WATER SYSTEM in

PHARMACEUTICAL
INDUSTRY
By Prima Happy R.

MATA KULIAH FARMASI INDUSTRI

PROGRAM STUDI S1 FARMASI, FAKULTAS MIPA
UNIVERSITAS LAMBUNG MANGKURAT
2019
Water for Pharmaceutical Use
Introduction

 Look at information on specifications of Water for

Pharmaceutical Use (WPU)
 Which Quality of water to be used in production and
control
 APIs, finished products, etc.

 GMP for design, installation, operation of systems

 Supplementary to general GMP guidelines
 See also other guidelines, pharmacopoeia, etc.
 Additional guidelines

 WHO Guideline for Drinking water

quality (WHO)
 Water and steam systems (ISPE)
 Bioprocessing Equipment Standard
(ASME – BPE 2000)
 European Pharmacopoeia, United
States Pharmacopeia, International
Pharmacopoeia
 Inspection of Utilities (PIC/S)
Principles

 Like any starting material, production of

water should conform to Good Manufacturing
Practice (GMP) norms
 Potential for microbial growth
 Systems must be properly validated /
qualified
 Water for parenteral use should not
Contaminants of water (1)

 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
Contaminants of water (2)

Problem minerals
● Calcium, magnesium, copper, aluminium,
heavy metals, arsenic, lead, cadmium,
nitrates
● Iron, manganese, silicates, carbon dioxide
● Hydrogen sulfide
● Phosphates
Contaminants of water (3)

Microorganisms – Biofilm formation

● Protozoa
 Cryptosporidium
 Giardia
● Bacteria
 Pseudomonas
 Gram negative, non-fermenting
bacteria
 Escherichia coli and coliforms
What is Pharmaceutical Water
 Water is the one of the major
commodities used by the
pharmaceutical industry
 Water is the most widely used substance /
raw material
 Used in production, processing,
formulation, cleaning, quality control
 Unique chemical properties
 Able to dissolve, absorb, adsorb, suspend
compounds and contaminants

 Different grades of water quality available

Water may present as :
 Ingredient/Excipient, Solvent in the
processing, formulation and
manufacture of pharmaceutical
products, active pharmaceutical
ingredients (APIs) and
intermediates, compendial articles,
and analytical reagents.
a cleaning agent for rinsing vessels,
equipment and primary packing
material
Water requirements and use

 Control quality of water during production, storage

and distribution
 Contaminants, microbial and chemical quality
 Microbial contamination risk and concern
 Water is used on demand
 not like other materials where sampled and tested,
and THEN used. Thus no batch or lot release before
use. It has to meet the specification "on demand"
when used
 Micro test results require incubation periods therefore
results later after already used
Water requirements and use (1)

Microbial control is a high priority

Microbes may proliferate (production,
storage and distribution)
System design, periodic sanitization and
other measures
Different grades of water quality
(dependent on its use)
General Principles of water
systems

 Design, installation, commissioning, qualification /

validation, operation, performance and
maintenance to ensure reliable, consistent
production of water of required quality
 Prevent unacceptable microbial, chemical and
physical contamination during production,
storage and distribution
 Operate within design capacity
 Quality Assurance involved in approval of use
after installation and maintenance work, or
changes
Water system requirements
Regular monitoring of:
 Water quality
 Chemical and microbiological
 Endotoxin level where relevant

 System performance, storage and distribution

systems
 Records of results, trends and action taken
 Validated sanitization procedure followed on a
routine basis
Water quality specifications

These waters can be divided into two

general types

 bulk waters, which are typically

produced on site where they are used
 packaged waters, which are
produced, packaged, and sterilized to
preserve microbial quality throughout
their packaged shelf life
The 8 types of water :

 Non-potable
 Potable (drinkable) water
 USP purified water
 USP water for injection (WFI)

 Steril water for hemodialysis

 USP sterile water for injection (SWFI)
 USP bacteriostatic water for injection (BWFI)
 USP sterile water for irrigation

 USP sterile water for inhalation

Drinking water / potable water

 Must comply with specification (WHO, ISO and national

or regional agencies) – regular testing needed
 Supplied under continuous positive pressure
 Defect free plumbing system to prevent contamination
 Could be from public water supply system or natural
sources
 Source water quality influences the treatment required
 Treatment includes desalinization, softening,
removal of specific ions, particle reduction and
antimicrobial treatment.
Purified Water
 used as an excipient in the production of
nonparenteral preparations and in other
pharmaceutical applications, such as cleaning
of certain equipment and nonparenteral
product-contact components.
 Unless otherwise specified, Purified Wateris also to
be used for all tests and assays for which water is
indicated
 This source water may be purified using unit
operations that include deionization, distillation,
ion exchange, reverse osmosis, filtration, or other
suitable purification procedures.
Water for Injection

 used as an excipient in the production of parenteral

and other preparations where product endotoxin
content must be controlled, and in other
pharmaceutical applications, such as cleaning of
certain equipment and parenteral product-contact
components.
 The finished water must meet all of the chemical
requirements for Purified Wateras well as an
additional bacterial endotoxin specification.
 This source water may be pre-treated to render it
suitable for subsequent distillation (or whatever other
validated process is used according to the
monograph)
Water for Hemodialysis
 used for hemodialysis applications, primarily the
dilution of hemodialysis concentrate solutions.
 purified to reduce chemical and microbiological
components.
 It may be packaged and stored in unreactive
containers that preclude bacterial entry.
 The water contains no added antimicrobials and
is not intended for injection.
Sterile Purified Water
 Purified Water, packaged and rendered sterile.
 It is used in the preparation of nonparenteral
compendial dosage forms or in analytical
applications requiring Purified Water where
access to a validated Purified Watersystem is not
practical, where only a relatively small quantity is
needed, where sterile Purified Wateris required,
or where bulk packaged Purified Wateris not
suitably microbiologically controlled.
Sterile Water for Injection
 Water for Injection packaged and rendered
sterile.
 It is used for extemporaneous prescription
compounding and as a sterile diluent for
parenteral products.
 It may also be used for other applications where
bulk Water for Injection or Purified Water is
indicated but where assess to a validated water
system is either not practical or where only a
relatively small quantity is needed.
 SterileWater for Injectionis packaged in single-
dose containers not larger than 1 L in size.
Bacteriostatic Water for
Injection

 Sterile Water for Injection to which has been

added one or more suitable antimicrobial
preservatives.
 It is intended to be used as a diluent in the
preparation of parenteral products, most
typically for multi-dose products that require
repeated content withdrawals.
 It may be packaged in single-dose or multiple-
dose containers not larger than 30 mL.
Sterile Water for Irrigation

 Water for Injection packaged and sterilized in

single-dose containers of larger than 1 L in size
that allows rapid delivery of its contents.
 It need not meet the requirement under
small- volume injections. SO Not for
intravenous injection (For irrigation only)
 Sterile Water for Irrigation is hypotonic with an
osmolarity of zero mOsmol/L. It is intended for use
as an irrigation fluid and not for intravenous
administration or administration by other,
parenteral routes (e.g., subcutaneous or
intramuscular)
Sterile Water for Inhalation

 Water for Injection that is packaged and

rendered sterile and is intended for use in
inhalators and in the preparation of inhalation
solutions.
 It carries a less stringent specification for
bacterial endotoxins than Sterile Water for
Injection, and therefore, is not suitable for
parenteral applications.
Quality Parameters

 Conductivity
 Various ions
 Particles (SS)
 Bacteria
 Endotoxins
Absence of bacteria is a must for higher quality
waters
Control of Quality Water
Some of the standars of reference :

1. FDA Guide to inpections of high purity water

systems (7/93)
2. USP Monograph <1231> Water for
Pharmaceutical Purposes
3. WHO good manufacturing practices : water for
pharmaceutical use
Water purification systems

 Principles for pharmaceutical water systems

 Water quality specifications

– Drinking-water, Bulk purified water, Bulk highly purified water, Bulk
water for injections

 Specific types of water for processes and dosage forms

 General considerations for water purification systems