PharmaCeutiCal ResearCh Reprinted from LabPlus international - September 2002

Validation Requirements for

Laboratory Water Purification
Systems
by Alan Mortimer, C.Chem., FRSC

The increasing stringency of the regulations and quality

control guidelines that are applicable in many analytical
and process control laboratories means that more and
more systems that were previously taken for granted,
such as the water purification system, must undergo
routine validation. This article looks at what is involved in
such validation processes and describes how in prac-
tice a modern laboratory ultra pure water system incor-
porates these requirements

Just as in pharmaceutical production providing written evidence that the users

facilities, laboratories involved in phar-
maceutical quality control and drug dis-
covery are now becoming subject to
closer scrutiny and are required to oper-
ate within the various guidelines that are
an integral part of a regulated industry.
Generally speaking, most laboratories
operate within their own procedures,
which should be both documented and
audited, both internally and externally
to an ISO or NAMAS accredited stan-
dard.
The move towards formal validation of
both the water purification equipment
and the quality of purified water pro-
duced is a step towards harmonising
company procedures and ensuring the
same standards and protocols follow on
from research through pilot production
to full scale manufacture.
Validation can be defined as having
'documented evidence to ensure with a
high degree of certainty that a product
is operating consistently to the stated
specifications'.
To achieve this objective, a number of
'qualifications' and 'specifications' are
defined. These refer to the performance
of tests and procedures to ensure that a
specific item or performance parameter
conforms to the agreed specification.
In summary, validation simply means
are indeed receiving consistently what
they think and expect they are receiving
in terms of water quality.
The various qualification protocols are
the agreed procedures to test, maintain,
service and calibrate the equipment, as
prescribed by the manufacturer, in order
to ensure that the product continues to
function to specification.
Validation Support Manual
Typically with each item of water purifi-
cation equipment, a Validation Support
Manual (Figure 1) should be supplied.
This should contain all of the relevant
information to enable the user to validate
the system. Typically the manual should
contain the following sections:
Qualification Plan(QP); Installation
Qualification (IQ); Operational
Qualification (OQ); Performance
Qualification (PQ); Service/Maintenance
Requirements; Standards and Certificates
Qualification Plan (QP)
The objective of the Qualification Plan is
to detail and explain the approach to the
validation of the specific product or sys-
tem. As well as explaining the various
“qualifications” and protocols, it should
also define the procedure for reporting
Figure 1. The Validation Support Manual
contains all the information needed for
validation
and dealing with any deviations identi-
fied during the validation.
Installation Qualification (IQ)
The Installation Qualification is designed
to check methodically the various instal-
lation requirements, particularly in
respect of feed-water and environmental
considerations.
Operational Qualification (OQ)
The Operational Qualification will pro-
vide documented evidence to demon-
strate that the equipment operates as
intended in all of its various functional
modes, including special procedures,
such as cleaning and sanitisation.
Performance Qualification (PQ)
This qualification will provide document-
ed evidence that the product water quality
continues to achieve the desired specifica-
tion. Tests are performed both initially
during commissioning and on an ongoing
basis, depending on user requirements.
 PharmaCeutiCal ResearCh Reprinted from LabPlus International - September 2002

Maintenance Contract Standards & Certificates

An integral requirement of all laboratory
water purification equipment is to
ensure that it continues to provide the
desired quality of water on an on-going
basis. In this respect a service schedule
must be developed and applied to enable
Figure 2. The PURELAB Ultra water sys-
tem was designed from the outset to sup-
port validation of the system
key operational parameters to be
checked and documented.
Typically these will include the routine
changing of consumable items, such as
filters, but also re-calibration of the var-
ious in-built water quality sensors.
These are calibrated using substitution
boxes containing standards, which are
directly traceable to national reference
standard.
An important section in the Validation
Support Manual is reserved for inclu-
sion of the various Certificates of
Conformity and Certificates of
Calibration generated during the manu-
facturing and quality control pro-
cedures. These signed certificates act as
documented evidence that the product
was manufactured to the specifications
and instructions laid out in the product
master file and that it has been demon-
strated to perform as originally intend-
ed.
Additionally, Certificates of Compliance
are included, which are formal docu-
mentation that the product has passed
the various testing required to achieve
the appropriate certification, for exam-
ple, electromagnetic compatibility, CE
certification and ETL certification (rele-
vant to North America).
As well as the Validation Support
Manual, the latest generation of water
purification units have a number of in-
built features to assist the user in the
product validation and to assist in com-
pliance with good laboratory practice
(GLP).
Practical Implementation
of Validation Systems
The PURELAB Ultra (Figure 2) was
designed and developed to incorporate
practical features that facilitate the vali-
dation processes described above. Such
Figure 3. PURELAB Ultra display showing
printer icon
features were incorporated following
wide-ranging discussions with users and
potential users from a variety of indus-
tries. The features built-in to the system
include: Validation Support Manual;
Data Tag on Consumable Purification
Media Pack; Automatic Calibration of
Electronics; Printed Records; Real Time
Clock; PIN Access Code.
Data Tag
Each purification pack contains a
uniquely encrypted data tag, which not
only prevents incorrect operation, but
also contains information on the pack
manufacturing, traceability of active
media and usage history. When inserted
into the product, the electronic circuitry
recognises the new component and issues
an error message if it is not of the correct
specification for the application, if it is

Figure 4 a and b. Multi-stage monitoring guarantees both high quality and consistent purity. Multi-stage monitoring of resistivity gives
the user greater economy, convenience and security. At the end of the life of the first purification cartridge pack it is replaced by the second
pack which in turn is replaced by a new pack. Therefore a pack nearing the end of its life is never the final purification stage. This allows
better use of the media, avoids impurity break-through and removes the need to replace a pack the moment it indicates exhaustion
 PharmaCeutiCal ResearCh
Figure 5. As it is used up, organics and silica are released from an ion-
exchange pack pack before the resistivity of the product water drops
significantly. Use of two purification packs avoids this problem as the
second pack is never used up.
incorrectly fitted, if it is out of date, or if
it has been used previously.
Additionally, data tags are fitted to 'by-
pass blocks' during sanitisation. The
system senses that these are in place
and instigates the various procedures
automatically.
Automatic Calibration of
Electronics
The microprocessor management sys-
tem scans the water quality monitoring
circuitry via a multiplexer and com-
pares it to 2 traceable resistor standards
at each end of the monitoring range
and indicates if the electronics are out
of calibration. Additional portable and
traceable external calibrated setting
boxes are available if required.
Printed Records
Printed records containing all relevant
system operating parameters, including
time and date, are available at any time if
the printer accessory is installed
(Figure 3). Space is allowed on the print-
ed docket for an operator signature.
Similar information can be obtained
and stored using a computer link.
Real Time Clock
The PURELAB Ultra has a real time
clock with battery back-up. The time
and date is printed out with other data
as part of the system validation proto-
col. Adjustment of the time and date
Reprinted from LabPlus International - September 2002
Figure 6. Product water quality is protected by the second pack
as the intermediate resistivity of the water from the first pack falls
and it is replaced.
can be accessed via the PIN code,
which, if activated, will prevent unau-
thorised adjustment.
PIN Access Code
The PURELAB Ultra has a selectable PIN
code, which, if selected, will allow only
authorised personnel to change alarm set
points, etc. All other functions for normal
operation of the system will be available
to all users. This helps ensure that the
unit is operated in accordance with the
'User Requirement Specification'.
Technologies Used in
Ultrapure Water Systems
To achieve the very high degrees of water
purity required in modern laboratories,
multi-technology approaches are
required. These enable specifications to
be achieved economically and consistent-
ly. At the same time, the system must be
able to cope with a wide range of feed-
water types and conditions.
Typical technologies used are:
Microfiltration; Ultrafiltration; Reverse
Osmosis; Ion Exchange; UV Irradiation;
Adsorption.
One of the most significant approaches
to achieve both high quality and con-
sitently high purity is that of multi-stage
monitoring (Figure 4 a,b). This process,
which is incorporated into the PURELAB
Ultra, includes an additional final polish-
ing stage, which eliminates any water
quality variations during the exhaustion
of ion exchange media. On systems only
fitted with product water monitoring,
impurities can be present in the product
water due to the hysteresis between the
absolute water quality and the alarm trig-
ger point. By adding a further purifica-
tion stage after this, even easily eluting
contaminants are removed (Figure 5).
Not only does this give confidence in the
final water quality (Figure 6), but it also
minimises operating costs and signifi-
cantly improves the convenience of oper-
ation since the exhausted primary
deionisation cartridge can be replaced
when convenient, rather than immedi-
ately, which could be disruptive to other
lab work.
The latest range of high purity water
purification units recently released by
ELGA LabWater, the PURELAB Ultra,
have been specifically designed not only
for ease of use and ultimate, consistent
high water quality, but also to assist the
user in achieving their validation
requirements.
The Author
Alan Mortimer, C. Chem, FRSC,
R&D Director - ELGA LabWater
Vivendi Water Systems, High Wycombe,
Bucks, HP14 3JH, UK.
Tel + 44 1494 887500,
Fax + 44 1494 887505
e-mail info@elgalabwater.com
www.elgalabwater.com
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