Supplementary Training Modules on

Good Manufacturing Practice

Water for Pharmaceutical Use
Nc s dng trong
sn xut thuc
Part 1:
Introduction and treatment
Phn 1:
Phn gii thiu v x l nc

WHO Technical Report Series

No 929, 2005. Annex 3

Water | Slide 1 of 44 January 2006

 Water for Pharmaceutical Use
Objective (Mc ch)

Water system requirements (Cc yu cu ca h thng nc)

Water quality specifications (Cc tiu chun cht lng ca nc)

Application of specific water to processes and dosage forms (p dng

ca nc ch nh cho cc quy trnh sn xut v cc dng hm lng)

Water purification methods (Cc phng php tinh ch nc)

Storage and distribution systems (Cc h thng tn tr v phn phi)

Commissioning, qualification, operation and maintenance (a vo

hot ng, nh gi, vn hnh v bo tr)

Water | Slide 2 of 44 January 2006

 Water for Pharmaceutical Use
Introduction (Gii thiu)

Information on Water for Pharmaceutical Use (WPU) (Thng tin v nc dng cho
sn xut thuc)

Quality of water for APIs, finished products, etc. (Cht lng ca nc cho sn xut
nguyn liu thuc v thnh phm...)

GMP for design, installation, operation of systems (GMP v thit k, lp t, vn

hnh h thng)

Supplementary to general GMP guidelines (B sung cho cc nguyn tc chung ca

GMP)

See also other guidelines, pharmacopoeia, etc. (Tham kho cc nguyn tc ca t

chc khc, dc in...)
1.1

Water | Slide 3 of 44 January 2006

 Water for Pharmaceutical Use
Additional guidelines (Cc nguyn tc b sung)

WHO Guideline for Drinking water quality (WHO) (Nguyn tc WHO v cht
lng nc ung)
Water and steam systems (ISPE) (H thng nc v hi nc ca ISPE)
Bioprocessing Equipment Standard (ASME BPE 2000) (Tiu chun thit b
x l sinh hc ASME-BPE 2000)
European Pharmacopoeia, United States Pharmacopeia, International
Pharmacopoeia (Dc in chu u, dc in M, dc in quc t)
Inspection of Utilities (PIC/S) (K hoch hp tc v thanh tra Dc)

1.3

Water | Slide 4 of 44 January 2006

 Water for Pharmaceutical Use
Principles (Nguyn tc)
Like any starting material, production of water should conform to Good
Manufacturing Practice (GMP) norms (Ging nh bt c nguyn liu no, sn
xut nc phi ph hp vi cc nguyn tc GMP)

Potential for microbial growth (Tim nng pht trin vi sinh vt)

Systems must be properly validated / qualified (H thng phi c thm

nh/nh gi mt cch thch hp)

Water for parenteral use should not be contaminated with pyrogens or

endotoxins (Nc dng cho ng tim chch phi khng c c cht gy
st hay ni c t vi khun)

Specifications and periodic testing are required (Yu cu phi c tiu chun
cht lng v th nghim nh k)

Water | Slide 5 of 44 January 2006

 Water for Pharmaceutical Use
Why purify raw water? (Ti sao phi tinh ch nc)
Although reasonably pure, it is always variable due to seasonal variations, regional
variation in water quality (Mc d tng i tinh khit, lun lun c nhng thay i theo
ma, vng v cht lng nc)

Must remove impurities and control microbes to avoid contaminating products (Phi loi
b cc tp v kim sot vi sinh vt trnh nhim sn phm)

Treatment depends on waters chemistry and contaminants, influenced by, e.g. rainfall,
erosion, pollution, dissolution, sedimentation, decomposition (X l ty thuc vo ha
hc v cc cht gy nhim nc, cc nh hng do lng ma, s xi mn, s
nhim, s phn hy, s lng ng trm tch, s thi ra)

Water | Slide 6 of 44 January 2006

 Water for Pharmaceutical Use
Contaminants of water (1) (Cc cht gy nhim
nc (1))
There is no pure water in nature, as it can contain up to 90 possible unacceptable
contaminants (Khng c nc tinh khit trong t nhin, c th c ti 90 cht gy
nhim nc khng c chp nhn)
Contaminant groups: (Nhm cc cht gy nhim)
Inorganic compounds (Cc cht v c)
Organic compounds (Cc cht hu c)
Solids (Cc cht rn)
Gases (Cc kh)
Microorganisms (Vi sinh vt)

Water | Slide 7 of 44 January 2006

 Water for Pharmaceutical Use
Contaminants of water (2) (Cc cht lm nhim nc (2))
Problem minerals (Vn cc khong cht)

Calcium, magnesium, copper, aluminium, heavy metals, arsenic, lead,

cadmium, nitrates (Calci, magnesi, ng, kim loi nng, ch, cadmi,
nitrat)

Iron, manganese, silicates, carbon dioxide (St, mangan, silicat,

cacbon dioxid)

Hydrogen sulfide (Hydro sulfid)

Phosphates (Phot phat)

Water | Slide 8 of 44 January 2006

 Water for Pharmaceutical Use
Contaminants of water (3) (Cc cht lm nhim nc (3))

Microorganisms Biofilm formation (Vi sinh vt-S to mng

bm sinh hc)
Protozoa (Sinh vt n bo)
Cryptosporidium
Giardia

Bacteria (Vi khun)

Pseudomonas
Gram negative, non-fermenting bacteria
Escherichia coli and coliforms

Water | Slide 9 of 44 January 2006

 Water for Pharmaceutical Use
Biofilm formation (S to thnh mng sinh hc)
1. Free-swimming aquatic bacteria use polymucosaccharides to colonize
surfaces (Vi khun bi t do trong nc s dng polymucosaccharides
chim gi cc b mt)

2. Complex communities evolve which shed

microcolonies and bacteria (Cc cng ng lin hp pht trin pht ra cc
khm vi khun v vi khun)

Water | Slide 10 of 44 January 2006

 Water for Pharmaceutical Use
Background to water requirements and use (Kin thc
cc yu cu v nc v s dng nc)
Water is the most widely used substance / raw material (Nc l nguyn liu c s
dng nhiu nht)
Used in production, processing, formulation, cleaning, quality control (S dng trong sn
xut, qu trnh, thit k cng thc, lm v sinh, kim nghim)
Unique chemical properties (Cc c trng v ha hc)
Able to dissolve, absorb, adsorb, suspend compounds and contaminants (C th ha
tan, hp thu, ht, treo cc hp cht v cc cht gy nhim)
Different grades of water quality available (C cc cp khc nhau v cht lng nc)
See also EMEA "Note for guidance on the quality of water for pharmaceutical use (Xem
EMEA Ch gii v nguyn tc ca cht lng nc dng cho sn xut thuc)
1.2

Water | Slide 11 of 44 January 2006

 Water for Pharmaceutical Use

Background to water requirements and use (2) use (Kin

thc cc yu cu v nc v s dng nc (2))
Control quality of water (Kim tra cht lng nc)
Production (Sn xut)
Storage and distribution (Tn tr v phn phi)
Contaminants, microbial and chemical quality (Cc cht gy nhim, cht lng v ha hc v vi
sinh)
Microbial contamination risk and concern (Nguy c nhim vi sinh v mi quan ngi)
Water is used on demand (Nc c s dng theo yu cu)
not subjected to testing and batch or lot release before use, therefore has to meet
specification "on demand" when used (Khng bt buc th nghim cho xut xng mi l
trc khi s dng nn phi t tiu chun theo yu cu khi dng
Micro test results require incubation periods (Cc kt qu th nghim vi sinh cn thi gian )
1.2

Water | Slide 12 of 44 January 2006

 Water for Pharmaceutical Use
Water system requirements (Cc yu cu ca h thng
nc)
Design, installation, commissioning, qualification / validation, operation, performance
and maintenance to ensure reliable, consistent production of water of required quality
(Thit k, lp t, a vo hot ng, nh gi/thm nh, vn hnh, hiu nng v
bo tr bo m tin cy, sn xut n nh nc t cht lng yu cu)
Operate within design capacity (Hot ng ng cng sut thit k)
Prevent unacceptable microbial, chemical and physical contamination during
production, storage and distribution (Ngn nga cc nhim ha l, vi sinh trong khi
sn xut, bo qun v phn phi)
Quality Assurance involved in approval of use after installation and maintenance
work (m bo cht lng c lin quan trong ph duyt s dng sau khi lp t v
bo tr)
2.

Water | Slide 13 of 44 January 2006

 Water for Pharmaceutical Use
Water system requirements (Cc yu cu ca h thng
nc (2))
Monitoring of water sources regularly (Thng xuyn theo di ngun nc)
Chemical and microbiological (V ha hc v vi sinh)
Endotoxin level where relevant (Gii hn ni c t vi khun)
Monitoring of system performance, storage and distribution systems (Theo di hiu
nng h thng, cc h thng phn phi v tn tr)
Records of results, and action taken (Ghi h s cc kt qu v thc hin cc hnh
ng)

Validated sanitization procedure followed on a routine basis (Thc hin thng

xuyn quy trnh tit trng c thm nh)
2.

Water | Slide 14 of 44 January 2006

 Water for Pharmaceutical Use
Water quality specifications (Tiu chun cht lng ca nc)
Here address water in bulk (not for patient administration) ( y cp n nc vi
lng ln (khng phi nc s dng cho bnh nhn)
Specifications in pharmacopoeia relevant to national or international
recommendations. Types of water include: (Tiu chun cht lng trong dc in- cc
cc ngh ca quc t v quc gia c lin quan)
Drinking water / potable water (Nc ung c)
Purified water (PW) (Nc tinh khit)
Highly Purified Water (HPW) (Nc siu tinh)
Water for Injection (WFI) (Nc pha thuc tim)

3.

Water | Slide 15 of 44 January 2006

 Water for Pharmaceutical Use
Drinking water / potable water (Nc ung c)

Must comply with specification (WHO, ISO and national or regional agencies)
regular testing needed (Phi tun theo tiu chun cht lng (WHO, ISO v cc
c quan khu vc v quc gia))
Supplied under continuous positive pressure (c cung cp di p sut dng
lin tc)
Defect free plumbing system to prevent contamination (H thng hn khng c
khim khuyt trnh nhim)
Could be from public water supply system or natural sources (C th ly t h
thng cung cp nc cng cng hoc ngun thin nhin)
Source water quality influences the treatment required (Cht lng ngun nc
nh hng n cc yu cu v x l)
3.2.

Water | Slide 16 of 44 January 2006

 Water for Pharmaceutical Use

Drinking water: (Nc

ung c)

Natural sources could include

springs, wells, rivers and lakes
(Ngun t nhin bao gm sui, ging,
sng, h)

Treatment includes softening, ion

removal, particle reduction,
antimicrobial treatment (X l bao
gm lm mm, loi ion, gim bt cc
tiu phn, x l khng khun) 3.2

Water | Slide 17 of 44 January 2006

 Water for Pharmaceutical Use
Purified Water (PW) (Nc tinh khit)

Prepared from potable water source (iu ch t ngun nc

ung c)
Meet pharmacopoeia specification for chemical and microbial
purity (t tiu chun dc in v ha hc v vi sinh)
Protected from recontamination (c bo v chng ti nhim)
Protected from microbial proliferation (c bo v chng vi
khun pht trin)

3.3.

Water | Slide 18 of 44 January 2006

 Water for Pharmaceutical Use
Highly Purified Water (HPW)
Prepared from potable water source (iu ch t ngun nc ung c)
Specification only in the European Pharmacopoeia (Tiu chun cht lng
ch c trong dc in chu u)
Same quality standard as WFI including limit for endotoxins, but treatment
method considered less reliable than distillation (Cng tiu chun cht
lng nh nc pha thuc tim k c gii hn ni c t vi khun,
nhng phng php x l c xem nh t tin cy hn ct nc)
Prepared by combination of methods including reverse osmosis (RO),
ultrafiltration (UF) and deionization (DI) (iu ch bng s phi hp cc
phng php bao gm thm thu ngc, cc lc v kh ion)

3.4.

Water | Slide 19 of 44 January 2006

 Water for Pharmaceutical Use
Water for Injections (WFI) (Nc pha thuc tim)

Prepared from potable water source (iu ch t ngun nc ung

c)
WFI is not sterile (Khng v trng)
WFI is not a final dosage form (Khng phi l dng bo ch sau cng)
WFI is an intermediate bulk product (L sn phm trung gian)
According to The International and European Pharmacopoeias final
purification step should be distillation (Theo dc in quc t v
chu u-giai on tinh ch sau cng l ct)

3.5

Water | Slide 20 of 44 January 2006

 Water for Pharmaceutical Use
Application of specific water to processes and dosage forms (p
dng ca nc chuyn dng cho cc quy trnh sn xut v cc
dng hm lng)
Water used for different stages of: (Nc dng cho cc giai on khc nhau ca)
Washing, preparation, synthesis, production, formulation, control (Trng ra, pha
ch, tng hp, sn xut, thit k cng thc, kim nghim)
Which grade of water is suitable for a particular stage? (Loi no thch hp cho mt giai
on c th)
Consider nature and intended use of intermediate or finished product, and stage at which
water is used (Cn nhc bn cht v d nh s dng ca sn phm trung gian v thnh
phm v giai on s dng nc)
Let's look at types of water and indicate their use (Hy xem cc loi nc v ch nh ng
dng ca chng) 4.

Water | Slide 21 of 44 January 2006

 Water for Pharmaceutical Use
Complete the table (Hon tt bng sau)
Use (S dng) Which type of water? (Dng lai nc no)
Preparation of injectable products (Pha ch ?
thuc tim)
Final rinse of equipment after cleaning ?
(Trng thit b ln sau cng khi v sinh
xong)
Final rinse of equipment and components ?
that come into contact with injectable
products (Trng thit b v cc thnh phn
tip xc vi thuc tim)
? HPW (Nc siu tinh)

? Potable water (Nc ung c)

Water | Slide 22 of 44 January 2006

 Water for Pharmaceutical Use
Water purification methods (Cc phng php tinh ch nc)
Manufacturer to select appropriate method of purification (Nh sn xut la chn phng
php tinh ch ph hp)
Appropriate sequence of purification steps (Th t cc bc ph hp)
Influenced by, e.g. (nh hng bi)
Water quality specification (Tiu chun cht lng nc)
Yield (efficiency) of the system (Sn lng ca h thng)
Feed water quality (Cht lng nc ngun)
Reliability and robustness of treatment system ( tin cy v chc ca h thng
x l)
Supplier support, maintenance and operation costs (H tr ca nh cung cp, chi
ph bo tr v vn hnh)
5.1

Water | Slide 23 of 44 January 2006

 Water for Pharmaceutical Use
Water purification system considerations (Quan tm n
h thng tinh ch nc)

Leaching from contact materials (Thm qua t cc vt liu tip xc)

Adsorption (S hp th)
Hygienic and sanitary design (Thit k d lm v sinh v tit trng)
Corrosion resistance (Chng n mn)
Leakage (R r)
Proliferation of microbiological organisms (S pht trin vi sinh vt)

5.1

Water | Slide 24 of 44 January 2006

 Water for Pharmaceutical Use
Water purification system considerations (Quan tm
n h thng tinh ch nc (2))
Tolerance to cleaning and sanitizing agents (S dung np cc tc nhn tit trng
v lm v sinh)

Capacity and output capability (Cng sut v sn lng)

Instruments, sensors, controls, sampling points (Thit b, u d, b iu chnh,

cc im ly mu)

Space needed for installation and structural loading of premises (Khng gian cn
lp t v nh xng)

Access needed for maintenance (Mc tip cn bo tr)

5.1
Regeneration and sanitization (Hon nguyn v tit trng)
Water | Slide 25 of 44 January 2006
 Water for Pharmaceutical Use

Pre-treatment steps (Cc giai an tin x l)

Primary filtration and multimedia filter (Lc s cp v lc

nhiu lp)

Coagulation or flocculation (S kt bng)

Desalination (S kh mui)

Softening (S lm mm)

Water | Slide 26 of 44 January 2006

 Water for Pharmaceutical Use
Pretreatment Tin x l
schematic drawing s bn v
(Nc tha ti ch t thit b kh ion)
(lc than hot)
(Van phao) float excess water recycled activated
operated
from deioniser (lc ct) carbon
To water
valve
air filter sand filter filter softener &
(lc kh) DI plant
spray ball (i vo thit b
(Qu cu phun)
lm mm nc
Water is kept raw water in break tank & thit b kh
circulating (nc ngun) (bn gin on) ion)

(Nc phi lun cartridge (Lc ng

filter
tun hon) air break to drain
centrifugal pump
5 micrometers
5 micrometers)

(Nt gi ng thut nc) Bm ly tm

S trap to sewer (Con th thot ra cng)

Water | Slide 27 of 44 January 2006

 Water for Pharmaceutical Use

Water pre-treatment
complex in a pre-
treatment room
(Lin hp tin x l
nc trong phng
tin x l)

Water | Slide 28 of 44 January 2006

 Water for Pharmaceutical Use
Water Softener schematic drawing (Thit b lm mm nc - s
bn v) (nc mm i vo thit b kh ion)
by pass valve "soft" water to deioniser

(van r)
(bn nc mui & mui) brine and salt tank

brine zeolite water softener

(nc mui) -exchanges
-Ca and Mg for Na
(nc cng
(nha zeolite lm mm nc
i vo)
-trao i
"hard" water -Ca v Mg vi Na
in
(ch tho
nc)
drain

Water | Slide 29 of 44 January 2006

 Water for Pharmaceutical Use
Chlorine removal (Activated-carbon (AC)
filtration or bisulphite) (Loi b clo (Lc than
hot tnh hay bisulphit)
AC removes chlorine but bacteria can then grow (Than hot tnh
c th loi clo nhng vi khun c th pht trin)

AC filtration can remove organic impurities (Lc than hot tnh

c th loi cc tp cht hu c)

Bisulphite leaves sulphate residues but is antimicrobial

(Bisulphit li cn sulphat nh l cht khng khun)

Water | Slide 30 of 44 January 2006

 Water for Pharmaceutical Use
Production of drinking water (Sn xut nc ung
c)

Derived from raw water (e.g. well, river, reservoir) (Ly t nc ging, nc
sng, h cha)
Processes may include: (Qu trnh bao gm)
Filtration, softening (Lc, lm mm nc)
Disinfection or sanitization (Ty u, tit trng)
Iron (ferrous) removal (Loi b st)
Precipitation (Lng ng)
Inorganic / organic reduction (Gim cc cht v c/hu c)

5.2

Water | Slide 31 of 44 January 2006

 Water for Pharmaceutical Use

Production of drinking water (Sn xut nc ung c (2))

When done "in-house" steps used and system configuration documented, and water
quality routinely monitored (Khi thc hin ti c s-cc bc p dng v cu hnh h
thng c ghi h s v cht lng nc c theo di thng xuyn)

Change control in case of changes to system (Kim sot cc thay i trong trng hp
h thng thay i)

Storage of water: (Tn tr nc)

no degradation, ensure turnover, routine testing (Khng c thoi bin, m bo
quay vng, th nghim thng xuyn)

"indirect impact system" qualification not needed (H thng tc ng gin tip-khng

cn thit nh gi)
5.2

Water | Slide 32 of 44 January 2006

 Water for Pharmaceutical Use
Production of drinking water (Sn xut nc ung
c (3))
System permits draining and sanitization (H thng cho php tho nc v tit trng)

Storage tanks: (Bn cha)

Closed, with protected vents (ng kn, c thng kh c bo v)
Allows visual inspection, draining and sanitization (Cho php kim tra bng mt, tho nc
v tit trng)

Care to prevent and control microbiological contamination of sand filters, carbon beds, water
softeners (Ch ngn nga v kim sot nhim vi sinh do lc ct, lc cacbon, cht lm mm
nc)
Back-flushing, chemical or thermal sanitization and frequent regeneration, continuous
waterflow (Ra ngc, tit trng bng nhit hay ha cht v hon nguyn thng xuyn,
dng nc chy lin tc)
5.2

Water | Slide 33 of 44 January 2006

 Water for Pharmaceutical Use
Production of drinking water (Sn xut nc
ung c (4))
Drinking water supplied by tanker associated problems and risks (Nc
ung c cung cp bi tu ch-cc vn c lin quan v nguy c)

Required vendor assessment (Yu cu nh gi nh cung cp)

Authorized certification activities (Hot ng chng nhn ca nh chc trch)

Acceptability of delivery vehicle (C th chp nhn phn phi bng xe)

As receiving any other starting material (Nh tip nhn cc nguyn liu ban
u khc)

5.2

Water | Slide 34 of 44 January 2006

 Water for Pharmaceutical Use
Water treatment purification stages downstream of the
pre-treatment system may include: (Cc giai an
tinh ch nc sau khi tin x l bao gm)

Filtration (Lc)

Disinfection (Kh trng)

Reverse osmosis (RO) or deionization (DI) (Thm thu

ngc cn c gi l siu lc hay kh ion)

Distillation or ultrafiltration (Chng ct hay cc lc)

Water | Slide 35 of 44 January 2006
 Water for Pharmaceutical Use
Typical deionizer schematic (S thit b kh ion in hnh)
(t thit b lm from water softener
mm nc) HCl NaOH

6 6
5 5
4 4
3 3
2 2
1 1

(Nc phi Water (lc ng 1 m)

lun tun must be n UV Cationic column
(ct cation)
Anionic column
(ct anion)
Cartridge Cartridge

hon) kept UV light filter 5 m filter 1 m

my sinh ozon
(lc ng
circulating Eluates to cht ra gii t 5 m
neutralization thit b trung ha)
Ozone generator

plant (bm d lm sch)

Hygienic pump
Return to deionizer
(tr v thit b kh ion)
(u ra hay tn tr). Outlets or storage.
Drain line
(ng x)
Air break to sewer Nt gi ra cng

Water | Slide 36 of 44 January 2006

 Water for Pharmaceutical Use
Reverse osmosis (RO) theory (L thuyt thm thu ngc)

High pressure Low pressure

(p sut cao) (p sut thp)

Semi-permeable
membrane
(Nc ngun) Feed
water

under Purified water

(Di p sut) raw water
pressure
(Nc tinh khit)
(Nc th)
(Nc b loi)

(Nc thm qua)

Permeate
Reject
water

(Tho nc hay ti sinh) drain or recycle water

Water | Slide 37 of 44 January 2006

 Water for Pharmaceutical Use
Typical 2-stage RO schematic (S RO 2 giai on in hnh)
Water from softener or de-ionise (nc t thit b lm mm hay kh ion)

Second stage reject water goes back to first stage buffer tank (nc loi b giai on 2 (bn m giai on 1)
i vo bn m giai on 1)
(dch m c loi b giai oan 1)

1st stage buffer tank

Branch First stage RO cartridge (li RO giai on 1)
1st stage reject concentrate

Branch

First stage filtrate feeds second stage RO

. excess back to 1st stage buffer tank(dch lc giai on 1 i vo
with
giai on 2 RO, phn tha i vo bn m giai on 1)
Air break bn m giai on 2)
to sewer 2nd stage buffer tank
Second stage RO cartridge (li RO giai on 2)
(nt gi ra (bm cao p)
cng)

High pressure
High pressure pump
pump Cartridge
(lc ng filter 1 m Hygienic pump (bm sch)
(bm cao p) 1 m
(ncc RO giai on 2 Second stage RO water
t cc tiu chun dc in) meets Pharmacopoeia Water returns to 1st stage buffer tank
standards Outlets or storage ( (Nc hi v bn m giai on 1)
u ra hay tn tr)

Water | Slide 38 of 44 January 2006

 Water for Pharmaceutical Use
Use of reverse osmosis (S dng thm thu ngc)
Advantages (u im)
Disadvantages (Hn ch)
Many uses (Nhiu ng dng)
purified water (Nc tinh khit)
feeding of distillation units or ultrafiltration units (Ngun nc
cho thit b ct hay my siu lc)
Water for Final Rinse (Nc trng ra ln cui)
Water for Injections (if permissible) (Nc pha thuc tim
(nu c chp nhn))

Water | Slide 39 of 44 January 2006

 Water for Pharmaceutical Use
Production of Purified Water (PW) (Sn xut nc tinh
khit)
Use appropriate, qualified methods for production (Dng cc phng php c tiu chun ha
thch hp sn xut)
Factors to consider: (Cc yu t cn quan tm)
Feed water quality and required water quality specification (Cht lng nc ngun v tiu
chun cht lng nc tinh khit)
Sequence of purification stages needed (Chui cc qu trnh tinh ch cn thit)
Energy consumption, extent of pre-treatment needed (Tiu th nng lng, quy m tin x l
cn thit)
Yield and efficiency of unit treatment steps (Sn lng v hiu nng ca cc cc bc x l)
Location and design of sampling points (V tr v thit k cc im ly mu)
Appropriate instrumentation for measurements (Thit b o lng ph hp)

5.3

Water | Slide 40 of 44 January 2006

 Water for Pharmaceutical Use
Production of Purified Water (2) (Sn xut nc
tinh khit (2))
Measurements: (o lng)
Flow (Dng)
Pressures (p sut)
Temperature (Nhit )
Conductivity ( dn)
pH (pH)
Total organic carbon (TOC), etc. (Tng cacbon hu c)

Appropriately controlled, monitored, records maintained (Kim sot, theo di,

lu h s)
5.3

Water | Slide 41 of 44 January 2006

 Water for Pharmaceutical Use
Production of Purified Water (3) (Sn xut nc tinh khit
Ambient temperature PW systems are susceptible to microbiological contamination especially wh
and periods of low or no demand (Nhit mi trng ca h thng sn xut nc tinh khit lm c
nhim vi sinh vt-nht l khi nc tnh v khi khng c hoc nhu cu thp)

Controls may include: (Kim sat bao gm)

Maintain flow at all times (Lun duy tr dng chy)
Control temperature in the system ( <25 degrees Celsius) (Kim sat nhit h thng < 25o
UV disinfection (Kh trng bng UV)
Water treatment components that can be thermally sanitized (Cc thnh phn ca h thng x
th st trng bng nhit)
Chemical sanitization (e.g. with ozone) (St trng bng ha cht (th d ozon)

5.3

Water | Slide 42 of 44 January 2006

 Water for Pharmaceutical Use
Production of Highly Purified Water (HPW) (Sn
xut nc siu tinh khit)

Use appropriate, qualified methods for production (Dng cc phng php

c tiu chun ha thch hp sn xut)

Appropriate sequence of techniques (Chui cc k thut thch hp)

As for PW (Nh l nc tinh khit)

Processes may include: (Qu trnh c th l)

Ion exchange (Trao i ion)
Ultrafiltration (Cc lc)
Reverse Osmosis (Thm thu ngc hay cn gi l siu lc)
5.4

Water | Slide 43 of 44 January 2006

 Water for Pharmaceutical Use
Production of Water for Injections (WFI) (Sn xut
nc pha thuc tim)
Pharmacopoeia requires distillation as preferred technique for final purification step
(Dc in yu cu nn chn phng php ct trong giai an tinh ch sau cng)

Factors to consider: (Cc yu t cn quan tm)

Feed water quality (Cht lng nc ngun)
Required water quality specification (Tiu chun cht lng nc)
Optimum generator sizing (prevent frequent start/stop) (C thit b sn xut ph
hp (trnh tt/m thng xuyn)
Blow-down and dump functions (Chc nng x b cc cht lng hoc rn)
Cool-down venting (avoid contamination ingress) (Thng kh lm ngui (trnh
nhim i vo))
5.5

Water | Slide 44 of 44 January 2006