T CHC Y T TH GII - WHO

HNG DN
THC HNH TT SN XUT THUC

Thc hanh tot san xua t sinh pham

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WHO Technical Report Series 822 (1992)

 World Health Organization

WHO Technical Report Series, No. 822, 1992

Ph lc 1
Thc hnh tt sn xut sinh phm
1. Phm vi p dng....................................................................................................... 2
2. Nguyn tc chung..................................................................................................... 2
3. Nhn s.................................................................................................................... 3
4. Nh xng v thit b ............................................................................................... 4
5. Khu chn nui v chm sc ng vt ....................................................................... 6
6. Sn xut ................................................................................................................... 7
7. Ghi nhn ................................................................................................................... 7
8. H s l v h s phn phi sn phm .................................................................... 8
9. m bo cht lng v kim tra cht lng ............................................................ 9
Tc gi .......................................................................................................................... 10
Li cm n .................................................................................................................... 10
Ti liu tham kho ......................................................................................................... 11

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1. Phm vi p dng
Ti liu ny l nhng ni dung b sung thm cho hng dn Thc hnh tt sn xut (GMP)
dc phm (WHO TRS 823, 1992, ph lc 1).
Cc quy nh cn thit kim tra cht lng sinh phm phn ln c xc nh bi
ngun gc sn phm v phng php sn xut. Phm vi ti liu ny bao gm cc quy trnh
sn xut sau y
-

Nui cy cc chng vi sinh vt v t bo c nhn (eukaryot);

Chit xut hot cht t m ngi, ng vt v m thc vt (allergens: d nguyn cht

gy d ng);

K thut ti t hp ADN (rDNA);

K thut lai to (hybridoma);

Nhn ging vi sinh vt trong phi hoc ng vt.

Sinh phm c sn xut theo nhng phng php trn y gm c d nguyn, khng
nguyn, vc xin, hormone, cytokine, enzyme, dn cht t huyt tng hay mu ton phn,
huyt thanh min dch, cc globulin min dch (bao gm cc khng th n dng), cc sn
phm ca qu trnh ln men (bao gm cc dn xut t rDNA) v cc cht chn on in vitro.

2. Nguyn tc chung
C s sn xut sinh phm phi p ng nguyn tc c bn v Thc hnh tt sn xut GMP.
Ti liu ny c xem nh l phn b sung thm vo cc yu cu chung trong Thc hnh
tt sn xut (GMP) dc phm (WHO TRS 823, 1992, ph lc 1) v quy nh c lin quan
n vic sn xut v kim tra cht lng sinh phm. Trong qu trnh son tho hng dn
ny c tham kho n bn tho Hng dn v m bo cht lng sinh phm i vi c
quan qun l (c cng b chnh thc ti Ph lc 2, WHO TRS 822, 1992).
Do phng thc sn xut, kim tra cht lng v s dng ca sinh phm khin chng cn
thit phi c quan tm c bit. Khng nh sn phm dc phm truyn thng c sn
xut kim nghim bng cc k thut ha, l c tnh lp li, sinh phm c sn xut bi cc
nguyn liu v quy trnh sinh hc nh nui cy t bo hay chit xut hot cht t nguyn
liu l t chc c th sng. Nhng bc x l nh vy mang theo nhiu s bin thin, do
chng loi v bn cht cc sn phm ph (by-products) cng bin thin nh vy. Bi vy
nguyn tc GMP cn phi c tun th y trong tt c cc bc sn xut sinh phm,
bt u t giai on sn xut cc hot cht.
Vic kim tra cht lng gn nh lun lin quan n cc k thut sinh hc c dao ng
ln hn nhiu so vi cc phng php ha l. Hot ng kim tra/gim st trong qu trnh
(in-process controls) ng vai tr ht sc quan trng trong sn xut sinh phm v c nhng
sai st khng th pht hin c bng nhng th nghim kim tra trn thnh phm cui
cng.
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Ti liu hng dn ny khng a ra c nhng yu cu chi tit cho cc loi sinh phm c
th; thay v l nhng hng dn khc ca WHO, chng hn nh ti liu Cc yu cu i
vi hot cht sinh hc - Requirements for Biological Substances, trong bao gm cc yu
cu i vi vc xin (Ph lc 7, WHO TRS 822, 1992).

3. Nhn s
3.1
Vic thit lp c s sn xut v nhn s ca c s cn c s ng ca ngi c
thm quyn c o to v k thut sn xut hot cht sinh phm v c hiu bit khoa hc
v sn xut sinh phm. Nhn lc ca c s cn phi l nhng chuyn gia c o to ph
hp v nhng sn phm c sn xut.
3.2
Cc nhn vin lm vic trong vng sch v trong khu v trng cn c la chn cn
thn, m bo tin tng h tun theo hng dn thc hnh, khng c bnh tt hoc c
nguy c gy nh hng sn phm. Yu cu cao v v sinh c nhn v lm sch ht sc cn
thit. Nhn vin cn c hng dn vic bo co bt k tnh trng no ca c nhn (tiu
chy, cm, ho, nhim trng da, bnh v tc, vt thng h hoc st khng r nguyn nhn)
c th gy pht tn vi sinh vt vo mi trng lm vic. Nhng ngi c biu hin khoogn
bnh thng gy nh hng n cht lng sn phm cn c ngn khng cho v khu vc
sn xut.
3.3
Hn ch ti a s nhn vin c mt trong vng sch v khu v trng khi ang sn
xut. Vic thanh tra, gim st (i vi khu vc ny) nn c thc hin t bn ngoi, cng
xa cng tt.
3.4
Trong qu trnh sn xut, nhn vin khng c php i t khu vc c kim sot v
vi sinh vt sng hoc ng vt n cc khu vc c kim sot khc tr khi c hng
dn p dng cc bin php lm v sinh ph hp, bao gm thay qun o giy dp. Nhng
ngi khng lin quan khng c php i vo khu vc sn xut tr mc ch c bit. Khi
h cn phi v sinh c nhn vi bo h ph hp.
3.5
Nhm nhn vin lm vic trong cc xng sn xut v nhm nhn vin chm sc
ng vt cn c lp vi nhau.
3.6
Tn v bng cp chuyn mn ngi ph duyt quy trnh sn xut l cn phi c
ng k vi c quan qun l nh nc (National control authority).
3.7
sn xut c sn phm t cht lng cao, nhn vin cn c o to v thc
hnh tt sn xut/phng kim nghim nhng lnh vc ph hp nh vi khun hc, vi rt
hc, sinh trc hc, ha hc, min dch hc, dc phm hay thuc th y.
3.8

Lu tr h s o to v nh k nh gi hiu qu chng trnh o to.

3.9
Nhn vin sn xut, bo tr, th nghim, chm sc ng vt (v thanh tra vin) cn
phi c tim phng cc vc xin thch hp, khi cn thit, phi c th pht hin bnh

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lao tin trin; c bin php cch ly i vi nhng nhn vin phi nhim tc nhn nhim
trng, c t hay cht gy d ng trnh ri ro gy nhim n sn phm.
3.10 i vi c s sn xut vc xin BCG, s lng nhn cn c hn ch v phi c
nh k khm sc khe cn thn. Cc c s sn xut sn phm t mu hoc huyt tng
ngi, nhn vin cn c tim vc xin nga vim gan B.

4. Nh xng v thit b
4.1
Nh xng cn phi c xc nh v tr, thit k, xy dng, bo tr, bo dng ph
hp vi nhng hot ng din ra. Phng th nghim, operating rooms v cc phng khc, v
xng sn xut (k c khu chm sc ng vt) ca c s sn xut sinh phm phi c
thit k v xy dng bng vt liu c tiu chun cao, d lm v sinh, khng tch t bi, nga
c cn trng su mt v c duy tr tt.
4.2
B mt bn trong (tng, sn v trn) phi nhn, khng c vt nt, khng sinh bi,
d lm v sinh, kh trng. Ming thot nc cn c hn ch ti a, v khng c c
trong khu vc v trng. Ming thot nc c lp t phi c np si phng, cho php v
sinh d dng v hiu qu, c khoang trng (air break) chng tro ngc. Cc np ming
thot c th c lp thm b phn un nng bng in hoc theo nhng cch thc khc
kh trng. Nu c rnh thot nc trn sn th chng cn c h, nng, d lm v sinh
v tip ni vi ming thot bn ngoi khu vc ngn nga c s xm nhp ca tp
nhim vi sinh vt.
4.3
Bn ra khng c c trong khu vc v trng. Bn ra trong cc khu vc sch
khc cn c lm bng vt liu ph hp d lm v sinh, chng hn nh bng thp khng r,
khng c trn; nc cp cho bn phi t cht lng nc ung c. Cn ch
trnh nhim t h thng thot cht thi nguy hi. Trnh s pht tn qua khng kh ca vi
khun gy bnh hay virut dng trong sn xut hoc nguy c tp nhim cc cht hay loi vi
rt khc trong qu trnh sn xut, k c t nhn vin.
4.4
nh sng, nhit , thng kh v, nu cn, iu ha khng kh cn c thit k
duy tr nhit , m tng i, gim thiu kh nng gy nhim v to iu kin thun
li cho nhn vin mang trang phc bo h lao ng. iu kin nh xng cn c nh k
xem xt tin hnh sa cha khi cn thit. Cn ch c bit m bo vic sa cha
hay bo tr nh xng khng nh hng n cht lng sn phm. Khng gian xng sn
xut phi rng cho cc hot ng din ra, lung sn xut hp l v d dng cho vic
thng tin hay gim st cng vic. Cc phng phi sch v c v sinh thng xuyn. Nu
phng sn xut hot cht sinh hc c s dng cho mc ch khc th cn phi c v
sinh thu o, v nu cn, phi c lm v sinh li trc khi quay li sn xut hot cht
sinh hc. Khu vc sn xut t nguyn liu m ng vt v vi sinh vt khng thuc phm vi
quy trnh sn xut hin ti v khu vc thc hin cc php th lin quan n ng vt v vi

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sinh vt phi c tch ring khi khu sn xut sinh phm v trng v c h thng iu ha
khng kh v nhn s ring.
4.5
Trng hp cc sn phm c sn xut theo chin dch th yu cu v thit k nh
xng v thit b cho php kh trng hiu qu, xng tit khun khi cn thit, v c lm
v sinh ton din sch s sau mi chin dch sn xut.
4.6
Chng ging (seed lots) v ngn hng t bo (cell banks) dng trong sn xut sinh
phm cn c bo qun ring so vi nhng nguyn liu khc. Ch ngi c phn s mi
c vo khu vc bo qun ny.
4.7
Vi sinh vt sng nui cy trong cc thit b phi c m bo rng vic nui cy
c duy tr trng thi thun khit v khng b tp nhim trong sut qu trnh sn xut.
4.8
Vic phn chia vo dng c cha ca nhng sn phm sau bt hot nh vc xin cht,
bao gm cc sn phm sn xut bng cng ngh ti t hp rDNA, cc gii c t v dch
chit vi khun, c th c thc hin cng nh xng vi cc sinh phm v trng khc,
vi iu kin c nhng bin php kh nhim c tin hnh sau khi chit rt, nu cn. bao
gm c vic tit trng v ra.
4.9
Sn phm sinh bo t cn c sn xut trong khu vc ring bit cho n khi hon
thnh cng on bt hot. Vi cc chng Bacillus anthracis, Clostrium botulium v
Clostridium tetani th cn c dy chuyn cch ly tuyt i cho mi sn phm. Khi sn xut
vi cc vi sinh vt sinh bo t theo chin dch trong mt khu vc hoc mt cm khu vc,
yu cu ch c mt sn phm c sn xut trong cng thi im.
4.10 Ch phm t mu hay huyt tng cn c sn xut trong xng v thit b ring
bit.
4.11 Tt c dng c cha nguyn liu sinh phm d ang bt k cng on sn xut no
cng phi c gn nhn nhn dng c gn chc chn. Tnh trng nhim cho cn c
ngn nga bi mt s hoc tt c cc bin php sau:
-

Ch bin v chit rt nhng khu vc ring bit;

Khng sn xut cc sn phm khc nhau trong cng mt thi im, tr khi chng c
phn cch hiu qu;
Vn chuyn dng c cha phi qua cht gi, my ht khng kh, thay i qun o, tm
ra cn thn v kh trng thit b.
Phng nga nhng nguy c nhim trng gy ra do s dng li khng kh khng c
x l hoc do nhim ngc kh bn.
S dng h thng sn xut khp kn;
Phng nga vic to phun m trong khng kh (do ly tm hay trn gy nn);
Khng mang mu bnh phm xt nghim vo khu vc sn xut vacxin v sinh phm.
S dng dng c cha c tit trng hoc loi c nguy c gy nhim vi sinh
(bioburden) thp.

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4.12 Khu vc c p sut dng nn c dng sn xut sn phm v trng. Khu vc

c p sut m c chp nhn trong mt s trng hp c bit nh khi sn xut loi sn
phm l tc nhn gy bnh. Ni chung, vi nhng sn phm c tnh cht gy bnh cn c
sn xut trong khu vc c thit k c bit c p sut m km cc yu cu bo v sn
phm (in accordance with containment requirements for the product concerned).
4.13 Cn b tr cc n v x l khng kh (AHU Air Handling Unit) ring cho khu vc
sn xut. Khng kh t cc phng sn xut cc sn phm c tnh cht gy bnh th khng
c tun hon ti s dng. Trng hp sinh vt thuc nhm nguy c cao hn nhm 2
(phn loi theo Laboratory Biosafety Manual, 2nd edition, Geneva, WHO), khng kh thi ra
cn phi qua mng lc v trng trc khi thi ra mi trng; nh k phi kim tra hiu
qu ca lc.
4.14 Cn p dng cc bin php c bit kh trng cht thi trong trng hp s dng
cc nguyn liu ly nhim hay c nguy c ly nhim trong qu trnh sn xut.
4.15 ng ng, van v lc thng kh cn c thit k thun li cho vic lm v sinh v
tit trng. Cc van ca thng ln men phi c kh nng tit trng trit bng hi nc.
Lc thng kh phi l loi k nc v cn c nh gi ph hp vi mc ch s dng.
4.16 Mt lng nh nhng nguyn liu c dng phi cn/o trong qu trnh sn xut
(nh m) c th c bo qun trong khu vc sn xut vi iu kin chng khng c
a tr li kho. Mt khc, nhng nguyn liu dng bt dng pha m hay mi trng
nui cy cn c cn v pha ch trong mt khu vc kn bn ngoi khu vc tinh ch v thao
tc v trng ngn nga nhim tiu phn vo sn phm.

5. Khu chn nui v chm sc ng vt

5.1
ng vt thng c s dng trong vic sn xut v kim tra cht lng sinh
phm. Chng phi c nht trong khu bit lp c ring h thng iu ha khng kh.
Nhng khu ny cn c thit k v xy dng ph hp bng nhng loi vt liu cho php
bo dng thun li, lm v sinh d dng, khng c cn trng su mt v duy tr bo dng
thng xuyn. Khu chm sc ng vt cn c phng cch ly nhng ng vt mi a v v
phng d tr thc n chn nui; c phng tim ring bit so vi phng m ng vt; c
phng v sinh lng/ci, bng hi nng nu c th, v l thiu cht thi hay xc ng vt.
5.2
Cn c bin php kim sot v ghi li h s v tnh trng sc khe v ngun gc cc
loi ng vt c s dng nh l nguyn liu ban u hay dng trong kim tra cht lng
hay th nghim an ton. Nhn vin lm vic trong khu ng vt phi c trang b bo h
lao ng vi phng v sinh cc nhn tm ra thay ph hp. C s s dng kh trong vic
sn xut v kim tra cht lng sinh phm cn c nhng yu cu thm c quy nh trong
ti liu Cc yu cu i vi hot cht sinh hc, S 7 (Requirements for Biological
Substances No. 7) (Cc yu cu i vi vc xin Bi lit ung - Requirements for Poliomyelitis

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vaccine (oral) ca Hi ng chuyn gia v tiu chun sinh phm - WHO expert Committee on
Biological Standardization, WHO TRS 800, Ph lc 1).

6. Sn xut
6.1
Cn sn c cc quy trnh thao tc chun c cp nht cho mi hot ng din ra
trong qu trnh sn xut.
6.2
Tiu chun nguyn liu ban u cn th hin c th v ngun gc, phng php sn
xut v kim tra cht lng nht l vi cc php th vi sinh vt, m bo ph hp vi
yu cu s dng. Kt qu kim tra cht lng nguyn liu ban u l iu kin bt buc khi
xem xt xut xng thnh phm.
6.3
Vic cho mi trng nui cy v cht dinh dng vo thng ln men hay cc thng
cha khc cn phi c tin hnh thn trng vi bin php thch hp trnh gy
nhim. Cn m bo lp rp khp ng cc thng cha khi cho mi trng vo.
6.4
Mi trng cn c tit trng ti ch nu c th. C th lc v khun trc tip trn
ng ng dn khi a kh gas, mi trng, acid, kim, cht chng to bt vo thng ln
men.
6.5

Cn tin hnh thm nh cc phng php tit trng.

6.6
Trng hp quy trnh sn xut c cng on bt hot, cn lu n cc bin php
trnh nguy c nhim cho.
6.7
C nhiu loi thit b khc nhau trong phng php sc k. Ni chung, nhng thit b
nh vy cn dnh ring cho vic tinh ch i vi mi sn phm v chng cn phi c lm
v sinh hoc tit trng gia cc l sn xut. Vic s dng lp i lp li cng mt thit b vi
cng mt hoc cc cng on khc nhau c th dn n cc s c v nhim hoc tinh sch.
Thi gian s dng cc ct sc k v phng php tit trng cn c xc nh r. Cn ch
c bit n vic gim st vi sinh v ni c t.

7. Ghi nhn
7.1
Mi sn phm cn c nhn r rng, gn chc chn vo cha, trong mi iu kin
bo qun. Vic gn nhn khng nh hng n vic kim tra kim sot sn phm bn
trong. Nu sn phm cui khng th gn nhn c (chng hn nh ng mao qun) th
nhn phi c gn trn bao gi.
7.2
Ni dung nhn trn thng cha v trn bao gi cn c ph duyt bi c quan
qun l nh nc (National control authority).
7.3
-

Nhn thng cha cn phi th hin c:

Tn sn phm;

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Danh sch cc hot cht v hm lng tng hot cht, v s lng hoc khi lng
tnh, v d s liu, khi lng hoc th tch;

S l sn phm cui do nh sn xut quy nh;

Hn dng;

iu kin bo qun v cnh bo cn thit;

Hng dn s dng v cnh bo cn thit;

Bn cht, hm lng ca bt k cht no c s dng trong qu trnh sn xut sinh

phm c kh nng gy tc dng ph i vi mt s ngi dng;

Tn, a ch nh sn xut v/hoc ngi chu trch nhim a thuc lu hnh trn th
trng.

7.4
Nhn trn bao gi ngoi cc thng tin trn thng, ti thiu cn phi c tn/s lng
bt k cht bo qun hay t dc/cht ph gia no c trong sn phm.
7.5

T hng dn s dng cn c ni dung chng ch nh hay phn ng ph tim tng.

8. H s l v h s phn phi sn phm

8.1
H s sn phm cn phi cung cp y thng tin qu trnh sn xut ca mi l
sinh phm; cho thy sn phm c sn xut, kim tra cht lng, ng gi v phn
phi ph hp vi h s ng k c duyt.
8.2

Cn c h s ring cho mi l sinh phm, gm nhng ni dung sau:

Tn, liu sn phm;

Ngy sn xut;

S l nhn dng;

Cng thc l y bao gm nhn dng chng v cc nguyn liu ban u;

S l ca mi thnh phn s dng trong cng thc;

Sn lng tng cng on ca l sn xut;

Cc bin bn c ch k xc nhn tng bc thc hin, cc ch v cc nh gi c bit

thc hin trong sut qu trnh sn xut l sn phm;

Bin bn ghi li cc test kim sot trong quy trnh v kt qu thu c;

Mu nhn;

Nhn nhn dng ca bao gi, chai l, np/nt s dng;

Ngy thng ch k ca ngi c trch nhim ph duyt hot ng sn xut;

Bo co phn tch, c ngy thng ch k ca ngi c trch nhim, th hin l sn

phm p ng cc tiu chun c nu trong quy trnh thao tc chun (SOP)
c c quan qun l nh nc (National control authority) ph duyt;

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H s v quyt nh xut xng hay loi b l sn phm ca phng qun l cht lng
v h s tiu hy hay tn dng trong trng hp sn phm loi b;

8.3
Nhng h s ny cn phi c ph duyt bi c quan qun l nh nc (National
control authority); c lu gi t nht 2 nm sau ngy l phm ht hn dng v lun sn
c trong mi thi im phc v hot ng thanh tra ca c quan qun l nh nc.
8.4
H s cn phi m bo sao cho c th truy nguyn (trace back) c tt c cc
bc ca qu trnh sn xut v kim nghim ca mt l sn phm, v phi bao gm c h s
tit trng ca tt c thit b v nguyn liu c dng trong sn xut l . H s phn phi
phi c lu gi theo cch thc cho php thu hi nhanh chng bt k l sn phm no khi
cn thit.

9. m bo cht lng v kim tra cht lng

9.1

Phng m bo/kim tra cht lng cn c cc trch nhim sau:

Chun b cc hng dn chi tit cho tng th nghim, phn tch;

m bo nhn dng v phn tch cc mu th ph hp, trnh nhn ln, nhim cho;

m bo vic gim st mi trng v vic thm nh thit b c thc hin ph

hp c th nh gi c iu kin sn xut;

Chp nhn hay loi b nguyn liu th v cc sn phm trung gian khi cn thit;

Chp nhn hay loi b bao b, nhn mc v cha thnh phm;

Xut xng hay loi b l thnh phm;

nh gi iu kin bo qun nguyn liu th, sn phm trung gian v thnh phm;

nh gi cht lng v n nh ca thnh phm v, nu cn, ca nguyn liu th v

bn thnh phm;

Thit lp hn dng da trn kt qu theo di n nh sn phm iu kin bo

qun c th;

Xy dng, r sot/sa i khi cn thit quy trnh kim nghim v tiu chun cht
lng;

Kim tra, nh gi cht lng sn phm tr v quyt nh chp nhn, ti ch hay tiu
hy. Lu gi h s phn phi ca nhng loi sn phm ny.

9.2
Phng kim nghim cn c b tr cch bit khi khu vc sn xut; tt hn ht l
c b tr trong ta nh ring. Phng kim nghim cn c thit k rng v trang b
cc thit b phn tch c th t hot ng c lp; c quy hoch ni lu tr, bo qun
h s, mu, ni chun b h s v ni tin hnh thao tc th nghim.
9.3
Hot ng kim tra trong qu trnh (In-process control) ng vai tr ht sc quan
trng trong vic m bo cht lng n nh ca sinh phm. Nhng th nghim quan trng

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trong vic kim tra cht lng nhng khng th thc hin c i vi thnh phm cui
cng th cn phi c thc hin trong qu trnh sn xut nhng cng on thch hp.
9.4
Vic thc hin tt c cc ch tiu nh tnh hay nh lng trong tiu chun nguyn
liu ban u c th c thay bng h thng cc Giy chng nhn (Certificate) ca nh sn
xut nguyn liu ban u , vi iu kin:
-

Nh sn xut nguyn liu c lch s qu trnh sn xut ng tin cy;

Nh sn xut nguyn liu c thanh tra (audit) nh k; v
C t nht mt php th nh tnh c tnh c hiu c thc hin bi chnh c s sn
xut thnh phm c s dng nguyn liu .

9.5
Mu ca sn phm trung gian v thnh phm phi c lu s lng v c
bo qun iu kin thch hp cho php thc hin lp li hoc xc nhn li vic kim
nghim cht lng ca mt l sn phm. Tuy nhin, mu i chiu (reference sample) ca
mt s nguyn liu ban u nht nh, chng hn nh cc thnh phn ca mi trng nui
cy th khng cn thit phi lu mu.
9.6
Mt s hot ng nht nh yu cu vic theo di d liu lin tc trong qu trnh sn
xut, chng hn nh vic theo di v ghi chp cc thng s vt l trong sut qu trnh ln
men.
9.7
Cn quan tm c bit i vi cc yu cu kim tra cht lng i vi vic sn xut
sinh phm bng phng php nui cy lin tc (continuous culture).

Tc gi
Ti liu Thc hnh sn xut tt cho sinh phm c d tho ln u tin vo thng 1 nm
1991 do Dr V. P. Grachev, Scientist v Dr D.I. Magrath, Chief, Biologicals, WHO, Geneva,
Switzerland.

Li cm n
Li cm n xin c gi ti cc chuyn gia sau v nhng nhn xt v gp ca h vi bn
tho Thc hnh sn xut tt cho sinh phm: Professor I. Addae-Mensah, Chemistry
Department, University of Ghana, Accra, Ghana; Professor H. Blume, German Pharmacists'
Central Laboratory, Eschborn, Germany; Dr A. Fenyves, Paul Ehrlich Institute, Langen,
Germany; Dr C. Guthrie, General Manager, Blood Products Division, CSL Ltd., Parkville,
Australia; Dr U. Ihrig, German Pharmacists' Central Laboratory, Eschborn, Germany; Mr K.
Kawamura, Takeda Chemical lndustries Ltd., Nihonbashi, Chuo-ku, Tokyo, Japan; Mr L. G.
Kinnander, Chief, Pharmaceutical Industries Ltd.: Nihonbashi, Chuo-ku, Tokyo: Japan; Mrs S. F.
Langlois, Director, Regulatory Affairs: Connaught Laboratories Ltd., A Pasteur Merieux
Company, Willowdale, Ontario, Canada; Mr P. Lemoine, institute of Hygiene and Epidemiology,
Brussels, Belgium; Mr J. Lyng, State Serum Institute, Copenhagen, Denmark; Professor N.V.
Medunitsin, Director, Tarasevich State Institute for the Standardization and Control of Medical
Biological Preparations, Moscow, USSR; Dr R. Netter, Paris, France; Professor A.A. Olaniyi:

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 World Health Organization

WHO Technical Report Series, No. 822, 1992
Pharmaceutical & Chemistry Department, Faculty of Pharmacy, University of Ibadan, Ibadan,
Nigeria.

Ti liu tham kho

1.

Good manufacturing practices for pharmaceutical products. In: WHO Expert Committee
on Specifications for Pharmaceutical Preparations. Thirty-second Report. Geneva, World
Health Organization, 1992 (WHO Technical Report Series, No.823), Annex l.

2.

WHO Expert Committee on Biological Standardization. Forty-second Report. Geneva,

World Health Organization, 1992 (WHO Technical Report Series, No. 822).

3.

Laboratory biosafety manual, 2nd ed. Geneva, World Health Organization, in press.

4.

Quality management for chemical safety testing. Geneva, World Health Organization,
1992 (Environmental Health Criteria, No.141).

5.

WHO Expert Committee on Biological Standardization. Fortieth Report. Geneva, World

Health Organization, 1990 (WHO Technical Report Series, No. BOO), Annex 1.

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