2. PHARMA WATER QUALITY SPEC.

&
DESIGN CRITERIA

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company

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WATER QUALITY
DECISION TREE
DRINKING WATER MEETS
QUALITY ATTRIBUTES OF
EPA NATIONAL
PRIMARY DRINKING
WATER REGULATIONS

USP

Typical Treatment Steps:

- Softening
- Dechlorization
- Deionization

FOR
OTHER
USES

WATER FOR SPECIAL

PHARMACEUTICAL
PURPOSES
(e.g. bulk pharmaceutical
chemicals, process water)

PURIFIED
WATER

Packaging and
Sterilization

INGREDIENT
WATER

NONPARENTERAL
DOSAGE
FORMS

STERILE
PURIFIED
WATER

- Reverse Osmosis
- Ultrafiltration
- Distillation

Distillation
or Reverse
Osmosis

WATER FOR
INJECTION
(WFI)

Packaging and
Sterilization

To be
harmonized
with USP27
WFI monograph

PACKAGED WATER
STERILE WATER FOR INJECTION
STERILE WATER FOR IRRIGATION
STERILE BACTERIOSTATIC WATER
FOR INJECTION
STERILE WATER FOR INHALATION

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SOURCE: USP 27 page 2630 - Fig. 2. Water for pharmaceutical purposes.

PHARMA WATERS QUALITY SPECS &

NEW TREND
COMPENDIAL
WATER

PURIFIED WATER
( in bulk )

WATER FOR INJECTION

( in bulk )

WATER
HIGHLY
PURIFIED
( in bulk )
E.P. 5th Ed.

PHARMACOPOEIA

PARAMETERS

Conductivity
TOC
Oxidizable
substances
Nitrates

E.P. 5th Ed.

USP xx

4.3 S/cm
(20C)

It meets the
requirements 645
(1)

0.5 mg/l

0.5 mg/l 643

Pass the test

(2)

Deleted

Pass the test

Not considered

Heavy metals

0.1 ppm

Deleted

Aluminium

Pass the test

(3)

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E.P. 5th Ed. (Only

By Distillation)

(By Distillation
or equivalent /
superior)

(Double-pass
Reverse Osmosis
coupled with other
suitable
techniques
as
ultrafiltration and
deionisation)

It meets the
requirements
of all the tests
under Purified
Water

It meets the
requirements of
all the tests
under Water for
injection

USP xx

1.1 S/cm
(20C)

It meets the
requirements of all
the tests under
Purified Water

Not considered

PHARMA WATERS QUALITY SPECS &

NEW TREND
COMPENDIAL
WATER

PURIFIED WATER
( in bulk )

WATER FOR INJECTION

( in bulk )

WATER
HIGHLY
PURIFIED
( in bulk )
E.P. 5th Ed.

PHARMACOPOEIA

PARAMETERS

E.P. 5th Ed.

5th

USP xx

E.P.
Ed.
(Only By Distillation)

Microbial
contamination
(action limit)

100 CFU/ml

100 CFU/ml

10 CFU/100 ml

Bacterial
endotoxins

0.25 IU/ml
(3)

N.A.

0.25 IU/ml

USP xx
(By Distillation or
equivalent /
superior)

10 CFU/100 ml

0.25 EU/ml

(Double-pass
Reverse Osmosis
coupled with other
suitable techniques
as
ultrafiltration
and deionisation)

10 CFU/100 ml

0.25 IU/ml

NOTES
(1)Stage 1 :Table Temperature Versus Conductivity (e.g. 1.1 S/cm (20C))
Stage 2 : 2.1 S/cm (25C)
Stage 3 : 2.1 C 4.7 S/cm (25C) as function of pH
(2)Alternatively to TOC test
(3)Only if water is intended for use in the manufacture of dialysis solutions
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P.W./WFI DESIGN CRITERIA

PW

WFI

Production

Cold (20C)

Hot (85C - 95C)

Storage

Cold (T 20C)

Hot ( 70 T 85C)

Distribution

Cold (T 20)

Hot/cold (At User Points)

To be studied case by case

Type of User Points

Manual

Manual/Automatic

Sanitiz/Steriliz

Heating at 85C

Superheated WFI at 125C

Ozone
(Specific Cases)

Pure Steam

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P.W./WFI DESIGN CRITERIA

EQUIPMENT DESIGN AND MATERIALS
-RESISTANT TO HIGH PURITY WATER
-RESISTANT TO SANITIZATION (HEAT OR CHEMICALS)
-ADEQUATE SURFACE FINISHES
-DRAINABLE
-PREVENTION OF CONTAMINATION BY OTHER FLUIDS (HEAT EXCHANGERS)
-PREVENTION OF CONTAMINATION BY MATERIAL (SEAL PUMPS, GASKETS)

-EXPOSED TOTALLY TO SANITIZING AGENTS

-VALVES / INSTRUMENTS
-NO DEAD AREAS / NO DEAD LEGS

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P.W./WFI DESIGN CRITERIA

CRITICAL PROCESS PARAMETERS CONTROL AND RECORD
-TEMPERATURE
-CONDUCTIVITY
-FLOW-RATE
-PRESSURE
-TOC

DESIGN FOR PROPER MONITORING

-INSTRUMENTS
-SAMPLING POINTS

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P.W./WFI DESIGN CRITERIA

DISTRIBUTION LOOPS

POINTS TO CONSIDER
-CONTINUOUS RECIRCULATION SYSTEMS: LOOP
-CONTROL OF TEMPERATURE (PRODUCTION/SANITIZATION)
-CONTROL OF RETURN LOOP MINIMUM VELOCITY (or better Reynolds Number)
-CONTROL OF RETURN LOOP CONDUCTIVITY
-VENTING FILTRATION OF STORAGE TANK

-HEATING OF FILTER (only WFI)

-STERILIZATION OF FILTER (only WFI)
-TESTING FOR INTEGRITY OF FILTER (only WFI)

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P.W./WFI DESIGN CRITERIA

POINTS TO CONSIDER
-POSSIBILITY TO SANITIZE STORAGE TANK + LOOP
-DRAINABILITY
-SPRAY-BALLS INSIDE THE STORAGE TANK
-ABSENCE OF DEAD-LEGS
-TURBOLENT FLOW IN DISTRIBUTION SYSTEM
-NO POINT OF USE FILTERS

-RESPECT OF CONTEMPORARY USAGE FACTOR

-SAMPLING POINTS

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DISTRIBUTION SYSTEM: LOOPS

DESIGN
1. CONTINUOUS RECIRCULATION SYSTEMS: LOOP
2. RESPECT OF CONTEMPORARY USAGE FACTOR
3. TURBOLENT FLOW IN DISTRIBUTION SYSTEM
4. ABSENCE OF DEAD-LEGS
5. SAMPLING POINTS
6. DRAINABILITY
7. AUTOMATIC SANITIZATION OF STORAGE TANK + LOOP
8. SPRAY-BALLS INSIDE THE STORAGE TANK

MONITORING & CONTROL

1. CONTROL OF TEMPERATURE (PRODUCTION/SANITIZATION)
2. CONTROL OF RETURN LOOP MINIMUM FLOW VELOCITY
3. CONTROL OF RETURN LOOP CONDUCTIVITY
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3. THE PRODUCTS
DISTRIBUTION SYSTEM: LOOPS
PW storage and
distribution
system.
For HPW
systems UVLamps can be
installed to
control the
bacterial
growth.

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DISTRIBUTION SYSTEM: LOOPS

Storage tank and delivery
pumps.

The heat exchanger on the return

allows the temperature keeping and
the sterilization by overheated
water.
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DISTRIBUTION SYSTEM: LOOPS

The heat exchanger
on the loop return
allows the
temperature keeping
and the sterilization
by overheated water.
Sub-loops with local
coolers can feed
cold points of use.

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REGULATORY REFERENCES &

STANDARDS
1.

EMEA ICH Q7A (API GMP)

2.

EMEA CPMP/QWP/158/01(Note for Guidance on Pharm. Water Quality)

3.

European Pharmacopoeia 5th Ed. (Water Monograph & Tests)

4.

European Union / USA / WHO / PIC/S / GMP

5.

USP 31

6.

USP 31(Water Monograph & Tests)

7.

WHO-Water for Pharmaceutical Use (WPU)

8.

FDA Guide to Inspection of High Purity Water Systems

9.

PDA Technical Report No. 4 _ Design Concepts for the Validation of a Water for
Injection System

10.

ISPE Baseline Pharmaceutical Engineering Guide Vol. 4: Water and Steam

Systems January 2001

11.

ASME BPE-2002 Bioprocessing Equipment

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