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Pharmaceutical Water Requirements

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Pharmaceutical Waters

Potable water
Potable water / water intended for human consumption
Potable water, or water intended for human consumption, is
also used as feed water for the production of purified water and
water for injections. Potable water may be used to rinse
product-contacting surfaces of equipment.

Potable water (treated)

Treated potable water has the same uses as potable water and
water intended for human consumption but has been treated to
reduce its microbial content.

Purified water (PW)

Purified water in bulk
is used as an excipient in the preparation of non-sterile products
and as a starting material in the preparation of water for injec-
tion and pharmaceutical-grade pure steam. It is also used for
rinsing purposes (cleaning of containers) and in the preparation
of cleaning solutions.

Purified water in containers

is purified water in bulk that has been filled and stored in condi-
tions designed to assure the required microbiological quality. It
must be free from any added substances.

Highly purified water (HPW)

Is used in the preparation of medicinal products where bacterial
endotoxins need to be controlled, except where water for injec-
tion is required. Current methods for the preparation include
double-pass reverse osmosis, reverse osmosis combined with
Ultrafiltration and distillation.

Water for injections (WFI)

Sterilized water for injections
Is used for dissolving or diluting substances or preparations for
parenteral administration.

Water for injections in bulk

Is used in the manufacture of parenteral and ophtalmic pro-
ducts. It is also used for final rinsing of containers (e.g. primary
packaging materials) and manufacture of these products.
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USP* / Ph. Eur.**

Purified Water

Parameter Unit USP Ph. Eur. (Bulk)

TOC ppm C 0.50 0.5
Conductivity µS/cm@20 °C — ≤ 4.3
Conductivity µS/cm@25 °C ≤ 1.3 —
Nitrate (NO3) ppm — ≤ 0.2
Heavy metals ppm as Pb — ≤ 0.1
Aerobic bacteria CFU/ml ≤ 100 ≤ 100

Highly purified water

Parameter Unit USP Ph. Eur. (Bulk)

TOC ppm C n.c.st. 0.5
Conductivity µS/cm@20 °C n.c.st. ≤ 1.1
Nitrate (NO3) ppm n.c.st. ≤ 0.2
Heavy metals ppm as Pb n.c.st. ≤ 0.1
Aerobic bacteria CFU/100ml n.c.st. ≤ 10
Bacterial endotoxins I.U./ml n.c.st. ≤ 0.25
n.c.st. = no comparable standard

Water for injections

Parameter Unit USP Ph. Eur. (Bulk)

TOC ppm C 0.50 0.5
Conductivity µS/m@20 °C — ≤ 1.1
Conductivity µS/m@25 °C ≤ 1.3 —
Nitrate (NO3) ppm — ≤ 0.2
Heavy metals ppm as Pb — ≤ 0.1
Aerobic bacteria CFU/100 ml ≤ 10 ≤ 10
Bacterial endotoxins EU/ml ≤ 0.25 —
Bacterial endotoxins I.U./ml — ≤ 0.25

* current United States Pharmacopeia

** current European Pharmacopeia
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Production of PW, HPW and WFI

United States Pharmacopoeia

Water Production by Suitable System

PW • Suitable process • OSMOTRON

WFI • Suitable process • MULTITRON

• VAPOTRON
• OSMOTRON INJECT

European Pharmacopoeia

Water Production by Suitable System

PW • Ion exchange • OSMOTRON

• Distillation
• Other suitable methods

HPW • Distillation • OSMOTRON INJECT

• RO/UF • ULTRASTIL

WFI • Distillation • MULTITRON

• VAPOTRON

CHRIST CombiCAL WFI Heat Exchanger

Turnkey WFI system

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USP* / Ph. Eur.**

Fundamental objectives of USP

• To maintain or improve the existing water quality
• Improvement of the reliability of the measured
values by means of modern analytic instruments
• Reduction of the number of samples
• Authorization of the in-line measuring method

Important comments on Eur. Ph.

Sampling
Before taking samples the water must run for some time
(30 seconds to 1 minute) while opening and shutting the tap
several times. If the water for the production is fed through a
hose, the sample must also be taken from this hose. Appro-
priate containers for the samples are glass or PE bottles.

Methods of analysis
For the determination of chemical and physical parameters as
well as for the microbiological analysis only methods according
to USP or the Eur. Ph. may be used.

Procedure in case of exceeding limit values

Action limits which are exceeded according to GMP should lead
to an Out of Specification (OOS) procedure.

* current United States Pharmacopeia

** current European Pharmacopeia

Purified Water treatment plant

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Conductivity according to USP

Three-stage Philosophy

1. In-line Measurement:
A conductivity measurement without temperature compensa-
tion corresponding to a measured temperature. If the con-
ductivity is below 1.3 µS/cm at 25 °C (or values according to
Table A) the measurement is completed. If not, stage 2 is
required.

Advantages of the in-line Measurement in Stage 1

• Real-time information for conductivity and temperature
• Immediate limit value alarm
• Data output for recording and documentation of
the water quality
• Simple and reasonably-priced measurement
• Avoiding of errors due to sampling, handling and transport

2. Laboratory Measurement:
If the CO2 concentration of the sample is at equilibrium with
the air and the conductivity is below 2.1 µS/cm at 25 °C the
measurement is completed. If not, stage 3 is required.

3. Laboratory Measurement:
Add saturated KCI to the sample from stage 2 and measure
pH and conductivity. The measured conductivity must be
below the conductivity value shown in Table 1 at the measu-
red pH. If this is the case, the measurement is completed. If
not, the water does not conform to the standard.

Customer witnessed
Factory Acceptance Test
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Table A
Stage 1 Conductivity limits as a function of the temperature
Stage 3 Conductivity limits as a function of the pH-value

Stage 1 Stage 3
Temp.°C µS/cm pH µS/cm
0 0.6 5.0 4.7
5 0.8 5.1 4.1
10 0.9 5.2 3.6
15 1.0 5.3 3.3
20 1.1 5.4 3.0
25 1.3 5.5 2.8
30 1.4 5.6 2.6
35 1.5 5.7 2.5
40 1.7 5.8 2.4
45 1.8 5.9 2.4
50 1.9 6.0 2.4
55 2.1 6.1 2.4
60 2.2 6.2 2.5
65 2.4 6.3 2.4
70 2.5 6.4 2.3
75 2.7 6.5 2.2
80 2.7 6.6 2.1
85 2.7 6.7 2.6
90 2.7 6.8 3.1
95 2.9 6.9 3.8
100 3.1 7.0 4.6
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Complete range of products

Christ offers all known and well-established products and

processes for the production of purified water, highly purified wa-
ter and water for injections. This allows in-depth application-
oriented advice, resulting in optimal system solutions that meet
the requirements of the pharmaceutical industry.
Christ systems and services range from processes for the pre-
treatment of raw water through to the purification and storage
of high-purity water, including the fully integrated control of all
process steps. Among the technologies offered by Christ are:

• OSMOSTIL Reverse Osmosis

• OSMOTRON skidded PW/HPW Generation Systems
with the patented SEPTRON® Electrodeionization spiral-
wound module
• ULTRASTIL Ultrafiltration plants
• VAPOTRON Pure Steam Generators
• MULTITRON WFI Distillation Plants
• LUMOSTIL UV-systems
• LOOPO skidded Distribution and Sanitisation Systems
• STERITRON Electrolytic Ozone Generators
• Including Validation Packages

Christ is specialized in providing all above mentioned proces-

ses in complete turn-key projects.

TenergyChrist.com