, 1998 c 6 t ngi, theo d bo c ny n nm 2050 th gii s c 9,4 t ngi v 10,4 t vo nm 2100,... Vit Nam, nm 1945 ta mi c 25 triu ng bo Nam Vit n 10/10/2002 theo thng k c 80 triu dn,...).

+ Bnh tt nhiu, cc bnh nhim khun, cc bnh ti pht,... cn bnh th k (HIV/AIDS), v cc bnh do virus khc,

V cht lng, ngi tiu dng i hi (PIES): Tinh khit (P: Pure), ng (I: Correctly Identifed), Hiu qu (E: Effective) v An ton (S: Safe).

* Nn sn xut thuc pht trin:

p ng nhu cu v thuc cho con ngi.

ng gp cho nn kinh t x hi.

ng dng nhng tin b k thut cng ngh mi ca cc ngnh nh: cng ngh ho dc, cng ngh sinh hc, cng ngh cy thuc, cng ngh bao b v cc ngnh khc nh c kh, in t, tin hc,...

* Xu th hi nhp:

Xu th hng ti nn kinh t ton cu v xu th tiu chun ho, ng b ho cc lut l Quc t. i vi thuc, vn cht lng l vn ton cu, c t ra mi quc gia, mi ni, mi lc. Mt trong nhng h thng m bo cht lng c nhiu nc t ra v thi hnh l GMP.

* Vit Nam gia nhp khi ASEAN, tr thnh mt thnh vin ca WTO. hi nhp vo khi ASEAN v Th gii, i vi ngnh Dc, B Y t ban hnh thng t s 12/BYT, ngy 12/9/1996 v vic trin khai p dng nguyn tc, tiu chun ASEAN GMP, nhm mc ch tng bc a cng nghip dc Vit Nam pht trin, nng cao cht lng thuc trong nc, phc v tt s nghip chm sc sc khe nhn dn, to iu kin cho thuc Vit Nam ho nhp th trng thuc ca khu vc v th gii... Phn u n ht ngy 31/12/2007, tt c cc c s sn xut thuc tn dc phi trin khai p dng, t nguyn tc, tiu chun WHO GMP v n ht ngy 31/12/2010, tt c cc c s sn xut thuc t dc liu phi t nguyn tc, tiu chun WHO GMP (theo quyt nh s 19 ngy 05/07/2005). l mt yu cu cp thit ca ngnh Dc.

1.2. Gii thiu s lc GMP cc nc v khu vc

c nhiu nc ra v thc hin GMP t lu.



Hoa K l mt trong nhng quc gia u tin c gng qun l ngnh dc. Sau mt s s kin xy ra lin quan ti sc khe con ngi, nm 1962, mt o lut v thc phm, thuc v m phm c C quan qun l thc phm v dc phm Hoa K (FDA) thng qua, ra i nhng quy nh u tin v GMP.

+ Nm 1963: GMP n bn ln th nht. + Nm 1975: Hng dn v thm nh ra i (sau v 11 ca t vong do thiu kim tra trong khi sn

xut thuc). + Nm 1976: Mt b GMP mi ra i, vi trng tm hng vo Thm nh v m bo cht lng

hn l kim tra cht lng. + Nm 1978: GMP n bn ln th hai. + Nm 1979: GMP tr thnh lut v yu cu cc nh sn xut phi c cc quy nh v thao tc chun

c ph duyt v cc h thng c thm nh. + Nm 1984, qua s kin Tylenol ngi ta phi xem xt li trong quy ch cc vn lin quan n

ng gi. c: GMP n bn ln th nht t 1969. Anh: + Nm 1971: GMP n bn ln th nht. + Nm 1977: GMP n bn ln th hai. + Nm 1983: GMP n bn ln th ba. Php: Vn bn Thc hnh sn xut tt (Pratiques de Bonne Fabrication PBF) ban hnh u tin

vo 3/10/1978. + 1/10/1985 ban hnh ng ngha GMP. + Nm 1993 thc hin GMP EEC. + Nm 1995 BPF GMP xut bn ln th ba. Cng ng chu u ECC: ban hnh ti liu hng dn v GMP chu u vo thng 1/1989. T chc Y t th gii (WORLD HEALTH ORGANIZATION WHO): * Nm 1967: ban hnh bn d tho Draft requirements for good manufacturing practice in the

manufacture and quality of drugs and pharmaceutical specialities. * Nm 1968: ban hnh GMP nh l mt ph lc trong bo co ln th 22 ca WHO v sau c

a vo bn ph lc ca The International Pharmacopoeia. 1971. * Nm 1969: ban hnh vn bn GMP nh l mt phn trong Certification Scheme on the Quality of

Pharmaceutical Products. 1975: chnh sa ban hnh li. * Nm 1992: xut bn GMP c chnh sa v b sung. Xut bn Validation of analytical

procedures used in the examination of pharmaceutical materials. * Nm 1999: xut bn Good manufacturing practices and inspection. * Nm 2000: Guide to good manufacturing practice for medicinal plants. * Nm 2003: xut bn ph lc 4 Good Manufacturing Practices for pharmaceuticals: main

principles trong lot bo co k thut ca WHO No.908.2003. ASEAN: * 1984 xut bn u tin gm 2 phn. * 1988 xut bn ln th hai.



* 1996 xut bn ln th ba. Vit Nam: cp ti GMP t 1984 v t chc cc cuc hi tho, tp hun GMP vo nhng nm

tip sau 1987,... 1997,... ti H Ni, TP. H Ch Minh, Cn Th, v.v...

T 1996 bt u p dng ASEAN GMP. T nm 2005 p dng WHO GMP.

1.3. Mc tiu v vai tr ca GMP

Mc tiu ca GMP nhm m bo mt cch chc chn rng dc phm c sn xut ra mt cch n nh, lun lun t cht lng nh nh sn (nh thuc nguyn mu ng k).

V tr v vai tr ca GMP l mt b phn ca cng tc nh gi cht lng nhm m bo cc sn phm c sn xut v kim sot ng nht tiu chun cht lng ph hp vi mc ch s dng v theo yu cu ca giy php lu hnh. Ni cch khc, GMP l mt yu t c bn ca m bo cht lng, v n thc hin phng chm phng sai li hn cha sai li, to nim tin cho khch hng.

GMP l ton b nhng khuyn ngh cn thc hin cho php m bo cht lng ca mt thuc xc nh trong iu kin tt nht. Nhng khuyn ngh ny m t nhng mc tiu khc nhau cn t ti lin quan n cc ni dung nh t chc, con ngi, c s trang thit b,... cng nh cc cch kim tra cn thit, kim tra t khu nguyn liu u vo n qu trnh sn xut, thnh phm, v.v... V cng ch ra nhng phng tin cn thit m bo cht lng thuc a ra th trng

Theo Anh 1983, GMP l nhng hng dn nhm khuyn co cc bin php m cc nh sn xut nn tun theo mi khi cn thit v ph hp, nhm m bo sn phm c tnh cht v cht lng nh mong mun, t mc ch nh. Ni mt cch khc GMP gip cho nh sn xut: Sn xut ra nhng thuc c cht lng n nh nh thuc ng k c cp giy php sn xut. Nhng thuc c cc thuc tnh: Tinh khit (P), ng (I), hiu nghim (E) v an ton (S) (PIES).

1.4. im qua GMP ASEAN

Trn c s nm yu t v cc nguyn tc c bn ca GxP, ASEAN GMP c th ho ra 10 iu khon v 4 ph lc nh sau:

+ 10 iu khon: 1. Cc iu khon chung 2. Nhn s 3. Nh xng 4. Thit b, dng c 5. Bin php v sinh v tiu chun v sinh 6. Sn xut 7. Kim tra cht lng 8. T thanh tra 9. X l khiu ni, thu hi v sn phm tr v. 10. Ti liu + 4 Ph lc l: 1/ Sn xut cc sn phm sinh hc. 2/ Sn xut cc cht kh Y hc. 3/ Sn xut bnh xt phn liu c p lc. 4/ Sn xut cc ch phm Y hc dn xut t mu ngi...

2. HNG DN THC HNH TT SN XUT THUC THEO KHUYN CO CA T CHC Y T TH GII (WHO GMP WORLD HEALTH ORGANIZATION GOOD MANUFACTURING PRACTICES)



Qua phn gii thiu, chng ta bit c cc nguyn tc chung, cc thut ng dng trong ti liu ny v quan nim v qun l cht lng trong cng nghip dc. Trn c s nm yu t, nhng nguyn tc v cc yu cu c bn ca GxP, WHO GMP ra nhng ni dung c th trong cc chng mc, v d nh v con ngi ( mc 9, 10, 11: nhn s, o to, v sinh c nhn); v c s vt cht, nh xng, mi trng c ghi mc 12; v my mc, trang thit b ghi mc 13; v nguyn vt liu mc 14 (nguyn liu u vo, dc cht cc hot cht, t dc) v h s ti liu mc 15. GMP WHO quan tm su sc ti sn xut v kim nghim theo hp ng c trnh by trong mc 2 v 7. Thm nh qu trnh sn xut l vn d l l trong cc c s sn xut thuc, c ra mc 4 v v sinh cht ch mc 3 v 11. C th theo trnh t sau:

WHO GMP Ni dung 17 iu khon

1. m bo cht lng (quality assurance) 2. Thc hnh tt sn xut thuc (GMP) 3. V sinh v iu kin v sinh (sanitation and hygiene) 4. nh gi v thm nh (qualification and validation) 5. Khiu ni (complaint) 6. Thu hi sn phm (product recalls) 7. Sn xut v kim nghim theo hp ng (contract production and analysis) 8. T thanh tra v thanh tra cht lng (selfinspection and quality audits) 9. Nhn s (personnel) 10. o to (training) 11. V sinh c nhn (personal hygiene) 12. Nh xng (premises) 13. Thit b (equipment) 14. Nguyn vt liu (materials) 15. H s ti liu (documentation) 16. Thc hnh tt trong sn xut thuc (good practices in production) 17. Thc hnh tt kim nghim (good practices in quality control)

Ngoi ra, cn c phn hng dn ph c iu chnh b sung nhm pht trin thm cc hng dn mi trong tng lai. V d: GMP Nhng dc phm chuyn bit nh dc phm tit trng, cc sinh phm, dc phm th lm sng trn ngi, dc tho. Tt c cc ti liu ny c th truy cp trn trang web WHO: (http.www.who.int/medicines/organization/qsm/activities/qualityassurance/gmpcover/htmlo).

2.1. m bo cht lng

2.1.1. m bo cht lng: nh trnh by phn Cc khi nim c bn

2.1.2. H thng m bo cht lng ph hp cho sn xut dc phm: nh trnh by phn Cc khi nim c bn

2.1.3. Nh sn xut phi chu trch nhim v cht lng sn phm m bo l chng ph hp vi



mc ch s dng, tun theo cc quy nh trong giy php lu hnh. Mc tiu cht lng c thc hin ph thuc vo trch nhim cc nh qun l cao cp, cc phng ban trong cng ty, nh cung cp, phn phi. C h thng m bo cht lng kt hp c GMP ln kim tra cht lng. Hot ng H thng m bo cht lng phi c lu tr h s y v theo di. C nhn vin, c s vt cht nh xng, my mc, trang thit b ph hp.

2.2. Thc hnh tt sn xut thuc (GMP)

GMP l mt phn ca m bo cht lng, gip m bo rng sn phm c sn xut ng nht v 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.

Cc nguyn tc trong GMP trc ht hng ti vic gim thiu cc nguy c d xy ra trong qu trnh sn xut dc phm (hai loi nguy c: nhim cho, ln do dn nhn sai) mang tnh phng nga. 10 yu cu/yu t c bn trong GMP phi c tn trng (xem thm phn Cc khi nim c bn).

2.3. Nguyn tc v sinh v thc hnh v sinh (NTVS v THVS)

Cc nguyn tc v thc hnh v sinh phi c thc hin nghim ngt trong qu trnh sn xut.

Phm vi thc hin: nhn vin, nh xng, my mc thit b, nguyn liu u vo, bt k th g c th l ngun ly nhim i vi sn phm. C chng trnh tng th (trnh by chi tit tng mc, nh mc 11: v sinh c nhn, mc 12: nh xng).

V d:

Bng 3.1. Tiu chun cp v sinh (ca WHO v ASEAN)

2.4. Thm nh

Thm nh l mt phn c bn trong GMP v cn phi c thc hin theo ng cng nh. Cn lp ra cc quy trnh thao tc (SOP) v quy trnh sn xut da trn c s mt nghin cu thm nh v phi c thm nh li theo nh k m bo rng cc quy trnh ny vn m bo cho kt qu mong mun. Cn c bit lu n vic thm nh cc SOP trong pha ch, kim nghim v lm v sinh.

Thm nh l hnh ng nhm chng minh, bng cc phng tin thch hp, rng mi nguyn liu,

Cp < grade > Hiu

sut lc cui,%

S tiu phn ti a / m3 khng kh

S vsv ti a /

1m3 khng

kh

S ln thay i khng kh / gi

WHO US FED

STD 209E

ASEAN 0.5 5 > 5

A < LAF > 100 IA Trng 99.997 3.500 Khng < 1 Lung khng kh nh hng

B 100 IB Trng 99.995 3.500 Khng 5 Min. 20 C 10.000 II Trng 99.95 350.000 2.000 100 Min. 20 D 100.000 III Xm 95.0 3.500.000 20.000 500 Min. 20

IV en 85.0 > > > 10 20



qu trnh, quy trnh, h thng, thit b c s dng trong sn xut hay kim tra, cho ra mt cch n nh nhng kt qu nh mong mun. Thm nh quy trnh sn xut, cc quy trnh sn xut trng yu phi c thm nh c trc v sau khi thc hin.

2.5. Khiu ni

2.5.1. Nguyn tc

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 theo cc quy trnh bng vn bn v cc bin php khc phc cn c thc hin.

2.5.2. Thc hnh

C 10 ni dung c th (xem c th ti liu tham kho) nh: Phn cng ngi chu trch nhim x l cc khiu ni v quyt nh bin php khc phc. C SOP m t bin php tin hnh, k c khi cn phai thu hi. Cn c bit ch n nhng khiu

ni v gi mo. Phi ghi thnh h s y chi tit bt k khiu ni no lin quan n sai hng sn phm. Nhng khiu ni ny cn c iu tra thu o.

Tt c cc quyt nh v bin php x l v khiu ni u phi ghi vo h s. H s v khiu ni cn c r sot thng xuyn tm ra nhng du hiu c bit hoc ti din

v c chng l thu hi nhng sn phm ang lu hnh. Cn thng bo cho c quan c thm quyn,

2.6. Thu hi sn phm

2.6.1. Nguyn tc

Cn phi c mt h thng thu hi nhanh chng, hiu qu cc sn phm bit hoc nghi ng b sai hng.

2.6.2. Thc hnh

C 7 ni dung (xem c th Ti liu tham kho) nh: C mt ngi chu trch nhim iu hnh v phi hp vic thu hi. C SOP c kim tra, cp nht thng xuyn gip cho t chc thu hi. Cn hng dn iu kin bo qun nhng sn phm thu hi khu vc tch bit. m bo sn sng cung cp h s phn phi sn phm cho ngi chu trch nhim. Ghi h s tin trnh thu hi v c bo co cui cng. Kim tra nh gi thng xuyn hiu qu k hoch thu hi.

2.7. Sn xut v kim nghim theo hp ng

2.7.1. Nguyn tc

Vic sn xut kim nghim theo hp ng cn c xc nh r rng, c s nht tr v c kim sot nhm trnh nhng hiu lm c th dn ti vic sn phm, cng vic, hoc hot ng kim tra cht lng



khng t cht lng mong mun. Cn c mt vn bn hp ng gia hai bn, trong xc lp r nhim v ca mi bn.

2.7.2. Quy nh chung

Tt c k hoch sn xut, kim nghim theo hp ng, k c nhng thay i d kin (k hoch, k thut) u phi theo ng giy php lu hnh sn phm.

Phi cho php bn hp ng c th kim tra c s bn nhn hp ng. Vic ph duyt xut hng cui cng phi do ngi c y quyn thc hin.

2.7.3. Quy nh c th

Cc yu cu c t ra nh sau: Bn hp ng + Bn hp ng chu trch nhim nh gi nng lc bn nhn hp ng, kh nng thc hin, GMP,

+ 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 khc.

+ Bn hp ng phi m bo tt c sn phm v nguyn vt liu pha ch do bn nhn hp ng giao u t tiu chun, v sn phm phi do ngi c y quyn k lnh xut.

Bn nhn hp ng + 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 vic do bn hp ng t ra. Ch c nhng c s c giy php sn xut mi c thc hin sn xut, kim nghim theo hp ng.

+ Bn nhn hp ng khng c chuyn cho i tc th ba cng vic k theo hp ng khi cha c bn hp ng thm nh v chp nhn.

+ Bn nhn hp ng phi trnh nhng vic lm bt li, nh hng n cht lng sn phm v/hoc kim nghim cho bn hp ng.

2.8. T thanh tra v thanh tra cht lng

2.8.1. T thanh tra

V nguyn tc: + Mc ch ca t thanh tra l nh gi vic thc hnh cc nguyn tc GMP trong mi lnh vc

sn xut v kim tra cht lng. Chng trnh t thanh tra c thit lp pht hin ra nhng khim khuyt trong thc hin GMP v khuyn ngh cc bin php khc phc cn thit.

+ T thanh tra cn tin hnh thng xuyn, ngoi ra c th tin hnh trong cc tnh hung c bit (thu hi sn phm, sn phm b loi b, hoc nhn c thng bo v k hoch thanh tra ca c quan Y t).

+ Ban t thanh tra gm nhng nhn vin c th nh gi khch quan vic thc hin GMP, tt c cc khuyn ngh bin php khc phc phi c thc thi.

+ T thanh tra phi c ghi vo h s, v c chng trnh theo di hiu qu. Thc hnh t thanh tra



Cc ni dung yu cu phi c (xem c th ti liu tham kho): + Danh mc t thanh tra: Phi c bn hng dn t thanh tra bao gm cc yu cu t thanh tra,

trong c th c cc cu hi v GMP. Danh mc t thanh tra ti thiu phi c (checklist) nh: nhn vin, nh xng, k c khu vc dnh cho nhn vin; vic duy tu bo dng nh xng v my mc, thit b; vic bo qun nguyn liu ban u v thnh phm, my mc thit b,

+ Ban t thanh tra, do lnh o ch nh mt Ban t thanh tra, tuyn ti ch, nhng chuyn gia chuyn ngnh v am hiu GMP. Thnh vin c th trong hoc ngoi cng ty.

+ nh k t thanh tra, tn s ty thuc yu cu cng ty, ti thiu mi nm/1 ln. + Bo co t thanh tra, lp bn bo co sau khi kt thc t t thanh tra, + Bin php theo di, cn c mt chng trnh theo di c hiu qu.

2.8.2. Thanh tra v cht lng

+ Vic thanh tra cht lng bao gm ni dung kim tra v nh gi ton b hoc mt phn ca h thng cht lng vi mc ch c th l hon thin h thng.

+ Vic thanh tra cht lng thng do cc chuyn gia bn ngoi v c lp hoc mt nhm do ban lnh o cng ty ch nh.

+ Phm vi thanh tra cht lng c th m rng n cc nh phn phi v cc n v hp ng (xem phn sn xut v kim nghim).

+ Thanh tra nh cung cp. B phn kim tra cht lng c trch nhim cng cc b phn lin quan trong vic quyt nh ph duyt cc nh cung cp nguyn liu, Cc nh cung cp nguyn liu ny cn c nh gi bng cc tiu chun quy nh trc khi duyt.

2.9. Nhn vin

Yu t con ngi l mt trong nm yu t c bn ca GMP

2.9.1. V nguyn tc

Vic thit lp v duy tr mt h thng m bo cht lng t yu cu sn xut cng nh kim tra cht lng chnh xc ty thuc vo yu t con ngi. V vy, cn:

+ i ng nhn vin c trnh thc hin cc nhim v thuc phm vi trch nhim ca nh sn xut. Trch nhim c nhn c ghi r trong bn m t cng vic.

+ Tt c nhn vin phi am hiu GMP.

2.9.2. Cc quy nh chung

+ nhn vin vi cc trnh chuyn mn, kinh nghim cn thit. Trch nhim mi ngi khng nn qu nhiu. Tt c phi nm vng GMP.

+ C bn m t cng vic, ghi r trch nhim cho tng ngi, khng c phn cng cng vic chng cho.

+ C bin php phng nhng ngi khng phn s ra vo khu vc sn xut.

2.9.3. V nhn vin ch cht



+ Nhn vin ch cht gm trng cc b phn (sn xut, kim nghim,) ngi c y quyn, trch nhim khng th y thc.

+ Yu cu nhn vin ch cht phi c trnh khoa hc, kinh nghim p ng quy nh ca lut php Quc gia. Trnh hc vn gm cc ngnh phi hp gia Ho hc, Vi sinh hc, Khoa hc v Cng ngh dc, Dc l v c cht hc hoc ngnh khoa hc c lin quan khc.

+ V tr Trng b phn sn xut v Trng b phn kim nghim c mt s trch nhim chung hoc cng thc hin lin quan n cht lng. Ty thuc tng quc gia, c th bao gm:

Ph duyt cc quy trnh bng vn bn v cc ti liu khc (c sa i). Theo di v kim sot mi trng sn xut. V sinh nh my. Thm nh quy trnh sn xut v kim nh dng c phn tch. o to, bao gm vic p dng v thc hnh nguyn tc m bo cht lng. Ph duyt v theo di nh cung cp nguyn liu,

a) Trng b phn sn xut, c nhng trch nhim (6 iu c th xem Ti liu tham kho) nh: m bo sn xut v bo qun sn phm theo ng h s, Ph duyt cc hng dn sn xut k c kim tra trong sn xut. m bo thm nh h s sn xut, v.v...

b) Trng b phn kim tra cht lng, c nhng trch nhim (9 iu c th xem ti liu tham kho) nh:

Ph duyt hoc loi b cc nguyn liu, sn phm trung gian, bn thnh phm v thnh phm. nh gi h s. m bo thc hin tt c cc php th cn thit. Ph duyt cc SOP ly mu, tiu chun cht lng, phng php phn tch v.v

2.10. o to

C 5 yu cu chnh: 1. Phi c k hoch v chng trnh o to bng vn bn cho tt c nhn vin. 2. Ngoi o to GMP, cn phi o to cho cc nhn vin mi nhng vn ph hp vi nhim v

c giao. o to lin tc, lu h s. 3. o to c bit i vi nhn vin lm vic nhng khu chuyn bit c nguy c tp nhim, c,

nguyn liu hot tnh cao. 4. Khng khch hng v nhn vin cha qua o to vo khu vc sn xut kim tra cht lng.

Nu khng trnh c th phi c thng bo trc, c bit v v sinh c nhn, trang phc v gim st cht ch.

5. Chuyn vin c vn v nhn vin hp ng cng phi c o to v lu h s.

2.11. V sinh c nhn

8 yu cu c ra:



1. Tt c nhn vin phi c kim tra sc kho trc v trong khi lm vic. 2. Tt c nhn vin phi c o to v thc hnh v sinh c nhn. Tun th v sinh c nhn mc

cao. Cn c vn bn hng dn v quy nh thc hin ni quy ny (SOP). 3. Bt k ai c biu hin m au, vt thng h c th nh hng ti cht lng sn phm khng

c php x l nguyn liu u vo, bao b, sn phm, 4. Tt c nhn vin phi c hng dn v khuyn khch bo co vi ngi ph trch nhng du

hiu c cho l nh hng bt li n cht lng sn phm. 5. Nhn vin trnh dng tay tip xc trc tip nguyn liu, bao b, sn phm trung gian, bn thnh

phm v thnh phm. 6. Nhn vin phi mc trang phc lao ng (c m) ph hp cng vic. 7. Khng c ht thuc, n ung, thc phm trong khu vc sn xut, kim tra cht lng, bo

qun, 8. SOP v sinh c nhn, s dng trang phc bo h lao ng cho tt c mi ngi.

2.12. Nh xng

y l mt trong nm yu t c bn ca GMP.

2.12.1. Nguyn tc

Nh xng phi c b tr, thit k, xy dng, lp t v bo dng ph hp vi cc thao tc thc hin trong khu vc sn xut.

2.12.2. Quy nh chung

1. Mt bng c b tr, thit k nhm gim thiu nhng ri ro sai st v d v sinh cng nh bo dng trnh nhng bt li cho cht lng sn phm.

2. B tr trong mi trng c cc bin php bo v qu trnh sn xut gim thiu nguy c gy tp nhim vi nguyn liu, sn phm.

3. Thit k v xy dng phi ph hp to iu kin m bo v sinh tt. 4. Thun tin cho cc hot ng bo dng, sa cha khng gy nguy hi n cht lng sn phm. 5. in, nh sng, nhit , m v vic thng gi phi ph hp, m bo khng nh hng bt li

ti dc phm trong qu trnh sn xut, bo qun, chnh xc ca my mc thit b. 6. Nh xng thit k v trang b m bo ngn nga cn trng v cc ng vt khc.

2.12.3. Quy nh c th mt s khu vc

a) Khu vc ph tr Cc khu vc gii lao, v sinh phi b tr tch bit khi cc khu vc sn xut v kim nghim. Phng thay v gi qun o, khu vc tm ra v v sinh phi thun tin v ph hp vi s lng

ngi s dng. Nh v sinh khng c thng trc tip vi khu vc sn xut v bo qun. Xng bo tr nn tch khi khu vc sn xut (nu c iu kin). Nh nui sc vt phi c cch ly tt khi cc khu vc khc.



b) Khu vc bo qun khng gian v din tch bo qun c th t nhiu loi nguyn vt liu, sn phm khc nhau,

sn phm trung gian, bn thnh phm, sn phm bit tr, sn phm loi b, b tr v hay thu hi. iu kin bo qun tt, kh ro, nhit , m,... C kim tra theo di. Khu vc nhn v gi hng phi m bo khng b nh hng bi thi tit. Khu vc bit tr phi ring bit, nh du ch dn, v.v B tr khu vc ly mu nguyn liu ban u. Nu ly ngay khu vc bo qun th phi vn hnh

th no trnh nhim cho. Nhng nguyn vt liu, sn phm loi b, thu hi phi bo qun khu ring. C khu an ton bo qun nhng ho cht gy nghin, cc cht nguy him. Bo qun an ton c bit cho cc vt liu bao b in sn,

c) Khu vc cn Phi c khu vc cn ring cho cc nguyn liu ban u, thit k kim sot bi, v.v

d) Khu vc sn xut B tr khp kn cho sn xut dc phm. Sn xut sn phm khng phi dc phm th khng nn tin hnh trong cng mt nh xng.

Trong trng hp ngoi l, phi ht sc cn trng. Nh xng phi c b tr hp thc, ni tip nhau theo trt t hp l tng ng vi trnh t hot

ng sn xut theo mc sch cn thit. Khng gian rng cho sn xut lp t my mc thit b, nguyn liu theo trt t trnh ln ln. Nhng ni nguyn vt liu, bao b, sn phm trung gian, bn thnh phm tip xc vi mi trng,

th b mt bn trong (tng, sn v trn) phi nhn v khng nt k. Cc ng dn, mng n, cc im thng gi v cc dch v khc phi thit k lp t trnh nhng

hc cha bi, kh v sinh. Cc ng thot nc ln, trnh chy ngc. Khu vc v sinh phi c thng gi tt. nh sng, c bit, c th kim tra bng mt. Khu vc ng gi phi thit k v b tr c bit trnh ln ln, nhim cho.

e) Khu vc kim tra cht lng Khu vc kim tra cht lng phi tch bit khu vc v sinh. Nhng khu vc th nghim sc vt, vi

sinh vt, ng v phng x phi b tr bit lp nhau. Phng kim nghim phi thit k ph hp cc hot ng d nh tin hnh, khng gian, trnh

nhim cho. Vt liu xy dng phng kim nghim phi ph hp tnh cht cng vic, cc cht s dng trong

vic kim nghim. B tr ring cho cc thit b phn tch trnh nh hng do in t, rung, m, cc yu t ngoi

cnh khc, hoc nu cn th b tr ring bit cc dng c phn tch.

2.13. My mc thit b



y l mt trong nm yu t c bn ca GMP, c th tm tt cc yu cu chnh: 1. Yu cu v thit k, cu trc, lp t, iu chnh v bo dng cho ph hp vi cc hot ng s

tin hnh, nhm gim thiu nhng sai st, nhim cho, tc ng bt li n cht lng sn phm. 2. Yu cu v v sinh, c SOP, lch trnh, phng tin, dng c lm v sinh, 3. My mc, thit b, dng c dng trong kim nghim phi ph hp vi quy trnh th nghim. 4. Cc b phn trong my mc, thit b tip xc sn phm, khng c gy bt li cho sn phm

trong qu trnh sn xut, khng a (thi, g) thm cht l.

2.14. Nguyn vt liu

y l mt trong nm yu t c bn ca GMP

2.14.1. V nguyn tc

Mc tiu chnh ca nh my dc phm l sn xut ra thnh phm dng cho bnh nhn bng cch phi hp cc nguyn liu (bao gm nguyn liu ban u, bao b, kh, dung mi, cht ph gia, thuc th, k c vt liu dng dn nhn,).


Cc vt liu lm v sinh, bi trn my mc thit b khng c tip xc sn phm. Tt c nguyn liu u vo v thnh phm u phi c bit tr ngay sau khi nhn hoc pha ch

cho n khi chng c xut em s dng hoc phn phi. Tt c cc nguyn liu v sn phm c bo qun trong iu kin ph hp do nh sn xut quy

nh, theo nguyn tc FIFO. Nc dng cho sn xut dc phm phi l nc ng tiu chun.

a) Nguyn liu ban u i vi nguyn liu ban u (starting materials), l mt khu quan trng, c cc yu cu: 1. Cn c ngi tham gia c kin thc ton din v sn phm v nh cung cp. 2. Ch nn mua ca nh cung cp c chp thun, hoc mua trc tip ca hng sn xut, thc

hin ng quy nh v nhn, ng gi, khiu ni,v.v 3. Phi kim tra tng chuyn hng: bao b, nim phong, phi khp vi n t hng v phiu giao

hng. 4. Tt c nguyn liu n u phi c kim tra, m bo l ng yu cu. 5. Tt c nhng tc nhn gy nh hng bt li ti cht lng nguyn liu (h hng,) u phi

c ghi chp v bo co b phn kim tra cht lng. 6. Nhiu l hng khc nhau trong mt t giao hng th phi ly mu, kim nghim mi l v xut

ring bit. 7. Nguyn liu ban u khu vc bo qun phi c dn nhn ph hp. Phi c nhng thng tin

ti thiu cn thit (xem thm ti liu tham kho). Khi s dng h thng bo qun bng vi tnh ho, khng nht thit phi ghi r rng trn nhn tt c

cc thng tin nu trn.



8. Cn c quy trnh/bin php nhn dng nguyn liu bn trong mi thng. 9. Ch nguyn liu kim tra cht lng ph duyt xut v cn hn dng mi c s dng. 10. Ch ngi c y quyn l c php cn nguyn liu theo SOP nh sn. 11. Tt c nguyn liu sau khi cn, cn kim tra li khi lng/th tch v ghi li. 12. Nguyn liu xut cho mi l thnh phm phi c tp kt cng mt ni, c nhn r rng.

b) Nguyn liu bao b 1. Vic mua v qun l, kim tra cc nguyn liu bao b trc tip v in sn phi thc hin nh

nguyn liu ban u. 2. Cn c bit ch n bao b in sn, phi c bo qun trong iu kin an ton. Ch ngi c y

quyn l c php cp nguyn liu bao b cho s dng theo quy trnh nh sn. 3. Mi ln giao hng phi cho mt m s/k hiu nhn dng ring. 4. Bao b ng gi/in sn nu ht hn/khng dng c phi hy v phi c a vo h s. 5. Tt c sn phm v nguyn liu bao b khi giao cho b phn ng gi phi c kim tra s

lng, nhn dng theo hng dn ca quy trnh ng gi.

c) Sn phm trung gian v bn thnh phm 1. Sn phm trung gian v bn thnh phm phi c gi trong iu kin ph hp. 2. Khi mua v phi c giao nhn theo quy trnh ging nh nguyn liu ban u.

d) Thnh phm 1. Thnh phm phi c bit tr ti khi c lnh xut (quy nh ca nh sn xut). 2. Vic nh gi thnh phm v h s ti liu cn thit cho vic ra lnh xut mt sn phm bn

c m t phn thc hnh tt kim tra cht lng.

e) Nguyn vt liu b loi b v ti s dng 1. Nguyn vt liu b loi b cn c nh du r rng v bo qun khu vc hn ch ra vo. 2. Vic ti ch sn phm b loi b ch p dng trong trng hp ngoi l. 3. Vic s dng mt phn/ton b l trc (t cht lng) vo mt l cng sn phm, bt u t

mt cng on sn xut nht nh, phi c ph duyt. 4. B phn kim tra cht lng cn cn nhc thm cc php th vi thnh phm c ti ch.

f) Sn phm thu hi Sn phm thu hi c phn bit v bo qun ring, cn c quyt nh x l sm. g) Hng b tr li: phi hy b tr khi cht lng ca chng vn t yu cu,

h) Thuc th v mi trng nui cy 1. Tt c thuc th v mi trng nui cy phi ghi h s sau khi tip nhn/ pha ch. 2. Cc thuc th c pha ti phng kim nghim theo quy trnh duyt sn, nhn ghi nng , h s

hiu chun, hn dng, ngy cn chun li v iu kin bo qun. Phi c ch k ngi pha ch v ngy thng.



3. Phi p dng cc php dng v m tnh xc nh tnh ph hp ca mi trng nui cy. C chng th dng tnh phi ph hp vi nhy ca php th.

i) Cht chun i chiu 1. Nn dng chun chnh thc 2. Cht chun i chiu chnh thc ch dng vo mc ch c m t trong chuyn lun ph

hp. 3. Cht chun i chiu do nh sn xut t iu ch phi c kim nghim, xut xng, bo qun

ging nh Cht chun i chiu chnh thc, c ngi v c khu vc bo qun t tiu chun. Cht chun th cp/cht chun phng th nghim c th c thit lp theo cc php th v kim

nghim ph hp m bo tiu chun ho. Tt c Cht chun i chiu c bo qun v s dng ng quy nh ( m bo cht lng).

k) Nguyn vt liu ph thi 1. Cn c khu vc bo qun an ton ring ch x l. 2. Nguyn vt liu phn tch khng c php tch ly, cho vo thng cha tp kt bn ngoi

khu vc sn xut.

l) Nhng vn khc. Thuc dit chut, cn trng, st trng lm v sinh khng c gy nhim my mc thit b,

nguyn vt liu, bao b, thnh phm,

2.15. H s ti liu

y l mt trong nm yu t c bn ca GMP, yu cu:

2.15.1 V nguyn tc

Qun l tt h thng h s ti liu l mt phn thit yu ca h thng m bo cht lng, v th n c lin quan ti mi kha cnh ca GMP.

Mc tiu ca c ch qun l ny l xc nh cc tiu chun cho tt c nguyn vt liu v phng php sn xut cng nh kim tra cht lng m bo l tt c nhn vin lin quan n sn xut u hiu cng vic phi lm, khi no lm, m bo l nhng ngi c thm quyn u nhn c mi thng tin cn thit khi quyt nh cho sn xut mt l thuc bn, m bo c cc bng chng, du hiu, h s, cc thng tin cn thit cho php tin hnh iu tra (khi cn thit).

Vic thit lp v s dng h s ti liu ty thuc vo nh sn xut.


1. H s ti liu cn c thit lp, chun b, r sot v phn phi thn trng. Tun th nhng quy nh trong giy php sn xut v lu hnh.

2. H s ti liu phi c duyt, ch k ca ngi c thm quyn, ghi ngy thng r rng. Khng c thay i khi cha nhn c s chp thun ca ngi c thm quyn.

3. Phi c ni dung r rng: tiu , tnh cht, mc ch ca h s ti liu. Trnh by th t d kim tra. Ti liu sao chp phi r rng, khng c sai st.



4. Thng xuyn r sot v cp nht. Khi mt ti liu c sa i, th phi c bin php ngn nga s dng ti liu c.

5. Cc h s ti liu phi nhp s liu r rng, d c, khng c ty xo, khong trng nhp s liu.

6. Bt k thay i no i vi mt ti liu cng phi k v ghi ngy thng. Nhng vn th hin sao cho c th c c thng tin gc, l do

7. Lp h s ti liu /in h s ti liu khi tin hnh bt k hot ng no, sao cho c th truy cp li c. H s ti liu v SOP c lin quan phi c lu tr t nht mt nm sau thnh phm lin quan ht hn.

2.15.3. H s ti liu cn thit

2.15.3.1. Nhn

1. Nhn dng cho bao b, thng cha, my mc thit b /nh xng: r rng, theo mu thng nht ca cng ty, mu sc,

2. Tt c thnh phm thuc phi dn nhn theo quy ch Quc gia, phi c cc thng tin ti thiu cn thit nh:

Tn sn phm. Danh mc hot cht (v tn chung quc t), hm lng mi hot cht. S l do nh sn xut quy nh. Ngy ht hn dng dng khng m ho. Nhng iu kin bo qun c bit/nhng lu khi x l. Hng dn s dng v lu cn thit. Tn v a ch nh sn xut/ cng ty/ hoc ngi chu trch nhim. 3. i vi cht chun i chiu, nhn/ ti liu i km phi ghi r ngy sn xut, ngy ht hn dng,

ngy m bao b ln u v iu kin bo qun, nu cn.

2.15.3.2. Tiu chun cht lng nguyn liu ban u v nguyn liu bao b

1. Tiu chun cht lng nguyn liu ban u v nguyn liu bao b trc tip v bao b in sn cn m t chi tit, ph hp, bao gm:

Tn nguyn liu (v tn chung quc t khng ng k c quyn INN, nu c) v s m ni b. Tham chiu (reference) chuyn lun Dc in, nu c. Quy trnh nh tnh v nh lng vi mc cht lng quy nh.

Ty thuc vo thc t cng ty, c th thm cc thng tin khc, (xem thm ti liu tham kho). Nguyn liu bao b phi t tiu chun cht lng quy nh, c bit ch ti tng k vi sn phm.

2) H s ti liu m t SOP kim nghim phi nu r tn sut nh lng li mi nguyn liu, ty thuc hn dng ca chng. SOP phi c thm nh trong iu kin nh xng, my mc thit b phn tch hin c.

Cn c cc tiu chun cht lng ph hp c ph duyt v ghi ngy thng, k c cc php th



nh tnh, nh lng, tp cht v xc nh cht lng i vi nguyn liu, bao b v thnh phm; nu c th, cn c c tiu chun cht lng sn phm trung gian, bn thnh phm, tiu chun cht lng ca nc, dung mi v thuc th (acid v base). Mi tiu chun cht lng u c ph duyt v lu tr b phn kim tra cht lng/m bo cht lng /trung tm h s ti liu.

Cc tiu chun cht lng cn c sa i b sung nh k p ng yu cu Dc in Quc gia/ Dc in khc.

Cn c trang b y cc Dc in, cc tiu chun tham kho, ph i chiu.

2.15.3.3. Tiu chun cht lng sn phm trung gian v sn phm ch ng gi (bn thnh phm:

Cn c ban hnh, tng t tiu chun cht lng nguyn liu, thnh phm, nu ph hp.

2.15.3.4. Tiu chun thnh phm

Tn sn phm v m tham kho nu c. Tn mi hot cht (v tn chung INN) Cng thc hoc tham kho cng thc. M t dng bo ch v chi tit ng gi. Hng dn cch ly mu v kim nghim hoc tham chiu quy trnh lin quan. Quy trnh nh tnh v nh lng vi mc cht lng quy nh. iu kin bo qun, cc lu nu c v hn dng.

2.15.3.5. Cng thc gc

Mi sn phm v c l sn xut cn c Cng thc gc c ph duyt chnh thc. Cng thc gc cn c:

1. Tn sn phm, c m tham kho lin quan n tiu chun cht lng sn phm. 2. M t dng bo ch, hm lng mi sn phm v c l. 3. Danh mc cc nguyn liu c s dng (tn chung quc t INN, nu c), s lng. 4. Cng b sn lng thnh phm d kin, gii hn cho php v sn lng sn phm trung gian, nu

c. 5. Nu a im sn xut v my mc thit b s dng. 6. Phng php, hoc s tham kho ca phng php. 7. Hng dn cc bc chi tit trong qu trnh ch bin. 8. Hng dn cc k thut trong qu trnh sn xut v gii hn cho php. 9. Quy nh v bo qun sn phm, iu kin bo qun c bit, nu cn. 10. Nhng iu c bit cn lu .

2.15.3.6. Hng dn ng gi

Cc hng dn ng gi chnh thc cho sn phm, quy cch ng gi v dng ng gi phi c ph duyt v ban hnh chnh thc. Thng gm:

1. Tn sn phm.



2. M t dng bo ch, hm lng v phng php s dng nu c. 3. Quy cch ng gi: s lng, khi lng/ th tch. 4. Nguyn liu bao b cho mt c l chun: s lng, c v chng loi, m/ s tham kho. 5. C v d/bn sao chp v mu bao b in sn c lin quan, trn ch ch ghi s l v ngy ht hn

dng. 6. Cn ghi cc lu c bit nh kim tra khu vc v my mc thit b ng gi. 7. M t thao tc ng gi, c thao tc ph tr v my mc thit b s dng. 8. M t cc thao tc kim tra trong qu trnh ng gi, c hng dn cch ly mu v gii hn cho

php.

2.15.3.7. H s pha ch l

1. Cn lu tr h s pha ch l cho mi mt l sn xut. H s thit lp da trn nhng phn lin quan n cng thc gc.

2. Kim tra v ghi chp: my mc thit b, khu vc sn xut, h s ti liu, sn phm. 3. Trong qu trnh pha ch cn ghi nhng thng tin vo thi im thc hin mi thao tc, sau khi

hon thnh h s ghi ngy thng, ch k ngi chu trch nhim pha ch, (chi tit xem thm ti liu tham kho).

2.15.3.8. H s ng gi l

1. Cn lu tr h s ng gi l cho mi l/ mt phn ca l pha ch. H s c thit lp theo hp ng ng gi. Phng php chun b h s cn quy nh c th.

2. Trc khi thao tc ng gi, cn kim tra: my mc thit b, khu vc thc hin thao tc, c ghi chp li vic kim tra ny.

3. Cn ghi li nhng thng tin (xem thm ti liu tham kho) nh: Tn sn phm, s l, lng bn thnh phm c ng gi, s l v lng thnh phm d kin v

lng thnh phm thc t, s lng cn i. Ngy gi thc hin thao tc ng gi. Tn ngi chu trch nhim tin hnh thao tc. Ch k tt ca nhn vin vn hnh cc cng on chnh. Cc kim tra nh tnh v thao tc theo hng dn ng gi, c kt qu kim tra. Cc thao tc thc hin, my mc thit b v dy chuyn s dng. v.v

2.15.3.9. Quy trnh thao tc chun (SOP) v h s s sch

1. Cc SOP v H s s sch v vic tip nhn mi chuyn hng nguyn liu, bao b, cn thit lp v ban hnh. H s s sch, chng t v bin nhn bao gm 8 mc (xem thm ti liu tham kho).

2. Cc SOP cho vic dn nhn, bit tr v bo qun ni b i vi nguyn liu ban u, nguyn liu bao b v nguyn liu khc, nu cn cng phi thit lp c th.

3. Cn ban hnh SOP cho mi my mc thit b v dng c, gn my mc thit b. 4. SOP hng dn cch ly mu, ghi r ngi c quyn ly mu.



5. Hng dn ly mu cn phi c: Phng php ly mu v k hoch ly mu, my mc thit b s dng. Cc lu cn thit trnh nhim cho. Lng mu cn ly. Hng dn vic chia nh mu theo quy nh. Loi bao b ng mu, ghi r dng cho mu v trng/thng. Cc lu c bit, nht l mu v trng hay c hi. 6. SOP h thng nh s l (m) nhm nhn dng l sn phm trung gian, bn thnh phm hay thnh

phm. 7. SOP cho vic nh s l t cng on pha ch, ng gi. 8. SOP cho vic nh s l phi m bo khng trng lp cng mt s l. 9. Vic ra s l cn ghi li ngay (ghi trong nht k sn xut), ngy ra s l. 10. Cn c SOP cho vic kim nghim nguyn vt liu v sn phm mi cng on (phng php

v my mc thit b). 11. H s s sch phn tch t nht phi c cc s liu: Tn nguyn vt liu/sn phm v dng bo ch, nu thch hp. S l v nh sn xut/nh cung cp. Tham chiu tiu chun cht lng v quy trnh kim nghim lin quan. Kt qu kim nghim, c nhn xt v tnh ton v mc cht lng quy nh. Ngy kim nghim v s tham kho ca thc nghim. Ch k tt ca ngi thc hin php th. Ch k ca ngi xc minh php th v tnh ton, nu thch hp. Kt lun cho t hoc loi b, ngy, ch k ngi chu trch nhim. 12. Cn c SOP xut/loi b nguyn vt liu, sn phm, c bit xut thnh phm ra th trng. 13. Cn lu gi h s s sch vic phn phi mi l sn phm, to iu kin khi thu hi. 14. C s nht k my mc thit b chnh quan trng, thm nh, ngy, ngi thc hin. 15. Ghi chp vic s dng cc my mc thit b chnh v khu vc pha ch theo thi gian. 16. SOP v sinh, phn cng trch nhim, chi tit lch, phng php, thit b,

2.16. Thc hnh tt trong sn xut thuc

2.16.1. V nguyn tc: Cc thao tc trong sn xut phi tun theo cc SOP xc nh r rng ph hp, c ph duyt ca ngi c trch nhim v sn xut v kinh doanh, vi mc tiu t c sn phm c cht lng cn thit.


1. Tt c cc vic x l nguyn liu v sn phm nh v sinh, bit tr, ly mu, lu kho, dn nhn, ch bin, ng gi v phn phi phi thc hin theo SOP, phi ghi chp vo h s lu.

2. Khng nn lm khc quy trnh nh. Nu phi lm khc trc th cng phi theo mt quy trnh



c duyt, c s tham gia ca phng kim tra cht lng. 3. Kim tra hiu sut bo m phn hao ht nm trong gii hn cho php. 4. Khng c tin hnh ch bin nhiu sn phm khc nhau trong cng mt lc hoc lin tip nhau

trong cng mt phng hay khu vc, tr khi xc nh khng c nguy c nhm ln/nhim cho. 5. Trong qu trnh sn xut, phi dn nhn hoc nh du tt c nhng nguyn liu, thng cha

nguyn liu, sn phm, ang ch bin, bao gm c hm lng v s l. 6. Cn phi hn ch ngi ra vo khu vc sn xut. 7. Khng c dng thit b sn xut dc phm vo mc ch sn xut khc. 8. Cc kim tra, kim sot trong qu trnh sn xut phi c thc hin trong khu vc sn xut.

2.16.3. Mt s yu cu phng nhim cho nhim khun

1. Cn thn trng khi sn xut bng cc nguyn liu kh trnh sinh bi v phn tn bi thuc trong khu vc sn xut. Cn phi kim sot cht ch s lu chuyn khng kh. Nguy c nhim bn nh bi, kh, vi sinh vt, t vt ca cc nguyn liu cn li trn thit b, my mc

2. C cc bin php ngn nga nhim cho, phi c kim tra nh k. 3. Khu vc sn xut, ni nhng sn phm d b nh hng (nhy cm) trong qu trnh sn xut phi

kim tra nh k (nh kim tra vi sinh v cc tiu phn).

2.16.4. Mt s yu cu i vi giai on ch bin

1. Khu vc sn xut v cc thit b u sch s v khng cn cc nguyn liu, sn phm, ca l trc.

2. Thc hin kim tra kim sot thit b. 3. Kim tra cc thit b v thit b cung cp kh, nc trc khi sn xut. Khng c s dng cc

thit b h hng, khng n nh. 4. V sinh sau khi sn xut, cn phi nu r thi gian gii hn tnh t khi thit b c v sinh n

khi s dng. 5. Cc yu cu i vi cc dng c sn xut nh thng cha thuc, cc phng tin vn chuyn sn

phm, cc dng c o lng, thit b phn tch, cng c ra.

2.16.5. Vi cng on ng gi sn phm, cc yu cu nghim ngt cng c ra trnh nhm ln, nhim bn

1. Cn thn trng trnh nhm ln, nhim bn sn phm trong ng gi. Cc sn phm khc nhau khng c ng gi cc khu vc gn nhau.

2. Khu vc ng gi, dy chuyn ng gi, my in nhn phi sch s v khng c c cc nguyn liu, sn phm, h s ca l trc. S kim tra phi c thc hin theo check list v kt qu kim tra phi c lu vo h s.

3. Phi c nhn ghi r tn thuc, s l mi trm ca dy chuyn ng gi. 4. Cn phi dn nhn ngay sau khi ng ng v hn ng. Phi c SOP thch hp trnh ln ln

hoc dn nhn nhm. 5. Kim tra cht ch ni dung in thm trn nhn, trnh mt ni dung trn nhn, kim tra khi ct nhn

bng my, qu trnh ng gi (xem thm ti liu tham kho).



2.17. Kim tra cht lng

y l ngi bn ng hnh ca sn xut.

2.17.1. Nguyn tc chung

Khng nh rng kim tra cht lng l mt phn ca GMP lin quan ti vic ly mu, tiu chun cht lng v kim nghim, v t chc, h s ti liu (lin quan n cht lng).

Yu cu mi mt c s sn xut phi c mt phng kim tra cht lng. B phn kim tra cht lng phi c lp. ngun lc, iu kin,... thc thi nhim v c giao.

2.17.2. Nhng yu cu c bn/ti thiu trong kim tra cht lng

Cn c vt cht v trang thit b, nhn vin, SOP ly mu v kim nghim nguyn liu ban u, bao b, sn phm trung gian, theo ng GMP.

Vic ly mu phi theo ng phng php v do nhn vin b phn kim tra cht lng tin hnh. Phng php kim nghim phi c thm nh. Phi lp h s chng minh cc SOP ly mu, thao tc, kim nghim c thc hin v ghi

li bt k s sai lch no. Thnh phm phi c thnh phn theo ng cng thc nh tnh, nh lng sn phm nh trong

giy php quy nh. Phi ghi chp li cc kt qu thanh kim tra v kim nghim cc nguyn vt liu, sn phm trung

gian, bn thnh phm v thnh phm theo tiu chun cht lng nh. Khng mt l sn phm no c em bn khi cha c chng nhn sn phm t yu cu theo quy

nh trong giy php ca ngi c thm quyn. Mu nguyn liu ban u v sn phm cn c lu tr c s kim tra sn phm sau ny khi

cn thit.

2.17.3. Nhim v khc ca b phn kim tra cht lng

Xy dng, nh gi v thc hin cc SOP kim tra cht lng. Thm nh, nh gi, duy tr v bo qun cht chun i chiu, m bo ng nhn trn bao b

nguyn liu, sn phm, theo di n nh ca sn phm v hot cht. Tham gia vo vic iu tra khiu ni lin quan n cht lng sn phm. Theo di mi trng. Tt c cc hot ng phi c thc hin theo SOP v nu cn phi c ghi chp li (xem thm ti

liu tham kho).

2.17.4. Kim sot nguyn liu, sn phm trung gian, bn thnh phm v thnh phm

C cc yu cu v: Cc th nghim u phi c thc hin theo quy trnh xc nh. Kt qu kim nghim phi

c kim tra bi ngi gim st. Mu phi i din c cho l nguyn liu.



Thao tc ly mu phi khng c gy nhim cho v nh hng n cht lng sn phm. Trnh nhm, ln. C nhn ghi trn bao b ng mu (ni dung c th xem thm ti liu tham kho).

Dng c ly mu phi sch s, c th tit trng nu cn.

2.17.5. Cc th nghim cn thit

a) i vi nguyn liu v bao b Phi c kim tra ng chng loi, tinh khit, hm lng v cc thng s khc trc khi a

vo s dng. Cc th nghim nh tnh phi c thc hin trn mi n v ng gi ca nguyn liu. Giy chng nhn cht lng ca nh sn xut nguyn liu phi l bn gc hoc bn photo c

chng thc, c cc ni dung cn thit (xem thm ti liu tham kho). Yu cu kim tra, kim sot l mt phn ca h s l.

b) Thnh phm Mi l thnh phm phi c mt phiu kim nghim. Sn phm khng t cc tiu chun phi c hon tr.

c) Kim tra h s l H s sn xut v kim nghim phi c kim tra khi xut l. Thi gian lu gi mu: t nht mt nm sau khi ht hn dng. Mu lu phi c gi trong bao b

v c bo qun trong iu kin ghi trn bao b. Cc nguyn liu khc cn c lu tr t nht hai nm nu n nh cho php. Lng nguyn liu hoc sn phm lu phi cho t nht hai ln kim tra ton din.

d) Nghin cu n nh Phng kim nghim phi nh gi cht lng v n nh ca thnh phm, nguyn liu cng

nh bn thnh phm nu cn. Phng kim nghim phi xc nh hn dng v tui th trn c s nghin cu n nh. C mt chng trnh nghin cu n nh di hn tip sau . n nh phi c xc nh trc khi a ra th trng.

TI LIU THAM KHO 1. Hong Minh Chu, Gio trnh Cng nghip Dc Bi ging lp D5, THYD, TP. HCM, 1997.

2. B Y t, Hng dn ASEAN GMP 1996 (Bn dch 1997).

3. LE HIR, Abrgs de Pharmacie galnique, R.F.Paris 2, 2000.

4. B Y t, Hng dn thc hnh tt sn xut thuc theo khuyn co ca T chc Y t Th gii(WHO GMP), H Ni, 2004.



CU HI LNG GI * CHN CU NG: 1. Yu cu i hi phi c GMP l do

a) Nhu cu thuc ngy cng tng; b) KHCN sn xut thuc pht trin p ng nhu cu v thuc; c) Xu th hi nhp v Vit Nam gia nhp ASEAN; d) C a, b, c kt hp ng.

2. Vit Nam trin khai p dng cc nguyn tc tiu chun GMP ca ASEAN t a) 1984; b) 1987; c) 1990; d) 1996.

3. Mc tiu ca GMP a) m bo mt cch chc chn dc phm c sn xut ra mt cch n nh; b) Lun lun t cht lng nh nh (nh thuc ng k); c) Sn xut ra thuc cht lng tt; d) a, b kt hp ng.

4. GMP l a) Ton b nhng khuyn ngh cn thc hin cho php m bo cht lng ca mt thuc xc nh trong iu kin tt nht;

b) Nhng khuyn ngh ny m t nhng mc tiu khc nhau phi t ti; c) V t chc, con ngi, c s; d) a, b, c lin kt ng.

5. GMP gip cho nh sn xut a) Sn xut ra nhng thuc c cht lng n nh nh thuc nguyn mu c cp giy php

sn xut;

b) Nhng thuc c cc thuc tnh: Tinh khit (P), ng (I), hiu nghim (E) v an ton (S); c) m bo cht lng, hiu qu v an ton; d) a v b lin kt ng.

6. Nm yu t c bn ca GMP a) Con ngi, nguyn ph liu, mi trng (c s sn xut), quy trnh (phng php), trang thit

b; b) Con ngi, my mc, nguyn liu, v sinh, an ton; c) Nguyn liu, c s sn xut, ti liu, v sinh, an ton; d) C s vt cht, mi trng, ti liu, con ngi, a im.

7. Yu t con ngi trong mt c s sn xut thuc t GMP i hi a) v s lng;



b) v tiu chun (cht lng); c) C thc v thi quyt tm thc hin GMP; d) a, b, c kt hp ng.

8. Yu t nguyn vt liu l mt yu t khng th thiu c, i hi a) Hot cht tt, ng, s lng, cht lng, hiu qu; b) Cc cht t dc tt, t tiu chun cht lng; c) Nguyn liu bao b ng gi m bo tnh nng cn thit, ch loi tip xc vi thuc; d) a, b, c kt hp ng.

9. Mi trng, c s sn xut i vi mt x nghip dc phm t GMP i hi a) a im thun tin, xa ngun nhim, khng gy nhim; b) ng chc nng cho cc dy chuyn sn xut; c) m bo cp v sinh; d) a, b, c kt hp ng.

10. Quy trnh v phng php sn xut (ti liu), h thng ti liu phi y a) Cc ti liu k thut; b) H s l; c) Cc quy trnh k thut; d) b, c kt hp ng.

11. Vit Nam p dng WHO GMP t nhng nm... v c... iu khon a) 2002 v c 15 iu khon; c) 2004 v c 17 iu khon; b) 2003 v c 16 iu khon; d) 2005 v c 17 iu khon.

12. Thm nh l: a) Mt phn c bn trong GMP v cn phi c thc hin theo ng cng nh; b) Hnh ng nhm chng minh, bng cc phng tin thch hp, rng mi nguyn liu, qu

trnh, quy trnh, h thng, thit b c s dng trong sn xut hay kim tra, cho ra mt cch n nh nhng kt qu nh mong mun;

c) a, b kt hp ng; d) a, b u sai.

13. Sn xut theo hp ng tun th WHO GMP quy nh chung a) Tt c k hoch sn xut theo hp ng, k c nhng thay i d kin (k hoch, k thut) u phi theo ng giy php lu hnh sn phm;

b) Phi cho php bn hp ng kim tra c s bn nhn hp ng; c) Vic ph duyt xut hng cui cng phi do ngi c y quyn thc hin; d) b, c kt hp ng.

14. Tiu chun cp v sinh ca WHO GMP

Cp < grade > Hiu sut lc cui,%



Bi 3 (tip) THC HNH TT PHNG KIM NGHIM THUC

(GOOD LABORATORY PRACTICE GLP)

1. M U

1.1. Mc ch v phm vi p dng

1.1.1. Mc ch

Vic thc hnh tt cc nguyn tc kim nghim thuc nhm nng cao tnh hiu qu ca h thng cc phng kim nghim thuc trn c hai mt qun l nghip v v qun l k thut, k c khu vc qun l nh nc v doanh nghip, nhm m bo tnh khch quan, trung thc v chnh xc trong vic nh gi cht lng thuc.

1.1.2. Phm vi p dng

Nguyn tc Thc hnh tt phng kim nghim thuc c p dng cho cc phng kim nghim ca Nh nc v ca cc doanh nghip, k c cc doanh nghip c vn u t nc ngoi, cc phng kim nghim t nhn hay phng kim nghim c lp.

1.2. Mt s thut ng s dng trong gio trnh

V d nh n v kim nghim, h thng cht lng, h thng phn tch, v,v (xem thm ti liu

WHO US FED STD 209E (a) (b) (c) (d)

A < LAF > 100 99.997 99.995 99.997 99.995 B 100 99.995 99.95 99.95 99.95 C 10.000 99.95 95.0 95.50 95.0 D 100.000 95.0 90.5 85.0 85.0

MC TIU 1. Pht biu c mc ch v phm vi p dng nguyn tc Thc hnh tt phng kim nghim

thuc (GLP). 2. K ra v gii thch c nhng ni dung chnh (12 iu) ca GLP. 3. Vn dng vo vic thc hin ti c s sn xut.



tham kho).

2. NGUYN TC THC HNH TT PHNG KIM NGHIM THUC Trn c s 5 yu t v cc nguyn tc c bn ca GxP, GLP c th ho vo ni dung 12 iu ph

hp vi yu cu ca phng kim nghim thuc.

2.1. V con ngi

Th hin iu khon 1: T chc, nhn s v o to.

2.1.1. V t chc, b tr sp xp cc phng, cc n v qun l nghip v, k thut

Mt phng kim nghim thuc thng c chia lm nhiu n v kim nghim hoc cc b phn c chuyn mn ho da trn k thut kim nghim (v d: Ho l, Vt l, Vi sinh vt) hoc chia theo cc i tng l sn phm c kim nghim (v d: khng sinh, vitamin, dc liu...). i khi phng kim nghim cn c cc n v kim nghim chuyn bit phc v cc nhu cu nh th v trng, th ch nhit t, o lng vt l c bit...

Chc nng nhim v ca mi n v kim nghim cn phi c xy dng v c ngi c thm quyn ban hnh chnh thc.

Ngoi cc n v kim nghim (hay cn gi l cc phng chuyn mn), mi phng kim nghim cn phi c b phn ng k mu v b phn lu tr h s tiu chun cht lng. B phn ng k mu c nhim v nhn mu v cc ti liu km theo, phn pht mu n cc phng chuyn mn v tr li kt qu kim nghim. B phn lu tr h s tiu chun cht lng phi m bo cung cp cc tiu chun cht lng cp nht v cc ti liu lin quan cho cc n v kim nghim.

Ngoi ra, phng kim nghim cn c mt s n v hu cn phc v cho vic cung ng trang thit b, vt t, ho cht, dng c v sc vt th nghim.

2.1.2. V nhn s

Phi c y nhn vin c o to thch hp, c chuyn mn v kinh nghim hon thnh cng vic c giao, khng c lm thm nhng cng vic c mu thun vi cng tc kim nghim.

Yu cu trnh chuyn mn ca cn b, nhn vin k thut:

a) Trng phng kim nghim v trng cc b phn phi c trnh i hc hoc sau i hc, c kinh nghim trong lnh vc phn tch kim nghi

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