GMP WHO 2014 en Vi For Share

WHO Technical Report Series 986
WHO Expert Committee

on Specifications
for Pharmaceutical
Preparations
Forty-eighth report Bo co s 48
Annex 2 Ph lc 2:
WHO good manufacturing Thc hnh tt sn xut sn
practices for pharmaceutical phm dc phm WHO:
products: main principles cc nguyn tc c bn
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WHO TRS 986 Annex 2: WHO good manufacturing practices for pharmaceutical products: main principles
Table of Contents | Mc lc
Glossary.......................................................................................................................3
Gii thch thut ng....................................................................................................3
Quality management in the medicines industry: philosophy and essential elements 8
Qun l cht lng trong cng nghip dc: l lun v cc yu t c bn................8
1 Pharmaceutical quality system................................................................................8
1 H thng qun l cht lng dc phm.................................................................8
2. Good manufacturing practices for pharmaceutical products...............................13
2. Thc hnh tt sn xut dc phm.......................................................................13
3. Sanitation and hygiene.........................................................................................14
3 V sinh v kh trng..............................................................................................14
4. Qualification and validation..................................................................................14
4. Thm nh.............................................................................................................14
5. Complaints............................................................................................................15
5. Khiu ni...............................................................................................................15
6. Product recalls......................................................................................................16
6. Thu hi sn phm..................................................................................................16
7. Contract production, analysis and other activities...............................................17
7. Sn xut, th nghim v cc hot ng khc theo hp ng...............................17
8. Self-inspection, quality audits and suppliers audits and approval......................19
8. T thanh tra, thanh tra cht lng, thanh tra v ph duyt nh cung cp..........19
9. Personnel...............................................................................................................21
9 Nhn vin...............................................................................................................21
10. Training...............................................................................................................25
10. o to................................................................................................................25
11. Personal hygiene.................................................................................................25
11. V sinh c nhn...................................................................................................25
12. Premises..............................................................................................................26
12. Nh xng...........................................................................................................26
13. Equipment...........................................................................................................30
13. My mc thit b.................................................................................................30
14. Materials.............................................................................................................31
14. Nguyn vt liu...................................................................................................31
15. Documentation....................................................................................................36
15. H s ti liu.......................................................................................................36
16. Good practices in production..............................................................................45
16. Thc hnh tt trong sn xut..............................................................................45
17. Good practices in quality control........................................................................50
17. Thc hnh tt trong kim tra cht lng............................................................50
References / Ti liu tham kho................................................................................55
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Glossary Gii thch thut ng

The definitions given below apply to the terms used Cc nh ngha nu ra di y p dng cho cc
in this guide. They may have different meanings in thut ng s dng trong ti liu hng dn ny.
other contexts. Chng c th c cc ngha khc nu c dng trong
cc hon cnh khc.
active pharmaceutical ingredient (API) hot cht dc dng
Any substance or mixture of substances intended to Bt k mt cht hoc hn hp cc cht d nh c

be used in the manufacture of a pharmaceutical s dng trong sn xut mt dng bo ch dc
dosage form and that, when so used, becomes an phm, v khi c s dng, n tr thnh thnh phn
active ingredient of that pharmaceutical dosage hot tnh ca dng bo ch . Nhng cht nh vy
form. Such substances are intended to furnish c dng vi mc ch em li tc dng dc l
pharmacological activity or other direct effect in the hoc cc tc dng trc tip khc trong chun on,
diagnosis, cure, mitigation, treatment, or prevention cha tr, lm gim nh, iu tr hoc phng nga
of disease or to affect the structure and function of bnh tt, hoc c tc dng ln cu trc v chc nng
the body. ca c th.
airlock Cht gi
An enclosed space with two or more doors, which is Mt khu vc kn c hai ca tr ln, nm gia hai hoc
interposed between two or more rooms, e.g. of nhiu phng, v d nh nm gia cc phng c mc
differing classes of cleanliness, for the purpose of sch khc nhau, vi mc ch kim sot lung
controlling the airflow between those rooms when khng kh gia nhng phng ny khi cn ra vo. Mt
they need to be entered. An airlock is designed for cht gi c thit k s dng cho ngi hoc
use either by people or for goods and/or equipment. hng ha v/hoc trang thit b.
authorized person ngi c y quyn
The person recognized by the national regulatory L mt ngi c c quan qun l quc gia tha
authority as having the responsibility for ensuring nhn l c trch nhim m bo rng mi l thnh
that each batch of finished product has been phm u c sn xut, kim nghim v duyt
manufactured, tested and approved for release in xut xng theo ng lut l v quy ch hin hnh
compliance with the laws and regulations in force in ca nc .
that country.
batch (or lot) m (hoc l)
A defined quantity of starting material, packaging L mt lng xc nh nguyn vt liu ban u,

material, or product processed in a single process or nguyn vt liu bao gi, hoc sn phm c ch
series of processes so that it is expected to be bin trong mt quy trnh n l hoc mt lot cc
homogeneous. It may sometimes be necessary to quy trnh v c tnh ng nht. i khi c th cn
divide a batch into a number of sub-batches, which phi chia l thnh mt s m, sau tp trung li
are later brought together to form a final hnh thnh mt l ng nht cui cng. Trong trng
homogeneous batch. In the case of terminal hp tit trng cng on cui, c l c xc nh
sterilization, the batch size is determined by the bi cng sut ca ni hp. Trong sn xut lin tc, l
capacity of the autoclave. In continuous manufacture, phi tng ng vi mt phn xc nh trong sn xut
the batch must correspond to a defined fraction of vi c trng ring l s ng nht d kin. C l c
the production, characterized by its intended th c sn xc nh nh mt lng sn phm c
homogeneity. The batch size can be defined either as nh hoc mt lng sn phm sn xut ra trong mt
a fixed quantity or as the amount produced in a fixed thi gian c nh.
time interval.
batch number (or lot number) s m (hoc s l)
A distinctive combination of numbers and/or letters L s kt hp ca cc con s v/hoc ch ci nhn

which uniquely identifies a batch on the labels, its dng duy nht mt l, c ghi trn nhn, trong h
batch records and corresponding certificates of s l, trn phiu kim nghim tng ng,....
analysis, etc.
batch records H s l
All documents associated with the manufacture of a Tt c ti liu c lin quan n vic sn xut mt l
batch of bulk product or finished product. They bn thnh phm hoc thnh phm. Chng th hin
provide a history of each batch of product and of all lch s ca mi m (l) sn phm, v ca nhng tnh

circumstances pertinent to the quality of the final hung lin quan n cht lng ca sn phm cui
product. cng.
bulk product bn thnh phm
Any product that has completed all processing stages Sn phm qua tt c cc cng on sn xut, tr
up to, but not including, final packaging. cng on ng gi cui cng.
calibration hiu chun
The set of operations that establish, under specified Mt lot cc thao tc nhm thit lp trong iu kin
conditions, the relationship between values indicated nht nh, mt mi quan h gia cc gi tr c c
by an instrument or system for measuring (especially do mt thit b hay mt h thng o c (c bit l
weighing), recording, and controlling, or the values cn) ghi li, v kim sot, hoc cc gi tr th hin
represented by a material measure, and the bi mt vt liu o lng, so vi cc gi tr tng ng
corresponding known values of a reference standard. c bit n ca mt chun i chiu. Cn xc
Limits for acceptance of the results of measuring lp cc gii hn chp nhn ca cc kt qu o lng.
should be established.
Clean area khu vc sch
An area with defined environmental control of Mt khu vc c thc hin cc bin php kim sot
particulate and microbial contamination, constructed mi trng xc nh i vi cc tiu phn v vi sinh
and used in such a way as to reduce the introduction, vt, c xy dng v s dng theo cch thc sao cho
generation, and retention of contaminants within the c th gim vic em vo, to nn v lu gi cc yu
area. t gy tp nhim trong phm vi khu vc .
consignment (or delivery) chuyn hng (hay t giao hng)
The quantity of a pharmaceutical or pharmaceuticals, Mt lng ca mt dc phm hoc nhiu dc phm

made by one manufacturer and supplied at one time c sn xut bi mt nh sn xut v c cung cp
in response to a particular request or order. A mt t (ti mt thi im) theo mt ngh hay n
consignment may comprise one or more packages or t hng c th. Mt chuyn hng c th bao gm
containers and may include material belonging to mt hoc nhiu thng hng hoc container v c th
more than one batch bao gm sn phm ca mt hoc nhiu m (l)
contamination tp nhim
The undesired introduction of impurities of a L s nhim khng mong mun cc tp cht c bn

chemical or microbiological nature, or of foreign cht ha hc hoc vi sinh, hoc tiu phn l vo mt
matter, into or on to a starting material or nguyn liu ban u hoc sn phm trung gian trong
intermediate during production, sampling, packaging qu trnh sn xut, ly mu, ng gi hoc ng gi
or repackaging, storage or transport. li, bo qun hoc vn chuyn.
critical operation thao tc quan trng
An operation in the manufacturing process that may Mt thao tc trong qu trnh sn xut c th gy ra
cause variation in the quality of the pharmaceutical nhng bin i v cht lng sn phm.
product.
cross-contamination nhim cho
Contamination of a starting material, intermediate Vic nhim mt nguyn liu ban u, sn phm trung
product or finished product with another starting gian, hoc thnh phm vo mt nguyn liu ban u
material or product during production. hoc sn phm khc trong qu trnh sn xut.
finished product thnh phm
A finished dosage form that has undergone all stages Mt dng bo ch hon thin tri qua tt c cc
of manufacture, including packaging in its final cng on sn xut, k c ng gi vo bao b cui
container and labelling. cng v dn nhn.
in-process control kim tra trong qu trnh sn xut
Checks performed during production in order to Nhng kim tra c thc hin trong qu trnh sn
monitor and, if necessary, to adjust the process to xut nhm gim st, v nu cn, iu chnh quy trnh

ensure that the product conforms to its m bo sn phm t c cc tiu chun d

specifications. The control of the environment or nh. Vic kim sot mi trng hoc trang thit b
equipment may also be regarded as a part of in- cng c th coi l mt phn ca vic kim tra trong
process control. qu trnh sn xut.
intermediate product sn phm trung gian
Partly processed product that must undergo further Sn phm ch bin mt phn v cn phi tip tc
manufacturing steps before it becomes a bulk qua cc cng on sn xut khc na mi tr thnh
product. bn thnh phm.
large-volume parenterals thuc tim truyn th tch ln
Sterile solutions intended for parenteral application Nhng dung dch v trng dng ng tim
with a volume of 100 ml or more in one container of truyn vi bao b ng gi thnh phm c th tch t
the finished dosage form. 100ml tr ln.
manufacture sn xut
All operations of purchase of materials and products, Tt c cc hot ng t khi mua nguyn liu v sn
production, quality control (QC), release, storage and phm, sn xut, kim tra cht lng (QC), xut
distribution of pharmaceutical products, and the xng, bo qun v phn phi thnh phm v cc
related controls. bin php kim sot c lin quan khc.
manufacturer nh sn xut
A company that carries out operations such as Mt cng ty thc hin cc hot ng v d nh sn
production, packaging, repackaging, labelling and xut, ng gi, ng gi li, dn nhn v dn nhn li
relabelling of pharmaceuticals. dc phm.
marketing authorization (product licence, giy php lu hnh (giy php sn phm, giy
registration certificate) chng nhn ng k)
A legal document issued by the competent medicines Ti liu php l do c quan qun l dc quc gia c
regulatory authority that establishes the detailed thm quyn cp, trong xc nh thnh phn chi
composition and formulation of the product and the tit v cng thc ca sn phm ca sn phm v cc
pharmacopoeial or other recognized specifications of tiu chun dc in hoc cc tiu chun c cng
its ingredients and of the final product itself, and nhn khc i vi cc thnh phm hot cht ca sn
includes details of packaging, labelling and shelf-life. phm, v ca chnh bn thn sn phm, k c chi tit
v quy cch ng gi, nhn v tui th.
master formula cng thc gc
A document or set of documents specifying the Mt ti liu hoc b ti liu ch r cc nguyn liu
starting materials with their quantities and the ban u v khi lng ca chng, nguyn liu bao
packaging materials, together with a description of gi, cng vi bn m t cc quy trnh v nhng im
the procedures and precautions required to produce cn thn trng sn xut ra mt lng xc nh
a specified quantity of a finished product as well as thnh phm, cng nh cc ch dn v ch bin, k c
the processing instructions, including the in- process kim tra trong qu trnh sn xut.
controls.
master record h s gc
A document or set of documents that serve as a basis Mt ti liu hoc b ti liu dng lm bn gc cho h
for the batch documentation (blank batch record). s l (h s l trng)
packaging ng gi
All operations, including filling and labelling, that a Tt c cc thao tc, k c ng chai v dn nhn,
bulk product has to undergo in order to become a cho mt bn thnh phm tr thnh mt thnh phm.
finished product. Filling of a sterile product under ng chai mt sn phm v trng trong iu kin v
aseptic conditions or a product intended to be trng, hoc mt sn phm c tit trng cng
terminally sterilized, would not normally be regarded on cui thng khng c coi l mt phn ca
as part of packaging. ng gi.
packaging material nguyn liu bao gi

Any material, including printed material, employed in Nguyn vt liu, k c vt liu c in n, s dng
the packaging of a pharmaceutical, but excluding any trong gi mt dc phm, tr ng gi bn ngoi
outer packaging used for transportation or shipment. vn chuyn. Nguyn liu bao gi cp n y
Packaging materials are referred to as primary or c gi l bao b s cp hoc th cp ty thuc vo
secondary according to whether or not they are vic chng c tip xc trc tip vi sn phm hay
intended to be in direct contact with the product. khng.
pharmaceutical product dc phm
Any material or product intended for human or Mt nguyn liu hoc sn phm d nh s dng cho
veterinary use presented in its finished dosage form ngi hoc th y, c trnh by dng bo ch
or as a starting material for use in such a dosage thnh phm hoc dng nguyn liu ban u dng
form, that is subject to control by pharmaceutical cho dng thnh phm , phi chu s iu chnh ca
legislation in the exporting state and/or the lut l v dc c quc gia xut khu v/hoc quc
importing state. gia nhp khu.
production hot ng sn xut
All operations involved in the preparation of a Tt c cc thao tc c lin quan n vic bo ch mt

pharmaceutical product, from receipt of materials, dc phm, t khi nhn nguyn liu, qua cng on
through processing, packaging and repackaging, ch bin, ng gi v ng gi li, dn nhn v dn
labelling and relabelling, to completion of the nhn li, cho ti khi hon thin thnh phm.
finished product.
qualification thm nh
Action of proving that any premises, systems and Mt hot ng nhm chng minh rng mt c s nh
items of equipment work correctly and actually lead xng, h thng v trang thit b hot ng chnh xc
to the expected results. The meaning of the word v thc s em li kt qu nh mong mun. Ngha
validation is sometimes extended to incorporate ca t cng nhn gi tr i khi c m rng
the concept of qualification. bao gm khi nim thm nh
quality assurance m bo cht lng

See Part 1 (6) Xem Phn 1 (6)
quality control kim tra cht lng

See Part 1 (6) Xem Phn 1 (6)
quality unit(s) (cc) n v cht lng
An organizational unit independent of production Mt n v t chc c lp vi sn xut bao gm c

which fulfils both quality assurance (QA) and quality trch nhim m bo cht lng (QA) v kim sot
control (QC) responsibilities. This can be in the form cht lng (QC). iu ny c th hnh thnh tch bit
of separate QA and QC units or a single individual or n v QA v QC hoc mt n v n l hoc nhm,
group, depending upon the size and structure of the ph thuc vo quy m v cu trc ca t chc.
organization.
quarantine bit tr
The status of starting or packaging materials, Tnh trng nguyn liu ban u hoc nguyn liu bao
intermediates, or bulk or finished products isolated gi, sn phm trung gian, bn thnh phm hoc
physically or by other effective means while a thnh phm c tch ring bit mt cch c hc,
decision is awaited on their release, rejection or hoc bng cc bin php hiu qu khc, trong khi
reprocessing. ch i quyt nh cho php xut xng, loi b hoc
ti ch.
reconciliation i chiu
A comparison between the theoretical quantity and Vic so snh gia lng l thuyt v lng thc t.
the actual quantity.
recovery phc hi
The introduction of all or part of previous batches (or Vic a mt phn hay ton b l sn phm trc
of redistilled solvents and similar products) of the (hoc dung mi c chng ct li hoc cc sn

required quality into another batch at a defined stage phm tng t) c cht lng t quy nh, vo mt
of manufacture. It includes the removal of impurities l sn xut khc mt cng on xc nh trong qu
from waste to obtain a pure substance or the trnh sn xut. Phc hi bao gm c vic loi b tp
recovery of used materials for a separate use. cht ra khi cht thi c c mt cht tinh khit
hoc phc ch cc nguyn vt liu qua s dng
dng li cho mc ch khc.
reprocessing ch bin li
Subjecting all or part of a batch or lot of an in- Vic em ton b hoc mt phn ca mt l / m
process medicine, bulk process intermediate (final thuc ang ch bin, sn phm trung gian (sn phm
biological bulk intermediate) or bulk product of a sinh hc cui cng trc khi ng gi) hoc bn
single batch/lot to a previous step in the validated thnh phm ca mt l / m n l tr li bc sn
manufacturing process due to failure to meet xut trc trong qu trnh sn xut c thm
predetermined specifications. nh, v khng p ng c cc tiu chun cht
lng nh trc.
Reprocessing procedures are foreseen as Qu trnh ch bin li i khi l cn thit i vi cc
occasionally necessary for biological medicines and, sn phm sinh hc, trong trng hp , vic ch
in such cases, are validated and pre-approved as part bin li phi c thm nh v ph duyt trc
of the marketing authorization. trong giy php lu hnh.
reworking ti ch
Subjecting an in-process or bulk process Vic em sn phm ang ch bin hoc sn phm
intermediate (final biological bulk intermediate) or trung gian (sn phm sinh hc cui cng trc khi
final product of a single batch to an alternate ng gi) hoc thnh phm ca mt m n (l) ch
manufacturing process due to a failure to meet bin li theo mt quy trnh sn xut khc do khng
predetermined specifications. t cc tiu chun nh.
Reworking is an unexpected occurrence and is not Vic ti ch nh vy l trng hp khng mong mun
pre-approved as part of the marketing authorization. v khng c ph duyt trc trong giy php sn
phm.
self-contained area khu vc khp kn
Premises which provide complete and total Nhng c s nh xng m bo tch bit hon ton
separation of all aspects of an operation, including trn mi phng din, k c vic di chuyn ca nhn
personnel and equipment movement, with well vin v trang b, theo cc quy trnh c thit lp tt,
established procedures, controls and monitoring. c kim sot v gim st cht ch. Khu vc khp
This includes physical barriers as well as separate kn bao gm c cc ro chn c hc cng nh h
air-handling systems, but does not necessarily imply thng x l khng kh tch bit, nhng khng nht
two distinct and separate buildings. thit phi t hai ta nh ring bit.
specification tiu chun
A list of detailed requirements with which the Mt danh mc cc yu cu c th m sn phm hoc

products or materials used or obtained during nguyn vt liu s dng hoc thu c trong qu
manufacture have to conform. They serve as a basis trnh sn xut phi t c. Tiu chun c dng
for quality evaluation. lm c s nh gi cht lng.
standard operating procedure (SOP) quy trnh thao tc chun (SOP)
An authorized written procedure giving instructions Mt quy trnh bng vn bn v c ph duyt,

for performing operations not necessarily specific to a ra cc ch dn cho vic thc hin cc thao tc,
a given product or material (e.g. equipment khng nht thit phi c th cho tng sn phm hoc
operation, maintenance and cleaning; validation; nguyn liu (v d: vn hnh, bo dng v lm v
cleaning of premises and environmental control; sinh my; thm nh; lm v sinh nh xng v kim
sampling and inspection). Certain SOPs may be used sot mi trng; ly mu v thanh tra). Mt s SOP
to supplement product-specific master and batch c th c s dng b sung cho h s sn phm
production documentation. v h s sn xut l gc cho sn phm c th.
starting material nguyn liu ban u
Any substance of a defined quality used in the Mt cht c cht lng xc nh c s dng trong
production of a pharmaceutical product, but sn xut mt dc phm, nhng khng phi l
excluding packaging materials. nguyn liu bao gi.

validation thm nh
Action of proving, in accordance with the principles Mt hot ng nhm chng minh trong mt quy trnh
of GMP, that any procedure, process, equipment, thao tc, quy trnh ch bin, my mc, nguyn vt
material, activity or system actually leads to the liu, hot ng hoc h thng no thc s em li
expected results (see also qualification). cc kt qu nh mong mun, theo ng cc nguyn
tc ca GMP (xem qualification).
Quality management in the Qun l cht lng trong cng

medicines industry: philosophy nghip dc: l lun v cc yu
and essential elements t c bn
In the medicines industry at large, quality Trong cng nghip dc ni chung, qun l cht
management is usually defined as the aspect of lng c xc nh l mt phn trong chc nng
management function that determines and qun l, ng vai tr thit lp v thc hin chnh
implements the quality policy, i.e. the overall sch cht lng, l d nh v nh hng tng th
intention and direction of an organization regarding ca mt cng ty i vi vn cht lng, c
quality, as formally expressed and authorized by top gii chc lnh o cao nht ca cng ty chnh thc
management. tuyn b v chp nhn.
The basic elements of quality management are: Nhng yu t c bn trong qun l cht lng gm:
an appropriate infrastructure or quality system, mt c s h tng hay mt h thng cht lng
encompassing the organizational structure, ph hp, bao gm c cu t chc, cc quy trnh thao
procedures, processes and resources; and tc, quy trnh ch bin v ngun lc;
systematic actions necessary to ensure adequate cc hot ng c tnh h thng cn thit m
confidence that a product (or service) will satisfy bo c tin cy rng mt sn phm (hay dch v) s
given requirements for quality. p ng cc yu cu nht nh v cht lng
The totality of these actions is termed QA. Within Tng th ca ton b cc hot ng ny c gi
an organization, QA serves as a management tool. In bng thut ng m bo cht lng (QA). Trong ni
contractual situations, QA also serves to generate b mt cng ty, m bo cht lng c s dng
confidence in the supplier. nh mt phng tin qun l. Trong trng hp sn
xut theo hp ng, m bo cht lng cng c
s dng to s tin cy ca nh cung cp.
The concepts of QA, GMP, QC and quality risk Khi nim m bo cht lng (QA), GMP, kim sot
management (QRM) are interrelated aspects of cht lng (QC) v qun l ri ro v cht lng
quality management and should be the responsibility (QRM) l cc kha cnh tng h trong qun l cht
of all personnel. They are described here in order to lng v phi l trch nhim ca tt c mi ngi.
emphasize their relationship and their fundamental Cc yu t ny c m t y nhm nhn mnh
importance to the production and control of mi quan h v tm quan trng c bn ca chng i
pharmaceutical products. vi sn xut v kim sot dc phm.
1 Pharmaceutical quality 1 H thng qun l cht lng

system dc phm
1.1 Principle. The manufacturer must assume 1.1 Nguyn tc. Nh sn xut phi chu trch nhim
responsibility for the quality of the pharmaceutical v cht lng cc sn phm dc phm m bo
products to ensure that they are fit for their intended rng chng ph hp cho mc ch s dng, ph hp
use, comply with the requirements of the marketing cc yu cu ca giy php lu hnh v khng t
authorization and do not place patients at risk due to bnh nhn vo tnh trng ri ro v an ton, cht
inadequate safety, quality or efficacy. lng, hiu qu iu tr.
The attainment of this quality objective is the t c mc tiu cht lng ny l trch nhim ca
responsibility of senior management and requires the lnh o cp cao v i hi s tham gia v cam kt
participation and commitment of staff in many ca nhn vin nhiu phng ban khc nhau v tt
different departments and at all levels within the c cc cp trong cng ty, nh cung cp ca cng ty
company, the companys suppliers and the v cc nh phn phi. t c mc tiu cht

distributors. To achieve this quality objective reliably lng ny chc chn phi c mt h thng cht lng
there must be a comprehensively designed and dc phm (PQS) c thit k mt cch ton din
correctly implemented pharmaceutical quality v thc hin chnh xc kt hp GMP v QRM
system (PQS) incorporating GMP and QRM
1.2 Senior management has the ultimate 1.2 Qun l cp cao c trch nhim cao nht trong
responsibility to ensure an effective PQS is in place, vic m bo mt PQS hiu qu c t ra, cung
is adequately resourced, and that roles, cp y ngun lc, v cc vai tr, trch nhim v
responsibilities, and authorities are defined, quyn hn c quy nh, thng bo v thc hin
communicated and implemented throughout the ton b t chc. Lnh o v ch ng tham gia lnh
organization. Senior managements leadership and o cp cao trong PQS l iu cn thit. Lnh o
active participation in the PQS is essential. This phi m bo s h tr v cam kt ca nhn vin
leadership should ensure the support and tt c cc cp, cc a im trong t chc i vi
commitment of staff at all levels and sites within the PQS.
organization to the PQS.
1.3 Quality management is a wide-ranging concept 1.3 Qun l cht lng l mt khi nim rt rng bao
covering all matters that individually or collectively gm tt c cc vn c nh hng n l hay cng
influence the quality of a product. It is the totality of gp n cht lng ca sn phm. l ton b cc
the arrangements made with the object of ensuring sp xp c thc hin vi mc ch m bo rng
that pharmaceutical products are of the quality cc sn phm dc phm c cht lng theo yu cu
required for their intended use. Quality management, cho mc ch s dng ca chng. Qun l cht lng,
therefore, incorporates GMP and other factors, do , kt hp GMP v cc yu t khc, bao gm c
including those outside the scope of this guide, such nhng i tng bn ngoi phm vi ca hng dn
as product design and development. ny, chng hn nh thit k sn phm v pht trin.
1.4 GMP applies to the life-cycle stages from the 1.4 GMP p dng cho cc giai on t sn xut cc
manufacture of investigational medicinal products, sn phm thuc nghin cu, chuyn giao cng ngh,
technology transfer, and commercial manufacturing, sn xut v thng mi, thng qua ngng sn
through to product discontinuation. The PQS can xut. Cc PQS c th m rng n cc giai on
extend to the pharmaceutical development life-cycle trong chu k pht trin dc phm v nn to iu
stage and should facilitate innovation and continual kin cho s i mi v ci tin lin tc v tng cng
improvement and strengthen the link between s lin kt gia cc hot ng pht trin v sn xut
pharmaceutical development and manufacturing dc phm. Tt c cc b phn ca PQS nn c
activities. All parts of the PQS should be adequately trang b y ngun lc v duy tr, k c c cung
resourced and maintained, including being provided cp nhn vin c nng lc ph hp, nh xng,
with sufficient competent personnel, suitable trang thit b v c s vt cht ph hp.
premises, equipment and facilities
1.5 The PQS appropriate to the manufacture of 1.5 Cc PQS thch hp sn xut cc sn phm
pharmaceutical products should ensure that: dc phm phi m bo rng:
(a) product realization is achieved by designing, (a) to sn phm c thc hin bng cch thit k,
qualifying, planning, implementing, maintaining thm nh, lp k hoch, thc hin, duy tr v
and continuously improving a system that allows khng ngng ci thin mt h thng cho php
the consistent delivery of products with giao hng ph hp ca sn phm vi cc thuc
appropriate quality attributes; tnh cht lng ph hp;
(b) product and process knowledge is managed (b) tri thc v qu trnh v sn phm c qun l
throughout all life-cycle stages; trong ton b cc giai on chu k sn phm.
(c) pharmaceutical products are designed and (c) sn phm dc phm c thit k v pht trin
developed in a way that takes account of the theo cch p ng cc yu cu ca GMP v cc
requirements of GMP and other associated codes quy tc thc hnh lin quan khc nh GLP v GCP
such as those of good laboratory practice (GLP)
and good clinical practice (GCP);
(d) production and control operations are clearly (d) cc hot ng sn xut v kim sot phi m t r
specified in a written form and GMP requirements rng bng vn bn v cc yu cu ca GMP phi
are adopted; c p dng.
(e) managerial responsibilities are clearly specified in (e) trch nhim qun l c m t r rng trong cc
job descriptions; bn m t cng vic
(f) arrangements are made for the manufacture, (f) cc sp xp phi c thc hin cho sn xut,
supply and use of the correct starting and cung cp v s dng ng cc nguyn liu ban
packaging materials, the selection and monitoring u v vt liu bao gi, la chn v gim st nh

of suppliers and for verifying that each delivery is cung cp v thm tra xc nhn rng mi chuyn
the correct material from the approved supply giao hng chuyn giao ng cc nguyn vt liu
chain; t chui cung ng c duyt.
(g) all necessary controls on starting materials, (g) tt c cc bin php kim sot cn thit i vi
intermediate products, and bulk products and nguyn liu ban u, sn phm trung gian, bn
other in-process controls, calibrations and thnh phm v cc bin php kim sot trong qu
validations are carried out; trnh khc, hiu hun v thm nh phi c thc
hin.
(h) the finished product is correctly processed and (h) sn phm sau cng phi c sn xut v kim
checked, according to the defined procedures; tra chnh xc, tun theo cc th tc nh sn.
(i) pharmaceutical products are not sold or supplied (i) sn phm dc phm khng c bn hoc cung
before the authorized persons (see also sections cp trc khi c ngi c thm quyn (xem
9.11 and 9.12) have certified that each production phn 9.11 & 9.12) chng nhn tng m sn phm
batch has been produced and controlled in c sn xut v c kim sot theo cc yu
accordance with the requirements of the cu nu trong giy php lu hnh v mi yu cu
marketing authorization and any other regulations khc c lien quan n sn xut, kim sot v
relevant to the production, control and release of duyt xut sn phm dc phm.
pharmaceutical products;
(j) processes are in place to assure the management (j) cc qu trnh c thc hin m bo qun l
of outsourced activities; cc hot ng thu ngoi.
(k) satisfactory arrangements exist to ensure, as far (k) cc sp xp tha ng m bo, cng c th
as possible, that the pharmaceutical products are cng tt, rng cc sn phm dc phm c bao
stored, distributed and subsequently handled so qun, phn phi v x l tip theo duy tr c
that quality is maintained throughout their shelf- cht lng trong sut hn s dng ca sn phm.
life;
(l) there is a procedure for self-inspection and/or (l) c mt th tc cho vic t thanh tra v/hoc nh
quality audit that regularly appraises the gi cht lng nh gi nh k tnh hiu lc v
effectiveness and applicability of the PQS; kh nng p dng ca PQS
(n) product and processes are monitored and the (n) sn phm v qu trnh c gim st v kt qu
results taken into account in batch release, in the phi c xem xt khi duyt xut m, trong iu
investigation of deviations and, with a view to tra sai lch v vi mt quan im tm kim v thc
taking preventive action to avoid potential hin hnh ng ngn nga cc sai lch tim n c
deviations occurring in the future; th xy ra trong tng lai.
(m) arrangements are in place for the prospective (m) cc sp xp phi c thc hin nh gi tim
evaluation and approval of planned changes and nng v ph duyt cc thay i hoch nh
their approval prior to implementation taking into trc khi chng c thc hin, iu ny phi tnh
account regulatory notification and approval n quy nh thng bo v ph duyt khi c yu
where required. After implementation of any cu. Sau khi thc hin bt k thay i no, mt
change, an evaluation is undertaken to confirm nh gi phi c thc hin xc nhn rng
that the quality objectives were achieved and that cc mc tiu cht lng t c v rng
there was no unintended adverse impact on khng c mt tc ng tiu cc no khng lng
product quality; trc c v cht lng sn phm.
(n) regular reviews of the quality of pharmaceutical (n) cc xem xt nh k cht lng sn phm dc
products are conducted with the objective of phm c thc hin vi mc ch xc minh tnh
verifying the consistency of the process and nht qun ca qu trnh v nhn bit ni cn ci
identifying where there is a need for tin.
improvement;
(o) a state of control is established and maintained by (o) mt kim sot c thit lp v duy tr thng qua
developing and using effective monitoring and vic pht trin v s dng cc h thng gim st
control systems for process performance and hiu qu i vi kt qu thc hin cc qu trnh
product quality; v cht lng sn phm
(p) continual improvement is facilitated through the (p) to iu kin thun li cho cc hot ng ci tin
implementation of quality improvements lin tc thng qua vic thc hin cc ci tin cht
appropriate to the current level of process and lng thch hp vi mc tri thc hin c v qu
product knowledge; trnh v sn phm.

(q) there is a system for QRM; (q) c h thng qun l ri ro cht lng (QRM)
(r) deviations, suspected product defects and other (r) cc sai lch, sn phm sai li tim n v cc vn
problems are reported, investigated and recorded. khc c bo co, iu tra v ghi h s. Phn
An appropriate level of root cause analysis is tch nguyn nhn gc r c p dng trong qu
applied during such investigations. The most trnh iu tra. (Cc) nguyn nhn gc phi c
likely root cause(s) should be identified and xc nh v cc hnh ng khc phc v/hoc
appropriate corrective actions and/or preventive phng nga (CAPA) thch hp c nhn dng v
actions (CAPAs) should be identified and taken. thc hin. Tnh hiu lc ca cc CP phi c
The effectiveness of CAPAs should be monitored. gim st.
1.6 There should be periodic management reviews, 1.6 Phi xem xt ca lnh o nh k, vi s tham
with the involvement of senior management, of the gia ca lnh o cp cao, cc thnh phn iu hnh
operation of the PQS to identify opportunities for PQS xc nh c hi ci tin lin tc sn phm qu
continual improvement of products, processes and trnh v thng. Vic xem xt phi c thc hin ti
the system itself. Unless otherwise justified, such thiu mi nm 1 ln.
reviews should be conducted at least annually.
1.7 The PQS should be defined and documented. A 1.7 PQS phi c xc nh v lp thnh vn bn.
quality manual or equivalent documentation should Mt s tay cht lng hoc ti liu tng ng phi
be established and should contain a description of c thit lp v phi bao gm m t v h htng
the quality management system including qun l cht lng bao gm cc trch nhim qun l.
management responsibilities.
Quality risk management Qun l ri ro cht lng

1.8 QRM is a systematic process for the assessment, 1.8 QRM l mt qu trnh c h thng cho vic nh
control, communication and review of risks to the gi, kim sot, truyn t thng tin v xem xt cc
quality of the medicinal product. It can be applied ri ro lin quan n cht lng dc phm. C th p
both proactively and retrospectively. dng c vic xem xt c giai on trc v sau.
1.9 QRM should ensure that: 1.9 QRM phi m bo:
the evaluation of the risk to quality is based on nh gi ri ro lin quan n cht lng c thc
scientific knowledge, experience with the process hin da trn cc kin thc khoa hc, kinh nghim
and ultimately links to the protection of the patient; qu trnh v cc lin kt sau cng i vi vic bo v
bnh nhn;
the level of effort, formality and documentation of cc mc , hnh thc v ti liu ca qu trnh
the QRM process is commensurate with the level of QRM phi tng xng vi mc ca ri ro.
risk.
Product quality review Xem xt cht lng sn phm

1.10 Regular, periodic or rolling quality reviews of all 1.10 Vic xem xt cht lng nh k, hoc cun
pharmaceutical products, including export-only chiu i vi tt c cc dc phm, bao gm c cc
products, should be conducted with the objective of sn phm xut khu, phi c thc hin vi mc
verifying the consistency of the existing process and tiu thm tra tin cy ca qu trnh hin hu, s
the appropriateness of current specifications for both thch hp ca cc tiu chun k thut hin hnh cho
starting materials and finished product, to highlight cc nguyn liu ban u v sn phm phn nh
any trends and to identify product and process bt k khuynh hng no v nhn din nhu cu
improvements. ci tin sn phm v qu trnh.
Such reviews should normally be conducted and Vic xem xt nn c thc hin v lp thnh vn
documented annually, taking into account previous bn hng nm, bao gm vic xem xt cc kt qu
reviews, and should include at least: trc o, v phi bao gm ti thiu :
(a) review of starting materials and packaging (a) vic xem xt nguyn vt liu ban u v
materials used for the product, especially nguyn vt liu bao gi c s dng, c
those from new sources and in particular the bit l t cc ngun cung cp mi v trong
review of supply chain traceability of active mi lin h vi xem xt truy vt chui cung
substances; ng hot cht.

(b) a review of critical in-process controls, and (b) vic xem xt v cc im kim sot ti hn
finished product results; trong qu trnh v kt qu sn phm cui;
(c) a review of all batches that failed to meet (c) vic xem xt tt c cc l (m) khng t cc
established specification(s) and their tiu chun thit lp v kt qu iu tra;
investigation;
(d) a review of all significant deviations or non- (d) vic xem xt tt c cc sai lch c ngha
conformances, the related investigations and hoc s khng ph hp, cc iu tra lin
the effectiveness of resultant CAPAs taken; quan v tnh hiu lc ca cc hnh ng khc
phc, phng nga c thc hin;
(e) a review of all changes made to the processes (e) vic xem xt tt c cc thay i i vi cc
or analytical methods; qu trnh hoc cc phng php phn tch;
(f) a review of dossier variations submitted, (f) vic xem xt h s c gi, c duyt hoc
granted or refused; t chi;
(g) a review of the results of the stability (g) vic xem xt cc kt qu ca chng trnh
monitoring programme and ny adverse theo di n nh v bt k khuynh hng bt
trends; li no;
(h) a review of all quality-related returns, (h) vic xem xt tt c cc trng hp tr v c

complaints and recalls and the investigations lin quan n cht lng, khiu ni v thu hi
performed at the time; v kt qu iu tra;
(i) a review of adequacy of any other previous (i) vic xem xt s tng xng ca bt k hnh
corrective actions on product processes or ng khc phc trc i vi qu trnh
equipment; sn xut hoc thit b;
(j) post-marketing commitments for new (j) vic xem xt cc cam kt trong giy php lu
dossiers and variations to the dossiers; hnh i vi cc h s mi;
(k) the qualification status of relevant equipment (k) tnh trng thm nh ca cc thit b v tin
and utilities, e.g. heating, ventilation and air- ch lin quan, nh gia nhit, thng kh v
conditioning (HVAC), water or compressed iu ha khng kh (HVAC), nc, hoc kh
gases and a review of the results of gas v xem xt kt qu gim st u ra ca
monitoring the output of such equipment and thit b v ng lc;
utilities;
(l) a review of technical agreements to ensure (l) vic xem xt cc tha thun k thut nhm
that they are up to date. m bo rng chng c cp nht.
The manufacturer and, where different, marketing Khi nh sn xut v c quan ch qun, nu khc
authorization holder, should evaluate the results of nhau, phi nh gi cc kt qu ca vic xem xt ny
the review and an assessment should be made as to v mt cuc nh gi phi c thc hin xem liu
whether CAPA or any revalidation should be cc hnh ng khc phc v hnh ng phng nga
undertaken, under the PQS. CAPAs should be hoc vic ti thm nh c c thc hin, trong
completed in a timely and effective manner, PQS. Cc CAPA cn c hon thnh mt cch kp
according to documented procedures. There should thi v hiu qu, theo th tc bng vn bn. Cn c
be procedures for the ongoing management and th tc cho vic qun l lin tc v xem xt cc hnh
review of these actions, and the effectiveness of ng ny, v tnh hiu lc ca cc th tc ny cn
these procedures should be verified during self- c xc nhn trong qu trnh t thanh tra. Xem xt
inspection. Quality reviews may be grouped by cht lng c th c nhm li theo loi sn phm,
product type, e.g. solid dosage forms, liquid dosage v d: dng bo ch rn, dng bo ch lng, hoc cc
forms, or sterile products, where scientifically sn phm v trng, theo c s khoa hc. Khi ngi
justified. Where the marketing authorization holder nm quyn lu hnh khng phi l nh sn xut, cn
is not the manufacturer, there should be a technical c mt tha thun k thut gia cc bn xc nh
agreement in place between the various parties that trch nhim ca mi bn trong vic xem xt cht
defines their respective responsibilities in producing lng. Ngi c thm quyn chu trch nhim cp
the quality review. The authorized person responsible giy chng nhn cho l hng cui cng, cng vi
for final batch certification, together with the nhng ngi nm quyn lu hnh, phi m bo rng
marketing authorization holder, should ensure that vic xem xt cht lng c thc hin mt cch kp
the quality review is performed in a timely manner thi v chnh xc.
and is accurate.

2. Good manufacturing 2. Thc hnh tt sn xut dc

practices for pharmaceutical phm
products
2.1 GMP is that part of quality management 2.1 GMP l mt phn ca h qun l cht lng
which ensures that products are consistently nhm m bo rng sn phm c sn xut ng
produced and controlled according to the quality u v c kim sot theo cc tiu chun cht lng
standards appropriate to their intended use and as thch hp theo nh hng s dng v theo yu cu
required by the marketing authorization, clinical trial ca giy php lu hnh, giy php th nghim lm
authorization or product specification. GMP is sng hoc tiu chun sn phm. GMP lin quan n
concerned with both production and QC. GMP is c sn xut v QC. GMP nhm ch yu vo qun l v
aimed primarily at managing and minimizing the gim thiu ri ro tn ti trong lnh vc sn xut dc
risks inherent in pharmaceutical manufacture to phm m bo cht lng, an ton v hiu qu
ensure the quality, safety and efficacy of products. ca sn phm. Vi GMP:
Under GMP:
(a) all manufacturing processes are clearly (a) tt c cc qu trnh c m t r rng, xem
defined, systematically reviewed for xt c h thng i vi cc ri ro lin quan
associated risks in the light of scientific bng kin thc v kinh nghim khoa hc, v
knowledge and experience, and shown to be ch ra kh nng sn xut n nh cc sn
capable of consistently manufacturing phm dc ph tha mn cc yu cu cht
pharmaceutical products of the required lng theo cc tiu chun k thut ca
quality that comply with their specifications; chng;
(b) qualification and validation are performed; (b) thc hin thm nh v nh chun;
(c) all necessary resources are provided, (c) tt c cc ngun lc cn thit phi cung cp,
including: gm:
i. sufficient and appropriately qualified and i. nhn s c o to v c bng cp
trained personnel; thch hp.
ii. adequate premises and space; ii. khng gian v nh xng y ;
iii. suitable equipment and services; iii. dch v v thit b ph hp;
iv. appropriate materials, containers and iv. nguyn vt liu, vt cha v nhn thch
labels; hp;
v. approved procedures and instructions; v. cc th tc v hng dn c duyt;
vi. suitable storage and transport; vi. vn chuyn v bo qun ph hp;
vii. adequate personnel, laboratories and vii. nhn s, phng th nghim v thit b
equipment for in-process controls; cho kim sot trong qu trnh;
(d) instructions and procedures are written in (d) cc th tc v hng dn c vit ra r

clear and unambiguous language, specifically rng, bng ngn ng d hiu, c th p dng
applicable to the facilities provided; c.
(e) procedures are carried out correctly and
personnel are trained to do so; (e) cc th tc c thc hin chnh xc bi cc
(f) records are made (manually and/or by nhn s c o to;
recording instruments) during manufacture (f) cc h s c thit lp (bng tay v/hoc
to show that all the steps required by the bng thit b ghi nhn) trong sut qu trnh
defined procedures and instructions have in sn xut chng minh rng tt c cc bc
fact been taken and that the quantity and yu cu bi th tc v hng dn nh trc
quality of the product are as expected. Any c thc hin v rng s lng v cht
significant deviations are fully recorded and lng sn phm p ng mong i. Bt k sai
investigated with the objective of lch ng k no cng phi c ghi h s v
determining the root cause and appropriate iu tra vi mc tiu xc nh nguyn nhn
corrective and preventive action is gc r v thc hin cc hnh ng khc phc
implemented; v phng nga thch hp.
(g) records covering manufacture and
distribution, which enable the complete (g) Cc h s sn xut v phn phi cho php
history of a batch to be traced, are retained truy vt li lch s m sn xut c duy tr
in a comprehensible and accessible form; mt y v sn sng truy cp.
(h) the proper storage and distribution of the
products minimizes any risk to their quality (h) Phn phi v bo qun ph hp gim thiu
and takes account of good distribution mi ri ro v cht lng sn phm v thc
practices (GDP); hin thc hnh phn phi tt (GDP)
(i) a system is available to recall any batch of

product from sale or supply; (i) mt h thng sn sng cho vic thu hi bt
k m sn phm no t th trng hoc knh
(j) complaints about marketed products are phn phi.
examined, the causes of quality defects (j) Cc khiu ni v sn phm lu hnh c
investigated, and appropriate measures kim tra, nguyn nhn sai li cht lng c
taken in respect of the defective products to iu tra v cc bin php thch hp c thc
prevent recurrence. hin ngn nga sai li sn phm ti din.
3. Sanitation and hygiene 3 V sinh v kh trng

3.1 A high level of sanitation and hygiene should be 3.1 Cn thc hin cc nguyn tc v sinh v kh
practised in every aspect of the manufacture of trng mc cao mi mt ca qu trnh sn xut
medicines products. The scope of sanitation and dc phm. Phm vi v sinh v kh trng bao gm
hygiene covers personnel, premises, equipment and nhn vin, nh xng, my mc, thit b, dng c,
apparatus, production materials and containers, nguyn vt liu sn xut v bao gi, sn phm dng
products for cleaning and disinfection, and anything lm v sinh v kh trng, v bt k th g c th
that could become a source of contamination to the tr thnh ngun gy tp nhim vo sn phm. Nhng
product. Potential sources of contamination should ngun gy tp nhim tim n phi c loi b thng
be eliminated through an integrated comprehensive qua chng trnh v sinh v kh trng. (V v sinh c
programme of sanitation and hygiene. (For Personal nhn xem phn 11, v v sinh nh xng xem phn
hygiene see section 11, and for sanitation see section 12, nh xng.)
12, Premises.)
4. Qualification and validation 4. Thm nh

4.1 In accordance with GMP, each pharmaceutical 4.1 Theo cc nguyn tc GMP, mi cng ty c
company should identify what qualification and phm phi xc nh nhng cng vic thm nh cn
validation work is required to prove that the critical thc hin chng minh rng nhng kha cnh quan
aspects of their particular operation are controlled. trng trong cc thao tc c th c kim sot.
4.2 The key elements of a qualification and validation 4.2 Nhng yu t ch yu trong chng trnh thm
programme of a company should be clearly defined nh ca mt cng ty cn c xc nh r rng v
and documented in a validation master plan. trnh by trong mt k hoch thm nh gc.
4.3 Qualification and validation should establish and 4.3 Vic thm nh phi thit lp v cung cp bng
provide documentary evidence that: chng trn h s ti liu rng:
(a) The premises, supporting utilities, equipment (a) nh xng, khu vc ph tr, trang thit b v
and processes have been designed in quy trnh c thit k theo ng nh yu
accordance with the requirements for GMP cu ca GMP (thm nh thit k hay DQ);
(design qualification or DQ);
(b) the premises, supporting utilities and (b) nh xng, khu vc ph tr v trang thit b
equipment have been built and installed in c xy dng v lp t theo ng tiu
compliance with their design specifications chun thit k ca chng (thm nh lp t
(installation qualification or IQ); hay IQ);
(c) the premises, supporting utilities and (c) nh xng, khu vc ph tr v trang thit b
equipment operate in accordance with their hot ng theo ng tiu chun thit k ca
design specifications (operational chng (thm nh vn hnh hay OQ);
qualification or OQ);
(d) a specific process will consistently produce a (d) mt quy trnh c th s lin tc sn xut ra
product meeting its predetermined mt sn phm p ng cc tiu chun v c
specifications and quality attributes (process tnh cht lng nh trc ca n (thm nh
validation or PV, also called performance quy trnh hay PV, cn c gi l thm nh
qualification or PQ). hiu nng hay PQ).
4.4 Any aspect of operation, including significant 4.4 Bt k kha cnh no ca thao tc, k c nhng
changes to the premises, facilities, equipment or thay i ng k i vi nh xng, c s, trang thit
processes, which may affect the quality of the b hay quy trnh, c th nh hng n cht lng
product, directly or indirectly, should be qualified sn phm, d trc tip hay gin tip, cng u phi
and validated. c thm nh.
4.5 Qualification and validation should not be 4.5 Khng nn coi thm nh l bi tp lm mt ln.

considered as one-off exercises. An ongoing Cn phi c chng trnh lu di theo sau ln thc
programme should follow their first implementation hin u tin v ly c s l vic r sot li hng
and should be based on an annual review. nm.
4.6 The commitment to maintain continued validation 4.6 Cn c tuyn b cam kt duy tr tnh trng thm
status should be stated in the relevant company nh lin tc trong cc ti liu lin quan ca cng ty,
documentation, such as the quality manual or v d nh s tay cht lng hoc k hoch thm nh
validation master plan. gc.
4.7 The responsibility of performing validation should 4.7 Cn xc nh r trch nhim thc hin vic thm
be clearly defined. nh.
4.8 Validation studies are an essential part of GMP 4.8 Cc nghin cu thm nh l mt phn thit yu
and should be conducted in accordance with ca GMP v cn c thc hin theo ng cng
predefined and approved protocols. c xc nh v c duyt trc.
4.9 A written report summarizing the results 4.9 Cn chun b v lu gi mt bn bo co tm tt

recorded and the conclusions reached should be cc kt qu ghi li c v kt lun.
prepared and stored.
4.10 Processes and procedures should be established 4.10 Cn xy dng cc quy trnh sn xut v quy
on the basis of the results of the validation trnh thao tc trn c s cc kt qu thm nh.
performed.
4.11 Particular attention should be paid to the 4.11 Cn c bit lu ti vic thm nh phng
validation of analytical test methods, automated php phn tch, cc h thng t ng v quy trnh
systems and cleaning procedures. lm v sinh.
5. Complaints 5. Khiu ni
5.1 Principle. All complaints and other information 5.1 Nguyn tc. Tt c cc khiu ni v thng tin
concerning potentially defective products should be khc lin quan n sn phm c kh nng b sai hng
carefully reviewed according to written procedures u phi c xem xt theo cc quy trnh bng vn
and the corrective action should be taken. bn v phi c bin php khc phc.
5.2 A person responsible for handling the complaints 5.2 Cn c mt ngi chu trch nhim x l cc
and deciding the measures to be taken should be khiu ni v quyt nh bin php x l, bn cnh
designated, together with sufficient supporting staff phi c nhn vin h t ngi ny. Nu ngi ny
to assist him or her. If this person is different from khng phi l ngi c u quyn, th ngi c y
the authorized person, the latter should be made quyn phi c thng bo bt k khiu ni, iu tra
aware of any complaint, investigation or recall. hay thu hi no.
5.3 There should be written procedures describing 5.3 Cn c mt quy trnh bng vn bn m t bin
the action to be taken, including the need to consider php tin hnh, c nu vic cn cn nhc n bin
a recall, in the case of a complaint concerning a php thu hi, trong trng hp khiu ni lin quan
possible product defect. n mt sai hng c th xy ra n vi sn phm.
5.4 Special attention should be given to establishing 5.4 c bit ch trng vo vic xc nhn rng sn
that the product that gave rise to a complaint was phm b khiu ni c sai hng.
defective.
5.5 Any complaint concerning a product defect 5.5 Bt k khiu ni no lin quan n sn phm b
should be recorded with all the original details and sai hng u phi c lp thnh h s vi y
thoroughly investigated. The person responsible for cc chi tit vi giy t gc, v phi c iu tra thu
QC should normally be involved in the review of such o. Ngi chu trch nhim v kim tra cht lng
investigations. thng s phi tham gia vo vic iu tra.
5.6 If a product defect is discovered or suspected in a Nu sn phm b sai hng hoc nghi ng mt l,
batch, consideration should be given to whether cn tnh n vic kim tra cc l khc nhm xc nh
other batches should be checked in order to xem chng c b sai hng tng t khng. c bit
determine whether they are also affected. In phi kim tra cc l c s dng sn phm ti ch t
particular, other batches that may contain l c sai st.
reprocessed product from the defective batch should
be investigated.

5.7 Where necessary, appropriate follow-up action, 5.7 Nu cn thit phi tin hnh cc bin php ph
possibly including product recall, should be taken hp tip theo, c th l thu hi sn phm, sau khi
after investigation and evaluation of the complaint. iu tra v nh gi v khiu ni.
5.8 All decisions made and measures taken as a 5.8 Tt c cc quyt nh v bin php thc hin lin
result of a complaint should be recorded and quan n khiu ni u phi c ghi vo h s v
referenced to the corresponding batch records. tham chiu ti h s l tng ng.
5.9 Complaints records should be regularly reviewed 5.9 H s v khiu ni cn c r sot mt cch
for any indication of specific or recurring problems thng xuyn tm ra du hiu ca nhng vn
that require attention and might justify the recall of c bit hoc vic lp li cc sai st c th dn n
marketed products. vic thu hi nhng sn phm lu hnh.
5.10 The competent authorities should be informed if 5.10 Cn thng bo cho c quan c thm quyn trong
a manufacturer is considering action following trng hp nh sn xut ang tnh n bin php x
possibly faulty manufacture, product deterioration, a l cc trng hp c th do li ca sn xut, sn
suspect product or any other serious quality phm mt phm cht, b lm gi hoc bt k vn
problems with a product. cht lng nghim trng no ca mt sn phm.
6. Product recalls 6. Thu hi sn phm

6.1 Principle. There should be a system to recall from 6.1 Nguyn tc. Cn c mt h thng thu hi mt
the market, promptly and effectively, products known cch nhanh chng v c hiu qu cc sn phm c
or suspected to be defective. bit hoc nghi ng l c sai hng trn th trng.
6.2 The authorized person should be responsible for 6.2 Ngi c y quyn phi chu trch nhim iu
the execution and coordination of recalls. He/she hnh v phi hp vic thu hi. Ngi ny phi c
should have sufficient staff to handle all aspects of nhn vin x l tt c cc kha cnh trong thu hi
the recalls with the appropriate degree of urgency. mc khn cp thch hp.
6.3 There should be established written procedures, 6.3 Cn c cc quy trnh bng vn bn c sa i
which are regularly reviewed and updated, for the v cp nht thng xuyn gip cho vic t chc cc
organization of any recall activity. Recall operations hot ng thu hi. Cc hot ng thu hi phi c kh
should be capable of being initiated promptly down nng trin khai nhanh chng ti cc tuyn cn thit
to the required level in the distribution chain. trong h thng phn phi.
6.4 An instruction should be included in the written 6.4 Trong cc quy trnh thao tc chun cn c mt
procedures to store recalled products in a secure hng dn bo qun cc sn phm thu hi v ti mt
segregated area while their fate is decided. khu vc bit lp an ton trong khi ch quyt nh x
l.
6.5 All competent authorities of all countries to 6.5 Cn ngay lp tc thng bo cho cc c quan c
which a given product has been distributed should be thm quyn ca tt c cc nc ni sn phm
promptly informed of any intention to recall the c phn phi v d nh thu hi mt sn phm v
product because it is, or is suspected of being, n b sai hng hoc nghi ng l c sai hng.
defective.
6.6 The distribution records should be readily 6.6 H s phn phi phi m bo sn sng ngi
available to the authorized person, and they should c y quyn xem xt, h s ny phi c y
contain sufficient information on wholesalers and thng tin v nhng i l bn bun v nhng khch
directly supplied customers (including, for exported hng c cung cp trc tip (k c nhng ngi
products, those who have received samples for nhn mu th lm sng v mu cho bc s) vic
clinical tests and medical samples) to permit an thu hi c hiu qu.
effective recall.
6.7 The progress of the recall process should be 6.7 Phi theo di v ghi li vo h s din tin ca
monitored and recorded. Records should include the qu trnh thu hi. H s phi bao gm bin php x
disposition of the product. A final report should be l i vi sn phm b thu hi. Cn c mt bn bo
issued, including a reconciliation between the co cui cng, trong c s liu i chiu gia
delivered and recovered quantities of the products. lng sn phm phn phi v lng sn phm thu
hi v.
6.8 The effectiveness of the arrangements for recalls 6.8 Cn thng xuyn kim tra v nh gi hiu qu
should be tested and evaluated from time to time. ca k hoch thu hi.

7. Contract production, 7. Sn xut, th nghim v cc

analysis and other activities hot ng khc theo hp ng
7.1 Principle. Contract production, analysis and any 7.1 Nguyn tc. Hp ng sn xut, phn tch v bt
other activity covered by GMP must be correctly k hot ng no khc bao trm bi GMP phi c
defined, agreed and controlled in order to avoid xc nh chnh xc, ng thun v c kim sot
misunderstandings that could result in a product, or theo cch trnh cc hiu nhm c th a n kt
work or analysis, of unsatisfactory quality. qu khng t cht lng v sn phm, cng vic
hoc kt qu phn tch.
General Quy nh chung

7.2 All arrangements for contract production and 7.2 Tt c cc tha thun i vi sn xut v th
analysis, including technology transfer and any nghim theo hp ng, bao gm chuyn giao cng
proposed changes in technical or other ngh v bt k ngh thay i no v cng ngh
arrangements, should be in accordance with the hoc cc tha thun khc, phi tun theo giy php
marketing authorization for the product concerned. lu hnh sn phm c lin quan.
7.3 The contract should permit the contract giver to 7.3 Hp ng phi cho php bn hp ng nh gi
audit the facilities and activities of the contract c s v cc hot ng ca bn nhn hp ng hoc
acceptor or mutually agreed subcontractors. cc nh thu ph c chp nhn.
7.4 In the case of contract analysis, the final approval 7.4 Trong trng hp th nghim theo hp ng, vic
for release must be given by the authorized person in duyt xut sau cng phi do ngi c thm quyn
accordance with GMP and the marketing thc hin tun theo GMP v cc yu cu giy php
authorization as specified in the contract. lu hnh nh cp trong hp ng.
The contract giver Bn hp ng

7.5 The PQS of the contract giver should include the 7.5 PQS ca bn hp ng phi bao gm kim sot v
control and review of any outsourced activities. The xem xt bt k hot ng thu ngoi no. Bn hp
contract giver is responsible for assessing the ng c trch nhim nh gi tnh hp php, s ph
legality, suitability and competence of the contract hp v nng lc ca bn nhn hp ng v kh nng
acceptor to successfully carry out the work or tests p ng cc yu cu cng vic hoc th nghim,
required, for approval for contract activities, and for ph duyt cc hot ng hp ng v m bo cc
ensuring by means of the contract that the principles nguyn tc c bn ca GMP tch hp vi cc nguyn
of GMP incorporating QRM principles are followed. tc QRM c tun theo.
7.6 The contract giver should provide the contract 7.6 Bn hp ng phi cung cp cho bn hp ng
acceptor with all the information necessary to carry tt c cc thng tin cn thit tin hnh cc hot
out the contracted operations correctly in ng theo hp ng mt cch chnh xc theo ng
accordance with the marketing authorization and any giy php lu hnh v cc quy nh lut php khc.
other legal requirements. The contract giver should Bn hp ng phi m bo rng bn nhn hp ng
ensure that the contract acceptor is fully aware of nhn thc y v mi vn lin quan n sn
any problems associated with the product, work or phm, cng vic hay php th c th gy hi cho nh
tests that might pose a hazard to premises, xng, my mc thit b, nhn vin, cc nguyn vt
equipment, personnel, other materials or other liu hoc cc sn phm khc.
products.
7.7 The contract giver should review and assess the 7.7 Bn hp ng phi xem xt v nh gi h s v
records and results related to the outsourced kt qu lin quan n cc hot ng thu ngoi. Bn
activities. The contract giver should ensure that all hp ng phi m bo rng tt c cc sn phm v
products and materials delivered by the contract nguyn vt liu c chuyn giao t bn nhn hp
acceptor have been processed in accordance with ng c sn xut theo GMP v giy php lu
GMP and the marketing authorization; comply with hnh; s ph hp ca chng vi tiu chun k thut
their specifications and that the product has been lin quan v sn phm c duyt xut bi ngi
released by the authorized person in accordance with c thm quyn theo GMP v giy php lu hnh.
GMP and the marketing authorization.
7.8 The contract giver should monitor and review the 7.8 Bn hp ng phi gim st v xem xt kt qu
performance of the contract acceptor including the thc hin ca bn nhn hp ng bao gm vic thc
implementation of any needed improvements and hin bt k cc ci tin cn thit no v tnh hiu lc
their effectiveness. ca chng.

7.9 The contract giver is responsible for ensuring 7.9 Bn hp ng c trch nhim m bo rng bn
that the contract acceptor understands that his or nhn hp ng hiu r cc hot ng ca h c s
her activities may be subject to inspection by c kim tra nh gi bi cp thm quyn c
competent authorities. nng lc.
The contract acceptor Bn nhn hp ng

7.10 The contract acceptor must have adequate 7.8 Bn nhn hp ng phi c nh xng, my
premises, equipment, knowledge, and experience mc thit b, kin thc v kinh nghim cng nh
and competent personnel to carry out satisfactorily nhn vin nng lc thc hin tha ng cng
the work ordered by the contract giver. Contract vic do bn hp ng t ra. Ch nhng c s c giy
manufacture may be undertaken only by a php sn xut mi c thc hin sn xut theo hp
manufacturer who holds a manufacturing ng.
authorization.
7.11 The contract acceptor should not pass to a third 7.11 Bn nhn hp ng khng c chuyn giao n
party any of the work entrusted to him or her under bn th ba bt k phn no ca cng vic c
the contract without the contract givers prior giao ph theo hp ng m cha c nh gi v
evaluation and approval of the arrangements. chp thun ca bn hp ng v cc sp xp chuyn
Arrangements made between the contract acceptor giao. Cc tha thun gia bn nhn hp ng v bt
and any third party should ensure that information k bn th ba no phi m bo rng thng tin v tri
and knowledge, including that from assessments of thc, bao gm c vic nh gi s ph hp ca ben
the suitability of the third party, are made available th ba, phi c thit lp v sn c tng t nh
in the same way as between the original contract hp ng gia bn hp ng v bn nhn hp ng.
giver and contract acceptor.
7.12 The contract acceptor should refrain from any 7.12 Bn nhn hp ng khng nn tham gia vo bt
activity (including unauthorized changes outside the k hot ng no (bao gm c cc thay i cha c
terms of the contract) that may adversely affect the duyt bn ngoi phm vi hp ng) c th nh hng
quality of the product manufactured and/or analysed xu n cht lng sn phm c sn xut v/hoc
for the contract giver. phn tch th nghim ca bn hp ng.
The contract Bn hp ng
7.13 There must be a written contract between the 7.13 Phi c bn hp bng vn bn gia bn hp
contract giver and the contract acceptor which ng v bn nhn hp ng bao gm cc trch nhim
clearly establishes the responsibilities of each party, r rng ca mi bn, bao gm c cc hot ng thu
covering the outsourced activities, the products or ngoi, sn phm hoc cc hot ng c lin quan,
operations to which they are related, communication cc qu trnh truyn thng lin quan n cc hot
processes relating to the outsourced activities and ng thu ngoi v bt k tha thun k thut no c
any technical arrangements made in connection with lin quan.
it.
7.14 The contract must clearly state the way in which 7.12 Bn hp ng phi nu r cch ngi c y
the authorized person, in releasing each batch of quyn thc hin y trch nhim ca mnh trong
product for sale or issuing the certificate of analysis, vic ph duyt xut mi l sn phm ra th trng
exercises his or her full responsibility and ensures hoc cp phiu kim nghim m bo sau cho mi
that each batch has been manufactured in, and l c sn xut v kim tra t theo cc yu cu ca
checked for, compliance with the requirements of the giy php lu hnh.
marketing authorization.
7.15 Technical aspects of the contract should be 7.13 Nhng kha cnh k thut ca hp ng phi do
drawn up by competent persons with suitable nhng ngi c nng lc, c kin thc ph hp v
knowledge of pharmaceutical technology, analysis cng ngh dc, kim nghim dc phm v v GMP.
and GMP.
7.16 All arrangements for production and analysis 7.14 Tt c cc k hoch sn xut v kim nghim
must be in accordance with the marketing phi theo ng giy php lu hnh v thng nht
authorization and agreed by both parties. gia hai bn.
7.17 The contract should clearly describe who is 7.17 Hp ng phi m t r rng ai l ngi chu
responsible for contracted activities, e.g. knowledge trch nhim vi cc hot ng hp ng, v d qun
management, technology transfer, supply chain, l tri thc, chuyn giao cng ngh, chui cug ng,
subcontracting, testing and releasing materials and thu ph, kim tra v duyt xut nguyn liu v sn
undertaking production and QC, including in-process phm v QC, bao gm kim sot trong qu trnh v ai
controls, and who has responsibility for sampling and chu trch nhim i vi vic ly mu v phn tch.

analysis. In the case of contract analysis, the contract Trong trng hp hp ng phn tch, hp ng phi
should state whether or not the contract acceptor tuyn b bn nhn hp ng c ly mu ti c s sn
should take samples at the premises of the xut hay khng.
manufacturer.
7.18 Manufacturing, analytical and distribution 7.16 H s sn xut, kim nghim, phn phi v mu
records, and reference samples, should be kept by, or i chiu phi c lu tr bi hoc phi c sn i
be available to, the contract giver. Any records vi bn hp ng. Bt c h s no c lin quan ti
relevant to assessing the quality of a product in the vic nh gi cht lng ca mt sn phm b khiu
event of complaints or a suspected defect, or to ni hoc nghi ng c sai hng, hoc cn iu tra
investigating in the case of a suspected falsified trong trng hp sn phm b nghi l sn phm li
product or laboratory fraud, must be accessible and hoc kt qu th nghim khng t, phi c truy
specified in the procedures of the contract giver. cp v cp n trong quy trnh x l sai hng / thu
hi ca bn hp ng.
7.19 The contract should describe the handling of 7.17 Bn hp ng phi m t vic x l nguyn liu
starting materials, intermediate, bulk and finished ban u, sn phm trung gian, bn thnh phm v
products, if they are rejected. It should also describe thnh phm nu chng b loi. Trong cng phi
the procedure to be followed if the contract analysis m t quy trnh cn thc hin nu vic kim nghim
shows that the tested product must be rejected. theo hp ng cho thy sn phm c kim nghim
phi b loi.
8. Self-inspection, quality 8. T thanh tra, thanh tra cht

audits and suppliers audits lng, thanh tra v ph duyt
and approval nh cung cp
8.1 Principle. The purpose of self-inspection is to 8.1 Nguyn tc. Mc ch ca t thanh tra l nh
evaluate the manufacturers compliance with GMP in gi vic tun th ca nh sn xut theo nguyn tc
all aspects of production and QC. The self-inspection GMP trong mi lnh vc sn xut v kim tra cht
programme should be designed to detect any lng. Cn lp chng trnh t thanh tra pht hin
shortcomings in the implementation of GMP and to nhng khim khuyt trong vic thc hin GMP v
recommend the necessary corrective actions. Self- khuyn ngh cc bin php khc phc cn thit. Cn
inspections should be performed routinely, and may tin hnh t thanh tra thng xuyn, ngoi ra c th
be, in addition, performed on special occasions, e.g. thanh tra trong cc hon cn c bit, v d trong
in the case of product recalls or repeated rejections, trng hp thu hi sn phm hoc sn phm lin tip
or when an inspection by the health authorities is b loi, hoc khi nhn c k hoch thanh tra ca c
announced. The team responsible for self- inspection quan qun l y t. Nhm chu trch nhim v t
should consist of personnel who can evaluate the thanh tra cn bao gm nhng nhn bin c th nh
implementation of GMP objectively. All gi khch quan vic thc hin GMP. Tt c cc bin
recommendations for corrective action should be php khc phc khuyn ngh u phi c thc
implemented. The procedure for self-inspection thi. Quy trnh t thanh tra phi c ghi thnh vn
should be documented, and there should be an bn, v cn c chng trnh khc phc tip theo c
effective follow-up programme. hiu qu.
Items for self-inspection Nhng mc t thanh tra

8.2 Written instructions for self-inspection should be 8.2 Cn xy dng cc hng dn t thanh tra nhm
established to provide a minimum and uniform a ra cc yu cu chun ti thiu v thng nht.
standard of requirements. These may include Hng dn c th bao gm cc cu hi lin quan n
questionnaires on GMP requirements covering at cc yu cu ca GMP t nht v cc lnh vc sau:
least the following items:
(a) personnel; (a) nhn vin;

(b) premises including personnel facilities; (b) nh xng, k c khu vc dnh cho nhn
(c) maintenance of buildings and equipment; vin;
(d) storage of starting materials and finished (c) vic bo dng nh xng v my mc thit
products; b;
(e) equipment; (d) vic bo qun nguyn liu ban u v thnh
(f) production and in-process controls; phm;
(g) QC; (e) my mc thit b;
(h) documentation; (f) sn xut v kim tra trong qu trnh sn
(i) sanitation and hygiene; xut;
(j) validation and revalidation programmes; (g) kim tra cht lng;

(k) calibration of instruments or measurement (h) h s ti liu;

systems; (i) nguyn tc v sinh v v sinh;
(l) recall procedures; (j) chng trnh thm nh v thm nh li;
(m) complaints management; (k) hiu chun thit b v h thng o lng;
(n) labels control;
(o) results of previous self-inspections and any (l) quy trnh thu hi;
corrective steps taken. (m) x l khiu ni;
(n) kim sot nhn;
(o) kt qu nhng ln t thanh tra trc v
nhng bin php khc phc thc hin.
Self-inspection team Nhm t thanh tra

8.3 Management should appoint a self-inspection 8.3 Lnh o cng ty cn ch nh mt nhm t thanh
team consisting of experts in their respective fields tra c thnh vin l cc chuyn gia trong lnh vc c
and familiar with GMP. The members of the team th v hiu r v GMP. Thnh vin ca nhm c th
may be appointed from inside or outside the c ch nh t ni b hoc bn ngoi cng ty.
company.
Frequency of self-inspection Tn sut t thanh tra

8.4 The frequency at which self-inspections are 8.4 Tn sut t thanh tra c th ty thuc vo nhu
conducted may depend on company requirements cu ca cng ty, nhng t nht phi l hng nm. Tn
but should preferably be at least once a year. The sut t thanh tra cn c nu r trong quy trnh t
frequency should be stated in the procedure. thanh tra.
Self-inspection report Bo co t thanh tra

8.5 A report should be made at the completion of a 8.5 Cn c mt bn bo co sau khi kt thc t t
self-inspection. The report should include: thanh tra. Bn bo co cn bao gm:
(a) self-inspection results; (a) kt qu tu thanh tra;
(b) evaluation and conclusions; and (b) nh gi v kt lun;
(c) recommended corrective actions. (c) khuyn ngh cc bin php khc phc.
Follow-up action Hnh ng tip theo

8.6 There should be an effective follow-up 8.6 Cn phi c mt chng trnh tip theo c hiu
programme. The company management should qu. Ban lnh o cng ty cn nh gi bn bo co
evaluate both the self-inspection report and the t thanh tra cng nh cc bin php khc phc nu
corrective actions as necessary. cn.
Quality audit Thanh tra v cht lng

8.7 It may be useful to supplement self-inspections 8.7 Vic thc hin thanh tra v cht lng nhm h
with a quality audit. A quality audit consists of an tr cho t thanh tra. Thanh tra v cht lng bao
examination and assessment of all or part of a quality gm vic kim tra v nh gi ton b hoc mt phn
system with the specific purpose of improving it. A h thng cht lng vi mc ch c th l hon
quality audit is usually conducted by outside or thin h thng. Thanh tra v cht lng thng c
independent specialists or a team designated by the tin hnh bi cc chuyn gia bn ngoi hoc c lp,
management for this purpose. Such audits may also hoc mt nhm do ban lnh o cng ty ch nh.
be extended to suppliers and contractors (see section Thanh tra cht lng c th m rng sang thanh tra
7, Contract production and analysis). c nh cung cp v bn nhn hp ng (xem mc 7
Sn xut v kim nghim theo hp ng)
Suppliers audits and approval nh gi la chn nh cung cp

8.8 The person responsible for QC should have 8.3 Cn b chu trch nhim v kim tra cht lng
responsibility together with other relevant phi cng phi hp vi cc b phn chc nng c lin
departments for approving suppliers who can reliably quan khc trong vic chp thun nh cung cp
supply starting and packaging materials that meet m bo l nhng nh cung cp ng tin cy, c
established specifications. th cung cp nguyn liu ban u v vt liu bao gi
t cc tiu chun quy nh.
8.9 Before suppliers are approved and included in 8.9 Trc khi nh cung cp c ph duyt a
the approved suppliers list or specifications, they vo danh sch cc nh cung cp c ph duyt cn

should be evaluated. The evaluation should take into phi tin hnh nh gi h. Vic nh gi ny phi
account a suppliers history and the nature of the xem xt n lch s ca nh cung cp v tnh cht
materials to be supplied. If an audit is required, it ca nguyn liu cung cp. Nu tin hnh thanh tra
should determine the suppliers ability to conform c s ca nh cung cp, phi xc nh c kh nng
with GMP standards. ca nh cung cp trong vic tun th cc nguyn tc
GMP.
9. Personnel 9 Nhn vin

9.1 Principle. The establishment and maintenance of 9.1 Nguyn tc. Vic thit lp v duy tr mt h thng
a satisfactory system of QA and the correct m bo cht lng t yu cu v tnh chnh xc ca
manufacture and control of pharmaceutical products vic sn xut cng nh kim tra cht lng dc
and active ingredients rely upon people. For this phm v hot cht dc dng ph thuc vo yu t
reason there must be sufficient qualified personnel to con ngi. V vy phi c nhn vin c trnh
carry out all the tasks for which the manufacturer is thc hin tt c cc cng vic thuc phm vi trch
responsible. Individual responsibilities should be nhim ca nh sn xut. Cn xc nh r trch nhim
clearly defined and understood by the persons c nhn, trch nhim ny phi c c nhn c lin
concerned and recorded as written descriptions. quan hiu r v c ghi li trong bn m t cng
vic.

9.2 The manufacturer should have an adequate 9.2 Nh sn xut cn c nhn vin c trnh
number of personnel with the necessary chuyn mn cng nh kinh nghim thc t cn thit.
qualifications and practical experience. The Trch nhim giao cho mi c nhn khng nn qu
responsibilities placed on any one individual should nhiu khin c th dn n nguy c i vi cht
not be so extensive as to present any risk to quality. lng sn phm.
9.3 Responsible staff should have its specific duties 9.3 Tt c cc cn b c trch nhim u phi c bn
recorded in written descriptions and adequate m t cng vic c th v phi c giao quyn thch
authority to carry out its responsibilities. hp thc hin cc trch nhim .
Its duties may be delegated to designated deputies of Nhim v ca h c th c u quyn cho cc cn

a satisfactory qualification level. There should be no b cp ph c trnh t yu cu. Khng nn c cc
gaps or unexplained overlaps in the responsibilities khon h cng nh s chng cho thiu l gii trong
of personnel concerned with the application of GMP. trch nhim ca cc nhn vin lin quan n vic p
The manufacturer should have an organization chart. dng GMP. Nh sn xut phi c mt s t chc.
9.4 All personnel should be aware of the principles of 9.4 Tt c nhn vin u phi nm bt c cc
GMP that affect them and receive initial and nguyn tc ca GMP c nh hng n h v phi
continuing training, including hygiene instructions, c o to ban u cng nh o to lin tc lin
relevant to their needs. All personnel should be quan n nhu cu cng vic ca h, k c cc hng
motivated to support the establishment and dn v sinh. Tt c cc nhn vin phi c
maintenance of high quality standards. khuyn khch ng h vic xy dng v duy tr cc tiu
chun cht lng cao.
9.5 Steps should be taken to prevent unauthorized 9.5 Cn tin hnh cc bc phng ngi khng c
people from entering production, storage and QC nhim v ra vo khu vc sn xut, bo qun v kim
areas. Personnel who do not work in these areas tra cht lng. Nhng nhn vin khng lm vic
should not use them as a passageway. nhng khu vc ny khng c s dng nhng khu
vc ny thnh li qua li.
Key personnel Nhn vin ch cht

9.6 Key personnel include the heads of production, 9.6 Nhn vin ch cht bao gm (cc) trng b
the head(s) of quality unit(s) and the authorized phn sn xut, (cc) trng b phn cht lng v
person. The quality unit(s) typically comprise the ngi c u quyn. Cc b phn cht lng in
quality assurance and quality control functions. In hnh bao gm chc nng m bo cht lng v kim
some cases, these could be combined in one sot cht lng. Trong mt s trng hp, cc chc
department. The authorized person may also be nng ny c th c kt hp trong mt b phn duy

responsible for one or more of these quality unit(s). nht. Ngi c u quyn cng c th chu trch
Normally, key posts should be occupied by full-time nhim cho mt hoc nhiu b phn cht lng ny.
personnel. The heads of production and quality Thng thng, cc v tr ch cht phi l cn b lm
unit(s) should be independent of each other. In large vic ton thi gian. Cc v tr trng b phn sn
organizations, it may be necessary to delegate some xut v trng b phn cht lng phi c lp vi
of the functions; however, the responsibility cannot nhau. Trong cc cng ty ln, c th cn phi u
be delegated. quyn mt s chc nng, tuy nhin trch nhim th
khng th u thc.
9.7 Key personnel responsible for supervising the 9.7 Nhn vin ch cht chu trch nhim gim st
production and quality unit(s) for pharmaceutical vic sn xut v kim tra cht lng dc phm phi
products should possess the qualifications of a c cc trnh khoa hc v kinh nghim thc tin
scientific education and practical experience theo quy nh ca lut php quc gia. Chuyn ngnh
required by national legislation. Their education o to ca h nn bao gm ngnh hc phi hp
should include the study of an appropriate gia:
combination of:
(a) chemistry (analytical or organic) or (a) ho hc (ho hu c hoc ho phn tch) hoc
biochemistry; ho sinh;
(b) chemical engineering; (b) cng ngh ho;
(c) microbiology; (c) vi sinh hc;
(d) pharmaceutical sciences and technology; (d) dc khoa v cng ngh dc;
(e) pharmacology and toxicology; (e) dc l hc hoc cht c hc;
(f) physiology; (f) sinh l hc; v
(g) other related sciences. (g) cc ngnh khoa hc c lin quan khc.
They should also have adequate practical experience Nhn vin ch cht cng cn c kinh nghim thc
in the manufacture and QA of pharmaceutical t trong sn xut v m bo cht lng dc phm.
products. In order to gain such experience, a c c cc kinh nghim nh vy, c th cn phi
preparatory period may be required, during which c giai on chun b h thc tp di s hng
they should exercise their duties under professional dn v chuyn mn. Trnh chuyn mn khoa hc
guidance. The scientific education and practical v kinh nghim thc t ca cc chuyn gia phi t
experience of experts should be such as to enable ti mc sao cho h c th thc hin cc nh gi
them to exercise independent professional chuyn mn mt cch c lp, da trn vic p dng
judgement, based on the application of scientific cc nguyn tc v hiu bit khoa hc v nhng vn
principles and understanding to the practical thc tin gp phi trong qu trnh sn xut v
problems encountered in the manufacture and QC of kim tra cht lng dc phm.
pharmaceutical products.
9.8 The heads of the production and the quality 9.8 Ni chung, cc v tr trng b phn sn xut v
unit(s) generally have some shared, or jointly trng (cc) b phn cht lng c mt s trch
exercised, responsibilities relating to quality. nhim chung, hoc cng thc hin mt s cng vic
lin quan n cht lng.
These may include, depending on national Tu thuc vo lut php quc gia, cc trch nhim
regulations: ny c th bao gm:
(a) authorization of written procedures and other (a) ph duyt quy trnh thao tc bng vn bn v
documents, including amendments; cc ti liu khc, k c cc sa i;
(b) monitoring and control of the manufacturing (b) theo di v kim sot mi trng sn xut;
environment;
(c) plant hygiene; (c) m bo vn v sinh trong nh my;
(d) process validation and calibration of (d) thm nh qu trnh v hiu chun thit b
analytical apparatus; phn tch;
(e) training, including the application and (e) o to, k c vic p dng cc nguyn tc
principles of QA; m bo cht lng;
(f) approval and monitoring of suppliers of (f) ph duyt v theo di nh cung cp nguyn
materials; vt liu;
(g) approval and monitoring of contract (g) ph duyt v theo di nh sn xut theo hp
manufacturers; ng;
(h) designation and monitoring of storage (h) quy nh v theo di iu kin bo qun
conditions for materials and products; nguyn liu v sn phm;
(i) performance and evaluation of in-process (i) thc hin v nh gi cc kim sot trong
controls; qu trnh;
(j) retention of records; (j) lu gi h s;
(k) monitoring of compliance with GMP (k) theo di vic tun th quy nh GMP; v
requirements; and
(l) inspection, investigation and taking of (l) kim tra, iu tra v ly mu, nhm theo di

samples in order to monitor factors that may cc yu t c th nh hng n cht lng

affect product quality. sn phm.
9.9 The head of the production generally has the 9.9 Trng b phn sn xut nhn chung c nhng
following responsibilities: trch nhim sau:
(a) to ensure that products are produced and (a) m bo sn phm c sn xut v bo
stored according to the appropriate qun theo ng h s ti liu ph hp c
documentation in order to obtain the c cht lng yu cu;
required quality;
(b) to approve the instructions relating to (b) ph duyt cc hng dn lin quan n thao
production operations, including the in- tc sn xut, k c cc kim tra qu trnh sn
process controls, and to ensure their strict xut, v m bo chng c thc hin mt
implementation; cch nghim ngt;
(c) to ensure that the production records are (c) m bo h s sn xut c nh gi v k
evaluated and signed by a designated person; bi mt ngi c giao nhim v ny;
(d) to check the maintenance of the department, (d) kim tra vic bo tr nh xng v my mc
premises and equipment; thit b lin quan n sn xut;
(e) to ensure that the appropriate process (e) m bo vic thm nh qu trnh v hiu
validations and calibrations of control chun cc thit b kim sot c thc
equipment are performed and recorded and hin v ghi chp li trong h s bo co;
the reports made available;
(f) to ensure that the required initial and (f) m bo vic thc hin o to ban u v
continuing training of production personnel o to lin tc cho nhn vin sn xut v
is carried out and adapted according to need. vic o to c iu chnh ph hp vi nhu
cu.
9.10 The head(s) of the quality unit(s) generally have 9.10 (Cc) trng b phn cht lng nhn chung c
the following responsibilities: nhng trch nhim sau:
(a) to approve or reject starting materials, (a) chp thun hoc loi b nguyn liu ban u,
packaging materials, and intermediate, bulk nguyn vt liu bao gi, sn phm trung gian,
and finished products in relation with their bn thnh phm v thnh phm theo tiu
specifications; chun ca chng;
(b) to evaluate batch records; (b) nh gi h s l;
(c) to ensure that all necessary testing is carried (c) m bo tt c cc php th cn thit u
out; c thc hin;
(d) to approve sampling instructions, (d) ph duyt cc hng dn ly mu, tiu
specifications, test methods and other QC chun, phng php th v cc quy trnh
procedures; kim sot cht lng khc;
(e) to approve and monitor analyses carried out (e) ph duyt v theo di vic kim nghim theo
under contract; hp ng;
(f) to check the maintenance of the department, (f) kim tra vic bo dng c s, nh xng v
premises and equipment; my mc thit b;
(g) to ensure that the appropriate validations, (g) m bo cc thm nh ph hp, k c thm
including those of analytical procedures, and nh phng php phn tch v hiu chun
calibrations of control equipment are carried thit b kim nghim c thc hin;
out;
(h) to ensure that the required initial and (h) m bo vic o to ban u v o to lin
continuing training of quality unit personnel tc cho nhn vin b phn cht lng v vic
is carried out and adapted according to need; o to c iu chnh sao cho ph hp vi
(i) establishment, implementation and nhu cu;
maintenance of the quality system; (i) thit lp, thc hin v duy tr h thng cht
(j) supervision of the regular internal audits or lng
self-inspections; (j) gim st thanh tra ni b hoc t thanh tra;
(k) participation in external audit (vendor audit);
(l) participation in validation programmes. (k) tham gia cc cuc nh gi bn ngoi (nh
gi nh cung cp); tham gia vo cc chng
trnh thm nh.
Other duties of QC are summarized in sections 17.3 Cc trch nhim khc ca b phn QC c tm tt
and 17.4. ti phn 17.3 v 17.4.
9.11 The authorized person is responsible for 9.11 Ngi c u quyn chu trch nhim tun th
compliance with technical or regulatory cc yu cu chuyn mn v qun l lin quan n
requirements related to the quality of finished cht lng ca sn phm cui v chu trch nhim
products and the approval of the release of the ph duyt xut thnh phm bn hoc cung cp.
finished product for sale or supply.

9.12 Assessment of finished products should embrace 9.12 nh gi sn phm cui phi bao qut tt c cc
all relevant factors, including the production yu t lin quan, bao gm iu kin sn xut, kt qu
conditions, the results of in-process testing, the kim tra trong qu trnh, ti liu sn xut (bao gm
manufacturing (including packaging) documentation, c bao gi), s ph hp vi tiu chun i vi sn
compliance with the specification for the finished phm cui, v kim tra bao gi cui cng.
product, and an examination of the finished pack.
9.13 No batch of product is to be released for sale or 9.13 Khng l sn phm no c xut bn hoc
supply prior to certification by the authorized cung cp trc khi c chng nhn bi (nhng)
person(s). In certain countries, by law, the batch ngi c u quyn. Tu theo lut php quc gia,
release is a task of the authorized person from vic duyt xut l hng l trch nhim ca ngi
production together with the authorized person from c u quyn t b phn sn xut cng vi ngi
QC. c u quyn t QC.
9.14 The authorized person responsible for 9.14 Ngi c u quyn chu trch nhim i vi
approving a batch for release should always ensure vic duyt xut sn phm cn lun m bo rng cc
that the following requirements have been met: yu cu di y c p ng:
(a) the marketing authorization and the (a) cc yu cu trong giy php lu hnh v giy
manufacturing authorization requirements php sn xut sn phm u c p ng
for the product have been met for the batch l sn phm c lin quan;
concerned;
(b) the principles and guidelines of GMP, as laid (b) cc nguyn tc v hng dn ca GMP, nh
down in the guidelines published by WHO, nu trong cc hng dn c pht hnh
have been followed; bi WHO u c thc hin;
(c) the principal manufacturing and testing (c) cc nguyn tc sn xut v qu trnh th
processes have been validated, if different; nghim u c thm nh, nu khc
bit;
(d) all the necessary checks and tests have been (d) tt c cc bin php kim tra v th nghim
performed and account taken of the cn thit u c thc hin v c tnh
production conditions and manufacturing n iu kin sn xut v h s sn xut;
records;
(e) any planned changes or deviations in (e) bt k thay i nh trc hoc sai lch
manufacturing or quality control have been trong qu trnh sn xut hoc kim sot cht
notified in accordance with a well defined lng u c bo co theo mt h thng
reporting system before any product is bo co trc khi cho xut by k sn phm
released. Such changes may need notification no. Nhng thay i nh vy c th cn phi
to, and approval by, the medicines regulatory thng bo cho c quan qun l dc v phi
authority; c ph duyt;
(f) any additional sampling, inspection, tests and (f) bt k mt hot ng ly mu, thanh tra,
checks have been carried out or initiated, as kim nghim hay kim tra b sung no
appropriate, to cover planned changes and c thc hin hoc trin khai, nu cn, i
deviations; vi nhng thay i nh trc hoc cc sai
lch;
(g) all necessary production and QC (g) tt c h s sn xut v kim tra cht lng
documentation has been completed and u c hon tt v thng qua cc cn
endorsed by supervisors trained in b gim st c o to ph hp;
appropriate disciplines;
(h) appropriate audits, self-inspections and spot- (h) cc nh gi thch hp, t thanh tra v kim
checks are carried out by experienced and tra ngu nhin c thc hin bi cc nhn
trained staff; s c o to v c kinh nghim
(i) approval has been given by the head of QC (i) ph duyt bi trng b phn QC
(j) all relevant factors have been considered, (j) tt c cc yu t lin quan u c xem
including any not specifically associated with xt, bao gm c cc yu t khng lin quan
the output batch directly under review (e.g. c th n l hng c xem xt (v d vic
subdivision of output batches from a common chia nh cc l t mt lng u vo chung,
input, factors associated with continuous nhng yu t lin quan n qu trnh sn
production runs). xut lin tc)
9.15 The function of the approval of the release of a 9.15 Chc nng ph duyt cho xut mt l thnh
finished batch or a product can be delegated to a phm hoc sn phm c th c giao cho mt ngi
designated person with appropriate qualifications c trnh v kinh nghim ph hp, ngi ny s
and experience who will release the product in xut sn phm theo ng quy trnh c ph
accordance with an approved procedure. This is duyt. iu ny thng c thc hin bi QA thng
normally done by QA by means of batch review. qua vic xem xt h s l.

10. Training 10. o to

10.1 The manufacturer should provide training in 10.1 Nh sn xut cn t chc o to theo mt
accordance with a written programme for all chng trnh bng vn bn cho tt c nhn vin c
personnel whose duties take them into nhim v trong khu vc sn xut v phng kim tra
manufacturing areas or into control laboratories cht lng (k c nhn vin k thut, bo dng v
(including the technical, maintenance and cleaning lm v sinh), v nhng nhn vin khc nu cn.
personnel) and for other personnel as required.
10.2 Besides basic training on the theory and 10.2 Bn cnh vic o to c bn v l thuyt v
practice of GMP, newly recruited personnel should thc hnh GMP, nhn vin mi tuyn cn c o
receive training appropriate to the duties assigned to to v nhng vn ph hp vi nhim v c giao.
them. Continuing training should also be given, and Vic o to phi lin tc, v hiu qu o to phi
its practical effectiveness periodically assessed. c nh gi nh k. Cn c chng trnh o to
Approved training programmes should be available. c ph duyt chnh thc v lu gi h s v o
Training records should be kept. to.
10.3 Personnel working in areas where 10.3 Nhn vin lm vic trong nhng khu vc c
contamination is a hazard, e.g. clean areas or areas nguy c b tp nhim, v d khu vc sch hoc nhng
where highly active, toxic, infectious or sensitizing khu vc x l cc nguyn vt liu c hot tnh cao,
materials are handled, should be given specific c, truyn nhim hoc gy d ng, cn c o to
training. chuyn su.
10.4 The concept of QA and all the measures which 10.4 Khi nim m bo cht lng v tt c cc bin
aid its understanding and implementation should be php c kh nng nng cao nhn thc v vic thc
fully discussed during the training sessions. hin m bo cht lng cn c bn lun thu o
trong cc kho o to.
10.5 Visitors or untrained personnel should 10.5 Khch tham quan v nhn vin cha qua o to
preferably not be taken into the production and QC tt nht l khng nn cho vo khu vc sn xut v
areas. If this is unavoidable, they should be given kim tra cht lng. Nu khng trnh c vic ny
relevant information in advance (particularly about h phi c thng bo trc nhng thng tin c lin
personal hygiene) and the prescribed protective quan (c bit l v v sinh c nhn) v c trang b
clothing. They should be closely supervised. cc trang phc bo h cn thit. Cn gim st h
cht ch.
10.6 Consultant and contract staff should be qualified 10.6 Ngi t vn v cc nhn vin hp ng phi c
for the services they provide. Evidence of this should chuyn mn v dch v m h cung cp. Cc giy t
be included in the training records. chng minh trnh chuyn mn cn phi c b
sung vo h s o to.
11. Personal hygiene 11. V sinh c nhn

11.1 All personnel, prior to and during employment, 11.1 Tt c nhn vin cn c kim tra trc v khi
as appropriate, should undergo health examinations. ang c tuyn dng. Nhng nhn vin hin vic
Personnel conducting visual inspections should also kim tra bng mt cn phi nh k kim tra mt.
undergo periodic eye examinations.
11.2 All personnel should be trained in the practices 11.2 Nhn vin phi c o to v thc hnh v
of personal hygiene. A high level of personal hygiene sinh c nhn. Tt c nhn vin tham gia sn xut u
should be observed by all those concerned with phi tun th cc quy nh v sinh c nhn mc
manufacturing processes. In particular, personnel cao. C th l, nhn vin phi c hng dn ra
should be instructed to wash their hands before tay trc khi vo khu vc sn xut. Cn c bin
entering production areas. Signs to this effect should hng dn v iu ny phi c thc hin nghim
be posted and instructions complied with. tc.
11.3 Any person shown at any time to have an 11.3 Bt k ai vo bt k lc no c biu hin b m
apparent illness or open lesions that may adversely ao r rt hoc c vt thng h c th c nh hng
affect the quality of products should not be allowed bt li ti cht lng sn phm u khng c php
to handle starting materials, packaging materials, in- tham gia x l nguyn liu ban u, nguyn vt liu
process materials or medicines products until the bao gi, nguyn vt liu trong qu trnh sn xut,
condition is no longer judged to be a risk. hoc sn phm, cho ti khi tnh trng sc kho c

nh gi l khng cn nguy c na.
11.4 All employees should be instructed and 11.4 Tt c nhn vin phi c hng dn v
encouraged to report to their immediate supervisor khuyn khch bo co cho ngi ph trch trc tip
any conditions (relating to plant, equipment or bt k tnh trng no (lin quan n nh my, my
personnel) that they consider may adversely affect mc thit b hoc nhn vin) m h cho l c th nh
the products. hng bt li n sn phm.
11.5 Direct contact should be avoided between the 11.5 Nhn vin vn hnh cn trnh tip trc tip
operators hands and starting materials, primary bng tay vi nguyn liu ban u, nguyn vt liu
packaging materials and intermediate or bulk bao gi trc tip, sn phm trung gian v bn thnh
product. phm.
11.6 To ensure protection of the product from 11.6 bo v sn phm khi b tp nhim, nhn
contamination, personnel should wear clean body vin cn mc trang phc sch, ph hp vi nhim v
coverings appropriate to the duties they perform, c giao, k c m trm tc ph hp. Qun o
including appropriate hair covering. Used clothes, if dng ri, nu cn dng li phi c ct trong cc
reusable, should be stored in separate closed ngn kn ring cho ti khi c git sch v ty trng
containers until properly laundered and, if necessary, hoc v trn nu cn.
disinfected or sterilized.
11.7 Smoking, eating, drinking, chewing, and 11.7 Khng c php ht thuc, n, ung, nhai,
keeping plants, food, drink, smoking material and cy ci, thc phm, ung v thuc ht cng nh
personal medicines should not be permitted in thuc cha bnh c nhn tng khu vc sn xut,
production, laboratory and storage areas, or in any phng kim tra cht lng v khu vc bo qun, hoc
other areas where they might adversely influence trong cc khu vc khc c th gy nh hng bt li
product quality ti cht lng sn phm.
11.8 Personal hygiene procedures including the use 11.8 Quy trnh v sinh c nhn, k c vic s dng
of protective clothing should apply to all persons qun o bo h phi p dng cho tt c cc nhn
entering production areas, whether they are vin i vo khu vc sn xut, cho d l nhn vin
temporary or full-time employees or nonemployee, chch thc hay thi v, hoc khng phi l nhn vin,
e.g. contractors employees, visitors, senior v d nh nhn vin ca bn hp ng, khch tham
managers and inspectors. quan, cc cn b qun l cao cp, v thanh tra vin.
12. Premises 12. Nh xng

12.1 Principle. Premises must be located, designed, 12.1 Nguyn tc. Nh xng phi c v tr, c thit
constructed, adapted and maintained to suit the k, xy dng, sa cha v bo dng ph hp vi
operations to be carried out. thao tc sn xut s din ra.

12.2 The layout and design of premises must aim to 12.2 B tr mt bng v thit k ca nh xng phi
minimize the risk of errors and permit effective nhm mc ch gim ti a nguy c sai st v m
cleaning and maintenance in order to avoid cross- bo lm v sinh cng nh bo dng c hiu qu
contamination, build-up of dust or dirt, and in trnh nhim cho, tch t bi hoc rc, v ni chung
general, any adverse effect on the quality of l bt k nh hng bt li no ti cht lng sn
products. phm.
12.3 Where dust is generated (e.g. during sampling, 12.3 nhng ni sinh bi (v d trong thao tc ly
weighing, mixing and processing operations, mu, cn, trn v ch bin ng gi thuc bt), cn
packaging of powder), measures should be taken to c bin php trnh nhim cho v to iu kin
avoid cross-contamination and facilitate cleaning. lm v sinh d dng.
12.4 Premises should be situated in an environment 12.4 Nh xng phi c t trong mi trng cng
that, when considered together with measures to vi cc bin php bo v qu trnh sn xut gim
protect the manufacturing process, presents ti a nguy c gy tp nhim i vi nguyn liu
minimum risk of causing any contamination of hoc sn phm.
materials or products.
12.5 Premises used for the manufacture of finished 12.5 Nh xng s dng cho sn xut thnh phm

products should be suitably designed and phi c thit k v xy dng ph hp m bo

constructed to facilitate good sanitation. iu kin v sinh tt.
12.6 Premises should be carefully maintained, and it 12.6 Nh xng cn c bo dng cn thn, phi
should be ensured that repair and maintenance m bo cc hot ng bo dng v sa cha khng
operations do not present any hazard to the quality l nguy c cho cht lng sn phm.
of products.
12.7 Premises should be cleaned and, where 12.7 Nh xng phi c lm v sinh v ty trng
applicable, disinfected according to detailed written nu cn theo cc quy trnh chi tit bng vn bn. Cn
procedures. Records should be maintained. lu h s cng vic v sinh.
12.8 Electrical supply, lighting, temperature, 12.8 Ngun in, nh sng, nhit , m, thng
humidity and ventilation should be appropriate and gi phi ph hp sao cho chng khng c nh hng
such that they do not adversely affect, directly or bt li trc tip hoc gin tip ti dc phm trong
indirectly, either the pharmaceutical products during khi sn xut v bo qun, hoc nh hng n vic
their manufacture and storage, or the accurate vn hnh chnh xc ca my mc thit b.
functioning of equipment.
12.9 Premises should be designed and equipped so 12.9 Nh xng phi c thit k v trang b sao
as to afford maximum protection against the entry of cho c th bo v ti a khi s xm nhp ca cn
insects, birds or other animals. There should be a trng, chim chc hoc cc ng vt khc. Cn c mt
procedure for rodent and pest control. quy trnh kim sot loi gm nhm v ng vt gy
hi.
12.10 Premises should be designed to ensure the 12.10 Nh xng phi c thit k m bo rng
logical flow of materials and personnel. dng lun chuyn hp l ca nguyn vt liu v nhn
vin.
Ancillary areas Khu ph

12.11 Rest and refreshment rooms should be 12.11 Cc phng v sinh v ngh gii lao phi tch
separate from manufacturing and control areas. bit khi khu vc sn xut v kim nghim
12.12 Facilities for changing and storing clothes and 12.12 Phng thay v gi qun o, khu vc tm ra v
for washing and toilet purposes should be easily v sinh phi d dng tip cn v ph hp vi s ngi
accessible and appropriate for the number of users. s dng. Nh v sinh khng c thng trc tip vi
Toilets should not communicate directly with khu vc sn xut v bo qun.
production or storage areas.
12.13 Maintenance workshops should if possible be 12.13 Nu iu kin cho php, xng bo dng nn
separated from production areas. Whenever parts tch khi khu vc sn xut. Trng hp c ph
and tools are stored in the production area, they tng v dng c trong khu vc sn xut, phi
should be kept in rooms or lockers reserved for that trong phng hoc t c kho dnh ring cho mc
use. ch .
12.14 Animal houses should be well isolated from 12.14 Nh nui ng vt phi cch ly tt khi cc
other areas, with separate entrance (animal access) khu vc khc, vi li ra vo ring (li vo ch ring
and air-handling facilities. cho ng vt) v thit b x l khng kh ring.
Storage areas Khu vc bo qun

12.15 Storage areas should be of sufficient capacity 12.15 Khu vc bo qun phi rng, cho php bo
to allow orderly storage of the various categories of qun c trt t nhiu loi nguyn vt liu v sn
materials and products with proper separation and phm, c s phn bit v cch ly ph hp: nguyn
segregation: starting and packaging materials, liu ban u v nguyn vt liu bao gi, sn phm
intermediates, bulk and finished products, products trung gian, bn thnh phm v thnh phm, sn
in quarantine, and released, rejected, returned or phm bit tr, sn phm c php xut, b loi,
recalled products. b tr v hay sn phm thu hi.
12.16 Storage areas should be designed or adapted 12.16 Khu vc bo qun phi c thit k hoc iu
to ensure good storage conditions. In particular, they chnh m bo iu kin bo qun tt. c bit l

should be clean, dry, sufficiently lit and maintained phi sch s, kh ro, nh sng v duy tr nhit
within acceptable temperature limits. Where special chp nhn c. Trong khu cn iu kin bo
storage conditions are required (e.g. temperature, qun c bit (v d nh v nhit , m) th phi
humidity) these should be provided, controlled, m bo cc iu kin ny, c kim tra, theo di v
monitored and recorded where appropriate. ghi chp li mt cch thch hp.
12.17 Receiving and dispatch bays should be 12.17 Khu vc nhn v xut hng phi b tr ring
separated and protect materials and products from bit v bo v c nguyn vt liu v sn phm
the weather. Receiving areas should be designed and trc thi tit. Khu vc nhn phi c thit k v
equipped to allow containers of incoming materials trang b cho php cc thng nguyn liu c lm
to be cleaned if necessary before storage. sch nu cn trc khi bo qun.
12.18 Where quarantine status is ensured by storage 12.18 Khi bit tr c m bo bng cch bo qun
in separate areas, these areas must be clearly nhng khu vc ring bit, nhng khu vc ny phi
marked and their access restricted to authorized c bin hiu r rng v ch nhng ngi c thm
personnel. Any system replacing the physical quyn mi c php ra vo. Nu s dng mt h
quarantine should give equivalent security. thng khc thay th bit tr c hc h thng phi
m bo an ton mc tng ng.
12.19 Segregation should be provided for the storage 12.19 Cn bo qun tch ring nguyn vt liu v
of rejected, recalled, or returned materials or sn phm phm b loi, thu hi hoc b tr v.
products.
12.20 Highly active and radioactive materials, 12.20 Nhng nguyn vt liu c hot tnh cao v tnh
narcotics, other dangerous medicines, and phng x, cht gy nghin, hoc cc thuc nguy him
substances presenting special risks of abuse, fire or , v cc cht c bit c nguy c b lm dng, bt la
explosion should be stored in safe and secure areas. hoc gy n phi c bo qun khu vc an ton v
c bo v.
12.21 Printed packaging materials are considered 12.21 Nguyn liu bao gi in sn c coi l rt quan
critical to the conformity of the pharmaceutical trng trong vic m bo dc phm ng vi ni
product to its labelling and special attention should dung trn nhn, cn c bit ch n vic ly mu
be paid to sampling and the safe and secure storage v bo qun an ton nhng nguyn vt liu ny.
of these materials.
12.22 There should normally be a separate sampling 12.22 Thng cn phi c khu vc ring ly mu
area for starting materials. (If sampling is performed nguyn liu ban u. (Nu ly mu ngay khu vc
in the storage area, it should be conducted in such a bo qun, phi tin hnh sao cho c th trnh c
way as to prevent contamination or cross- tp nhim hay nhim cho)
contamination.)
Weighing areas Khu vc cn

12.23 The weighing of starting materials and the 12.23 Vic cn nguyn liu ban u v c tnh sn
estimation of yield by weighing should be carried out lng bng cch cn thng c thc hin khu
in separate weighing areas designed for that use, for vc cn ring bit c thit k cho mc ch ny, v
example, with provisions for dust control. Such areas d c bin php kim sot bi. Khu vc ny c
may be part of either storage or production areas. th nm trong khu vc bo qun hoc khu vc sn
xut.
Production areas Khu vc sn xut

12.24 In order to minimize the risk of a serious 12.24 hn ch ti a nguy c gy nguy him
medical hazard due to cross-contamination, nghim trng cho sc kho do sn xut b nhim
dedicated and self-contained facilities must be cho, cn c nh xng chuyn bit v khp kn cho
available for the production of particular vic sn xut nhng dc phm c bit, v d nhng
pharmaceutical products, such as highly sensitizing nguyn vt liu d gy d ng (v d penicillin), hoc
materials (e.g. penicillins) or biological preparations sinh phm (v d cc sinh vt sng). Vic sn xut
(e.g. live microorganisms). The production of certain mt s sn phm c hot tnh cao khc, v d mt s
other highly active products, such as some khng sinh, hc mn, cht c t bo v nhng sn
antibiotics, hormones, cytotoxic substances and phm khng phi dc phm, khng nn tin hnh
certain non-pharmaceutical products, should not be trong cng mt nh xng. Trong nhng trng hp

conducted in the same facilities. In exceptional cases, ngoi l, c th chp nhn nguyn tc sn xut theo
the principle of campaign working in the same chin dch trong cng nh xng vi iu kin l phi
facilities can be accepted provided that specific c bit thn trng v c tin hnh cc thm nh
precautions are taken and the necessary validations cn thit (k co thm nh quy trnh v sinh). Vic
(including cleaning validation) are made. The sn xut cc thuc c chuyn ngnh, v d nh
manufacture of technical poisons, such as pesticides thuc dit cn trng hoc thuc dit c, khng c
and herbicides, should not be allowed in premises php tin hnh nh xng dnh cho sn xut dc
used for the manufacture of pharmaceutical phm.
products.
12.25 Premises should preferably be laid out in such 12.25 Mt bng nh xng phi c b tr sao cho
a way as to allow the production to take place in vic sn xut c thc hin trong nhng khu vc
areas connected in a logical order corresponding to tip ni vi nhau theo mt trt t hp l tng ng
the sequence of the operations and to the requisite vi trnh t ca cc hot ng sn xut v tng ng
cleanliness levels. mc sch cn thit.
12.26 The adequacy of the working and in-process 12.26 Phi c din tch lm vic v bo qun trong
storage space should permit the orderly and logical qu trnh sn xut c th t my mc thit b v
positioning of equipment and materials so as to nguyn vt liu mt cch c trt t v hp l, sao cho
minimize the risk of confusion between different hn ch ti a nguy c ln ln gia cc sn phm
pharmaceutical products or their components, to hoc qu cc thnh phn ca sn phm, trnh nhim
avoid cross-contamination, and to minimize the risk cho, v gim ti a nguy c b st hoc p dng sai
of omission or wrong application of any of the bt k mt bc sn xut hay kim tra no.
manufacturing or control steps.
12.27 Where starting and primary packaging 12.27 nhng ni nguyn liu ban u, nguyn vt
materials and intermediate or bulk products are liu bao gi trc tip v sn phm trung gian, bn
exposed to the environment, interior surfaces (walls, thnh phm tip xc vi mi trng, b mt bn
floors and ceilings) should be smooth and free from trong (ca tng, sn v trn nh) phi nhn v
cracks and open joints, should not shed particulate khng c k nt cng nh ch ni h, khng c
matter, and should permit easy and effective cleaning sinh tra cc ht tiu phn, cho php lm v sinh v
and, if necessary, disinfection. ty trng nu cn, d dng v c hiu qu.
12.28 Pipework, light fittings, ventilation points and 12.28 Cc ng dn, mng n, cc im thng gi v
other services should be designed and sited to avoid cc dch v khc phi c thit k v lp t sao
the creation of recesses that are difficult to clean. As cho trnh to thnh cc hc kh lm v sinh. Khi bo
far as possible, for maintenance purposes, they dng, cn tip cn nhng dch v ny t bn ngoi
should be accessible from outside the manufacturing khu vc sn xut, nu c.
areas.
12.29 Drains should be of adequate size and 12.29 Cc ng thot nc phi ln, c thit
designed and equipped to prevent back-flow. Open k v trang b trnh tro ngc. Nu c th, cn
channels should be avoided where possible, but if trnh ng thot nc h. Nhng nu cn cn thit
they are necessary they should be shallow to phi c th nn nng d lm v sinh v ty trng.
facilitate cleaning and disinfection.
12.30 Production areas should be effectively 12.30 Khu vc sn xut phi c thng gi tt, c
ventilated, with air- control facilities (including thit b kim sot khng kh (bao gm thit b lc gi
filtration of air to a sufficient level to prevent mc ngn nga tp nhim v nhim cho
contamination and cross-contamination, as well as cng nh kim sot c nhit v m nu cn)
control of temperature and, where necessary, ph hp vi cc sn phm ang c sn xut, ph
humidity) appropriate to the products handled, to the hp vi hot ng sn xut v vi mi trng bn
operations undertaken and to the external ngoi. Nhng khu vc ny cn c theo di thng
environment. These areas should be regularly xuyn trong khi sn xut v c khi khng sn xut
monitored during both production and non- m bo vn p ng c tiu chun thit k.
production periods to ensure compliance with their
design specifications.
12.31 Premises for the packaging of pharmaceutical 12.31 Khu vc xng ng gi dc phm phi c
products should be specifically designed and laid out thit k v b tr c bit trnh ln ln, nhim bn
so as to avoid mix ups, contamination or cross- hoc nhim cho.
contamination.
12.32 Production areas should be well lit, 12.32 Khu vc sn xut phi sng, c bit
particularly where visual online controls are carried nhng ni thc hin vic kim tra bng mt thng
out. trong qu trnh sn xut.

Quality control areas Khu vc kim tra cht lng

12.33 QC laboratories should be separated from 12.33 Phng kim tra cht lng phi c tch bit
production areas. Areas where biological, khi khu vc sn xut. Nhng khu vc tin hnh
microbiological or radioisotope test methods are php th sinh hc, vi sinh, hoc th ng v phng x
employed should be separated from each other. phi cch bit nhau.
12.34 QC laboratories should be designed to suit the 12.34 Phng kim nghim phi c thit k ph hp
operations to be carried out in them. Sufficient space vi hot ng s tin hnh ti . Cn c din tch
should be given to avoid mix ups and cross- trnh ln ln v nhim cho. Cn c din tch
contamination. There should be adequate suitable ph hp bo qun mu, cht chun (nu cn, c
storage space for samples, reference standards (if h thng lm mt), dung mi, thuc th v h s.
necessary, with cooling), solvents, reagents and
records.
12.35 The design of the laboratories should take into 12.35 Thit k cc phng kim nghim phi tnh n
account the suitability of construction materials, tnh ph hp ca vt liu xy dng, trnh khi v
prevention of fumes and ventilation. There should be thng gi. Cn c h thng cung cp khng kh ring
separate air supply to laboratories and production bit cho khu vc sn xut v cc phng kim nghim.
areas. Separate air-handling units and other Cc phng kim nghim sinh hc, vi sinh v ng v
provisions are needed for biological, microbiological phng x phi c ring thit b x l khng kh v cc
and radioisotope laboratories. thit b khc.
12.36 A separate room may be needed for 12.36 C th cn c phng ring cho dng c th
instruments to protect them against electrical nghim bo v chng khi b nhiu in t, rung
interference, vibration, contact with excessive ng, tip xc vi m qu mc, v cc yu t
moisture and other external factors, or where it is ngoi cnh khc, hoc khi cn phi tch ring cc
necessary to isolate the instruments. dng c ny.
13. Equipment 13. My mc thit b

13.1 Equipment must be located, designed, 13.1 My mc thit b phi c b tr, thit k, kt
constructed, adapted and maintained to suit the cu, lp t v bo dng ph hp vi cc thao tc s
operations to be carried out. The layout and design of thc hin. Vic b tr v thit k ca my mc phi
equipment must aim to minimize the risk of errors nhm mc ch gim ti a nguy c sai st v cho
and permit effective cleaning and maintenance in php lm v sinh v bo dng c hiu qu, nhm
order to avoid cross-contamination, build-up of dust trnh nhim cho, tch t bi v bn, v ni chung l
or dirt, and, in general, any adverse effect on the trnh nhng tc ng bt li i vi cht lng sn
quality of products. phm.
13.2 Equipment should be installed in such a way as 13.2 My mc thit b phi c lp t sao cho hn
to minimize any risk of error or of contamination. ch c ti a nguy c sai st hoc tp nhim.
13.3 Fixed pipework should be clearly labelled to 13.3 Cc ng ng c nh cn c dn nhn r

indicate the contents and, where applicable, the rng ch r ni dung bn trong v hng dng chy,
direction of flow. nu thch hp.
13.4 All service pipings and devices should be 13.4 Tt c cc ng ng v thit b phc v u
adequately marked and special attention paid to the phi c nh du thch hp. Cn c bit lu n
provision of non-interchangeable connections or nhng im ni hoc thit b ni khng i ch c
adaptors for dangerous gases and liquids ca cc ng dn kh hoc dung dch nguy him.
13.5 Balances and other measuring equipment of an 13.5 Phi c cn v nhng thit b o lng khc c
appropriate range and precision should be available khong v chnh xc ph hp cho cc hot ng
for production and control operations and should be sn xut v kim tra cht lng. Cc thit b ny phi
calibrated according to a fixed schedule. c hiu chun theo lch c nh.
13.6 Production equipment should be thoroughly 13.6 My mc thit b sn xut phi c lm v sinh
cleaned according to a fixed schedule. ton din theo mt k hoch c nh.
13.7 Laboratory equipment and instruments should 13.7 Thit b v dng c dng trong kim nghim
be suited to the testing procedures undertaken. phi ph hp vi quy trnh th nghim cn thc hin.

13.8 Washing, cleaning and drying equipment should 13.8 My mc thit b sy, ra v lm v sinh phi
be chosen and used so as not to be a source of c la chn v s dng sao cho khng tr thnh
contamination. ngun gy tp nhim.
13.9 Production equipment should not present any 13.9 My mc thit b sn xut khng c gy nguy
hazard to the products. The parts of the production him cho sn phm. Nhng b phn ca my mc
equipment that come into contact with the product thit b sn xut c tip xc vi sn phm khng
must not be reactive, additive, or absorptive to an c gy phn ng, to ra thm cht hay hp thu
extent that would affect the quality of the product. cht mc c th nh hng ti cht lng sn
phm.
13.10 Defective equipment should be removed from 13.10 My mc thit b hng cn c a ra khi
production and QC areas. If this is not possible, it khu vc sn xut v kim tra cht lng. Nu khng
should be clearly labelled as defective to prevent use. chuyn ra ngoi c, t nht thit b cng phi c
dn nhn ghi r l hng, phng v s dng.
13.11 Closed equipment should be used whenever 13.11 Bt c khi no c th, nn s dng cc thit b
appropriate. Where open equipment is used or kn. Khi dng cc my mc thit b h, hoc khi m
equipment is opened, precautions should be taken to my mc thit b, cn thn trng hn ch ti a tp
minimize contamination. nhim.
13.12 Non-dedicated equipment should be cleaned 13.12 Nhng my mc thit b khng chuyn dng
according to validated cleaning procedures between phi c lm v sinh theo nhng quy trnh v sinh
being used for production production of different c thm nh khi chuyn i sn phm trnh
pharmaceutical products to prevent cross- nhim cho.
contamination.
13.13 Current drawings of critical equipment and 13.13 Cn lu gi bn v ca cc my mc thit b v

support systems should be maintained. h thng thit b ph tr.
14. Materials 14. Nguyn vt liu

14.1 Principle. The main objective of a 14.1 Nguyn tc. Mc tiu chnh ca mt nh my
pharmaceutical plant is to produce finished products dc phm l sn xut ra thnh phm dng cho bnh
for patients use from acombination of materials nhn bng vic phi hp cc nguyn vt liu (nguyn
(starting and packaging). liu ban u v bao b)
14.2 Materials include starting materials, packaging 14.2 Nguyn vt liu gm c nguyn liu ban u,
materials, gases, solvents, process aids, reagents and nguyn vt liu bao gi, kh, dung mi, cht ph gia,
labelling materials. thuc th v cc vt liu nhn mc.

14.3 Khng mt nguyn vt liu no s dng cho cc
14.3 No materials used for operations such as
hot ng nh lm v sinh, bi trn thit b v kim
cleaning, lubrication of equipment and pest control,
sot cn trng c cho tip xc trc tip vi sn
should come into direct contact with the product.
phm. Nu c th, nhng nguyn vt liu ny phi
Where possible, such materials should be of a
t mt tiu chun ph hp hn (v d tiu chun
suitable grade (e.g. food grade) to minimize health
thc phm) nhm hn ch ti a nguy c cho sc
risks.
kho.
14.4 All incoming materials and finished products 14.4 Tt c cc nguyn vt liu u vo v thnh
should be quarantined immediately after receipt or phm phi c bit tr ngay sau khi nhn hoc ch
processing, until they are released for use or bin, cho n khi chng c em s dng hoc
distribution. phn phi.
14.5 All materials and products should be stored 14.5 Tt c nguyn liu v sn phm u phi c
under the appropriate conditions established by the bo qun trong iu kin ph hp do nh sn xut
manufacturer and in an orderly fashion to permit quy nh v theo trt t gip phn bit c cc l v
batch segregation and stock rotation by a first- theo nguyn tc ht hn trc xut trc (FEFO).
expire, first-out rule.

14.6 Water used in the manufacture of 14.6 Nc s dng trong sn xut dc phm phi
pharmaceutical products should be suitable for its ph hp vi mc ch s dng.
intended use.
Starting materials Nguyn liu ban u

14.7 The purchase of starting materials is an 14.7 Vic mua nguyn liu ban u l mt hot ng
important operation that should involve staff who quan trng cn c s tham gia ca nhng nhn vin
have a particular and thorough knowledge of the c hiu bit su v ton din v sn phm v cc nh
products and suppliers. cung cp.
14.8 Starting materials should be purchased only 14.8 Nguyn liu ban u ch nn mua ca nh cung
from approved suppliers and, where possible, cp c ph duyt, v nu c th, mua trc tip
directly from the producer. It is also recommended ca hng sn xut. Cc tiu chun do nh sn xut
that the specifications established by the t ra cho nguyn liu ban u nn c tho lun
manufacturer for the starting materials be discussed vi nh cung cp. S c li nu tt c cc kha cnh
with the suppliers. It is of benefit that all critical quan trng trong sn xut v kim tra cht lng
aspects of the production and control of the starting nguyn liu ban u, k c cc yu cu v qun l,
material in question, including handling, labelling dn nhn, v ng gi, cng nh quy trnh khiu ni
and packaging requirements as well as complaints v loi b, u c nht tr bng hp ng gia nh
and rejection procedures, are contractually agreed sn xut v nh cung cp.
between the manufacturer and the supplier.
14.9 For each consignment, at a minimum, the 14.9 Vi mi chuyn hng, thng hng t nht phi
containers should be checked for at least integrity of c kim tra xem bao b v nim phong c nguyn
package and seal and for correspondence between vn khng, v s tng ng gia n t hng, phiu
the order, the delivery note, and the suppliers labels. giao hng v nhn ca nh cung cp.
14.10 All incoming materials should be checked to 14.10 Tt c cc nguyn liu trc khi nhp kho u
ensure that the consignment corresponds to the phi c kim tra m bo giao ng vi n
order. Containers should be cleaned where necessary t hng. Cc thng hng phi c lm sch khi
and labelled, if required, with the prescribed cn, v dn nhn nu cn thit vi nhng thng tin
information. Where additional labels are attached to quy nh. Khi dn nhn ph trn thng hng, khng
containers, the original information should not be c che mt thng tin gc.
lost.
14.11 Damage to containers and any other problem 14.11 Thng hng b h hi hoc b bt k vn g
that might adversely affect the quality of a material c th nh hng bt li ti cht lng ca nguyn
should be recorded and reported to the QC liu cng phi c ghi chp li v bo co cho b
department and investigated. phn kim tra cht lng, sau phi tin hnh iu
tra.
14.12 If one delivery of material is made up of 14.12 Nu mt t giao hng bao gm nhiu l khc
different batches, each batch must be considered as nhau, mi l phi c tch ring ly mu, kim
separate for sampling, testing and release. nghim v xut cho s dng.
14.13 Starting materials in the storage area should 14.13 Nguyn liu ban u khu vc bo qun phi
be appropriately labelled. Labels should bear at least c dn nhn ph hp. Nhn t nht phi c nhng
the following information: thng tin sau:
(a) the designated name of the product and the (a) tn sn phm v m ni b khi cn p dng;
internal code reference where applicable;
(b) the batch number given by the supplier and, (b) s l do nh cung cp quy nh, v s kim
on receipt, the control or batch number given sot hoc s l ca nh sn xut, nu c,
by the manufacturer, if any, documented so phi c ghi vo h s m bo truy li
as to ensure traceability; ngun gc;
(c) the status of the contents (e.g. on quarantine, (c) tnh trng ca nguyn liu ng bn trong (v
on test, released, rejected, returned, d: ang bit tr, ang kim nghim, xut,
recalled); b loi, b tr li, b thu hi);
(d) where appropriate, an expiry date or a date (d) nu thch hp, ghi ngy ht hn hoc ngy
beyond which retesting is necessary. cn phi tin hnh kim nghim li.
When fully validated computerized storage systems Khi s dng h thng bo qun hon ton bng my
are used, not all of the above information need be in tnh c thm nh, khng nht thit phi c tt

a legible form on the label. c cc thng tin ny ghi r rng trn nhn.
14.14 There should be appropriate procedures or 14.14 Cn c cc quy trnh hoc bin php ph hp
measures to ensure the identity of the contents of m bo nhn dng c nguyn liu ng bn
each container of starting material.Bulk containers trong mi thng nguyn liu ban u. Cn phn bit
from which samples have been drawn should be r cc thng nguyn liu c ly mu.
identified.
14.15 Only starting materials released by the QC 14.15 Ch nhng nguyn liu ban u c b
department and within their shelf-life should be used. phn kim tra cht lng duyt cho xut s dng
v vn cn trong hn dng mi c em s dng.
14.16 Starting materials should be dispensed only by 14.16 Ch ngi c giao nhim v mi c php
designated persons, following a written procedure, to cp pht nguyn liu ban u theo mt quy trnh
ensure that the correct materials are accurately bng vn bn, m bo ng loi nguyn liu c
weighed or measured into clean and properly cn hoc o lng chnh xc vo cc thng ng sch
labelled containers. c dn nhn ng.
14.17 Each dispensed material and its weight or 14.17 Mi nguyn liu sau khi c cp pht v
volume should be independently checked and the trng lng hay th tch ca chng phi c kim
check recorded. tra li mt cch c lp. Vic kim tra ny phi c
ghi chp li.
14.18 Materials dispensed for each batch of the final 14.18 Nguyn liu cp pht sn xut mi l thnh
product should be kept together and conspicuously phm phi c gi cng vi nhau v dn nhn r
labelled as such. rng nhn bit iu .
Packaging materials Nguyn vt liu bao gi

14.19 The purchase, handling and control of primary 14.19 Vic mua, qun l, kim tra cc nguyn vt liu
and printed packaging materials should be as for bao gi trc tip v bao b in sn u phi c thc
starting materials. hin nh i vi nguyn liu ban u.
14.20 Particular attention should be paid to printed 14.20 Cn c bit ch n bao b in sn. Bao b in
packaging materials. They should be stored in secure sn phi c bo qun trong iu kin an ton
conditions so as to exclude the possibility of loi tr kh nng b tip cn tri php. Nn s dng
unauthorized access. Roll feed labels should be used nhn dnh dng cun nu c th. Cc loi nhn ct
wherever possible. Cut labels and other loose printed ri in khc phi c bo qun v vn chuyn
materials should be stored and transported in trong cc thng ring ng kn trnh ln ln. Ch
separate closed containers so as to avoid mix-ups. c ngi c giao nhim v mi c php cp pht
Packaging materials should be issued for use only by nguyn liu bao gi theo mt quy trnh bng vn bn
designated personnel following an approved and c duyt.
documented procedure.
14.21 Each delivery or batch of printed or primary 14.21 Mi ln giao hng hoc mi l bao b trc tip
packaging material should be given a specific hoc bao b in sn phi c cp mt m s c bit
reference number or identification mark. hoc mt k hiu nhn dng ring.
14.22 Outdated or obsolete primary packaging 14.22 Bao b ng gi trc tip hoc bao b in sn ht
material or printed packaging material should be hn hoc khng cn dng c phi em hu v vic
destroyed and its disposal recorded. hu b ny phi c lu h s.
14.23 All products and packaging materials to be 14.23 Tt c sn phm v nguyn liu bao gi khi
used should be checked on delivery to the packaging giao cho b phn ng gi s dng phi c kim
department for quantity, identity and conformity with tra v s lng, nhn dng, v t yu cu theo
the packaging instructions. hng dn ng gi.
Intermediate and bulk products Sn phm trung gian v bn thnh

phm
14.24 Intermediate and bulk products should be kept 14.24 Sn phm trung gian v bn thnh phm phi
under appropriate conditions. c bo qun trong iu kin ph hp.

14.25 Intermediate and bulk products purchased as 14.25 Sn phm trung gian v bn thnh phm nhp
such should be handled on receipt as though they kho phi c x l khi nhn nh i vi nguyn liu
were starting materials. ban u.
Finished products Thnh phm

14.26 Finished products should be held in quarantine 14.26 Thnh phm phi c bit tr cho ti khi c
until their final release, after which they should be php xut, sau chng c bo qun vo khu vc
stored as usable stock under conditions established hng s dng c trong nhng iu kin do nh sn
by the manufacturer. xut quy nh.
14.27 The evaluation of finished products and the 14.27 Vic nh gi thnh phm v h s ti liu cn
documentation necessary for release of a product for thit cho vic duyt xut mt sn phm ra th trng
sale are described in section 17, Good practices in c m t trong phn 17 thc hnh tt kim tra
quality control. cht lng.
Rejected, recovered, reprocessed and Nguyn vt liu b loi, phc hi, ti ch

reworked materials v ch bin li.
14.28 Rejected materials and products should be 14.28 Nguyn vt liu v sn phm b loi cn c
clearly marked as such and stored separately in dn nhn r rng ch r tnh trng v bo qun ring
restricted areas. They should either be returned to trong khu vc hn ch ra vo. Chng c th c tr
the suppliers or, where appropriate, reprocessed or li cho nh cung cp hoc c ti ch hoc hu kp
destroyed in a timely manner. Whatever action is thi, tu trng hp. Bin php no trc khi p
taken should be approved by authorized personnel dng cng phi c php ca ngi c u quyn
and recorded. v phi c ghi trong h s.
14.29 The reworking or recovery of rejected products 14.29 Vic ti ch hoc phc hi sn phm b loi ch
should be exceptional. It is permitted only if the c php trong trng hp ngoi l v ch c thc
quality of the final product is not affected, if the hin nu cht lng ca thnh phm khng b nh
specifications are met, and if it is done in accordance hng, nu cc ch tiu cht lng vn t, v nu
with a defined and authorized procedure after c thc hin theo ng cc quy trnh xc nh
evaluation of the risks involved. A record should be c ph duyt, sau khi nh gi nhng nguy c
kept of the reworking or recovery. A reworked batch c th xy ra. Cn lp h s theo di vic ti ch v
should be given a new batch number. phc hi. L ti ch s c cho s l mi.
14.30 The introduction of all or part of earlier 14.30 Vic a mt phn hoc ton b nhng l trc
batches, conforming to the required quality t cht lng yu cu vo mt l sau cng ca
standards, into a batch of the same product at a sn phm mt cng on sn xut nht nh u
defined stage of manufacture should be authorized phi c ph duyt trc. Vic phc hi ny phi
beforehand. This recovery should be carried out in c thc hin theo ng quy trnh nh sau khi
accordance with a defined procedure after nh gi nhng nguy c c th xy ra, k c nh
evaluation of the risks involved, including any hng c th c i vi tui th sn phm. Vic phc
possible effect on shelf-life. The recovery should be hi phi c ghi vo h s.
recorded.
14.31 The need for additional testing of any finished 14.31 B phn kim tra cht lng cn cn nhc s
product that has been reprocessed, reworked or into cn thit phi tin hnh thm cc php th i vi
which a recovered product has been incorporated, bt k thnh phm no c ti ch, ch bn li
should be considered by the QC department. hoc c s dng sn phm phc hi t l trc.
Recalled products Sn phm thu hi

14.32 Recalled products should be identified and 14.32 Sn phm thu hi phi c nhn dng v bo
stored separately in a secure area until a decision is qun ring bit trong khu vc m bo an ninh cho
taken on their fate. The decision should be made as ti khi c quyt nh x l chng. Quyt nh ny cn
soon as possible. c cng sm cng tt.

Returned goods Hng ho b tr v

14.33 Products returned from the market should be 14.33 Nhng sn phm b tr v t th trng phi
destroyed unless it is certain that their quality is c hu, tr khi chc chn c l cht lng ca
satisfactory; in such cases they may be considered chng vn t yu cu; trong trng hp , chng
for resale or relabelling, or alternative action taken c th c cn nhc cho bn li, dn nhn li, hoc
only after they have been critically assessed by the tin hnh mt bin php no khc ch sau khi c
QC function in accordance with a written procedure. b phn kim tra cht lng nh gi mt cch
The nature of the product, any special storage nghim ngt theo mt quy trnh bng vn bn. Cn
conditions it requires, its condition and history, and nh gi tt c cc yu t nh tnh cht ca sn
the time elapsed since it was issued should all be phm, iu kin bo qun c bit nu c yu cu,
taken into account in this assessment. Where any iu kin v lch s ca sn phm, v khong thi
doubt arises over the quality of the product, it should gian tri qua k t khi sn phm c bn ra. Khi
not be considered suitable for reissue or reuse. Any c bt k nghi ng no v cht lng sn phm,
action taken should be appropriately recorded. khng c cn nhc cho xut bn li hoc s dng
li. Bt k bin php p dng no cng phi c
ghi vo h s.
Reagents and culture media Thuc th v mi trng nui cy

14.34 There should be records for the receipt and 14.34 Tt c cc thuc th v mi trng nui cy
preparation of reagents and culture media. u phi ghi vo h s sau khi nhn hoc pha ch.
14.35 Reagents made up in the laboratory should be 14.35 Cc thuc th c chun b ti phng kim
prepared according to written procedures and nghim phi c pha ch theo cc quy trnh bng
appropriately labelled. The label should indicate the vn bn v dn nhn ph hp. Nhn phi ch r nng
concentration, standardization factor, shelf-life, the , h s hiu chun, tui th, ngy cn chun li,
date when restandardization is due, and the storage v iu kin bo qun. Trn nhn phi c ch k ca
conditions. The label should be signed and dated by ngi pha ch v ghi ngy pha ch.
the person preparing the reagent.
14.36 Both positive and negative controls should be 14.36 Phi p dng c cc php th dng tnh v m
applied to verify the suitability of culture media each tnh xc minh tnh ph hp ca mi trng nui
time they are prepared and used. The size of the cy mi khi pha ch v s dng. Kch c ca chng
inoculum used in positive controls should be s dng trong php th dng tnh phi ph hp vi
appropriate to the sensitivity required. nhy cn thit.
Reference standards Cht chun

14.37 Whenever official reference standards exist, 14.37 Cn s dng cht chun chnh thc bt c khi
these should preferably be used. no c th.
14.38 Official reference standards should be used 14.38 Cht chun chnh thc ch nn dng vo mc
only for the purpose described in the appropriate ch c m t trong chuyn lun tng ng dc
monograph. in.
14.39 Reference standards prepared by the producer 14.39 Cht chun do nh sn xut t pha ch phi
should be tested, released and stored in the same c th nghim, cp pht v bo qun nh i vi
way as official standards. They should be kept under cht chun chnh thc. Cht chun phi do mt ngi
the responsibility of a designated person in a secure c u quyn chu trch nhim bo qun khu vc
area. an ton.
14.40 Secondary or working standards may be 14.40 Cht chun th cp hoc cht chun lm vic
established by the application of appropriate tests c th c thit lp bng cch p dng cc php th
and checks at regular intervals to ensure v kim tra ph hp theo nh k m bo s
standardization. chun ho.
14.41 Reference standards should be properly 14.41 Cht chun phi c dn nhn ph hp, nhn
labelled with at least the following information: t nht phi c cc thng tin sau:
(a) name of the material; (a) tn cht chun;

(b) batch or lot number and control number; (b) s l / m hoc s kim sot;

(c) date of preparation; (c) ngy pha ch;

(d) shelf-life; (d) tui th;
(e) potency; (e) hot lc;
(f) storage conditions. (f) iu kin bo qun;
14.42 All in-house reference standards should be 14.42 Tt c cc cht chun ca nh sn xut u
standardized against an official reference standard, phi c chun ho theo cht chun chnh thc, nu
when available, initially and at regular intervals c, ngay sau khi pha ch v nh k sau .
thereafter.
14.43 All reference standards should be stored and 14.43 Tt c cht chun u phi c bo qun v
used in a manner that will not adversely affect their s dng sao cho khng nh hng bt li ti cht
quality. lng ca chng.
Waste materials Nguyn vt liu ph thi

14.44 Provision should be made for the proper and 14.44 Cn c khu vc dnh ring cho vic bo qun
safe storage of waste materials awaiting disposal. thch hp v an ton i vi cc nguyn vt liu ph
Toxic substances and flammable materials should be thi ang ch x l. Cc cht c hi v nguyn vt
stored in suitably designed, separate, enclosed liu d chy phi c bo qun trong cc t kn,
cupboards, as required by national legislation. ring bit v c thit k ph hp, theo quy nh
ca lut php quc gia.
14.45 Waste material should not be allowed to 14.45 Nguyn vt liu ph thi khng c lu
accumulate. It should be collected in suitable cu. Chng phi c dn vo cc thng cha ph
receptacles for removal to collection points outside hp chuyn ra ch tp hp bn ngoi to nh v
the buildings and disposed of safely and in a sanitary phi c hu an ton, hp v sinh mt cch thng
manner at regular and frequent intervals. xuyn, nhanh chng.
Miscellaneous Nhng vn khc

14.46 Rodenticides, insecticides, fumigating agents 14.46 Thuc dit cn trng, thuc dit chut, cc
and sanitizing materials should not be permitted to cht st trng v cc nguyn vt liu lm v sinh
contaminate equipment, starting materials, khng c gy nhim cho my mc thit b,
packaging materials, in-process materials or finished nguyn liu ban u, nguyn vt liu bao gi, nguyn
products vt liu trong qu trnh sn xut, hoc thnh phm.
15. Documentation 15. H s ti liu

15.1 Principle. Good documentation is an essential 15.1 Nguyn tc. H s ti liu tt l mt phn thit
part of the quality assurance system and, as such, yu ca h thng m bo cht lng v v th, cn
should exist for all aspects of GMP. Its aims are to phi c cho mi kha cnh ca GMP. Mc ch ca h
define the specifications and procedures for all s ti liu l xc nh cc tiu chun v quy trnh
materials and methods of manufacture and control; cho tt c cc nguyn liu v xc nh phng php
to ensure that all personnel concerned with sn xut cng nh kim tra cht lng; m bo
manufacture know what to do and when to do it; to tt c nhn vin c lin quan n sn xut u hiu
ensure that authorized persons have all the cn phi lm g vo lc no; m bo nhng ngi
information necessary to decide whether or not to c u quyn c tt c nhng thng tin cn thit khi
release a batch of a medicine for sale, to ensure the quyt nh cho xut mt l thuc ra th trng; v
existence of documented evidence, traceability, and m bo c nhng bng chng trn h s, c th tm
to provide records and an audit trail that will permit li c v cung cp cho thanh tra nhng h s cng
investigation. It ensures the availability of the data nh u mi tin hnh iu tra. H s ti liu m
needed for validation, review and statistical analysis. bo c s liu cn thit cho vic thm nh, r sot v
The design and use of documents depend upon the phn tch thng k. Vic thit k v s dng h s ti
manufacturer. In some cases some or all of the liu tu thuc vo nh sn xut. Trong mt s trng
documents described below may be brought hp mt vi hoc ton b cc ti liu m t di y
together, but they will usually be separate. c gp chung vi nhau, nhng thng chng c
tch ring.


15.2 Documents should be designed, prepared, 15.2 H s ti liu cn c thit k, son tho, r
reviewed and distributed with care. They should sot v phn pht mt cch thn trng. H s ti liu
comply with the relevant parts of the manufacturing phi tun th cc phn c lin quan ca giy php
and marketing authorizations. sn xut v lu hnh.
15.3 Documents should be approved, signed and 15.3 H s ti liu phi c ngi c thm quyn
dated by the appropriate responsible persons. No ph hp ph duyt, k v ghi ngy thng. Khng c
document should be changed without authorization thay i h s ti liu khi cha c php.
and approval.
15.4 Documents should have unambiguous contents: 15.4 H s ti liu phi c ni dung r rng: nu r
the title, nature and purpose should be clearly stated. tiu , bn cht v mc ch ca h s ti liu. Phi
They should be laid out in an orderly fashion and be trnh by c trt t v d kim tra. Nhng ti liu sao
easy to check. Reproduced documents should be chp phi r rng v d c. Khi sao chp cc ti liu
clear and legible. The reproduction of working gc c ti liu lm vic khng c c sai st
documents from master documents must not allow trong qu trnh sao chp.
any error to be introduced through the reproduction
process.
15.5 Documents should be regularly reviewed and 15.5 Ti liu cn c sot xt v cp nht nh k.
kept up to date. When a document has been revised, Khi mt ti liu c sa i, phi c h thng nhm
a system should exist to prevent inadvertent use of ngn nga vic s dng cc ti liu li thi. Ti liu
the superseded version. Superseded documents li thi phi c duy tr trong mt khong thi gian
should be retained for a specific period of time. c th.
15.6 Where documents require the entry of data, 15.6 Nhng h s ti liu i hi phi nhp s liu,
these entries should be clear, legible and indelible. th s liu nhp phi r rng, d c v khng ty xo
Sufficient space should be provided for such entries. c. Cn c khong trng cho vic nhp s liu
.
15.7 Any alteration made to a document should be 15.7 Bt k thay i no i vi mt ti liu cng
signed and dated; the alteration should be done in phi c k v ghi ngy; vic thay i phi m bo
such a way as to permit the reading of the original c th c c thng tin ban u. Khi thch hp,
information. Where appropriate, the reason for the phi ghi li cc l do sa i.
alteration should be recorded.
15.8 Records should be made or completed when any 15.8 Cn lp h s hoc hon tt h s khi tin hnh
action is taken and in such a way that all significant bt k hot ng no sao cho mi hot ng quan
activities concerning the manufacture of trng lin quan n sn xut dc phm u c th
pharmaceutical products are traceable. Records truy ngc li. H s s sch phi c lu gi cho
should be retained for at least one year after the n t nht mt nm sau khi thnh phm lin quan
expiry date of the finished product. ht hn.
15.9 Data (and records for storage) may be recorded 15.9 S liu (v h s cn lu gi) c th c ghi li
by electronic data-processing systems or by bng h thng x l s liu in t hoc cch ghi
photographic or other reliable means. Master hnh hoc cc phng tin ng tin cy khc. Cn
formulae and detailed SOPs relating to the system in phi c cng thc gc v quy trnh thao tc chun chi
use should be available and the accuracy of the tit lin quan n h thng s dng v phi kim tra
records should be checked. If documentation is chnh xc ca s liu ghi chp. Nu h s ti liu
handled by electronic data-processing methods, only c x l bng phng php x l s liu in t,
authorized persons should be able to enter or modify ch c ngi c u quyn mi c php nhp hoc
data in the computer system, and there should be a thay i s liu trong my tnh, v lun phi c mt
record of changes and deletions; access should be h s ghi li cc thay i hay xo b . Phi hn ch
restricted by passwords or other means and the entry truy cp bng cch s dng mt khu hoc cc bin
of critical data should be independently checked. php khc v vic nhp s liu quan trng cn c
Batch records stored electronically should be kim tra mt cch c lp. H s l c lu trn
protected by back-up transfer on magnetic tape, my tnh phi c bo v bng cch sao li sang
microfilm, electronic discs, paper printouts or other bng t, vi phim, in ra giy hoc cc bin php khc.
means. It is particularly important that, during the iu c bit quan trng l trong thi gian lu gi,
period of retention, the data are readily available. s liu phi lun sn sng khi cn truy cp.
Documents required Nhng h s ti liu cn thit

Labels Nhn
15.10 Labels applied to containers, equipment or 15.10 Nhn dng cho bao b ng, my mc thit b
premises should be clear, unambiguous and in the hoc nh xng phi r rng, khng mp m v phi
companys agreed format. It is often helpful in theo mu chung thng nht ca cng ty. Thng bn
addition to the wording on the labels to use colours cnh cu ch trn nhn, vic s dng mu sc ch
to indicate status (e.g. quarantined, accepted, tnh trng cng rt hu ch (v d dang bit tr,
rejected, clean). c chp nhn, b loi hoc sch).
15.11 All finished medicines products should be 15.11 Tt c thc thnh phm u phi c nhn
identified by labelling, as required by the national dng bng nhn theo quy nh ca quc gia, v t
legislation, bearing at least the following nht phi c nhng thng tin sau:
information:
(a) the name of the medicines product; (a) tn sn phm

(b) a list of the active ingredients (if applicable, (b) danh mc hot cht (nu c, ghi tn chng
with the INNs), showing the amount of each quc t khng s hu - INN), ch r lng ca
present and a statement of the net contents mi hot cht, v cng b lng tnh (v d s
(e.g. number of dosage units, weight, n v liu lng, cn nng hoc th tch);
volume); (c) s l do nh sn xut t;
(c) the batch number assigned by the (d) ngy ht hn dng khng m ho;
manufacturer; (e) nhng iu kin bo qun c bit hoc
(d) the expiry date in an uncoded form; nhng thn trng cn thit trong x l;
(e) any special storage conditions or handling
precautions that may be necessary; (f) hng dn s dng v nhng cnh bo v
(f) directions for use, and warnings and thn trng cn thit;
precautions that may be necessary; (g) tn v a ch ca nh sn xut hoc cng ty
(g) the name and address of the manufacturer or hay ngi chu trch nhim a sn phm ra
the company or the person responsible for th trng.
placing the product on the market.
15.12 For reference standards, the label and/or 15.12 i vi cht chun, nhn v/hoc ti liu i
accompanying document should indicate potency or km phi ch r hot lc hay nng , ngy sn xut,
concentration, date of manufacture, expiry date, date ngy ht hn, ngy m bao b ln u, iu kin bo
the closure is first opened, storage conditions and qun v s kim sot nu c.
control number, as appropriate.
Specifications and testing procedures Tiu chun v quy trnh kim nghim
15.13 Testing procedures described in documents 15.13 Quy trnh kim nghim m t trong h s ti
should be validated in the context of available liu phi c thm nh trong hon cnh nh xng
facilities and equipment before they are adopted for v my mc thit b hin c trc khi c ph duyt
routine testing. s dng cho kim nghim thng quy.
15.14 There should be appropriately authorized and 15.14 Cn c cc tiu chun c ph duyt ph hp
dated specifications, including tests on identity, v ghi ngy thng, bao gm cc php th nh tnh,
content, purity and quality, for starting and nh lng, tp cht, v cht lng, i vi nguyn
packaging materials and for finished products; where liu ban u, nguyn liu bao gi v thnh phm; nu
appropriate, they should also be available for c cn c tiu chun cho c sn phm trung gian
intermediate or bulk products. Specifications for v bn thnh phm. Cn c cc tiu chun i vi
water, solvents and reagents (e.g. acids and bases) nc, dung mi v thuc th (v d nhu cc acids v
used in production should be included. bases) s dng trong sn xut.
15.15 Each specification should be approved, signed 15.15 Mi tiu chun u phi c ph duyt, k v
and dated, and maintained by the QC, QA units or ghi ngy thng v lu gi b phn QC, QA hoc
documentation centre. Specifications for starting trung tm ti liu. Cc tiu chun i nguyn liu
materials, intermediates, and bulk, finished products ban u, sn phm trung gian, bn thnh phm,
and packaging materials are referred to in sections thnh phm v nguyn vt liu bao gi c cp
15.1815.21. cc khon 15.18 15.21.
15.16 Periodic revisions of the specifications may be 15.16 C th cn phi nh k sa i li cc tiu

necessary to comply with new editions of the national chun chng ph hp vi cc phin bn mi ca
pharmacopoeia or other official compendia. dc in quc gia hoc cc dc in chnh thc
khc.

15.17 Pharmacopoeias, reference standards, 15.17 Cn phi c dc in, cc tiu chun tham
reference spectra and other reference materials kho, ph tham kho v cc ti liu tham kho khc
should be available in the QC laboratory. trong phng kim nghim.
Specifications for starting and packaging materials Specifications for starting and packaging materials
15.18 Specifications for starting, primary and printed 15.18 Tiu chun i vi nguyn liu ban u, bao b
packaging materials should provide, if applicable, a s cp v bao b c in n nu thch hp cn c m t
description of the materials, including: i vi nguyn vt liu, trng c:
(a) the designated name (if applicable, the INN) (a) tn c c (nu c th nu c tn INN) v
and internal code reference; m s ni b;
(b) the reference, if any, to a pharmacopoeial (b) tham chiu n chuyn lun ca dc in,
monograph; nu c;
(c) qualitative and quantitative requirements (c) cc yu cu v nh tnh v nh lng, vi
with acceptance limits. gii han cho php.
Depending on the companys practice other data may Tu thuc vo yu cu ca cng ty, tiu chun c th
be added to the specification, such as: c thm cc thng tin khc, v d nh:
(a) the supplier and the original producer of the (a) nh cung cp v nh sn xut gc ca
materials; nguyn vt liu;
(b) a specimen of printed materials; (b) mt mu bao b c in n;
(c) directions for sampling and testing, or a (c) hng dn ly mu v kim nghim, hoc
reference to procedures; tham chiu n quy trnh thc hin;
(d) storage conditions and precautions; (d) iu kin bo qun v cc thn trng;
(e) the maximum period of storage before re- (e) thi hn bo qun ti a trc khi kim
examination. nghim li.
Packaging material should conform to specifications, Nguyn vt liu bao gi phi t tiu chun, v phi
and should be compatible with the material and/or tng thch vi nguyn liu v/hoc sn phm cha
with the medicines product it contains trong .
The material should be examined for compliance with Nguyn vt liu cn c kim tra v tiu chun cht
the specification, and for defects as well as for the lng, cc sai hng v tnh chnh xc ca cc du
correctness of identity markings. hiu nhn dng.
15.19 Documents describing testing procedures 15.19 H s ti liu m t quy trnh kim nghim
should state the required frequency for re-assaying phi nu r tn sut quy nh i vi vic nh lng
each starting material, as determined by its stability. li mi nguyn liu ban u, tu thuc vo tui th
ca chng.
Specifications for intermediate and bulk products Tiu chun i vi sn phm trung gian v bn thnh
phm
15.20 Specifications for intermediate and bulk 15.20 Cn c tiu chun i vi sn phm trung gian
products should be available. The specifications v bn thnh phm. Cc tiu chun phi tng t
should be similar to specifications for starting nh tiu chun i vi nguyn liu ban u hoc
materials or for finished products, as appropriate. thnh phm. nu ph hp.
Specifications for finished products Tiu chun thnh phm
15.21 Specifications for finished products should 15.21 Tiu chun thnh phm cn c:
include:
(a) the designated name of the product and the (a) tn sn phm v m tham kho, nu c;
code reference, where applicable;
(b) the designated name(s) of the active (b) tn mi hot cht (v tn chng quc t
ingredient(s) (if applicable, with the INN(s)); khng b s hu - INN, nu c)
(c) the formula or a reference to the formula; (c) cng thc hoc tham chiu n cng thc;
(d) a description of the dosage form and package (d) m t dng bo ch v chi tit ng gi;

details;
(e) directions for sampling and testing or a (e) hng dn ly mu v kim nghim hoc
reference to procedures; tham chiu n quy trnh thc hin;
(f) the qualitative and quantitative (f) yu cu v nh tnh v nh lng, vi cc
requirements, with acceptance limits; gii hn cho php;
(g) the storage conditions and precautions, (g) iu kin bo qun v cc thn trng nu c;
where applicable; (h) tui th;
(h) the shelf-life.
Master formulae Cng thc gc
15.22 A formally authorized master formula should 15.22 Cn c cng thc gc c ph duyt chnh
exist for each product and batch size to be thc cho mi sn phm v mi c l sn xut;
manufactured.
15.23 The master formula should include: 15.23 Cng thc gc cn c:
(a) the name of the product, with a product (a) tn sn phm, c m tham kho ca sn
reference code relating to its specification; phm lin quan n tiu chun ca n;
(b) a description of the dosage form, strength of (b) m t dng bo ch, hm lng v c l;
the product and batch size; (c) danh mc cc nguyn liu ban u c s
(c) a list of all starting materials to be used (if dng (tn INN nu c), lng ca mi cht,
applicable, with the INNs), with the amount c m t bng tn v k hiu tham kho
of each, described using the designated name thng nht cho loi nguyn liu (cn nu
and a reference that is unique to that r cht no s b mt i trong qu trnh ch
material (mention should be made of any bin)
substance that may disappear in the course
of processing);
(d) a statement of the expected final yield with (d) cng b sn lng thnh phm d kin v
the acceptable limits, and of relevant gii hn cho php, v sn lng sn phm
intermediate yields, where applicable; trung gian, nu c;
(e) a statement of the processing location and (e) nu a im ch bin v thit b s dng ch
the principal equipment to be used; yu;
(f) the methods, or reference to the methods, to (f) cc phng php, hoc tham chiu phng
be used for preparing and operating the php, c s dng chun b v vn hnh
critical equipment, e.g. cleaning (especially cc my mc thit b quan trng, v d nh
after a change in product), assembling, lm v sinh (c bit sau khi thay i sn
calibrating, sterilizing, use; phm), lp t, hiu chun, v trng, s
dng;
(g) detailed step-wise processing instructions (g) hng dn ch bin chi tit ln lt tng
(e.g. checks on materials, pretreatments, bc (v d kim tra nguyn vt liu, x l s
sequence for adding materials, mixing times, b, trnh t thm cc nguyn vt liu, thi
temperatures); gian trn, nhit )
(h) the instructions for any in-process controls (h) hng dn i vi cc kim tra trong qu
with their limits; trnh sn xut v cc gii hn tng ng;
(i) where necessary, the requirements for (i) nu cn, quy nh v bo qun sn phm, k
storage of the products, including the c bao b, nhn v cc iu kin bo qun
container, the labelling, and any special c bit;
storage conditions;
(j) any special precautions to be observed. (j) nhng iu cn c bit thn trng;
Packaging instructions Hng dn ng gi
15.24 Formally authorized packaging instructions 15.24 Cn c cc hng dn ng gi chnh thc

should exist for each product, pack size and type. c ph duyt cho mi sn phm, quy cch ng gi
These should normally include, or make reference to: v dng ng gi. Cc hng dn thng bao gm,
hoc c tham chiu, nhng ni dung sau:
(a) the name of the product; (a) tn sn phm;

(b) a description of its pharmaceutical form, (b) m t dng bo ch, hm lng, v ng s
strength and, where applicable, method of dng nu c;
application; (c) quy cch ng gi c nu bng s lng,
(c) the pack size expressed in terms of the trng lng, hoc th tch sn phm trong

number, weight or volume of the product in bao b ngoi cng;

the final container; (d) danh mc y tt c cc nguyn vt liu
(d) a complete list of all the packaging materials bao gi cn cho mt c l chun, bao gm s
required for a standard batch size, including lng, c, v dng, c m hoc s tham kho
quantities, sizes and types, with the code or lin quan n tiu chun cho mi loi nguyn
reference number relating to the vt liu bao gi;
specifications for each packaging material;
(e) where appropriate, an example or
reproduction of the relevant printed (e) nu ph hp, c v d hoc bn sao ca
packaging materials and specimens, nguyn vt liu c in n c lin quan v mu
indicating where the batch number and ca chng, trn ch r ch no ghi s l v
expiry date of the product have been marked; ngy ht hn;
(f) special precautions to be observed, including
a careful examination of the packaging area
and equipment in order to ascertain the line (f) cc thn trng c bin cn c thc hin,
clearance before and after packaging k c phi kim tra k khu vc v thit b
operations; ng gi nhm m bo dn quang dy
(g) a description of the packaging operation, chuyn trc v sau khi thc hin hot ng
including any significant subsidiary ng gi;
operations, and equipment to be used; (g) m t thao tc ng gi, bao gm c nhng
(h) details of in-process controls with thao tc ph tr quan trng, v my mc
instructions for sampling and acceptance thit b s dng;
limits. (h) chi tit nhng ln kim tra trong qu trnh
ng gi, c hng dn ly mu v gii hn
cho php.
Batch processing records H s ch bin l
15.25 A batch processing record should be kept for 15.25 Cn lu gi h s ch bin l cho mi mt l
each batch processed. It should be based on the sn xut. H s cn da trn nhng phn lin quan
relevant parts of the currently approved trong tiu chun gc c duyt hin s dng.
specifications on the record. The method of Phng php chun b h s l cn c thit k sao
preparation of such records should be designed to cho trnh c nhng sai st. (Nn sao chp li hoc
avoid errors. (Copying or validated computer dng cc chng trnh my tnh c thm nh.
programmes are recommended. Transcribing from Nn trnh vic chp tay li cc ti liu c
approved documents should be avoided.) duyt).
15.26 Before any processing begins, a check should 15.26 Trc khi bt u ch bin, cn kim tra
be made that the equipment and work station are m bo my mc thit b v ni sn xut khng cn
clear of previous products, documents, or materials nhng sn phm, h s ti liu hoc nguyn vt liu
not required for the planned process, and that the t l trc khng cn thit cho quy trnh ch bin
equipment is clean and suitable for use. This check hin ti, v my mc thit b sch v ph hp cho
should be recorded. mc ch s dng. Phi ghi chp li vic kim tra ny.
15.27 During processing, the following information 15.27 Trong khi pha ch, cn ghi li nhng thng tin
should be recorded at the time each action is taken, sau vo thi im tin hnh mi thao tc, v sau khi
and after completion the record should be dated and hon thnh h s ghi chp phi c ngy thng
signed by the person responsible for the processing v do ngi chu trch nhim pha ch k tn:
operations:
(a) the name of the product; (a) tn sn phm;

(b) the number of the batch being manufactured; (b) s l ang sn xut;
(c) dates and times of commencement, of
significant intermediate stages, and of (c) ngy v gi bt u, ngy gi thc hin cc
completion of production; cng on trung gian chnh, v ngy gi hon
(d) the name of the person responsible for each thnh vic sn xut;
stage of production; (d) tn ngi chu trch nhim mi cng on
(e) the initials of the operator(s) of different sn xut;
significant steps of production and, where (e) ch k tt ca nhn vin vn hnh mi bc
appropriate, of the person(s) who checked sn xut chnh v, nu ph hp, ca ngi
each of these operations (e.g. weighing); kim tra mi thao tc (v d khi cn);
(f) the batch number and/or analytical control
number and the quantity of each starting (f) s l v/hoc s kim sot phn tch v khi
material actually weighed (including the lng thc t ca mi nguyn liu ban u
batch number and amount of any recovered (k c s l v khi lng ca nguyn liu

or reprocessed material added); phc hi hoc ti ch cho thm vo);

(g) any relevant processing operation or event
and the major equipment used; (g) bt k thao tc ch bin c lin quan no, v
(h) the in-process controls performed, the initials nhng my mc thit b chnh c s dng;
of the person(s) carrying them out, and the (h) cc kim tra trong qu trnh sn xut thc
results obtained; hin, ch k tt ca ngi thc hin, v kt
(i) the amount of product obtained at different qu;
and pertinent stages of manufacture (yield), (i) lng sn phm c c mi cng on sn
together with comments or explanations for xut trng tm (sn lng), v nhng nhn
significant deviations from the expected xt hoc gii thch v nhng sai lnh c
yield; ngha so vi sn lng d kin;
(j) notes on special problems including details,
with signed authorization for any deviation (j) ghi ch v nhng s c c bit, nu r chi
from the master formula. tit, c ch k duyt nhng sai lch so vi
cng thc gc.
Batch packaging records H s ng gi l
15.28 A batch packaging record should be kept for 15.28 Cn lu gi h s ng gi l cho mi l hoc
each batch or part batch processed. It should be mt phn ca l ch bin. H s ny cn da trn
based on the relevant parts of the approved cc phn lin quan ca hng dn ng gi, v cn
packaging instructions, and the method of preparing c phng php chun b cc h s ny trnh
such records should be designed to avoid errors. nhng sai st trong sao chp. (Nu s dng bin
(Copying or validated computer programmes are php sao chp hoc dng cc chng trnh my tnh
recommended. Transcribing from approved c thm nh. Trch chp tay li cc ti liu
documents should be avoided.) c duyt.)
15.29 Before any packaging operation begins, checks 15.29 Trc khi bt u bt k thao tc ng gi no,
should be made that the equipment and work station cn kim tra m bo my mc thit b v ni
are clear of previous products, documents or ng gi khng cn sn phm ng gi trc , ti
materials not required for the planned packaging liu, hoc nguyn vt liu khng cn thit cho theo
operations, and that equipment is clean and suitable tc ng gi hin ti, v my mc thit b sch v
for use. These checks should be recorded. ph hp cho mc ch s dng. Cn ghi chp li vic
kim tra .
15.30 The following information should be recorded 15.30 Cn ghi chp li nhng thng tin sau y vo
at the time each action is taken, and the date and the thi im thc hin mi thao tc, cn ghi r ngy v
person responsible should be clearly identified by tn ngi chu trch nhim vi ch k ca ngi ny
signature or electronic password: hoc mt khu my tnh:
(a) the name of the product, the batch number (a) tn sn phm, s l, lng bn thnh phm
and the quantity of bulk product to be ch ng gi, cng nh s l v lng thnh
packed, as well as the batch number and the phm d kin, lng thnh phm c c
planned quantity of finished product that will trong thc t, v i chiu;
be obtained, the quantity actually obtained
and the reconciliation;
(b) the date(s) and time(s) of the packaging (b) ngy v gi thc hin thao tc ng gi;
operations;
(c) the name of the responsible person carrying (c) tn ngi chu trch nhim tin hnh cc
out the packaging operation; thao tc ng gi;
(d) the initials of the operators of the different (d) ch k tt ca nhn vin vn hnh cc bc
significant steps; chnh;
(e) the checks made for identity and conformity (e) cc kim tra nhn dng v kim tra vic tun
with the packaging instructions, including th theo hng dn ng gi, k c cc kt
the results of in-process controls; u kim tra trong qu trnh ng gi;
(f) details of the packaging operations carried (f) chi tit cc thao tc ng gi thc hin, v
out, including references to equipment and nu cn, cc hng dn v vic bo qun sn
the packaging lines used, and, when phm cha ng gi, hoc h s ghi li vic
necessary, the instructions for keeping the tr sn phm cha ng gi v khu vc bo
product unpacked or a record of returning qun;
product that has not been packaged to the
storage area;
(g) whenever possible, samples of the printed (g) bt c khi no c th, lu li mu bao b in
packaging materials used, including sn, k c mu c duyt em in, vic
specimens bearing the approval for the kim tra thng xuyn (nu ph hp) i vi

printing of and regular check (where s l, ngy ht hn v bt k thng tin thm

appropriate) of the batch number, expiry no;
date, and any additional overprinting;
(h) notes on any special problems, including (h) ghi ch v bt k s c c bin no, bao
details of any deviation from the packaging gm chi tit nhng sai lch so vi hng dn
instructions, with written authorization by an ng gi, c vn bn ph duyt ca ngi c
appropriate person; thm quyn;
(i) the quantities and reference number or (i) s lng v s tham kho hay nhn dng ca
identification of all printed packaging tt c bao b in sn v bn thnh phm
materials and bulk product issued, used, xut ra ng gi, ng gi, hu hoc
destroyed or returned to stock and the tr v kho, v s lng sn phm c c
quantities of product obtained to permit an c th i chiu y .
adequate reconciliation.
Standard operating procedures and records Quy trnh thao tc chun v h s ghi chp
15.31 SOPs and associated records of actions taken 15.31 Cn c cc quy trnh thao tc chun v h s
or, where appropriate, conclusions reached should be ghi li mi thao tc tin hnh hoc, cc kt lun
available for: i vi:
(a) equipment assembly and validation; (a) vic lp t v thm nh my mc thit b;

(b) analytical apparatus and calibration; (b) cc thit b phn tch v vic hiu chun thit
b phn tch;
(c) maintenance, cleaning and sanitization; (c) vic bo dng, lm v sinh v kh trng;
(d) personnel matters including qualification, (d) nhng vn c nhn, bao gm c trnh ,
training, clothing and hygiene; o to, trang phc v v sinh;
(e) environmental monitoring; (e) vic theo di mi trng;
(f) pest control; (f) vic kim sot cn trng;
(g) complaints; (g) khiu ni;
(h) recalls; (h) thu hi;
(i) returns. (i) nhng trng hp b tr li .
15.32 There should be SOPs and records for the 15.32 Cn c quy trnh thao tc chun v h s v
receipt of each delivery of starting material and vic tip nhn nguyn liu ban u, nguyn vt liu
primary and printed packaging material. bao gi s cp hoc bao b c in n.
15.33 The records of the receipts should include: 15.33 H s nhn hng cn c:
(a) the name of the material on the delivery note (a) tn nguyn vt liu trn phiu giao hng v
and the containers; trn thng hng;
(b) the in-house name and/or code of material (b) tn ni b v/hoc m nguyn vt liu nu
if different from (a); khc so vi tn mc (a);
(c) the date of receipt; (c) ngy nhn;
(d) the suppliers name and, if possible, (d) tn nh cung cp, v nu c th, tn nh sn
manufacturers name; xut;
(e) the manufacturers batch or reference (e) s l hoc s tham kho ca nh sn xut;
number;
(f) the total quantity, and number of containers (f) tng khi lng, v s thng hng nhn;
received;
(g) the batch number assigned after receipt; (g) s l quy nh sau khi nhn;\
(h) any relevant comment (e.g. state of the (h) bt k nhn xt c lin quan no khc (v d
containers). tnh trng thng hng,....).
15.34 There should be SOPs for the internal 15.34 Cn c cc quy trnh thao tc chun cho vic
labelling, quarantine and storage of starting dn nhn, bit tr, v bo qun nguyn liu ban u,
materials, packaging materials and other materials, nguyn vt liu bao gi v cc nguyn vt liu khc,
as appropriate. nu ph hp.
15.35 SOPs should be available for each instrument 15.35 Cn c cc quy trnh thao tc chun cho mi
and piece of equipment (e.g. use, calibration, loi thit b v dng c (v d: v vic s dng, hin
cleaning, maintenance) and placed in close proximity chun, v sinh, bo dng), cc quy trnh ny phi
to the equipment. c gn my mc thit b.
15.36 There should be SOPs for sampling, which 15.36 Cn c quy trnh thao tc chun cho vic ly
specify the person(s) authorized to take samples. mu, trong ch r ngi c u quyn ly mu.

15.37 The sampling instructions should include: 15.37 Hng dn ly mu cn c:
(a) the method of sampling and the sampling (a) phng php ly mu v k hoch ly mu;
plan;
(b) the equipment to be used; (b) dng c ly mu;
(c) any precautions to be observed to avoid (c) cc thn trng cn ch trnh tp nhim
contamination of the material or any cho nguyn vt liu hoc lm mt phm cht
deterioration in its quality; nguyn vt liu;
(d) the amount(s) of sample(s) to be taken; (d) lng mu cn ly;
(e) instructions for any required subdivision of (e) hng dn vic chia nh mu khi cn thit;
the sample;
(f) the type of sample container(s) to be used, (f) loi bao b dng ng mu, bao b ny dng
and whether they are for aseptic sampling or cho ly mu v trng hay ly mu thng
for normal sampling, and labelling; thng v vic dn nhn;
(g) any specific precautions to be observed, (g) bt k thn trng c bit cn lu , c bit
especially in regard to the sampling of sterile i vi vic ly mu nguyn liu v trng hay
or noxious material. c hi.
15.38 There should be an SOP describing the details 15.38 Cn c quy trnh thao tc chun m t chi tit
of the batch (lot) numbering system, with the h thng nh s l (m), mc ch l m bo
objective of ensuring that each batch of intermediate, mi l sn phm trung gian, bn thnh phm hay
bulk or finished product is identified with a specific thnh phm u c nhn dng bng mt s c
batch number. trng ring.
15.39 The SOPs for batch numbering that are applied 15.39 Quy trnh thao tc chun cho vic nh s l
to the processing stage and to the respective p dng cho cng on ch bin v cng on ng
packaging stage should be related to each other. gi tng ng phi lin quan n nhau.
15.40 The SOP for batch numbering should ensure 15.40 Quy trnh thao tc chun cho vic nh s l
that the same batch numbers will not be used phi m bao khng s dng trng lp cng mt s
repeatedly; this applies also to reprocessing. l; iu ny p dng cho c vic ti ch;
15.41 Batch-number allocation should be 15.41 Phi ngay lp tc ghi li vic nh gi s l, v

immediately recorded, e.g. in a logbook. The record d vo ghi trong nht k sn phm xut. Khi ghi chp
should include at least the date of allocation, product t nht phi nu r ngy ra s l, nhn dng sn
identity and size of batch. phm v c l.
15.42 There should be written procedures for testing 15.42 Cn c quy trnh bng vn bn cho vic kim
materials and products at different stages of nghim nguyn vt liu v sn phm mi cng on
manufacture, describing the methods and equipment khc nhau trong qu trnh sn xut, trong m t
to be used. The tests performed should be recorded. phng php v thit b s dng. Phi ghi li c cc
php th tin hnh.
15.43 Analysis records should include at least the 15.43 H s phn tch t nht phi c cc s liu sau:
following data:
(a) the name of the material or product and, (a) tn nguyn vt liu vt liu hay sn phm
where applicable, dosage form; dng bo ch, nu thch hp;
(b) the batch number and, where appropriate, (b) s lng v nh sn xut v/hoc nh cung
the manufacturer and/or supplier; cp, nu thch hp;
(c) references to the relevant specifications and (c) tham chiu tiu chun v quy trnh kim
testing procedures; nghim lin quan;
(d) test results, including observations and (d) kt qu kim nghim, k c cc nhn xt v
calculations, and reference to any tnh ton, v tham chiu tiu chun (gii
specifications (limits); hn);
(e) date(s) and reference number(s) of testing; (e) ngy v s tham chiu ca th nghim;
(f) the initials of the persons who performed the (f) ch k tt ca ngi thc hin php th;
testing;
(g) the date and initials of the persons who (g) ngy thng v ch k tt ca ngi xc minh
verified the testing and the calculations, php th v tnh ton, nu thch hp;
where appropriate;
(h) a clear statement of release or rejection (or (h) mt tuyn b r rng cho t hoc loi (hoc
other status decision) and the dated cc quyt nh khc v tnh trng) v ngy
signature of the designated responsible thng v ch k ca ngi c giao trch
person. nhim.
15.44 Written release and rejection procedures 15.44 Cn c quy trnh duyt xut hoc loi bng vn

should be available for materials and products, and bn i vi nguyn vt liu v sn phm, c bit i
in particular for the release for sale of the finished vi vic xut thnh phm ra th trng ca ngi
product by an authorized person. c u quyn.
15.45 Records should be maintained of the 15.45 Cn lu gi h s s sch v vic phn phi
distribution of each batch of a product in order, for mi l sn phm theo trt t, v d to iu kin
example, to facilitate the recall of the batch if cho vic thu hi l sn phm khi cn.
necessary.
15.46 Records should be kept for major and critical 15.46 Cn lu gi h s v vic thm nh, hiu
equipment, as appropriate, of any validations, chun, bo dng, lm v sinh, hoc sa cha cc
calibrations, maintenance, cleaning, or repair my mc thit b chnh v quan trng, nu ph hp,
operations, including dates and the identity of the c nu r ngy thng v tn ngi thc hin nhng
people who carried these operations out. cng vic .
15.47 The use of major and critical equipment and 15.47 Vic s dng cc my mc thit b chnh v
the areas where products have been processed quan trng cng nh khu vc tin hnh ch bin sn
should be appropriately recorded in chronological phm cn c lu h s thch hp theo trt t thi
order. gian.
15.48 There should be written procedures assigning 15.48 Cn c quy trnh bng vn bn giao trch
responsibility for cleaning and sanitation and nhim lm v sinh v kh trng c m t vi chi
describing in sufficient detail the cleaning schedules, tit v lch, phng php, thit b v vt liu lm v
methods, equipment and materials to be used and sinh cng nh nhng c s nh xng v my mc
facilities and equipment to be cleaned. Such written c lm v sinh. Nhng quy trnh bng vn bn ny
procedures should be followed. phi c thc hin.
16. Good practices in 16. Thc hnh tt trong sn

production xut
16.1 Principle. Production operations must follow 16.1 Nguyn tc. Cc thao tc sn xut phi c
clearly defined procedures in accordance with thc hin theo quy trnh nh ng vi giy php
manufacturing and marketing authorizations, with sn xut v lu hnh, mc ch l c c nhng
the objective of obtaining products of the requisite sn phm c cht lng t yu cu.
quality.
16.2 All handling of materials and products, such as 16.2 Vic x l nguyn vt liu v sn phm, v d
receipt and cleaning, quarantine, sampling, storage, nh tip nhn v lm sch, bit tr, ly mu, bo
labelling, dispensing, processing, packaging and qun, dn nhn, cp pht, ch bin, ng gi, v
distribution should be done in accordance with phn phi u phi thc hin theo ng cc quy trnh
written procedures or instructions and, where hoc hng dn bng vn bn v c ghi chp li
necessary, recorded. nu cn thit.
16.3 Any deviation from instructions or procedures 16.3 Cn ht sc trnh nhng sai lch so vi quy
should be avoided as far as possible. If deviations trnh hoc hng dn. Nu c xy ra sai lch, th sai
occur, they should be done in accordance with an lch cn phi c thc hin theo quy trnh
approved procedure. The authorization of the duyt. Sai lch phi c s ph duyt bng vn bn
deviation should be approved in writing by a ca ngi c trch nhim, vi s tham gia ca b
designated person, with the involvement of the QC phn kim tra cht lng, nu thch hp.
department, when appropriate.
16.4 Checks on yields and reconciliation of quantities 16.4 Cn tin hnh kim tra v sn lng v cn i
should be carried out as necessary to ensure that s lng khi cn m bo khng c s khc bit
there are no discrepancies outside acceptable limits. no so vi gii hn cho php.
16.5 Operations on different products should not be 16.5 Thao tc trn sn phm khc nhau khng nn

carried out simultaneously or consecutively in the tin hnh ng thi hoc lin tip trong cng phng
same room or area unless there is no risk of mix up tr khi khng c nguy c ln ln hoc nhim cho.
or cross-contamination.
16.6 At all times during processing, all materials, 16.6 Trong sut thi gian ch bin, tt c nguyn
bulk containers, major items of equipment, and liu, bao b ng bn thnh phm, nhng my mc
where appropriate, the rooms and packaging lines thit b chnh, v nu c c cc phng v dy
being used should be labelled or otherwise identified chuyn ng gi ang c s dng u phi c
with an indication of the product or material being dn nhn hoc nu khng phi c k hiu nhn dng
processed, its strength (where applicable) and the ghi tn sn phm hoc nguyn vt liu ang c ch
batch number. Where applicable, this indication bin, nng (nu thch hp), v s l. Nu c nn
should also mention the stage of production. In some nu c cng on sn xut. Trong mt s trng hp
cases it may be useful to also record the name of the c th cng cn phi ghi li tn ca sn phm c
previous product that has been processed. ch bin trc .
16.7 Access to production premises should be 16.7 Vic ra vo nh xng sn xut nn hn ch ch

restricted to authorized personnel. nhn vin c thm quyn mi c ra vo.
16.8 Normally, non-medicinal products should not be 16.8 Thng thng, nhng sn phm khng phi l
produced in areas or with equipment destined for the thuc khng c sn xut cng khu vc hoc trn
production of pharmaceutical products. cng my mc thit b dng sn xut dc phm.
16.9 In-process controls are usually performed within 16.9 Cc bin php kim tra trong qu trnh sn xut
the production area. The performance of such in- thng c thc hin c nh hng xu n cht
process controls should not have any negative effect lng sn phm ang ch bin hoc sn phm khc
on the quality of the product or another product (e.g. (v d gy nhim cho hay ln ln).
cross- contamination or mix up).
Prevention of cross-contamination and Ngn nga nghim cho v nhim

bacterial contamination during khun trong qu trnh sn xut
production
16.10 When dry materials and products are used in 16.10 Khi nguyn vt liu v sn phm kh c s
production, special precautions should be taken to dng trong sn xut, cn c bit thn trng trnh
prevent the generation and dissemination of dust. to ra v phn tn bi. Cn c thit b v bin php
Provision should be made for proper air control (e.g. kim sot khng kh thch hp (v d kh cp v kh
supply and extraction of air of suitable quality). thi t cht lng ph hp)
16.11 Contamination of a starting material or of a 16.11 Cn trnh mt nguyn liu ban u hoc
product by another material or product must be mt sn phm nhim vo mt nguyn liu hay sn
avoided. This risk of accidental cross- contamination phm khc. Nguy c nhim cho v tnh ny c th
arises from the uncontrolled release of dust, gases, xy ra do thiu kim sot s phn tn bi, kh tiu
particles, vapours, sprays or organisms from phn, hi, bi nc, hoc vi sinh vt t cc nguyn
materials and products in process, from residues on liu v sn phm trong qu trnh sn xut , t d
equipment, from intruding insects, and from cht bm li trn my mc thit b, t cn trng xm
operators clothing, skin, etc. The significance of this nhp, t trang phc v da ca nhn vin vn hnh,...
risk varies with the type of contaminant and of the Mc nghim trng ca nguy c ny thay i tu
product being contaminated. thuc vo loi yu t gy nhim v loi sn phm b
nhim.
Among the most hazardous contaminants are highly Trong s nhng yu t gy nhim nguy him nht c
sensitizing materials, biological preparations such as cc nguyn liu gy d ng, cc ch phm sinh hc v
living organisms, certain hormones, cytotoxic d nh cc vi sinh vt sng, mt s loi hc mn, cc
substances, and other highly active materials. cht c t bao, v cc nguyn vt liu ch hot tnh
cao khc.
Products in which contamination is likely to be most Nhng sn phm khi b tp nhim d gy nguy him
significant are those administered by injection or nht l nhng sn phm dng ng tim hoc dng
applied to open wounds and those given in large trn cc vt thng h, v nhng sn phm dng vi
doses and/or over a long time. liu ln v/hoc lu di.
16.12 Cross-contamination should be avoided by 16.12 Cn trnh nhim cho bng cc bin php k

taking appropriate technical or organizational thut v t chc ph hp, v d nh:

measures, for example:
(a) carrying out production in dedicated and self- (a) sn xut cc khu vc khp kn v ring bit
contained areas (which may be required for (c th cn thit cho nhng sn phm nh
products such as penicillins, live vaccines, penicillins, vaccines sng, cc ch phm vi
live bacterial preparations and certain other khun sng v mt s sinh phm khc);
biologicals);
(b) conducting campaign production (separation (b) tin hnh sn xut theo chin dch (tch
in time) followed by appropriate cleaning in ring bng thi gian) sau c lm v sinh
accordance with a validated cleaning thch ng theo quy trnh v sinh c
procedure; thm nh;
(c) providing appropriately designed airlocks, (c) c cc cht gi ph hp, chnh lch p sut,
pressure differentials, and air supply and h thng cp v thi khng kh;
extraction systems;
(d) minimizing the risk of contamination caused (d) hn ch ti a nguy c tp nhim gy ra do
by recirculation or re- entry of untreated or s ti tun hon hoc ti lu ca khng kh
insufficiently treated air; qua x l hoc x l cha m bo;
(e) wearing protective clothing where products (e) mc trang phc bo h nhng khu vc ch
or materials are handled; bin cc sn phm; hoc nguyn liu;
(f) using cleaning and decontamination (f) s dng cc quy trnh lm v sinh v kh
procedures of known effectiveness; trng c nh gi v hiu qu;
(g) using a closed system in production; (g) s dng mt h thng khp kn trong sn
xut'
(h) testing for residues; (h) kim tra d cht;
(i) using cleanliness status labels on equipment. (i) s dng nhn ghi tnh trng sch trn my
mc.
16.13 Measures to prevent cross-contamination and 16.13 Cn kim tra theo nh k cc bin php ngn
their effectiveness should be checked periodically nga nhim cho v hiu qu ca chng theo cc quy
according to SOPs. trnh thao tc chun.
16.14 Production areas where susceptible products 16.14 Mi trng ti nhng khu vc ch bin cc sn
are processed should undergo periodic phm nhy cm cn c gim nh k (v d theo
environmental monitoring (e.g. for microbiological di vi sinh vt v tiu phn nu ph hp).
monitoring and particulate matter where
appropriate).
Processing operations Thao tc ch bin
16.15 Before any processing operation is started, 16.15 Trc khi bt u bt k thao tc ch bin no,
steps should be taken to ensure that the work area cn tin hnh cc bc m bo l khu vc lm vic
and equipment are clean and free from any starting v my mc thit b c sch v khng c bt k
materials, products, product residues, labels or nguyn liu ban u, sn phm d, nhn hoc ti liu
documents not required for the current operation. khng cn thit cho thao tc sp din ra.
16.16 Any necessary in-process controls and 16.16 Cn tin hnh v ghi li tt c cc kim tra
environmental controls should be carried out and trong qu trnh sn xut v kim sot mi trng.
recorded.
16.17 Means should be instituted of indicating 16.17 Cn c, phng tin ch ra nhng sai st ca
failures of equipment or of services (e.g. water, gas) my mc hoc dch v cp cho my mc (v d nc,
to equipment. Defective equipment should be kh). My mc b hng phi ngng s dng cho ti
withdrawn from use until the defect has been khi h hng c khc phc. Sau khi s dng, my
rectified. After use, production equipment should be mc thit b sn xut phi c lm v sinh ngay
cleaned without delay according to detailed written theo cc theo cc quy trnh chi tit bng vn bn v
procedures and stored under clean and dry bo qun iu kin sch v kh trong khi vc ring
conditions in a separate area or in a manner that will bit sao cho trnh b tp nhim.
prevent contamination.
16.18 Time limits for storage of equipment after 16.18 Gii hn thi gian bo qun my mc thit b
cleaning and before use should be stated and based t sau khi lm v sinh n trc khi s dng phi
on data. c nu r v da trn s liu r rng.

16.19 Containers for filling should be cleaned before 16.19 Bao b ng gi thuc phi c lm sch
filling. Attention should be given to avoiding and trc khi ng gi thuc. Cn ch trnh v loi
removing any contaminants such as glass fragments sch mi yu t gy tp nhim, v d nh mnh v
and metal particles. ca thu tinh, hoc cc mnh kim loi.
16.20 Any significant deviation from the expected 16.20 Cn ghi chp v iu tra mi sai lch ng k
yield should be recorded and investigated. so vi sn lng d kin.
16.21 Checks should be carried out to ensure that 16.21 Cn kim tra m bo rng cc ng dn v
pipelines and other pieces of equipment used for the cc my mc thit b s dng chuyn sn phm t
transportation of products from one area to another khu vc ny sang khu vc kia c tip ni ng
are connected in a correct manner. cch.
16.22 Pipes used for conveying distilled or deionized 16.22 ng dn nc hoc nc kh ion v cc ng
water and, where appropriate, other water pipes ng nc khc, nu c, phi c lm v sinh v bo
should be sanitized and stored according to written qun theo ng quy trnh thao tc bng vn bn
procedures that detail the action limits for trong nu chi tit cc gii hn v vi sinh v bin
microbiological contamination and the measures to php cn tin hnh khi gii hn ny khng t.
be taken.
16.23 Measuring, weighing, recording, and control 16.23 My mc v dng c o lng, cn, ghi chp,
equipment and instruments should be serviced and v kim sot phi c bo dng v hiu chun theo
calibrated at prespecified intervals and records nh k nht nh v vic bo dng, hiu chun phi
maintained. To ensure satisfactory functioning, c lu h s. m bo my mc thit b hot
instruments should be checked daily or prior to use ng t yu cu, cn kim tra nng lc thc hin
for performing analytical tests. The date of th nghim ca dng c hng ngy hoc trc khi
calibration and servicing and the date when dng. Cn nu r ngy hiu chun v bo dng v
recalibration is due should be clearly indicated on a ngy cn hiu chun li, tt nht l ghi ngay trn
label attached to the instrument. nhn dn trn thit b.
16.24 Repair and maintenance operations should not 16.24 Cc thao tc sa cha v bo dng khng
present any hazard to the quality of the products. c gy nguy him cho cht lng sn phm.
Packaging operations Thao tc ng gi
16.25 When the programme for packaging operations 16.25 Khi ang lp chng trnh cho cc thao tc
is being set up, particular attention should be given ng gi, cn c bit ch gim ti a nguy c gy
to minimizing the risk of cross- contamination, mix- nhim cho, ln ln hoc b tro i. Cc sn phm
ups or substitutions. Different products should not be khc nhau khng nu c ng gi trong nhng khu
packaged in close proximity unless there is physical vc gn nhau, tr khi c vch ngn c hc hoc mt
segregation or an alternative system that will provide h thng ngn cch no khc c mc m bo tng
equal assurance. ng.
16.26 Before packaging operations are begun, steps 16.26 Trc khi bt u thao tc ng gi, cn c cc
should be taken to ensure that the work area, bc kim tra m bo rng l khu vc lm vic,
packaging lines, printing machines and other dy chuyn ng gi, my in, v cc my mc thit b
equipment are clean and free from any products, khc sch v khng c sn phm, nguyn vt liu
materials or documents used previously and which hay ti liu dng trc m khng cn cho thao tc
are not required for the current operation. The line hin thi. Vic dn quang dy chuyn cn tin hnh
clearance should be performed according to an theo ng quy trnh ph hp v danh mc kim tra,
appropriate procedure and checklist, and recorded. v phi c lu h s.
16.27 The name and batch number of the product 16.27 Tn v s l ca sn phm c x l trn dy
being handled should be displayed at each packaging chuyn phi c treo mi im hoc dy chuyn
station or line. ng gi.
16.28 Normally, filling and sealing should be followed 16.28 Thng thng, vic dn nhn phi i lin vi
as quickly as possible by labelling. If labelling is vic ng thuc v gn xi cng nhanh cng tt. Nu
delayed, appropriate procedures should be applied to cha dn nhn ngay c cn thc hin quy trnh
ensure that no mix ups or mislabelling can occur. ph hp m bo khng xy ra ln ln hoc dn
nhn nhm.
16.29 The correct performance of any printing (e.g. 16.29 Cn kim tra v ghi li tnh chnh xc khi in n

of code numbers or expiry dates) done separately or (v d in m s v ngy ht hn) c thc hin ring
in the course of the packaging should be checked and bit hoc trong khi ng gi. Cn ch n vic in
recorded. Attention should be paid to printing by bng tay, phi kim tra li theo nh k ph hp.
hand, which should be rechecked at regular
intervals.
16.30 Special care should be taken when cut labels 16.30 Cn c bit thn trng khi dng nhn ct
are used and when overprinting is carried out off- ri v khi thc hin nn s dng ngoi dy chuyn v
line, and in hand-packaging operations. Roll feed trong thao tc ng gi tay. Thng nn s dng
labels are normally preferable to cut labels in helping cun nhn ct khi dn trnh ln ln. Dng phng
to avoid mix ups. Online verification of all labels by php kim tra nhn bng thit b in t t ng
automated electronic means can be helpful in ngay trn dy chuyn s gip ch trong vic ngn
preventing mix ups, but checks should be made to nga ln ln, nhng cn kim tra m bo rng
ensure that any electronic code readers, label my c m, my m nhn hoc cc thit b in t
counters, or similar devices are operating correctly. tng t cc hot ng chnh xc. Khi nhn c dn
When labels are attached manually, in-process bng tay, cn thc hin cc kim tra trong qu trnh
control checks should be performed more frequently. thng xuyn hn.
16.31 Printed and embossed information on 16.31 Nhng thng tin c in hoc dp trn bao b
packaging materials should be distinct and resistant ng gi phi r rng, khng phai hoc kh ty xo.
to fading or erasing.
16.32 Regular online control of the product during 16.32 Kim tra thng xuyn sn phm trn dy
packaging should include at least checks on: chuyn trong khi ng gi t nht phi bao gm vic
kim tra i vi:
(a) the general appearance of the packages; (a) hnh thc chung ca bao gi;
(b) whether the packages are complete; (b) xem vic ng gi c hon thin khng;
(c) whether the correct products and packaging (c) xem c dng ng sn phm v bao gi
materials are used; khng;
(d) whether any overprinting is correct; (d) xem vic in c ng khng;
(e) the correct functioning of line monitors. (e) my gim st trn dy chuyn c hot ng
chnh xc khng;
Samples taken away from the packaging line should Mu ly ra khi dy chuyn ng gi khng c
not be returned. tr li.
16.33 Products that have been involved in an unusual 16.33 Nhng sn phm c lin quan n mt s c
event during packaging should be reintroduced into bt thng trong ng gi ch c a tr li quy
the process only after special inspection, trnh sau khi qua kim tra, iu tra c bit v
investigation and approval by authorized personnel. c ngi c thm quyn cho php. Cn c h s
A detailed record should be kept of this operation. chi tit v thao tc ny.
16.34 Any significant or unusual discrepancy 16.34 Nhng khc bit c ngha hoc bt thng
observed during reconciliation of the amount of bulk trong vic i chiu lng sn phm ch ng gi v
product and printed packaging materials and the bao b c in n, vi s lng n v thnh phm, cn
number of units produced should be investigated, c iu tra, cn nhc tho ng v ghi h s trc
satisfactorily accounted for, and recorded before khi cho xut l.
release.
16.35 Upon completion of a packaging operation, any 16.35 Khi hon thnh thao tc ng gi, mi nguyn
unused batch-coded packaging materials should be liu bao gi in s l m cha dng n u phi
destroyed and the destruction recorded. A hu, vic hu b phi c ghi h s. Nu bao b in
documented procedure requiring checks to be sn cha c s l c tr v th phi theo mt quy
performed before returning unused materials should trnh trong quy nh r cc kim tra cn thc hin
be followed if uncoded printed materials are trc khi tr li nguyn vt liu cha dng v kho.
returned to stock.
16.36 Production records should be reviewed as part 16.36 H s sn xut phi c xem xt nh mt
of the approval process of batch release before phn ca qu trnh duyt xut l trc khi chuyn
transfer to the authorized person. Any divergence or cho ngi c u quyn. Bt k tnh trng chch
failure of a batch to meet production specifications hng hoc sai st ca l sn phm so vi tiu chun
should be thoroughly investigated. The investigation sn xut u phi c iu tra thu o. Nu cn,
should, if necessary, extend to other batches of the vic iu tra phi m rng n cc l khc ca cng
same product and other products that may have been sn phm v cc sn phm khc c th c lin quan
associated with the specific failure or discrepancy. A n s sai lch so vi tiu chun. Mt bn ghi kt
written record of the investigation should be made qu iu tra phi c thit lp v phi bao gm cc

and should include the conclusion and follow- up kt lun v hnh ng tip theo.
action.
17. Good practices in quality 17. Thc hnh tt trong kim

control tra cht lng
17.1 QC is the part of GMP concerned with sampling, 17.1 Kim tra cht lng l mt phn ca GMP lin
specifications and testing, and with the organization quan n vic ly mu, tiu chun v kim nghim,
and documentation which ensure that the necessary cng ng thi lin quan n vn t chc, h s
and relevant tests are actually carried out and that ti liu v quy trnh duyt xut m bo tin
materials are not released for use, nor products hnh cc php th ph hp khng c xut em bn
released for sale or supply, until their quality has hay cung cp, nu nh chng cha c nh gi l
been judged to be satisfactory. QC is not confined to t cht lng. Kim tra cht lng khng ch b hp
laboratory operations, but may be involved in many trong cc hot ng ca phng th nghim, m bao
decisions concerning the quality of the product. gm mi quyt nh lin quan n cht lng sn
phm.
17.2 The independence of QC from production is 17.2 Tnh c lp ca b phn kim tra cht lng so
considered fundamental. vi b phn sn xut c coi l yu cu c bn.
17.3 Each manufacturer should have a QC function. 17.3 Mi nh sn xut cn phi c b phn QC. Cc
The QC function should be independent of other chc nng QC phi c lp ca cc phng ban khc
departments and under the authority of a person v thuc thm quyn ca mt ngi c trnh v
with appropriate qualifications and experience. kinh nghim ph hp. Ngun lc thch hp phi sn
Adequate resources must be available to ensure that c m bo rng tt c cc k hoch QC c
all the QC arrangements are effectively and reliably thc hin hiu qu v ng tin cy. Cc yu cu c
carried out. The basic requirements for QC are as bn cho QC nh sau:
follows:
(a) adequate facilities, trained personnel and (a) phi c c s trang thit b, nhn vin
approved procedures must be available for c o to v quy trnh c ph duyt
sampling, inspecting, and testing starting thc hin vic ly mu, kim tra v kim
materials, packaging materials, and nghim nguyn liu ban u, nguyn vt liu
intermediate, bulk, and finished products, bao gi, sn phm trung gian, bn thnh
and where appropriate for monitoring phm v thnh phm, v nu cn theo di
environmental conditions for GMP purposes; iu kin mi trng v mc ch tun th
(b) samples of starting materials, packaging nguyn tc GMP;
materials, intermediate products, bulk (b) Vic ly mu nguyn liu ban u, nguyn
products and finished products must be taken vt liu bao gi, sn phm trung gian, bn
by methods and personnel approved of by the thnh phm v thnh phm c thc hin
QC department; bng cc phng php v do nhng nhn
(c) qualification and validation; vin c b phn kim tra cht lng ph
(d) records must be made (manually and/or by duyt;
recording instruments) demonstrating that (c) phi thc hin vic ly thm nh;
all the required sampling, inspecting and (d) phi lp h s (bng tay v/hoc bng thit b
testing procedures have actually been carried ghi chp) chng minh rng tt c cc quy
out and that any deviations have been fully trnh ly mu, kim tra v kim nghim cn
recorded and investigated; thit u thc s c tin hnh, v bt k
(e) the finished products must contain sai lch no so vi quy trnh u c ghi
ingredients complying with the qualitative y vo h s v c iu tra;
and quantitative composition of the product (e) Thnh phm phi c cha cc cht theo ng
described in the marketing authorization; the thnh phn nh tnh v nh lng ca sn
ingredients must be of the required purity, in phm nh c m t trong giy php lu
their proper container and correctly labelled; hnh; cc thnh phn phi t mc tinh
khit quy nh, c ng trong bao b ph
(f) records must be made of the results of hp v dn nhn ng;
inspecting and testing the materials and
intermediate, bulk and finished products (f) phi ghi li kt qu kim tra v kim nghim
against specifications; product assessment theo tiu chun i vi cc nguyn vt liu v
must include a review and evaluation of the sn phm trung gian, bn thnh phm v
relevant production documentation and an thnh phm; cc nh gi sn phm phi bao

assessment of deviations from specified gm c vic r sot v nh gi cc h s ti

procedures; liu v sn xut cc lin quan, vic nh gi
(g) sufficient samples of starting materials and nhng sai lch so vi quy trnh nh;
products must be retained to permit future (g) Cn lu gi lng mu nguyn liu ban
examination of the product if necessary; the u v thnh phm c th kim nghim
retained product must be kept in its final sn phm sau ny nu cn thit; mu lu
pack unless the pack is exceptionally large, phi c gi trong tnh trng ng gi sau
which case one that is equivalent to the cng, tr phi dng bao gi ny qu ln, khi
marketed packaging system may be used. dng bao gi tng ng vi h thng bao
gi lu hnh c th c s dng.
17.4 Other QC responsibilities include: 17.4 Cc trch nhim khc ca QC bao gm:
(a) establishing, validating and implementing all (a) thit lp, thm nh v thc hin tt c cac
QC procedures; th tc QC;
(b) evaluating, maintaining and storing reference (b) nh gi, duy tr v bo qun cc tiu chun
standards for substances; vin dn ca cc cht;
(c) ensuring the correct labelling of containers (c) m bo ghi nhn ng trn cc thg cha
of materials and products; nguyn vt liu v sn phm;
(d) ensuring that the stability of the active (d) m bo tnh n nh ca cc nguyn liu
pharmaceutical ingredients and products is dc v sn phm c gim st;
monitored;
(e) participating in the investigation of (e) tham gia vo cc hot ng iu tra gii
complaints related to the quality of the quyt khiu ni lin quan n cht lng sn
product; phm;
(f) participating in environmental monitoring; (f) tham gia vo vic gim st mi trng;
(g) participation in QRM programmes. (g) tham gia vo cc chng trnh qun l ri ro
cht lng
These activities should be carried out in accordance Nhng hot ng ny phi c thc hin theo cc
with written procedures and, where necessary, th tc dng vn bn v, khi cn thit, lp h s.
recorded.
17.5 QC personnel must have access to production 17.5 Nhn vin b phn QC phi tip cn c khu
areas for sampling and investigation as appropriate. vc sn xut ly mu v iu tra, nu cn.
Control of starting materials and Kim sot nguyn liu ban u v sn

intermediate, bulk and finished phm trung gian, bn thnh phm v
products thnh phm.
17.6 All tests should follow the instructions given in 17.6 Tt c cc php th phi t theo cc hng dn
the relevant written test procedure for each material trong c quy trnh th nghim bng vn bn c lin
or product. The result should be checked by the quan i vi mi nguyn liu v sn phm. Kt qu
supervisor before the material or product is released phi c gim st vin kim sot li trc khi
or rejected. nguyn vt liu hay sn phm c xut hay b loi.
17.7 Samples should be representative of the batches 17.7 Mu ly phi i din cho l nguyn vt liu
of material from which they are taken in accordance c ly mu theo ng quy nh trnh bng vn bn
with the approved written procedure. c duyt.
17.8 Sampling should be carried out so as to avoid 17.8 Vic ly mu phi c thc hin sao cho trnh
contamination or other adverse effects on quality. c tp nhim hoc cc tc ng bt li khc i vi
The containers that have been sampled should be cht lng. Nhng thng hng c ly mu phi
marked accordingly and carefully resealed after c nh du v nim phng li cn thn sau khi ly
sampling. mu.
17.9 Care should be taken during sampling to guard 17.9 Cn thn trong khi ly mu trnh gy tp
against contamination or mix up of, or by, the nhim hay ln ln cho nguyn vt liu c ly mu
material being sampled. All sampling equipment that hoc khin n gy tp nhim hoc ln ln cho nhng
comes into contact with the material should be clean. nguyn vt liu khc. Tt c dng c ly mu c tip
Some particularly hazardous or potent materials may xc vi nguyn vt liu phi sch. Phi c bit thn
require special precautions. trng vi mt s loi nguyn vt liu c bit nguy
him hoc c hot lc mnh.

17.10 Sampling equipment should be cleaned and, if 17.10 Dng c ly mu phi c lm v sinh v nu
necessary, sterilized before and after each use and cn phi c v trng trc v sau mi ln s dng,
stored separately from other laboratory equipment. dng c ly mu phi c bo qun ring khng
cng ch vi cc thit b kim nghim khc.
17.11 Each sample container should bear a label 17.11 Mi bao b ng mu phi c nhn mang
indicating: nhng thng tin sau:
(a) the name of the sampled material; (a) tn nguyn vt liu c ly mu;
(b) the batch or lot number; (b) s l hoc m;
(c) the number of the container from which the (c) s ca thng hng t mu c ly;
sample has been taken;
(d) the number of the sample; (d) s mu ly;
(e) the signature of the person who has taken (e) ch k ca ngi ly mu;
the sample;
(f) the date of sampling. (f) ngy ly mu.
17.12 Out-of-specification results obtained during 17.12 Nhng kt qu khng t thu c khi kim
testing of materials or products should be nghim nguyn vt liu hoc sn phm cn c iu
investigated in accordance with an approved tra theo mt quy trnh c duyt. Cn lu h s
procedure. Records should be maintained. v vn ny.
Test requirements Yu cu th nghim
Starting and packaging materials Nguyn liu ban u v nguyn liu bao gi
17.13 Before releasing a starting or packaging 17.13 Trc khi cho xut mt nguyn liu ban u
material for use, the QC manager should ensure that hay nguyn vt liu bao gi cho s dng, trng
the materials have been tested for conformity with phng kim tra cht lng phi m bo rng nguyn
specifications for identity, strength, purity and other vt liu c kim nghim t tiu chun v
quality parameters. nh tnh, nng , tinh khit v cc ch tiu cht
lng khc.
17.14 An identity test should be conducted on a 17.14 Mi thng hng nguyn liu ban u phi c
sample from each container of starting material (see ly mu kim tra nh tnh (xem thm khon
also section 14.14). 14.14).
It is permissible to sample only a proportion of the C th ly mu ch mt phn ca cc thng hng nu

containers where a validated procedure has been c th tc thm nh nhm m bo rng khng
established to ensure that no single container of c thng hng nguyn liu ban u n l no c
starting material has been incorrectly labelled. dn nhn khng ng.
This validation should take account of at least the Vic thm nh ny phi bao gm ti thiu cc kha
following aspects: cnh sau:
the nature and status of the manufacturer and of tnh cht v tnh trng ca nh sn xut v ca
the supplier and their understanding of the GMP nh cung cp v s hiu bit ca h v cc yu cu
requirements; GMP.
the QA system of the manufacturer of the starting h thng m bo cht lng ca nh sn xut
material; nguyn liu ban u
the manufacturing conditions under which the iu kin sn xut ca nguyn vt liu ban u v
starting material is produced and controlled; and vic kim sot thc hin; v
the nature of the starting material and the tnh cht ca nguyn vt liu ban u v dc
medicinal products in which it will be used. phm c sn xut t nguyn liu ban u .
Under such a system it is possible that a validated Vi mt h thng nh vy c th c mt th tc

procedure for exemption from the requirement for c thm nh khng phi ly mu kim tra tng
identity testing of each incoming container of thng nguyn liu ban u nhn vo c th c
starting material could be accepted for the following: chp nhn cho cc trng hp sau:
starting materials coming from a single product nguyn vt liu ban u n t mt nh sn xut
manufacturer or plant; or sn phm n l; hoc
starting materials coming directly from a nguyn vt liu ban u nhn trc tip t nh sn

manufacturer, or in the manufacturers sealed xut, hoc trong thng cha cn nim phong ca nh
container where there is a history of reliability, and sn xut cho php tra cu cc thng tin lch s lin
regular audits of the manufacturers QA system are quan, v c h thng nh gi nh k h thng m
conducted by the purchaser (the manufacturer of the bo cht lng ca nh sn xut bi phng mua hng
medicinal product) or by an officially accredited body. (nh sn xut cc sn phm dc) hoc bi c quan
nh gi chng nhn.
It is improbable that such a procedure could be Khng th p dng mt th tc c thm nh nh

satisfactorily validated for either: trn cho cc trng hp:
starting materials supplied by intermediaries, such nguyn vt liu ban u c cung cp qua trung
as brokers, where the source of manufacture is gian, nh qua ngi mi gii, vi ngun sn xut
unknown or not audited; or khng c bit hoc khng c nh gi, hoc
starting materials for use in parenteral products. nguyn liu ban u s dng cho cc sn phm
dng ng tim.
17.15 Each batch (lot) of printed packaging materials 17.15 Mi l (m) nguyn vt liu bao gi c in n
must be examined following receipt. phi c kim tra sau khi nhn.
17.16 In lieu of full testing by the manufacturer, a 17.16 Thay v nh sn xut tin hnh kim nghim
certificate of analysis may be accepted from the y , c th chp nhn phiu kim nghim (COA)
supplier, provided that the manufacturer establishes ca nh cung cp, vi iu kin l nh sn xut phi
the reliability of the suppliers analysis through xc nh c tin cy ca cc kim nghim ca
appropriate periodic validation of the suppliers test nh cung cp thng qua vic thm nh kt qu kim
results (see sections 8.8 and 8.9) and through on-site nghim ca nh cung cp theo nh k ph hp (xem
audits of the suppliers capabilities. (This does not 8.8 & 8.9) v thng qua kim tra c s thc t
affect section 17.15.) Certificates must be originals nh gi nng lc ca nh sn xut. (iu ny khng
(not photocopies) or otherwise have their nh hng ti iu khon 17.15). Phiu kim nghim
authenticity assured. Certificates must contain at phi l bn gc (khng phi bn photo) hoc nu
least the following information (7): khng phi m bo v tnh php l ca chng. Phiu
kim nghim t nht phi c cc thng tin sau:
(a) identification (name and address) of the (a) c im nhn dng (tn v a ch) ca nh
issuing supplier; cung cp cp phiu;
(b) signature of the competent official, and (b) ch k ca cn b c thm quyn, v cng b
statement of his or her qualifications; v trnh ca ngi ;
(c) the name of the material tested; (c) tn ca nguyn vt liu c kim nghim;
(d) the batch number of the material tested; (d) s l ca nguyn vt liu c kim nghim;
(e) the specifications and methods used; (e) tiu chun v phng php s dng;
(f) the test results obtained; (f) kt qu kim nghim;
(g) the date of testing. (g) ngy kim nghim.
In-process control Kim tra trong qu trnh
17.17 In-process control records should be 17.17 H s kim sot trong qu trnh sn xut phi
maintained and form a part of the batch records (see c lu gi v tr thnh mt phn trong h s l
section 15.25). (xem 15.25)
Finished products Thnh phm
17.18 For each batch of medicines product, there 17.18 i vi mi l thnh phm, cn phi xc nh
should be an appropriate laboratory determination of bng bin php kim nghim ph hp rng sn phm
satisfactory conformity to its finished product tho mn cc tiu chun thnh phm trc khi c
specification prior to release. xut.
17.19 Products failing to meet the established 17.19 Nhng sn phm khng t tiu chun quy
specifications or any other relevant quality criteria nh hoc bt k tiu ch cht lng ph hp no u
should be rejected. phi b loi.
Batch record review Xem xt h s l
17.20 QC records should be reviewed as part of the 17.20 H s kim sot cht lng phi c xem xt
approval process of batch release before transfer to nh mt phn ca qu trnh duyt xut sn phm

the authorized person. Any divergence or failure of a trc khi chuyn cho ngi c u quyn. Bt k sai
batch to meet its specifications should be thoroughly lch hoc khng p ng tiu chun no ca l
investigated. The investigation should, if necessary, cng phi c iu tra thu o. Nu cn vic iu
extend to other batches of the same product and tra phi m rng sang cc l khc ca cng sn
other products that may have been associated with phm v c cc sn phm khc c th c lin quan
the specific failure or discrepancy. A written record n s sai hng hoc thiu st . Cn lp h s iu
of the investigation should be made and should tra trong c nu kt lun v bin php tip theo.
include the conclusion and follow-up action.
17.21 Retention samples from each batch of finished 17.21 Mu lu ca mi l thnh phm phi c lu
product should be kept for at least one year after the gi cho ti sau khi ht hn s dng t nht mt nm.
expiry date. Finished products should usually be kept Thnh phm thng phi c lu trong bao b cui
in their final packaging and stored under the cng v bo qun trong iu kin khuyn co. Nu
recommended conditions. If exceptionally large bao b cui cng c bit ln, c th lu mu nh hn
packages are produced, smaller samples might be trong c bao b ph hp. Mu lu ca hot cht phi
stored in appropriate containers. Samples of active c lu gi cho ti khi t nht mt nm sau khi ht
starting materials should be retained for at least one hn s dng ca thnh phm tng ng. Cc nguyn
year beyond the expiry date of the corresponding liu ban u khc (khng phi l dung mi, kh v
finished product. Other starting materials (other than nc), phi c lu ti thiu hai nm nu n nh
solvents, gases and water) should be retained for a ca chng cho php. Mu lu ca nguyn liu v sn
minimum of two years if their stability allows. phm phi cho t nht hai ln kim nghim li y
Retention samples of materials and products should cc ch tiu.
be of a size sufficient to permit at least two full re-
examinations.
Stability studies Nghin cu n nh
17.22 QC should evaluate the quality and stability of 17.22 B phn QC phi nh gi cht lng v n
finished pharmaceutical products and, when nh ca thnh phm dc v nu cn th ca c
necessary, of starting materials and intermediate nguyn liu ban u v sn phm trung gian.
products.
17.23 QC should establish expiry dates and shelf-life 17.23 B phn kim tra cht lng phi thit lp
specifications on the basis of stability tests related to c ngy ht hn v cc tiu chun v tui th da
storage conditions. trn c s c th nghim v n nh lin quan n
iu kin bo qun.
17.24 A written programme for ongoing stability 17.24 Cn xy dng v thc hin mt chng trnh
determination should be developed and implemented bng vn bn cho vic xc nh n nh lu di,
to include elements such as: chng trnh cn c cc yu t nh:
(a) a complete description of the medicine (a) m t y v thuc c nghin cu n

involved in the study; nh;
(b) the complete set of testing parameters and (b) b tiu ch th nghim y v phng
methods, describing all tests for potency, php th nghim, c m t tt c cc php
purity, and physical characteristics and th v hot lc, tinh khit, cc c tnh vt
documented evidence that these tests l v cc dn chng c trong h s ti liu
indicate stability; cho thy nhng th nghim ny chng minh
c n nh;
(c) provision for the inclusion of a sufficient (c) quy nh c s lng l nghin cu;
number of batches;
(d) the testing schedule for each medicine; (d) lch trnh kim nghim cho mi loi thuc;
(e) provision for special storage conditions; (e) quy nh iu kin bo qun;
(f) provision for adequate sample retention; (f) quy nh vic lu mu;
(g) a summary of all the data generated, (g) tm tt tt c cc s liu thu c, k c vic
including the evaluation and the conclusions nh gi v kt lun nghin cu.
of the study.
17.25 Stability should be determined prior to 17.25 n nh cn c xc nh trc khi cho lu

marketing and following any significant changes, for hnh sn phm v sau khi c nhng thay i ng k
example, in processes, equipment, packaging i vi quy trnh sn xut, my mc thit b, nguyn
materials, etc. vt liu bao gi, .

References / Ti liu tham kho

(1) Good manufacturing practices for pharmaceutical products. In: WHO Expert Committee on
Specifications for Pharmaceutical Preparations. Thirty-seventh report. Geneva, World Health
Organization, 2003 (WHO Technical Report Series, No. 908), Annex 4.
(2) Validation of analytical procedures used in the examination of pharmaceutical materials. In: WHO
Expert Committee on Specifications for Pharmaceutical Preparations. Thirty-second report. Geneva,
World Health Organization, 1992 (WHO Technical Report Series, No. 823), Annex 5.
(3) EudraLex Volume 4. Good manufacturing practice (GMP) Guidelines. European Commission.
(http://ec.europa.eu/health/documents/eudralex/vol-4/ index_en.htm).
(4) Pharmaceutical Inspection Convention, Pharmaceutical Inspection Co-operation Scheme (PIC/S). In:
Guide to good manufacturing practice for medicinal plants. Geneva, PIC/S Secretariat, 2000.
(5) Quality assurance of pharmaceuticals. WHO guidelines, related guidance and GXP training modules.
Geneva, World Health Organization, 2013 (CD-ROM).
(6) Good manufacturing practices for pharmaceutical products, Part one. In: WHO Expert Committee on
Specifications for Pharmaceutical Preparations. Thirty-second report. Geneva, World Health
Organization, 1992 (WHO Technical Report Series, No. 823), Annex 1; and in: Quality assurance of
pharmaceuticals. A compendium of guidelines and related materials. Vol. 2, 2nd updated edition.
Good manufacturing practices and Inspection. Geneva, World Health Organization, 2007; and in:
Quality assurance of pharmaceuticals. WHO guidelines, related guidance and GXP training modules.
Geneva, World Health Organization, 2013 (CD-ROM).
(7) Model certificate of analysis. In: WHO Expert Committee on Specifications for Pharmaceutical
Preparations. Thirty-sixth report. Geneva, World Health Organization, 2002 (WHO Technical Report
Series, No. 902), Annex 10.

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WHO Technical Report Series 986

WHO Expert Committee

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Glossary Gii thch thut ng

active pharmaceutical ingredient (API) hot cht dc dng

Any substance or mixture of substances intended to Bt k mt cht hoc hn hp cc cht d nh c

authorized person ngi c y quyn

batch (or lot) m (hoc l)

A defined quantity of starting material, packaging L mt lng xc nh nguyn vt liu ban u,

batch number (or lot number) s m (hoc s l)

A distinctive combination of numbers and/or letters L s kt hp ca cc con s v/hoc ch ci nhn

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bulk product bn thnh phm

calibration hiu chun

Clean area khu vc sch

consignment (or delivery) chuyn hng (hay t giao hng)

The quantity of a pharmaceutical or pharmaceuticals, Mt lng ca mt dc phm hoc nhiu dc phm

The undesired introduction of impurities of a L s nhim khng mong mun cc tp cht c bn

critical operation thao tc quan trng

cross-contamination nhim cho

finished product thnh phm

in-process control kim tra trong qu trnh sn xut

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ensure that the product conforms to its m bo sn phm t c cc tiu chun d

intermediate product sn phm trung gian

large-volume parenterals thuc tim truyn th tch ln

master formula cng thc gc

packaging material nguyn liu bao gi

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pharmaceutical product dc phm

production hot ng sn xut

All operations involved in the preparation of a Tt c cc thao tc c lin quan n vic bo ch mt

quality assurance m bo cht lng

quality control kim tra cht lng

quality unit(s) (cc) n v cht lng

An organizational unit independent of production Mt n v t chc c lp vi sn xut bao gm c

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self-contained area khu vc khp kn

specification tiu chun

A list of detailed requirements with which the Mt danh mc cc yu cu c th m sn phm hoc

standard operating procedure (SOP) quy trnh thao tc chun (SOP)

An authorized written procedure giving instructions Mt quy trnh bng vn bn v c ph duyt,

starting material nguyn liu ban u

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Quality management in the Qun l cht lng trong cng

1 Pharmaceutical quality 1 H thng qun l cht lng

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Quality risk management Qun l ri ro cht lng

1.9 QRM should ensure that: 1.9 QRM phi m bo:

Product quality review Xem xt cht lng sn phm

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(h) a review of all quality-related returns, (h) vic xem xt tt c cc trng hp tr v c

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2. Good manufacturing 2. Thc hnh tt sn xut dc

(d) instructions and procedures are written in (d) cc th tc v hng dn c vit ra r

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3. Sanitation and hygiene 3 V sinh v kh trng

4. Qualification and validation 4. Thm nh

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4.9 A written report summarizing the results 4.9 Cn chun b v lu gi mt bn bo co tm tt