VALIDATION PROTOCOL FOR PURIFIED WATER SYSTEM

Document No. /DM/01 Date of Issue Page No. 1 of 14

CONCURRENT VALIDATION
PROTOCOL
FOR
PURIFIED WATER SYSTEM
(Identification No. /DM/01)

AT
 VALIDATION PROTOCOL FOR PURIFIED WATER SYSTEM
Document No. /DM/01 Date of Issue Page No. 2 of 14

TITLE OF CONTENTS

S.NO TITLE PAGE No.

1.0 Objective
2.0 Scope

3.0 Responsibility

4.0 Back ground

Introduction
5.0
5.1 Locations

5.2 Frequency

5.3 Acceptance criteria

Procedure
6.0
6.1 General aspects of validation program
6.2 Brief description of the Major components of the water
system
6.3 Schematic representation of Water system
Annexure - I
6.4 Schematic representation of Water system Indicating
Sampling points Annexure - II
6.5 Sampling locations, Test plan and frequency

6.6 Test plan and Acceptance criteria

6.7 Presentation of validation results

6.8 Evaluation of data and preparation of summary report

6.9 Conclusions and Recommendations

6.10 Change control

1.0 OBJECTIVE:
 VALIDATION PROTOCOL FOR PURIFIED WATER SYSTEM
Document No. /DM/01 Date of Issue Page No. 3 of 14

1.1 This protocol describes the procedure for validating the entire water system to
ensure
the performance of the different sub-systems involved in the water treatment and
to assure the Quality of water.

2.0 SCOPE:
2.1 The Scope of this Protocol is applicable to the Water System of the Manufacturing
Facility of Pegasus Farmaco India Pvt.Ltd., 29, IDA, Bhongir, Nalgonda Dist.
3.0 RESPONSIBILITY
3.1 It is a joint responsibility of Engineering Department, Production Department,
Quality control and Quality Assurance Department. The detailed Responsibility
matrix is described in next page.
RESPONSIBILITY MATRIX

1 PROTOCOL PREPARATION CHEMIST-QC

2 PROTOCOL REVIEW
MANAGER -QC

INCHARGE - PLANT &

3 PROTOCOL EXECUTION
MANAGER PRODUCTION

SAMPLING & TESTING AS PER EXECUTIVE-QC

4
PROTOCOL MICRO-BIOLOGIST-QC

DATA COMPILATION AND

5 MANAGER -QC
REPORT PREPARATION

PROTOCOL APPROVAL
6
SUMMARY REPORT APPROVAL MANAGER-QA

4.0 BACK GROUND

 VALIDATION PROTOCOL FOR PURIFIED WATER SYSTEM
Document No. /DM/01 Date of Issue Page No. 4 of 14

4.1 Water is most commonly used in pharmaceutical manufacturing. It is used in the

manufacturing of dosage forms, cleaning of manufacturing equipment etc.
4.2 The quality attributes of water can vary seasonally without warning. Water
treatment systems are highly dynamic and unreliable to some degree. Hence
they must be validated and closely monitored and controlled.

5.0 INTRODUCTION
5.1 LOCATIONS
Sampling points are selected at predefined locations so as to monitor and assess
the effectiveness of each major system component. Chemical and
microbiological quality is tested as applicable and assessed. The detailed
locations of sampling points are schematically represented and specified in this
protocol.
5.2 FREQUENCY
The entire validation programme is sub-divided in to three phases.
5.2.1 Phase-I testing
5.2.1.1 A test period of 2 - 4 weeks is planned for monitoring the system
intensively. During this period the system should operate
continuously without failure or performance deviation. The test
plan details are provided at step 6.5.
5.2.2 Phase-II testing
5.2.2.1 A test period of 2 weeks is used for carrying out further
intensive monitoring after the satisfactory completion of phase 1.
Water can be used for manufacturing purposes during this
phase. The approach should demonstrate consistent operation
within established ranges.

5.2.3 Phase III

 VALIDATION PROTOCOL FOR PURIFIED WATER SYSTEM
Document No. /DM/01 Date of Issue Page No. 5 of 14

5.2.3.1 Phase 3 runs for 1 year after the satisfactory completion of phase
2.The main objective of the study is to demonstrate
extended reliable performance. And ensure that seasonal
variations are evaluated. The sample locations, sampling
frequencies and tests are reduced to the normal routine pattern.
5.3 ACCEPTANCE CRITERIA
5.3.1 While framing acceptance criteria the design parameters of the major
components of the water systems is kept in mind. .. Acceptance criteria
for the Purified water has been established taking into consideration the
pharmacopeial limits for Purified water

6.0 PROCEDURE
The Validation Approach, Different Sampling and Testing Plan, Acceptance Criteria and
Validation Assessment are detailed under the following sub sections of this protocol
6.1 General aspects of validation program
6.2 Brief description of the major components of the water system
6.3 Schematic representation of DM unit indicating sampling points
6.4 Schematic representation of Recirculation loop system indicating sampling points
6.5 Sampling locations ,test plan and frequency
6.6 Test plan and acceptance criteria
6.7 Presentation of validation results
6.8 Evaluation of data and preparation of summary report
6.9 Conclusions and recommendations
6.10 Change control

6.1 General Aspects of Validation Program

 VALIDATION PROTOCOL FOR PURIFIED WATER SYSTEM
Document No. /DM/01 Date of Issue Page No. 6 of 14

6.1.1 The basic validation strategy is to maintain the system under normal
operating conditions during which frequent and extensive sampling and
testing is taken up in-order to assess the water system
6.1.2 Installation Qualification (IQ) protocol ensures all the requirements to
verify the installation of the components of the water system as per the
requirement. Operational qualification (OQ) protocol specifies and
ensures the functioning of different components as per the manufacturer
manual. During the validation consistency of the performance of the
system over several months of time is assessed.
6.1.3 Operating procedure and key control parameters
6.1.3.1 Validation programme includes the verification of the procedures
used to operate the system and to keep it in a state of control.
Examples of these procedures include start-up and flushing prior
to daily use, daily monitoring of key control parameters,
cleaning, s and sanitization of pipe lines and storage tanks etc.
These procedures shall be consistently followed during the
validation study so that adequate experimental data are
obtained to support their effectiveness. Personnel operating the
system shall be trained in these procedures. Other key
parameters and their operating ranges shall be finalized after the
validation programme.
6.1.4 Maintenance procedure
6.1.4.1 Maintenance procedures shall ensure consistent delivery of the
desired quantity and quality of water. These procedures may
include sanitization, filter sanitization and change, UV light
monitoring and replacement etc. All the preventive maintenance
procedures must be consistently followed.
6.1.5 During the Phase-I studies sampling programme include sampling of the
water for chemical and microbial testing at various points on DM water
 VALIDATION PROTOCOL FOR PURIFIED WATER SYSTEM
Document No. /DM/01 Date of Issue Page No. 7 of 14

system and recirculation system covering various user points. The

effectiveness of the system is evaluated.
6.1.6 During the Phase II testing ,the frequency of sampling , number of
samples taken and number of sampling locations are reduced from
Phase-I
6.2 Brief Description of The Major Components Of The Water System
The unit consists of DM unit. The output of DM unit is passed through micron
filters and UV lamp unit . This arrangement helps in controlling the
microbiological quality of the water.
6.2.1 Source Water : Bore Water
6.2.2 Storage Tank for feed water
Storage tanks are sized properly depending on the projected peak
demand on the operating systems. The storage tank for source raw water
is of 10 KL capacity.
6.2.3 Sand Bed
6.2.4 Carbon Bed
6.2.5 R O Water
Reverse Osmosis is a technology that is used to remove a large majority
of contaminants from water by pushing the water under pressure through a
semi-permeable membrane.

6.2.6 Cation Bed

Here negatively charged ions are exchanged. Cationic resins are
regenerated with hydrochloric acid.
6.2. 7 Anion Bed
Here positively charged ions are exchanged. Anionic resins are
regenerated with sodium hydroxide, which replace captured negative ions
with hydroxide ions.
 VALIDATION PROTOCOL FOR PURIFIED WATER SYSTEM
Document No. /DM/01 Date of Issue Page No. 8 of 14

6.2.8 Mixed Bed

Mixed bed de-ionizes are used to give the final ion exchange purpose.
This bed is used for improving the chemical quality of water by removing
cations and anions.

6.2.9 Storage tank for purified water

The storage tank of purified water is made of SS 316 and is having a
bacterial air vent filter. The tank has a capacity of 2000 lts.
6.2.10 UV Light
UV light is used as a surface disinfectant. UV light is provided in the
recirculation loop system. This is useful in killing the Bacteria and to
reduce the bacterial proliferation.
6.2.11 Recirculation System
All the user points are maintained in continuous circulation to avoid any to
minimize the bio-burden development.
6.3 Schematic Representation Of Water System
Schematic representation of water system is given in Annexure-I
6.4 Sampling Locations, Test Plan and frequency
SAMPLING METHOD:
250ml of sample is drawn for microbial and 500 ml of water for chemical testing
should be drawn from the taps, after spraying the sampling points with 70% IPA
and then flushing out water for a few seconds. The sampling should be done in
an aseptic manner. Samples for microbial testing are collected in sterile bottles.
 VALIDATION PROTOCOL FOR PURIFIED WATER SYSTEM
Document No. /DM/01 Date of Issue Page No. 9 of 14

6.5 Sampling Locations:

Test frequency Test frequency for
Sampling
Sampling Location Test plan for 30 days next 15 days
Point No
( Phase I) (Phase II)
Chemical Analysis and As and when As and when
BW/ 01 Feed water
Microbial Analysis required required
Daily
RW /01 After Sand Bed Microbial testing Daily

Daily
RW/ 02 After Carbon Bed Microbial testing Daily

Chemical ( pH & Daily

ROW/ 01 R O Water conductivity) Microbial Daily
analysis
Daily
ROW /02 After Cation Bed Microbial analysis Daily

Daily
ROW /03 After Anion Bed Microbial analysis Daily

Daily
PW /01 After Mixed Bed Microbial analysis Daily

Purified water storage Chemical Testing Daily

PW /02 Daily
tank Microbial analysis

PW/ 03 After UV with 0.2 filter Microbial analysis Daily Daily

 VALIDATION PROTOCOL FOR PURIFIED WATER SYSTEM
Document No. /DM/01 Date of Issue Page No. 10 of 14

Sampling Point Sampling Test

for frequency
30 days Test frequency
15 daysfor next
Test plan
No Location ( Phase I) (Phase II)

Chemical testing
PW 04 to
USER POINTS on pooled sample Daily Daily
PW 07
from user points

Manufacturing Chemical testing,

PW/ 04 Daily Daily
Vessel after UV Microbial analysis

Daily
Chemical testing,
PW /05 Wash Room Daily
Microbial analysis

Daily
Chemical testing,
PW 06 Quality Control Daily
Microbial analysis

Daily
Chemical testing,
PW /07 Microbiology Daily
Microbial analysis

6.6 Acceptance Criteria

 VALIDATION PROTOCOL FOR PURIFIED WATER SYSTEM
Document No. /DM/01 Date of Issue Page No. 11 of 14

S.No Type of water Test Acceptance criteria

1 Feed water pH, Hardness, Microbial count Record
2 After Sand Bed pH, Hardness, Microbial count Record
3 After Carbon Bed pH, Hardness, Microbial count Record
4 R O Water pH 5.0-7.0
Conductivity NMT 4 s
Microbial count Not more than 500 cfu/ml
Pathogens Absent
3. After cation bed Microbial count Not more than 500 cfu/ml
Pathogens Absent
4. After anion bed Microbial count Not more than 500 cfu/ml
Pathogens Absent
5. After mixed bed pH 5.0-7.0
Conductivity Not more than 1 s
Microbial count NMT 500cfu/ml
pathogens Absent

6. Purified water storage tank Chemical tests as per purified As per IP

water specs pH : 5.0 - 7.0
IP &IH specs conductivity : NMT 1 s
Microbial count Not more than 100 cfu/ml
Pathogens Absent
7. After UV /0.2 filter Microbial count NMT 100cfu/ml
Pathogens Absent
8 User points Microbial count individually NMT 100 cfu/ml
Pathogens Absent
Chemical testing on pooled As per Purified water specs I.P
sample pH : 5.0-7.0
Conductivity : NMT 1 s

*Pathogens : E.coli, Salmonella, S.aureus, P.aeruginosa

 VALIDATION PROTOCOL FOR PURIFIED WATER SYSTEM
Document No. /DM/01 Date of Issue Page No. 12 of 14

6.7 Presentation of validation results

Validation test results are graphically presented along with their respective limits
The following control chart shall be included in the report
Source Raw Water:
Control chart for Total Hardness values of raw water
Control chart for Total Solids values of raw water
Control chart for Total Microbial count of raw water
Purified water:
Control chart for Total Microbial count after mixed bed
Control chart for Total Microbial count after UV Lamp
Control chart for Total Microbial count after storage tank
User Points:
Control chart for Total Microbial count

6.8 Evaluation of data and preparation of Summary Report

The validation results of phase I and phase II studies are evaluated. After the
evaluation of the test results, a summary report is made on the validation
findings. Protocol deviations, if any, are identified along with the reason for the
deviation and its impact on the outcome of the validation. It also includes a
discussion in which all findings, conclusions and recommendations are noted.
Protocol deviation should be justified and authorized by Quality Assurance
In summary report, all the Quality parameters at different locations are compared
with specified control Limits.
Summary report is prepared by Quality control department and approved by
Quality assurance department.

6.9 Conclusions and Recommendations

 VALIDATION PROTOCOL FOR PURIFIED WATER SYSTEM
Document No. /DM/01 Date of Issue Page No. 13 of 14

After the completion of monitoring the results covering all the three seasons, an
Annual Summary is made. Here the average value of each Quality parameter at
all sampling locations for each season is compared with respective limits.
Annual summary report is also correlated with the major break down (if any) and
normal preventive maintenance program of the Water System. Finally a
statement regarding the out come of the validation of the Water Treatment
System is made.
6.10 Change Control
In case of any subsequent changes to validated water treatment system like
change of a particular component etc can be made only through a proper change
control procedure. The procedure specifies a method for documenting proposed
changes and assigns responsibility to specific individuals for assessing the
impact of change on validated system.
An appropriate revalidation plan and a revalidation protocol will be required in
such case.
All change control, revalidations plan shall be reviewed and approved by Quality
Assurance

DEPARTMENT NAME SIGNATURE DATE

Engineering

Production

Quality control

Quality Assurance
 VALIDATION PROTOCOL FOR PURIFIED WATER SYSTEM
Document No. /DM/01 Date of Issue Page No. 14 of 14