Medevo Pharmaceuticals, Pvt. Ltd Lahore.

Title: Users Required Specifications for Document # Revisions: 00

WFI production plant QA/URS/ C&O/004 Date: 20-Apr-20

1 INTRODUCTION

Document Description: This document constitutes the User Requirement Document under
GAMP for a WFI-PS water system, distribution loop, and pure steam system. This document
starts with the manufacture of distilled water and pure steam. A separate document describes the
manufacture of purified feed water using Reverse Osmosis and Deionization methods.

2 OVERVIEW
The output water, (will be called “WFI” here) is primarily intended for use in the preparation of
medicated solution and semi-solid bulk to fill in eye drops and non collapsible tubes respectively,
that makes it a critical utility. Expected components of the system are as given below:
1. WFI-PS Generator
2. WFI Condenser
3. WFI Storage Tank
4. WFI Tank Vent Filter
5. WFI Circulation Pump
6. POU Heat Exchanger
7. POU Heat Exchanger
The storage tank and the hot circulation loop are self-sanitizing at 80 oC. Operator intervention is
not desired for periodic passivation and removal of accumulated rouge.

3 OPERATIONAL REQUIREMENTS
3.1 Functions
3.1.1 Operation
The WFI-PS generator of capacity commensurate with the production of WFI @ 75 L/Hour
produces steam is required to energize feed water (double R/O-EDI).
The WFI system will store and circulate water at 80C from a 100 litre SS316L storage tank and
through SS316L piping to two distribution points.
 Distribution Site 1: Solution preparation room for ophthalmic drops.
 Distribution Site 2: Bulk ointment preparation room for eye ointments.

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Medevo Pharmaceuticals, Pvt. Ltd Lahore.
Title: Users Required Specifications for Document # Revisions: 00
WFI production plant QA/URS/ C&O/004 Date: 20-Apr-20

The storage tank will be equipped with the PLC controlled WFI dispensing system to deliver WFI
in the SP tank.
The PS system will distribute pure steam through SS316L piping to two distribution points.
 Distribution Site 1: Solution preparation tank (For SIP)
 Distribution Site 2: Bulk ointment preparation tank (For SIP)
The system shall operate automatically. Automatic operation shall be initiated locally through
operator input. The system shall have fault/alarm indicator automatic shutdown based on operator
programming for the severity and type of fault.
3.1.2 I/O Streams
Input Streams:
 Cold RODI water to the WFI-PS Generation Equipment
 Hot WFI makeup from the WFI-PS Generation Equipment.
 Plant steam for WFI-PS generation, heating stored or circulating WFI, and for
maintaining the vent filters in a non-condensing condition.
 Chilled water for cooling (cold WFI drops and WFI generation).
Output Streams:
 Hot WFI (from hot WFI drops and WFI generation)
 Cold WFI (from cold WFI drops)
 PS
 Vents – tank and condensers are equipped with absolute rated 0.2 µm hydrophobic
vent filters to maintain vessel pressure at or near atmospheric. Gas & vapor flow
is in both directions, as required.
 Steam Condensate – discharged through steam traps to the process drain.
 Warm chilled water – returned from cold WFI drops and WFI generation.
 Pure steam condensate / excess steam – to drain.
3.1.3 Process Description:
The elements of the WFI-PS Generation and Storage and Distribution Systems work
together to maintain the quality of the WFI and PS from production through to delivery to
end users at various locations in the facility. The key concept is the continuous circulation

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Medevo Pharmaceuticals, Pvt. Ltd Lahore.
Title: Users Required Specifications for Document # Revisions: 00
WFI production plant QA/URS/ C&O/004 Date: 20-Apr-20

of hot WFI to maintain contacted surfaces in a sanitary and clean condition. The
following process flow description follows the flow of WFI and PS from the WFI-PS
Generator through the WFI Storage and Distribution Systems.
WFI-PS Generator
RODI water is fed to the Generator on a demand based on operating state of the
equipment.
The generator converts the RODI water through distillation into Pure Steam for
distribution to the users.
The Pure Steam is condensed into WFI at 80 ± 2ºC based on tank level. WFI is diverted
to drain until the proper temperature and conductivity levels are achieved.
WFI Storage Tank
WFI from the WFI-PS generation equipment is fed to the Storage Tank on a demand
based on level.
Storage Tank is maintained at 80 ± 2ºC by plant steam through a tank heating jacket. The
tank temperature is used to adjust the set point of the temperature controller.
WFI returning from the Hot WFI Circulation Loop is sprayed into Storage Tank through a
Spray Ball to ensure that the tank’s internal surfaces are completely and continuously
wetted by hot WFI and are thus maintained in a sanitary and clean condition.
The tank is maintained at atmospheric pressure by a steam-traced hydrophobic vent filter.
Hot WFI Circulation Loop
WFI is continuously circulated through a single 1.5” OD tubing supply header running
through the building.
The header is designed to maintain WFI velocity between 10 feet per second (fps) with no
user loads and 3 fps during periods of high demand. This ensures that flow is kept fully
turbulent in the header. This velocity range is maintained based on the hydraulic design
of the system; Pump is not speed-controlled.
WFI returning to Storage Tank is throttled to maintain a minimum backpressure of 20 psig
on the header. This maintains sufficient pressure at the user drops to ensure adequate WFI
flow and to maintain positive pressure at all points in the loop. Short periods of low end-

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Medevo Pharmaceuticals, Pvt. Ltd Lahore.
Title: Users Required Specifications for Document # Revisions: 00
WFI production plant QA/URS/ C&O/004 Date: 20-Apr-20

of-header flow due to high WFI demand do not adversely affect the ability of the system
to maintain a sanitary condition.
Header temperature is controlled by the heating jacket, with the controller set-point
adjusted based on the temperature in Storage Tank (cascade control).
End-of-header water conductivity is monitored on-line.
Pure Steam Distribution
PS is continuously distributed through a single 1.5” OD tubing supply header running
through the building.
The header is designed to supply PS at 45 psi with a pressure drop less than 10% of the
supply value.
The header is designed with sanitary steam traps to remove condensate on a continuous
basis.
3.1.4 Cleaning and Sanitization
 The WFI Storage and Distribution Systems are effectively self sanitizing and self
cleaning.
 On start-up, water from the WFI-PS Generator is directed to waste until it meets
specification. This feature is self contained on the condensing unit.
 The WFI Storage and Distribution Systems are periodically passivated to reduce
corrosion.
 The WFI Storage and Distribution Systems are periodically de-rouged to maintain
smooth, clean surfaces and reduce the potential for biological contamination.
3.1.5 Configuration (Arrangement & Materials of Construction)
WFI -PS Generator
The WFI-PS Generator is designed to produce Water-for-Injection (WFI) quality,
pyrogen-free steam. The pyrogen-free steam produced, when condensed, meets all criteria
for Water-for-Injection, as directed by the latest edition of the U.S. Pharmacopoeia. The
WFI-PS System is designed to produce sterile, pyrogen-free Water-for-Injection (WFI), as
well. The distillate produced meets all criteria directed by the latest edition of the U.S.

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Medevo Pharmaceuticals, Pvt. Ltd Lahore.
Title: Users Required Specifications for Document # Revisions: 00
WFI production plant QA/URS/ C&O/004 Date: 20-Apr-20

Pharmacopoeia. The WFI-PS System is configured to produce both pure steam and
distillate concurrently.
The WFI-PS Generator is designed and constructed to meet all requirements of current
Good Manufacturing Practices (cGMPs), as enforced by the U.S. Food and Drug
Administration.
The separation of entrained impurities and pyrogenic material is accomplished using
gravity and centrifugal force.
Impurities collected in the separation process are continuously removed through the waste
outlet.
All surfaces in contact with feed water and pure steam are constructed of type 316L
stainless steel for protection against carbide precipitation during the welding process.
Evaporator & Separator
The evaporator is a double-tubesheet, straight-tube, shell-and-tube heat exchanger,
welded and constructed per ASME, Section VIII, Division 1, for Unfired Pressure
Vessels.
All connections are sanitary-clamp type fittings.
Condenser
The condenser is a "U-tube" shell-and-tube heat exchanger of double-tubesheet
design, to ensure that coolant will not leak into the pure vapor and distillate.
The tube side of the condenser is ASME Code stamped per Section VIII, Division
1, for Unfired Pressure Vessels.
The condenser shell is mounted horizontally and pitched toward its round end,
with the distillate outlet at the lowest point to ensure full drainage.
The condenser is vented to atmosphere in order to remove non-condensable gases
and to equalize pressure during cooling. The vent is protected by a hydrophobic,
pharmaceutical-grade 0.2 µm filter preventing the passage of unfiltered air into the
condenser and protecting the condenser from microbial contamination. Filter shall
be heat traced with isolation valves for maintenance purposes.

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Medevo Pharmaceuticals, Pvt. Ltd Lahore.
Title: Users Required Specifications for Document # Revisions: 00
WFI production plant QA/URS/ C&O/004 Date: 20-Apr-20

The condenser is constructed of type 316L stainless steel. The connections for feed
water, pure steam, and distillate are sanitary-clamp type connections. Coolant
connections are NPT fittings.
Feed water Pump
The Feed water Pump is contained entirely on the WFI-PS Generator skid and
includes all piping and wiring for automatic operation, contactor and overload, and
alarm functions.
All connections are sanitary-clamp type fittings.
Minimum feed water pressure to the pump is 2 psig.
The pump is a sanitary, centrifugal-type, 316L stainless.
WFI Storage Tank:
The storage tank is a vertical, cylindrical tank of sanitary design. All WFI contact
surfaces are 316L stainless steel with a 20 µ inch Ra or better surface finish. All internal
surfaces on the tanks are kept wetted by spray balls on the circulation loop returns. The
tanks are designed to be free draining. Nozzles are designed for <2:1 depth to diameter
ratio to ensure good spray penetration. The tanks are ASME pressure vessels, although
they are normally operated at atmospheric pressure, maintained through steam heated,
hydrophobic aseptic filters. The following table summarizes the key characteristics of the
storage tank.
Table: WFI Storage Tank & Associated Equipment
Design Attribute WFI Storage Tank WFI Storage Tank
Jacket

Manufacturer/SN
Capacity 100 L N.A.
(Working)
Heads ASME F&D N.A.
Pressure Rating 45 psig & Full 100 psig
Vacuum
Temperature 132 C 132 C
Rating

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Medevo Pharmaceuticals, Pvt. Ltd Lahore.
Title: Users Required Specifications for Document # Revisions: 00
WFI production plant QA/URS/ C&O/004 Date: 20-Apr-20

Material 316L 304 (non-contact)

WFI Contact 20 µ-inch Ra, N.A.
Surfaces passivated
Nozzles <2:1 aspect ratio, free N.A.
draining, sanitary
fittings
Overpressure Sanitary Rupture None Installed
Protection Disc
WFI Tank Vent Filter
The WFI tank vent filter is a sanitary design absolute rated 0.2µm filter. The following
table summarizes the key characteristics of the one filter.
Table: WFI Tank Vent Filter
Design WFI Tank Vent Filter WFI Vent Filter Housing
Attribute Cartrdige
Millipore/Sartorius/Pau
Manufacturer ____
l
Model ____ ____
Type Sanitary Sanitary
Utility Side
125 ºC Continuous 150 psig / -20 to 350 F
Ratings
Utility N/A Steam
WFI Contact
PVDF 316L
MOC
Seals Viton Viton
WFI Side
Surface N/A <25 µ inch Ra
Finish
Filtration
____ ft2
Surface Area

WFI Circulation Pump:

The WFI pump is a sanitary design centrifugal pumps. The following table summarizes
the key characteristics of the one pump.
Table: WFI Circulation Pump

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Medevo Pharmaceuticals, Pvt. Ltd Lahore.
Title: Users Required Specifications for Document # Revisions: 00
WFI production plant QA/URS/ C&O/004 Date: 20-Apr-20

Design WFI Circulation Pump

Attribute
Inlet 2”
Outlet 1.5”
Impeller 115 mm
Rated Flow To suit the overall requirements
Rated TDH 85 feet
Material 316L
Internal 25 µ inch Ra
Surface Finish
Seal Type Double, SiC – SiC / C – Ceramic
w/ Silicone elastomers
Flush Yes
Speed 3500 rpm
HP 3 HP TEFC 3Φ/ 60 hz
230 / 460 V

POU Heat Exchangers

The heat exchangers are of similar design. All are 316L double tube sheet types to control
corrosion and eliminate possible WFI contamination due to steam or coolant leakage. The
following table summarizes the key characteristics of the two heat exchangers.
Table: Sanitary Heat Exchangers
Design WFI Cold WFI Cold
Attribute Drop Drop
Wash Sink Compounding
Manufacturer ____ ____
Model ____ ____
Year Mfg ____ ____
Type Sanitary Sanitary
WFI Side 150 psig / -20 150 psig / -20

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Medevo Pharmaceuticals, Pvt. Ltd Lahore.
Title: Users Required Specifications for Document # Revisions: 00
WFI production plant QA/URS/ C&O/004 Date: 20-Apr-20

Ratings to 350 F to 350 F

Utility Side 150 psig / -20 150 psig / -20
Ratings to 350 F to 350 F
Utility Chilled Water Chilled Water
WFI Contact
316L 316L
MOC
Seals Viton Viton
WFI Side
<25 µ inch <25 µ inch
Surface
Ra Ra
Finish
Ht-X Area ____ ft2 ____ ft2
Duty1 ____ BTU/hr ____ BTU/hr
2 gpm WFI 2 gpm WFI
WFI Side
176 – 104 ºF 176 – 73 ºF
____ water ____ water
Utility Side
42 - 52 ºF 42 - 52 ºF
Calculated
Uoa ____ ____
BTU/hr-ft2-F
WFI Piping:
WFI is distributed through 316L seamless tubing meeting the requirements of ASME
SA270 / BPE for sanitary tubing and fabrication. Tubing is specified with 20 µ inch Ra
internal and 30 µ inch Ra external surface finishes. All feasible WFI service welds are
made by automatic orbital welding equipment using qualified welding procedures and
operated by a certified operator. Manual WFI service welds are minimized. Where
necessary, they are made by a certified welder using qualified procedures in accordance
with ASME BPE (latest edition). All WFI service welds are 100% optically inspected and
permanent, retrievable records retained of the inspections. Welds not meeting the
acceptance criteria are replaced. All sanitary welds are individually marked to identify the
operator/welder.
WFI service welds are made in a controlled environment to maintain the tubing in a clean
condition. WFI service tubing is cleaned and passivated before entering service to reduce
corrosion in the heat affected zones. WFI piping is supported in accordance with good

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Medevo Pharmaceuticals, Pvt. Ltd Lahore.
Title: Users Required Specifications for Document # Revisions: 00
WFI production plant QA/URS/ C&O/004 Date: 20-Apr-20

engineering practices. WFI piping is designed to be free draining with a minimum slope
of 1/8” per foot of run. Valves and fittings in WFI service are of sanitary design and
utilize either butt weld (orbital) tube ends or sanitary clamp connections. Fittings comply
with the requirements of ASME BPE (latest edition).
Other Materials of Construction
Clean Steam piping matches WFI requirements for materials of construction and surface
finish. Non-sanitary vents and drains are copper. Plant steam piping is carbon steel, with
iron and bronze components, and is rated for 150 psig service. Coolant piping is brass,
with bronze or stainless steel components, and is rated for 125 psig service.
Insulation
As an additional barrier to prevent chloride contamination, the evaporator, separator, and
blow down cooler are painted with Thurmalox No. 70. These painted components are
insulated with 1-inch (3.8 cm) Parco Mineral Wool. The insulation is covered with
embossed aluminum as a vapor barrier. Type 304 stainless steel sheathing is available as
an option.
Distribution Piping will be insulated 1-inch (3.8 cm) Parco Mineral Wool with a PVC
cover.
Pure Steam Sampling
A Pure Steam Sampling to draw physical samples of condensed pure steam occasionally
is desired. Pure steam is bled off and condensed, and the condensed pure steam passes
into a sample well. The sample well is equipped with a sample valve through which a
sample may be drawn. When the sample valve is closed, the condensed pure steam is
routed to drain.
All components in contact with pure steam and condensed pure steam are constructed of
type 316L or type 316 stainless steel
.Components in contact with coolant are constructed of brass, bronze and type 316
stainless steel.
Includes a jacketed condenser, sample well, sample valve, and condensed pure steam
temperature control system.
Pure steam consumption is no more than 35 lbs/hr.

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Medevo Pharmaceuticals, Pvt. Ltd Lahore.
Title: Users Required Specifications for Document # Revisions: 00
WFI production plant QA/URS/ C&O/004 Date: 20-Apr-20

3.1.6 Operating Parameters and Quality Requirements

These tables summarize the key operating flow rates and conditions in the WFI Storage
and Distribution System.
Table: Approximate Operating Flow Rates and Conditions
Stream Flow Pressure Temperature
(l/pm) (psig) (ºC)
WFI Makeup from Still .100 Atmospheric 88 C
Hot Loop Circulation 30 gpm Pump Discharge – 35 80 ±2ºC
Rate @ 10 fps (3 m/s) psig
Tank Return – 20 psig
WFI Drops Various Minimum – 20 psig 80ºC (hot)
23ºC (cold)
Tank Conditions N.A. Atmospheric 80 ±2ºC

WFI drop demand varies with service. Cold drop flows may require control to achieve
specific temperatures exiting the heat exchangers.
Table: WFI Drop Flows
Drop Service Flow
(Lpm)
1 Solution Room 10
2 Ointment Preparation 10
WFI must meet USP requirements in the distribution system and at the various drops.
Requirements include meeting the following specifications:
 TOC Specification of < 500 ppb (Alert > 250 ppb, Action > 350 ppb).
 Conductivity (On-Line) to meet USP WFI requirements adjusted for temperature
(nominal conductivity <1.3 µS/cm at 25oC to pass Stage 1 requirements).
 Endotoxin levels ≤ 0.25 EU/mL (Alert ≥ 0.06 EU/mL, Action ≥ 0.12 EU/mL).
 Total Viable Organisms ≤ 10 CFU / 100 mL (Alert ≥ 5 CFU / 100 mL, Action ≥
10 CFU / 100 mL).
3.1.7 Utilities Required
 Chilled water supply/return.
 Power is required for the circulating pumps:

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Medevo Pharmaceuticals, Pvt. Ltd Lahore.
Title: Users Required Specifications for Document # Revisions: 00
WFI production plant QA/URS/ C&O/004 Date: 20-Apr-20

o 3 HP connected (11.2 KW) @ 460 V, 3-Φ

 Instrument air requirements are minor, for control valve actuation.
 Plant steam is required for process heaters:
o Jacket not rated for specific duty
o Minor consumption to maintain filters as non-condensing.
3.1.8 Control System
The WFI Storage and Distribution System is operated by the WFI-PS Generation
Equipment PLC and normally operates automatically.
Set up for periodic passivation and de-rouging requires operator intervention with the
equipment off-line. Local instrumentation is provided as documented on the P&IDs to aid
in system monitoring and troubleshooting.
A "ladder-logic" program, run through an Allen-Bradley SLC 500/03 programmable-logic
controller (PLC), controls the operation of the WFI-PS Generator.
An Allen-Bradley Panel View 550 operator-interface terminal (OIT) is provided for
complete system monitoring and configuration. Set points, delay times, and PID loop
parameters can be changed via the OIT (access to configuration screens is limited with
security measures).
Battery backup for both the SLC 500 and the Panel View 550 provides memory retention
for up to two (2) years without power. In addition, copies of the "ladder-logic" program
and the OIT configuration are stored in external "flash" memory devices, which should be
stored in a safe location. If the program in the SLC 500 or the Panel View should be lost
or become corrupted, the original program can be uploaded from the "flash" memory
device.

Two (2) data communication ports are provided. With the 500/03 CPU, communication
with the OIT is accomplished through the DH485 port, and the other communication port
(RS232/DF1 or DH485) is available for use.
A hard copy of the "ladder-logic" program, complete with I/O configuration, port settings,
and complete cross-reference is provided with the unit. A complete report of the Panel

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Medevo Pharmaceuticals, Pvt. Ltd Lahore.
Title: Users Required Specifications for Document # Revisions: 00
WFI production plant QA/URS/ C&O/004 Date: 20-Apr-20

View configuration, including screen images, alarm configuration, and terminal setup is
also provided with the unit.
The control enclosure is mounted on the WFI-PS Generator skid. The enclosure is NEMA
4 and consists of a carbon steel box with a smooth, ANSI-61, gray, polyurethane enamel
finish and a type 304 stainless steel door. The enclosure is ___ inches high, ___ inches
wide and ___ inches deep.
All devices and instruments located on the WFI-PS Generator skid (external of the control
enclosure) are connected to the control system via molded cord sets and mating
receptacles.
All cords are installed neatly in a plastic wireway mounted to the WFI-PS Generator skid.
Each cord set and receptacle is labeled for easy identification.
A separate enclosure contains the feed water pump and WFI distribution pump electronics
and houses the disconnect switches, motor starters and overloads, fuses, and control
transformers. The enclosure is NEMA 4 and consists of a carbon steel box with smooth,
ANSI-61, gray, polyurethane enamel finish and type 304 stainless steel door. The
enclosure is ___ inches high, ___ inches wide and ___ inches deep. Use of a separate
enclosure allows complete isolation of the high-voltage, 3-phase power required for the
pump.
The control system allows for the following operation modes:
 Pure Steam (Auto) - The pure steam production process starts and stops
automatically in response to an external signal.
 Pure Steam (Manual) - Once started manually, the pure steam production process
continues until it is shut off manually.
 Distillate (Auto) - The distillation process starts and stops automatically in
response to an external signal and/or a 7-day timer. (The pure steam production
process is in progress while the system is producing distillate.)
 Distillate (Manual) - Once started manually, the distillation process continues until
it is shut off manually. (The pure steam production process is in progress while the
system is producing distillate.)

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Medevo Pharmaceuticals, Pvt. Ltd Lahore.
Title: Users Required Specifications for Document # Revisions: 00
WFI production plant QA/URS/ C&O/004 Date: 20-Apr-20

The control system allows for the following control modes:

Local Only - Operation may be controlled from the OIT only.

Local/Remote - Operation may be controlled from the OIT or from the data
communication port.
The following control devices are located within the NEMA 4 control enclosure:
 SLC 500 PLC.
 Panel View 550 OIT.
 Operation hour meter.
 Distillate/Feed water conductivity analyzer.
 Loop Supply/Return water conductivity analyzer.
The following components are approved in the standard control system:
 Allen-Bradley SLC 500 PLC
 Yokogawa Conductivity Analyzer
Terminals are provided for connection of an "auto mode - remote start/stop input" signal
(e.g., WFI tank level signal) and for connection to a common alarm relay.
Each WFI-PS Generator requires only one electrical drop for power. A 24-volt DC power
supply is included to power the PLC inputs and outputs. A single 460 VAC, 3-phase drop
for the feed water pump is required. A single 460 VAC, 3-phase drop for the WFI
distribution pump is required. A step-down transformer (to 120 VAC) is included to
obtain the control voltage.
With the exception of the integral cables on RTDs and conductivity sensors, wiring is 18
AWG (minimum) and includes MTW/AWM insulation. Individual conductors are rated
for 600 volts, 105ºC operation. Non-shielded cables utilize PVC or PUR jackets and are
rated for 300 volts. Shielded cables, manufactured by Belden, utilize complete coverage
shields with PVC jackets and are rated for 300 volts.
3.1.9 Power Failure and Recovery
On power failure, the system shall fail into a “safe state.” On power restoration, the
system shall not restart without operator or communication-link input.

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Medevo Pharmaceuticals, Pvt. Ltd Lahore.
Title: Users Required Specifications for Document # Revisions: 00
WFI production plant QA/URS/ C&O/004 Date: 20-Apr-20

The Supplier shall design the system to include a “safe state” in which the likelihood of
injury to personnel and damage to the WFI-PS Generator is minimized.
All equipment must be designed to retain the PLC program in case of power loss, and be
able to recover with minimal operator actions.
3.1.10 “Emergency Stop” Switch
An emergency-stop switch shall be supplied, which, when activated, shall shut the system
down immediately in accordance with the following requirements:
3.1.11 Alarms and Warnings
The control system includes extensive alarm handling capabilities. Alarms provide
notification of problems and shut down the WFI-PS Generator. Each alarm is
accompanied by a specific message on the OIT display, a common alarm light, and an
audible horn. A common alarm relay is provided for remote indication. The last fifty (50)
alarms are stored in an alarm history file (accessible through the OIT).
The WFI-PS Generator shall be equipped with the following critical alarms and non-
critical warnings:
Alarm or Warning Critical* Non-
Critical**
Emergency Stop X
PLCOIT Communication X
(“Programmable Logic ControllerOperator-Interface
Terminal”)
Coolant Low-Pressure X
Instrument Air Low-Pressure X
Distillate Low-Temperature X
Distillate High-Temperature X
Distillate Temperature Input Error X
1st-Effect Low-Temperature X
1st-Effect High-Temperature X
1st-Effect Temperature Input Error X
1st-Effect Low-Level X

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Medevo Pharmaceuticals, Pvt. Ltd Lahore.
Title: Users Required Specifications for Document # Revisions: 00
WFI production plant QA/URS/ C&O/004 Date: 20-Apr-20

Alarm or Warning Critical* Non-

Critical**
1st-Effect High-Level X
Distillate Low-Resistivity/High-Conductivity X
Feed water Low-Resistivity/High-Conductivity X
Distillate/Feed water Analyzer Fault X
Distillate-to-Tank Valve Fail-to-Close X
Distillate-to-Tank Valve Fail-to-Open X
Distillate-to-Drain Valve Fail-to-Open X
Distillate-to-Drain Valve Fail-to-Close X
Loop Supply Low-Resistivity/High-Conductivity X
Loop Return Low-Resistivity/High-Conductivity X
Loop Supply/Return water Analyzer Fault X
Tank Low-Temperature X
Tank High-Temperature X
Tank Temperature Input Error X
Loop Supply Low-Temperature X
Loop Supply High-Temperature X
Loop Supply Temperature Input Error X
Loop Return Low-Temperature X
Loop Return High-Temperature X
Loop Return Temperature Input Error X

* “Critical alarms” shall take action automatically to shut the WFI-PS Generator down
and notify the operator. The operator shall be required to acknowledge the alarm before
the alarm can be reset and the system restarted. Once the alarm is reset, the system may
be restarted by the operator pressing the “start” button or by an input through the data-
communication link. No other action shall be required to restart the system.

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Medevo Pharmaceuticals, Pvt. Ltd Lahore.
Title: Users Required Specifications for Document # Revisions: 00
WFI production plant QA/URS/ C&O/004 Date: 20-Apr-20

** “Non-critical warnings” shall notify the operator but shall not shut the system down.
Non-critical warnings shall sound the alarm horn, illuminate the alarm indicator but allow
the system to continue to operate. The operator shall be required to acknowledge the
warning in order to silence the alarm horn, and the alarm indicator shall be extinguished
when the warning condition disappears.

3.2 Data & Security

3.2.1 Interfaces
The Programmable Logic Controller / Operator-Interface Terminal system (hereafter
referred to as the “PLC/OIT system”) shall include interfaces with the Operator,
Supervisors, external equipment, and the User’s control system to ensure safe, reliable,
continuous, and automatic operation and easy, safe, and reliable configuration.
3.2.2 Interface with Operators
The PLC/OIT system shall include interfaces with the Operator that ensures easy, safe,
and reliable operation.
An operator-interface panel shall be provided and mounted on the skid. This panel shall
provide the necessary switches, indicators, and devices to operate the WFI-PS Generator.
The following shall be displayed:
 Distillate Temperature
 Pure Steam Pressure
 Alarms and Warnings.
 System Status (e.g., “ready,” “running,” etc.).
 Conductivity (in and out)
 Distribution Loop Conductivity (supply and return)
 Distribution Loop Temperature (supply and return)
 Tank Temperature
 Tank Water Level
 Interface with Supervisors

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Medevo Pharmaceuticals, Pvt. Ltd Lahore.
Title: Users Required Specifications for Document # Revisions: 00
WFI production plant QA/URS/ C&O/004 Date: 20-Apr-20

 The PLC/OIT system shall include interfaces with Supervisors to ensure easy,
safe, and reliable configuration of the WFI-PS Generator.
3.2.3 The following shall be accessible only to Supervisors
 Control set points.
 Control loop variables (i.e., “PID terms”).
 Alarm set points.
3.2.4 Interface with Other Systems
Access to all Input/Output values and system status bits by an external computer
system(s) shall be provided through a data-communication link to the PLC and/or
PLC/OIT.
The PLC/OIT system shall include interfaces with the User’s control system to facilitate
automatic operation and configuration.
A system with an RS-232 communications port shall be provided.
The port shall be configured to communicate the following data to a supervisory control
and data acquisition (SCADA) node (Note: the SCADA system shall be supplied and
installed by the User):
 Distillate Temperature
 Distillate Resistivity
 Alarms and Warnings.
 System Status (e.g. “off,” “ on,” “standby” states, etc.).
 Tank Water Level
3.2.5 Data Collection
Data required for collection to be recorded at 30 minute intervals – continuous.
 Distillate Temperature
 Distillate Resistivity
 Feed water Resistivity
 Feed water Temperature
 Tank Water Level
 Tank Temperature

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 Loop Supply Conductivity

 Loop Supply Temperature
 Loop Return Conductivity
 Loop Return Temperature
3.2.6 Data Collection and Storage Requirements:
Compliance with 21CFR Part 11 (electronic records) is required. This includes especially
date and time of collection along with data. Data should be stored onto UPS backed
computer files and transferred to CD-R recording media once per month.

3.3 Environment
3.3.1 Layout
System must be installed in the allocated space on service floor as per attached layout
dimensions
3.3.2 Physical Conditions
The skid shall be mounted in an environment with a temperature range of 15C to 40C
and non-condensing humidity.
Vibration levels are: Negligible.
Electromagnetic interference levels are: Negligible.
This area is intended for the following use: General purpose/mechanical.

4 TIMELINES
The Supplier shall provide a written proposal within 2 weeks of receipt of this document at the
Supplier’s local office.
The Supplier shall provide a Functional and Design Specification within 3 weeks of receipt of the
purchase order.
The User shall review, comment and/or approve, and return the Functional and Design
Specification to the Supplier within 1 week of receipt from the Supplier.
The Supplier shall provide the Factory Acceptance Test Specification within 1 week of receipt of
approved the Functional and Design Specification. The User shall review, comment and/or

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approve, and return the Factory Acceptance Test Specification to the Supplier within 1 week of
receipt from the Supplier.

5. LIFE-CYCLE
5.1. Development
The Supplier shall have a quality system in place. Internal quality procedures shall be available
for customer review.
The Supplier shall provide a Project Manager for the project to provide a single communication
point.
4.1 Testing
In order to verify system performance, the User shall witness the execution of the Factory
Acceptance Test procedures. The Supplier shall notify the User 2 weeks in advance of the start
of this test.
Before shipment, the System undergoes extensive functional testing to ensure mechanical and
operational integrity. All operation functions are tested, including operation during a power
failure and upon recovery from a power failure. All alarm functions are tested.
Production capacities and utilities consumption data are recorded in the approved protocol.
A biological purity test is performed on the condensed pure steam by a suitable laboratory using
the Kinetic Turbidimetric LAL method. The feed water is spiked to a minimum concentration of
100 endotoxin units per milliliter (EU/ml). The maximum acceptable endotoxin concentration in
the condensed pure steam is 0.03 EU/ml (the U.S. Pharmacopoeia requirement for Water-for-
Injection is 0.25 EU/ml).
4.2 Delivery
The system with all options, equipment, and documentation listed herein, shall be delivered to the
User’s receiving dock.
4.3 Documentation
Installation, operation, and maintenance instruction documentation for the system shall be
developed to a level that is comprehensible to a high school graduate.
The Supplier shall provide documentation reflecting “as-built” condition with final delivery.

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All final documents shall be shipped with transmittals that identify them as contractually required
documents. All final documents and drawings shall reflect “as-built” condition.
All documents must be in English and may be delivered in Electronic Format as detailed below.
 Design Specifications Microsoft Word
 Controls Test Microsoft Word
 Hardware Installation Test Microsoft Word
 Operational Test Microsoft Word
 Factory Acceptance Test Microsoft Word
 Operator, Maintenance and Service Manuals Microsoft Word
 Process and Instrumentation Diagram (P&ID) AutoCAD
 Instrument Listing Microsoft Word or Excel
 Control Schematics AutoCAD
 Control Panel Assembly Drawings AutoCAD
 Equipment Assembly Drawings AutoCAD
 Bill of Materials Microsoft Word or Excel
 Spare Parts List Microsoft Word or Excel
 Component Cut Sheets Microsoft Word or Excel
 Certificates of compliance for materials, welding, surface finish inspection.
4.4 Support
 Start-up Support (vendor to indicate available options)
 Training (vendor to indicate available options)
 Post Start-up Support (vendor to indicate available options)
 Technical Support
 Telephone (Voice or Modem)
 Replacement Parts Availability List (Normal lead times shall be listed)
 User Site Support
 Preventative Maintenance (vendor to list maintenance contracts available)

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 System Improvements (supplier shall notify user of any improvements available on a

regular basis)

5 GLOSSARY

ASME – American Society of Mechanical Engineers, a source of recommended practices and

standards.

CFU – colony forming unit, a measure of the viable bacterial population in a sample.
Conductivity – a measure of the concentration of ionized materials, such as salts, in solution.
Measured in Siemans/cm (ohms-1/cm).

Chilled Water – non-purified water used to carry away heat from hot streams in heat exchangers.
Chilled water is supplied at a temperature lower than can be reliably obtained from the cooling
tower, increasing heat exchanger capacity.

De-rouging – Removal of surface corrosion from austenitic stainless steel surfaces. Rouge most
commonly forms in high temperature water and pure steam systems.

Endotoxin – primarily cell wall fragments (lipopolysaccharide-protein complexes) from gram

negative bacteria. Measured in standardized international units.

Passivation – Treatment of austenitic (300 series) stainless steels to enhance oxide film stability
and thus reduce corrosion.

PS – Pure Steam, a grade of high purity steam defined in the USP.

TOC – Total Organic Carbon, an acceptance criterion for Water for Injection.

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USP – United States Pharmacopeia, an organization establishing standards to assure the quality of
medicines for human and veterinary use. USP sets the quality standards for certain grades of
water used in the manufacture of pharmaceuticals.

WFI – Water for Injection, a grade of high purity water defined in the USP.

6 REFERENCES
1. P&IDs
2. ASME BPE-2002 Bioprocessing Equipment
3. ASTM A270-03a, Standard Specification for Seamless and Welded Austenitic and
Ferritic/Austenitic Stainless Steel Sanitary Tubing
4. ISPE Baseline Pharmaceutical Engineering Guide, Volume 4 Water and Steam Systems,
1st Edition, January 2001

7 CALCULATIONS
Following calculations will be provided by supplier that must commensurate overall requirements
 Water Consumption Data Sheet
 WFI Tank Simulation
 WFI Flow Rate Calculations
 Pump Selection

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