Water for

Pharmaceutical Use

Group 11
1.Riamayanti Hutasuhut, S.Far 2014001337
2.Rifatul Mauluda, S.Farm 2014001338
3.Rossy Hardiyanti, S.Farm 2014001339
4.Wahyuni, S.Farm
2014001280
5.Yumna Afifah N, S.Farm
2014001281

Fakultas Farmasi Universitas Pancasila

Jakarta
2015

Water for Pharmaceutical

Use/WPU
Have an important role in the
pharmaceutical industry,
because :
Water is a raw material and in
large quantities needed for :
Syrup Products, Liquid
Injectable Drugs, Intravenous
Fluids, etc.
So it should not be polluted

1. Water
Quality
Specificat
ions

2. Water
Purificati
on
System

3. Water
Storage
and
Distributi
on
Systems

1. Water Quality
Specifications
1. Feed Water
2. Purified Water
3. Highly Purified
Water/HPW
4. Water for Injection/WFI

Requirments Specification of Water

Quality

Water of Use

Sterile
Preparati
ons

Non
Sterile
Preparati
ons

Sterile Preparations
N
o

Preparati
ons

Water
Quality

Distributi
on
System

Restriction

Informatio
n

1.

Large
Volume
Parentral
(LVP)

Water
For
Injection
(WFI)

Hot Loop
Systems

Qualified

2.

Small
Volume
Parentral
(SVP)

Water
For
Injection
(WFI)

Hot Loop
Systems
Betalactam
and Nonbetalactam
split

If not using the

Feed Water
loop system,
: Purified
should be stored Water (PW)
no longer than
24 hours.
Validated

3.

Eye Drops

Purified

Loop

If not using the

TOC &
Conductivit
y
Requirment
s : The user
points

Conductivit

Non-Sterile Preparations
N
o

Prepara
tions

Water
Quality

Distributio
n System

Restriction

1.

Syrups,
Creams,
Gels,
and
Liquids
outside

Purified
Water
(PW)

Hot Loop
Systems

Qualified

2.

Solid
dosage
drugs,
Supposit
ories,
Ovules,
Ointmen
ts

Purified
Water
(PW)

Be without
Loop
Loop for
non-betalactam
Betalactam and
Non-betalactam split

Qualified
Periodic
Sanitation
Microbial
requirments :
max 100cfu/ml
No E.Coli and
Salmonella
sp/100ml

3.

Final
Wash in
the

Purified
Water
(PW)

Information
If not using the
loop system,
should be
stored no
longer than 24
hours

Conductivity
Requirments :
The user points

2. Water Purification
System
1. Multimedia Filter
4. Ultra Filtration (Reverse
Osmosis)
2. Active Carbon Filter
5. Electro De-Ionization (EDI)
3. Water Softener Filter

Pretreatment (Active Carbon

Filter)
float
operated
valve

excess water recycled

from deioniser
air filter

sand filter

activated
carbon
filter

To water
softener
& DI plant

spray ball

Water is kept
circulating

raw water in

break tank

air break to drain

centrifugal pump

S trap to sewer

cartridge
filter
5 micrometers

Water Softener Filter

by pass valve

"soft" water to deioniser

brine and salt tank

brine

"hard" water
in
drain

zeolite water softener

-exchanges
-Ca and Mg for Na

Reverse osmosis (RO)

Low pressure

High pressure

under
pressure

raw water

Purified water

Permeate
water

Reject
water
drain or recycle

Semi-permeable
membrane

Feed
water

Electronic De-Ionization (EDI)

from water softener

HCl

NaOH

5
4
3
2
1

5
4
3
2
1

Water
must be
Anionic column
Cartridge Cartridge
Cationic column
kept
UV light
filter 5 mfilter 1 m
circulatin
Eluates to
Ozone
g
neutralization
plant
Hygienic pump
Return to
deionizer
Outlets or storage.
Drain line
Air break to sewer

generator

Contaminants of water
There is no pure water in nature, as it

can contain up to 90 possible

unacceptable contaminants

Contaminant groups:
Inorganic compounds
Organic compounds
Solids
Gases
Microorganisms

Problem minerals
Calcium, magnesium, copper, aluminium, heavy
metals, arsenic, lead, cadmium, nitrates
Iron, manganese, silicates, carbon dioxide
Hydrogen sulfide
Phosphates
Microorganisms Biofilm formation
Protozoa
Cryptosporidium
Giardia
Bacteria
Pseudomonas
Gram negative, non-fermenting bacteria
Escherichia coli and coliforms

Why purify raw water?

Although reasonably pure, it is always
variable due to seasonal variations,
regional variation in water quality
Must remove impurities and control
microbes to avoid contaminating
products
Treatment depends on waters chemistry
and contaminants, influenced by, e.g.
rainfall, erosion, pollution, dissolution,
sedimentation, decomposition

Water Treatment Installation

WR-18-QM

3. Water Storage and

Distribution Systems
An important part of the entire system must be designed and
integrated with the water purification system components

Must be configured to prevent a repeat of the contamination after

processing

Configuration should be applying a combination of offline and online

monitoring to ensure water specification

Typical water storage and

distribution schematic
Feed
Water
from
DI or RO

Water must
be kept
circulating

Hydrophobic air filter

& burst disc
Cartridge
filter 1 m

Spray ball

Optional
in-line filter
0,2 m
UV light
Outlets

Heat Exchanger
Ozone Generator

Hygienic pumpAir break

to drain

Biocontamination Control
Techniques
One of issues that must be considered
during the storage and distribution of
water is a matter of controlling the
proliferation of microbes
Continuous turbulent flow circulation
Specified velocity proven

(qualification), and monitored

Avoid dead legs
Hygienic pattern diaphragm valves
Shortest possible length of pipe work
Pipe work of ambient temperature
systems, isolated from hot pipes

Biocontamination control techniques (2)

There should be no dead legs

D=25mm & distance X is

eater than 50mm, we have
dead leg that is too long

D
Flow direction
arrows
on pipes are
Dead leg section
important
X

>1.5D

Sanitary Valve
Water scours dead leg

Biocontamination Control Techniques

Periodic sanitization with hot water

Periodic sanitization with super-heated

hot water or clean steam

Reliable
Monitoring temperature during cycle
Routine chemical sanitization using, e.g.
ozone
Removal of agent before use of
water important

Qualification of Water
Treatment Systems

Qualification
WPU systems are "direct impact systems"
Therefore stages to be considered in

qualification should include DQ, IQ, OQ, PQ

DQ: Design review influenced by source water
and required water quality
IQ: Installation verification of the system
OQ: operational qualification
Presentation focusing on PQ
PQ demonstrates consistent and reliable

performance of the system

Three phase approach recommended over
extended period proves reliability and
robustness

Phase 1
A test period of 2-4 weeks monitoring the system
intensively
System to operate continuously without failure or
performance deviation
The following should be included in the testing
approach
Undertake chemical and microbiological testing in
accordance with a defined plan
Sample daily:
- incoming feed-water
- after each step in the purification process
- each point of use and at other defined sample
points
7.2
Develop:
- appropriate operating ranges
- and finalize operating, cleaning, sanitizing
and maintenance procedures

Phase 2
A further test period of 2-4 weeks further
intensive monitoring the system
Deploying all the refined SOPs after the
satisfactory completion of phase 1
Sampling scheme generally the same as in
phase 1
Water can be used for manufacturing purposes
during this phase
Demonstrate:
Consistent operation within established ranges
Consistent production and delivery of water of
the required quantity and quality when the7.2
system is operated in accordance with the
SOPs

Phase 3

Over 1 year after the satisfactory completion

of phase 2
Water can be used for manufacturing purposes
during this phase
Demonstrate:
extended reliable performance
that seasonal variations are evaluated
Sample locations, sampling frequencies and
tests should be reduced to the normal routine
pattern based on established procedures
7.2
proven during phases 1 and 2

Validation
phase

Duration

Sampling Frequency

Information

Performance
qualification
phase 1

Minimal
2-4 week

Everyday at every point of

monitoring

In this phase the water not be used for

production
Chemical and microbiological testing
parameters
Purpose:
- Define the parameters of water
treatment system including sampling
points
- Establish operating procedures,
cleaning, sanitation and maintenance
- set a limit alert and action limits

Performance
qualification
phase 2

Minimal
2-4 week

Everyday at every point of

monitoring

In this phase, the water may be used if it

meets the established specifications
Chemical and microbiological testing
parameters
Purpose:
- Verify the operational parameters
defined in phase 1

Performance
qualification
phase 3

Minimal
52 week

Everyday and in a week in

rotation should include all
monitoring points
Monitoring points, frequency,
and type of sampling testing
can be reduced based on the
monitoring result in phase 1
and phase 2

In this phase, the water may be used if it

meets the established specifications
Chemical and microbiological testing
parameters
Purpose:
- Ensure consistency of performance over
one year which includes variations due
to changing seasons