USP Standards for Purifed Water

Dear Fresh Water Systems,

Regarding pharmaceutical grades of water, purified water can be made using any
suitable method. However, it must pass the USP shelf-life standards which are detailed
in the folowing tables. It is the maintainence of the water production system that is of
concern to those in water treatment.

Purified Water is to be used in the production or compounding of USP products.

Manufacturing is controlled by the FDA ,while compounding is controlled at the state
level by the boards of pharmacy.

FB Scientific Staff, United States Pharmacopeia

USP Standards for Packaged Purified Water, Water for Injection and Sterile Purified
Water (USP24 effective 1/1/00)
The following are numerical value limits that are commonly used interpretations* of the
procedures listed on pages 1752 and 1753 under the individual monographs:

pH 5.0 to 7.0

Chloride 0.5
(mg/l)

Sulfate (mg/l) 1.0

Ammonia 0.03
(mg/l)

Calcium 1.0
(mg/l)

Carbon 5.0
Dioxide (mg/l)

Oxidizable Pass the USP

Substances Permanganate test
 Bacteria Purified Water
(CFU/ml) 100

WFI (CFU/100ml) 10

Sterile PW Pass the

USP Sterility test <71>

Endotoxin 0.25
WFI (EU/ml)

Note: The actual USP tests are colorimetric tests and the USP24 must be consulted for
the procedures. USP24 may be found at the libraries of pharmacy and medical schools
and some reference libraries. It may also be purchased by calling 800-822-8772. TOC
and Conductivity testing is not approved for packaged water because of interferences
from materials extracted from the plastic or glass containers. Purified Water and Sterile
Purified Water may be obtained by any suitable process. Water for Injection is water
purified by distillation or reverse osmosis. Regulatory agencies have required that
packaged PW and WFI be tested by the producer using TOC and conductivity prior to
packaging. It is advisable that the purchaser obtain this assurance.

Source: The PhRMA Water Quality Group

These limits are Guidelines found in General Chapter <1231>

The wet chemistry tests and the oxidizable substance test in the USP23 monographs
for PW and WFI were deleted. They were replaced with a Water Conductivity test for
ionic impurities and a Total Organic Carbon test (TOC) for organic impurities.
The current standards for PW and WFI are:
TOC 500 ppb Carbon
Conductivity 1.3 TS / cm @ 25
1.1 TS / cm @ 20
Bacteria PW-100 cfu/mL
(guidelines in <1231>) WFI-10 cfu/100mL
Bacterial Endotoxins WFI-0.25 USP Eu/mL
USP24 contains complete versions of all pharmaceutical water monographs p. 1752-
1754 and the general chapters <643> TOC, <645> Water Conductivity p. 1927-1929,
and <1231> Water for Pharmaceutical Purposes p. 2154-2163. You may
purchase USP24 by calling Customer Service at (800) 877-6733. We can not provide
photocopies of copyrighted material. The USP is also available at pharmacy colleges,
medical colleges, pharmaceutical manufacturers, equipment manufacturers, and some
reference libraries.
 You are advised that the TOC limit of 500 ppb C is the target limit response. The
actual number can vary based upon your equipment, the sucrose reference solution
prepared, background carbon etc. Also, accurate offline TOC testing requires a high
level of vigilance to avoid contamination during sampling and testing. The frequency of
system suitability testing is a program decision, taking into account your current Q.C.
practice and your regulatory risk. The Conductivity Test meter and the conductivity cell
must both be calibrated as per <645> and the use of a non-temperature-compensated
meter is required specifically in Stage 1 testing.
The monographs for all packaged pharmaceutical waters continue to require wet
chemistry tests and the Oxidizable Substance test because of possible contamination
from the packaging material used, which can influence test results. (See the Sterile
Purified Water monograph). The manufacture of PW & WFI has not changed. Purified
Water may be produced by any suitable process. WFI must be produced by distillation
or reverse osmosis only.
TOC reference standards may be purchased by calling the same general USP
number. Only USP reference standards have been tested and approved as suitable for
use in USP tests and assays.

Pharmacopoeia Water Quality

Grades of Compendial Water.

USP Purified Water

USP Water for Injection
Ph Eur Purified Water
Ph Eur WFI
USP, Ph Eur, JP Comparisons Purified Water
USP, EP. & JP Comparsions Water for Injection
USP Purified Water
Suggested processes by which it can be obtained include, deionisation, RO,
deionisation polishing, distillation, filtration etc. Systems must be validated,
feedwater must comply with drinking water standards and the system should be
frequently sanitised with microbiological monitoring.
Conductivity: <1.3 S/cm at 25C in line*
TOC:<500ppb (Online or off)
Bacteria:<100 cfu/ml**

*Non-temp. Compensated conductivity measurement

**Non-mandatory, generally considered appropriate Action Level

USP Water for Injection
The suggested process by which it can be obtained is distillation or a purification
process that is equivalent or superior to distillation in the removal of chemicals
and micro-organisms Systems must be validated, contain no added substances
and must be designed to prevent microbial contamination and formation of
microbial endotoxins.
Conductivity: <1.3 S/cm at 25C in line or table*
TOC:<500ppb (Online or off)
Endotoxins:<0.25 EU/ml
Bacteria:<10 cfu/100ml**

*Non-temp. Compensated conductivity measurement

**Non-mandatory, generally considered appropriate Action Level

Ph Eur Purified Water

Suggested processes by which it can be obtained include ion exchange, RO or
any other suitable process. Feedwater must comply with US, EU or Japanese
drinking water guidelines; appropriate measures must be taken to control
and monitor viable aerobic count, system must contain no added substances and
the storage & distribution must be designed to prevent growth of microorganisms
and to avoid any other contamination. System must be validated.
Conductivity:<4.3 S/cm at 25C in line or table*
TOC:<500ppb (Online or off)
Bacteria:<10 cfu/100ml**
Nitrates:<0.2 ppm
Heavy Metals:<0.1 ppm

*Non-temp. Compensated conductivity measurement

**Non-mandatory, generally considered appropriate Action Level

Ph Eur WFI
Suggested process by which it can be obtained is by distillation of drinking water
or purified water. Validated procedures are applied, appropriate measures must
be taken to control and monitor viable aerobic count, correct maintenance of the
distillation apparatus is essential and storage & distribution must be designed to
prevent growth of microorganisma and to avoid any other contamination
Conductivity: <1.1 S/cm at 20C in line *
TOC:<500ppb (Online or off)
Endotoxins:<0.25 EU/ml
 Bacteria:<10 cfu/100ml**

*Non-temp. Compensated conductivity measurement

**Non-mandatory, generally considered appropriate Action Level

USP, Ph Eur, JP Comparisons Purified Water

Constituent USP PhEur JP

Conductivity < 1.3 < 4.3 S/cm @ 20C -

S/cm @
25C

Nitrates - <0.2ppm test

Nitrites - - test

pH - - test

Chloride - - test (< 0.5 ppm)

Sulphate - - test (< 1.0 ppm)

Ammonia - - test

Heavy Metals - < 0.1 ppm Pb test

TOC < 500 < 0.5 -

ppb mg/l or oxidisable
substances test
 Oxidizable - test or TOC test
Substances

Total Solids - - test (10 ppm)

Total Bacteria - < 100 cfu/ml -

Count

Production Suitable Distillation, Ion Distillation, Ion

method Process Exchange or any Exchange, UF or
other suitable method combination of
these methods

For dialysis solution production the EP specifies the following additional

tests:

Aluminium < 10 g/l

Pyrogen < 0.25 EU/ml

USP, EP. & JP Comparsions Water for Injection

Constituent USP PhEur JP

Conductivity < 1.3 S/cm < 1.1 S/cm @ -

@ 25C 20C

Nitrates - < 0.2 ppm test

Nitrites - - test

pH - - test
Chloride - - test

Sulphate - - test

Ammonia - - test

Heavy Metals - < 0.1 ppm Pb test

TOC < 500 ppb < 0.5 mg/l or If using RO

oxidisable production use
substances test TOC test

Oxidizable - test test (not RO)

Substances

Total Bacteria - <10 cfu/100ml -

Count

Pyrogen < 0.25 EU/ml < 0.25 EU/ml < 0.25 EU/ml

Production Distillation or Distillation Distillation or

Method superior RO/UF
process