Indus Pharma (Pvt.) Ltd.

65/27, Korangi Industrial Area, Karachi – 74900

}}}

PROTOCOL FOR RE-QUALIFICATION OF WATER Page No. Page 1 of 9

DISTILLATION PLANT (WFI), STORAGE &
DISTRIBUTION SYSTEM Doc. No. EQP-UTI-001/V01

DEPARTMENT: VALIDATION
Issue Date 11-05-2018

Muhammad Waqas Signature

Prepared By
Validation Officer Date

Anam Khan Signature

Checked By
Assoc. Manager Validation & QO Date

Sohail Nisar Signature

Reviewed By
Manager Quality Control Date

Khurshid Ahmad Signature

Reviewed By
Sr. Manager Engineering Date

Waqas Bin Zakir Signature

Reviewed By
Head of Production Date

Muhammad Umair Signature

Approved By
Manger Quality Assurance Date
 Indus Pharma (Pvt.) Ltd.
65/27, Korangi Industrial Area, Karachi – 74900
}}}

PROTOCOL FOR RE-QUALIFICATION OF WATER Page No. Page 2 of 9

DISTILLATION PLANT (WFI), STORAGE &
DISTRIBUTION SYSTEM Doc. No. EQP-UTI-001/V01

DEPARTMENT: VALIDATION
Issue Date 11-05-2018

TABLE OF CONTENTS

S NO. CONTENTS
1. Purpose
2. Scope
3. Reference
4. Responsibilities
5. History of subject
6. Risk Assessment
7. Equipment Description
8. Pre-requisites
9. Performance Requalification
a. Description
b. Procedure
c. Testing Plan & Frequency
d. Acceptance Criteria
10. Deviation
11. Attachments
12. Final Report
 Indus Pharma (Pvt.) Ltd.
65/27, Korangi Industrial Area, Karachi – 74900
}}}

PROTOCOL FOR RE-QUALIFICATION OF WATER Page No. Page 3 of 9

DISTILLATION PLANT (WFI), STORAGE &
DISTRIBUTION SYSTEM Doc. No. EQP-UTI-001/V01

DEPARTMENT: VALIDATION
Issue Date 11-05-2018

1. PURPOSE:
The purpose of this protocol is to demonstrate the reliable performance of Water Distillation Plant
(WFI) along with storage and distribution system over an extended period and to evaluate the impact
of seasonal variation on system performance.

2. SCOPE:
This protocol is limited for the performance requalification of water for injection generation, storage
and distribution system.

3. REFERENCE:
WHO Technical Report Series, No. 970, Annex 2, 2012

4. RESPONSIBILITIES:
Department Responsibility
Engineering is responsible for:
Smooth operation of water system during qualification activity
Facilitate during water sampling
Engineering
Intimate validation if any major breakdown is observed during
qualification activity
Protocol and report review
QC is responsible for:
Sampling from different plant and user points as per sampling
plan
Quality Control
To perform water testing as per specification
To perform trend analysis during qualification study
Protocol and report review
Validation is responsible for:
To keep an effective follow-up with all concerns for
qualification activity
Protocol preparation and approval
Quality Assurance (Validation)
To ensure sampling and testing of water as per plan
Data collection and review
To prepare final report after completion of study
Report approval
 Indus Pharma (Pvt.) Ltd.
65/27, Korangi Industrial Area, Karachi – 74900
}}}

PROTOCOL FOR RE-QUALIFICATION OF WATER Page No. Page 4 of 9

DISTILLATION PLANT (WFI), STORAGE &
DISTRIBUTION SYSTEM Doc. No. EQP-UTI-001/V01

DEPARTMENT: VALIDATION
Issue Date 11-05-2018

5. HISTORY OF SUBJECT:

LAST VALIDATION
S.NO. DOC.NO. REASON
TYPE DATE

6. RISK ASSESSMENT:

S. No. RISK ACTION

1. Environmental Disturbance
2. Trainings
3. Safety & Precautions
Personnel Protective
4.
Equipment

7. EQUIPMENT DESCRIPTION:

Water Distillation Plant:

WFI generation plant produces pyrogen-free water and it engrosses with Liquid Vapor-Liquid phase
change to produce very high purity water. It removes the impurities at high temperature without using
any filtration medium. A four-effect distillation unit produces USP water for injection. The WFI
storage tank level transmitters control the operation of the still. Purified water flows into the WFI still
feed and produce WFI quality distillate. The multi-effect still is capable of producing clean steam for
periodic clean steam sterilization of the WFI storage and distribution systems. The distillation process
will provide a three-log reduction in endotoxin to meet the requirements of USP testing results.
Equipment Details
Date of Installation: August 2005
Model No. LD500/6G
Manufacturer Name: Watertown Pharmaceutical Equipment Co., Ltd.
Capacity: 500L/H
Location: Liquid Injectable Area (Compact Line I)
Equipment Identification Number:

WFI Storage System:

 Indus Pharma (Pvt.) Ltd.
65/27, Korangi Industrial Area, Karachi – 74900
}}}

PROTOCOL FOR RE-QUALIFICATION OF WATER Page No. Page 5 of 9

DISTILLATION PLANT (WFI), STORAGE &
DISTRIBUTION SYSTEM Doc. No. EQP-UTI-001/V01

DEPARTMENT: VALIDATION
Issue Date 11-05-2018

Water for injection is supplied to a storage vessel from the multi-effect still. WFI quality water is
maintained within the storage system by constant recirculation of the storage system contents at
greater than 80˚C. A plant steam jacket on the WFI storage vessel maintains the temperature of the
WFI within the storage system. The temperature of the vessel contents is maintained above 80˚C.

WFI Distribution Loop:

Distribution of WFI to all user points are provided in closed circulation loop. In distribution systems
where the water circulates at high temperature, dead legs and low flow should be avoided, and valve
tie-in points should have length-to-diameter ratios of six or less. Normal minimum velocity of WFI in
loop is 2.5m/s.

8. PRE-REQUISITE:
The following SOP’s should be approved and authorized prior to qualification study.

SOP Name SOP No. Approved & Approval

Authorized Date
SOP for the Operation of Multi Effect Water
Still or Water Distillation Plant
SOP for the Sanitization of Multi Column
Distillation Still & Water Supply Loops
SOP for Chemical Analysis of Water
SOP for Microbiological Analysis of Water
SOP for the Maintenance of Water Distillation
Plant

Following instruments shall be required for the performance qualification of WFI generation, storage
and distribution system.

Sr. Equipment Code / Calibration

Equipment Name Calibration Due On
No. Sr. No. Certificate No.
1. pH Meter
2. TDS / Conductivity
Meter
3. TOC Analyzer

be warranted.
9. PERFORMANCE RE-QUALIFICATION:
 Indus Pharma (Pvt.) Ltd.
65/27, Korangi Industrial Area, Karachi – 74900
}}}

PROTOCOL FOR RE-QUALIFICATION OF WATER Page No. Page 6 of 9

DISTILLATION PLANT (WFI), STORAGE &
DISTRIBUTION SYSTEM Doc. No. EQP-UTI-001/V01

DEPARTMENT: VALIDATION
Issue Date 11-05-2018

a) Description:

For the performance requalification of water distillation plant, Phase III study will be conducted in
which weekly sampling and testing will be carried out from sampling points of plant and user points
for a period of 1 year. The objective of Phase III is to demonstrate that the system is capable of
producing desired quality of water, on a consistent basis, when operated in accordance with the
established SOP’s over a long period of time and does not have any seasonal variations. Any
variations in the quality of the feed water that could affect the operation, and ultimately the water
quality, will be noticed during this phase of the validation. The sampling shall be done as per the
routine sampling procedures. Samples shall be collected from all sampling points of plant once a week
and shall cover all user points in a week. After the completion of phase III data of chemical and
microbial testing will be collected and report will be compiled.

b) Procedure:
The following procedure shall be used for performance requalification of water for injection
generation, storage and distribution system:
1. Sanitization of water generation system shall be performed as per respective SOP prior to
requalification.
2. QC microbiology section representative is responsible to perform sampling from all the sampling
points of plant and user point once a week as per SOP # QC-MIC-04 & QC-MIC-08
3. All the chemical and microbial results of water testing will be recorded on Annexure I
4. After completion of study graphical trending of the data for all the parameters will be done
individually and will be attached with the report.

5. Any deviation observed during performance requalification will be recorded as observed deviation
with justification and corrective action taken.

Identification of User Points:

S No. Sampling/User Points Point Code Location
 Indus Pharma (Pvt.) Ltd.
65/27, Korangi Industrial Area, Karachi – 74900
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PROTOCOL FOR RE-QUALIFICATION OF WATER Page No. Page 7 of 9

DISTILLATION PLANT (WFI), STORAGE &
DISTRIBUTION SYSTEM Doc. No. EQP-UTI-001/V01

DEPARTMENT: VALIDATION
Issue Date 11-05-2018

Feed Water for WFI

1 DI plant after storage C2 DI Plant Room
Sampling Points from WFI plant
2 Plant WI
Injectable Area
3 Storage tank MST
(Compact Line I)
4 Return loop WI6
WFI User Points
Solution preparation room
5 WI1
line I Injectable Area
Ampoule washing area (Compact Line I)
6 WI4
line I
Solution preparation room
7 WI2
line II Injectable Area
Ampoule washing area (Compact Line II)
8 WI3
line II
9 Eye drop section WI5 Eye Drop Section

c) Testing plan and frequency

S Sampling & Testing
Name of Sampling Point Applicable Test
No. Frequency (Phase 3)
Appearance, pH,
Feed Water for WFI (DI plant after Conductivity, TOC,
1 Weekly
storage) Nitrates, TAMC,
Heavy metals
2 Distillation Plant Weekly
3 Storage tank Weekly
4 Return loop Weekly
Appearance, pH,
5 Solution preparation room line I Weekly
Conductivity, TOC,
6 Ampoule washing area line I Weekly
Nitrates, TAMC, BET
7 Solution preparation room line II Weekly
8 Ampoule washing area line II Weekly
9 Eye drop section Weekly

d) Acceptance Criteria
 Feed water for WFI (Purified Water):

Tests Limits
Appearance Clear, odorless and tasteless liquid.
pH 5.0 – 7.0
 Indus Pharma (Pvt.) Ltd.
65/27, Korangi Industrial Area, Karachi – 74900
}}}

PROTOCOL FOR RE-QUALIFICATION OF WATER Page No. Page 8 of 9

DISTILLATION PLANT (WFI), STORAGE &
DISTRIBUTION SYSTEM Doc. No. EQP-UTI-001/V01

DEPARTMENT: VALIDATION
Issue Date 11-05-2018

Alert 4.0 µs.cm-1 (at 25°C ± 0.1°C)

Conductivity
Action 5.1 µs.cm-1 at 25°C ± 0.1°C
Oxidizable substance The solution remains faintly pink
Nitrates NMT 0.2ppm
Heavy Metals NMT 0.1ppm
Alert 50 cfu/ml
TAMC
Action 100 cfu/ml

 Water for Injection:

Tests Limits
Appearance Clear, odorless and tasteless liquid.
pH 5.0 – 7.0
Alert 1.1 µs.cm-1 (at 25°C ± 0.1°C)
Conductivity
Action 1.3 µs.cm-1 at 25°C ± 0.1°C
TOC Alert 0.4 ppm
Action 0.5 ppm
*Oxidizable
The solution remains faintly pink
substance
Nitrates NMT 0.2ppm
Alert 03 cfu/ml
TAMC
Action 10 cfu/ml
BET NMT 0.25EU/ml
*In case of any breakdown in TOC analyzer, the test of TOC will be substituted from Oxidizable substances.

10. DEVIATIONS:
Any discrepancy or variation observed during qualification of water distillation plant will be reported
along with the action taken.

11. ATTACHMENTS:
Format for Purified water testing (Annexure I)
Format for WFI testing (Annexure I)

12. FINAL REPORT:

Report will be drawn as per protocol including;
 Discussion
 Conclusion
 Indus Pharma (Pvt.) Ltd.
65/27, Korangi Industrial Area, Karachi – 74900
}}}

PROTOCOL FOR RE-QUALIFICATION OF WATER Page No. Page 9 of 9

DISTILLATION PLANT (WFI), STORAGE &
DISTRIBUTION SYSTEM Doc. No. EQP-UTI-001/V01

DEPARTMENT: VALIDATION
Issue Date 11-05-2018

 Recommendations (if any)