USER REQUIREMENT SPECIFICATION

[ URS ]
FOR PURE STEAM GENERATOR

CONTENTS

1. Intoduction

2. Purpose

3. Scope

4. System Desciption

5. Glossary/Definitions

6. Requirements

7. Appendix
1. INTRODUCTION

PT. Aditamaraya Farmindo is one of more than 200 pharmaceutical industries in Indonesia ,to
support activities develop sterile product manufacturing need to provide pure steam generators.
The pure steam generator will supply pure steam for sterilising autoclave and sterilisation in place
process. There for the equipment nor processes needs to be qualified or validated according to
standard practice in the pharmaceutical industry. For this reason the pure steam system for process
usage has been selected to comply with ISPE Guidelines, Pure Steam. This will employ the same
design,specification, installation and commissioning standards as that for a licenced GMP facility.

2. PURPOSE

The purpose of the user requirements specification ( URS ) s to define clearly and precisely what
the user needs the system to do and what physical and performance requirements and other
attributes are required. Attributes specified should be verifiable by testing. The URS fulfils the
following two key functions :

 Provides a formal definition of what the quality requirements and key operational
parameters are for the system
 Documenting the quality critical requirements which will form the basis for devising the
documented commissioning tests within the subsequent DV,IV,OV and PV ( Design,
Installation, Operation and Performance verification) protocols

3. SCOPE

Included within the scope of this document are the quality requirements for the pure steam
generation and distribution system that will install in PT.Aditamaraya Farmindo.

The Scope Included

* One Pure Steam Generation Unit

* Pure Steam Distribution Header

* Pure steam user points

* Sampling points for both condensate and pure steam

* Burner connection to Gas distribution system

* PSG connection to Pure water Storage and Loop system

Excluded from this scope is the supply of pure water it will be part of the Pure Water Generation,
Storage and distribution system
4. SYSTEM DESCRIPTION

A NEW Pure Steam Generation and Distribution System is required to supply pure steam to use
points in sterile product area manufacturing of PT Aditamaraya Farmindo. This will include one Pure
Steam generator , the distribution header, pure steam user points, sampling points for both
condensate and pure steam and connection from pure water distribution loop to feed the pure
steam generator unit, connection from Gas supply pipe to feed burner of PSG.

5. GLOSSARY/DEFINITION

TERM OR ACRONYM MEANING WITHIN THIS STANDARD OPERATING PROCEDURE

Non-critical A component of sub system within a system where the operation, contact,
component data control. Alarm, or failure will have an indirect, or no impact on the
quality of the product
Good automated Established Engineering methods and standards that are applied
Manufacturing throughout the project lifecycle in the design, implementation and
Practice (GAMP) validation of GxP automated systems
Good Engineering Established Engineering methods and standards that are applied
practice (GEP) throughout theproject lifecycle to deliver appropiate cost effective
solutions
System An organisation of components with defined operational function ( e.g PW
System, HVAC, Filling machine, HPLC, etc )
System Boundary A limit drawn around a system to logically define what is and is not included
in the system
Impact Assessment The process by which the impact of a system on product quality is
evaluated and the critical components within those systems are identified
Direct impact system A system that has a direct impact on product quality. In some instances,
direct impact systems will depend on indirect impact systems for effective
operation and therefoe, any interfaces need to be carefully assessed
Indirect impact A system that does not have a direct impact on product quality, but will
system support a direct impact system. These systems are designed and
commissioned following GEP only. Indirect impact systems can affect the
performance or operation of a direct impact system and therefore any
interfaces need to be carefully assessed. It must also be ensured that direct
impact systems can detect or prevent a product quality threatening
problem with an indirect impact system linked to it. In the instance when a
system can be used as both a direct and indirect impact system, the
requirements of the direct impact system must take precedence to ensure
compliance to cGMP
No Impact System A system that does not have any impact, either directly or indirectly, on
product quality. These systems are designed and commissioned following
GEP only
Critical Component A component or sub-system within a system, where the operation, contact,
data, control, alarm, or failure may have a direct impact on the quality of
the product
Current Good The part of quality assurance which ensures that medicinal products are
Manufacturing consistently produced and controlled to the quality standards appropriate
Practice ( cGMP ) to their intended use
Discrepancy A discrepency occurs when a test step does not meet its pre-defined
acceptance criteria. Discrepancies may be resolved during execution of the
qualification/ validation stage, but must still be recorded
Major Discrepancy Major discrepancies have an influence on safety or product quality. A major
discrepancy will prevent continuation of the qualification stage being
executed . Major discrepancies reqire resolution and QA approval prior to
the start of the next qualification/validation stage.
Minor discrepancy Minor discrepancies do not have an influence on safety product quality. A
minor discrepancy will not prevent the start of the next qualification stage
Raw Data Any source of primary ( unprocessed ) or supporting data completed or
collated during test execution in support of a qualification/validation
activity. This will include the executed test script fromthe protocol
(including associated information and results )
Validation Establishing documented evidence which provides a high degree of
assurance that a specific process will consistently produce a product
meeting its predetermined specification and quality attributes
Qualification Establishing documented evidence which privides a high degree of
assurance that a system fulfils its specified requirements
ASME American Society of Mechanical Engineers
BMS Building Management System
BPE Bioprocessing Equipment
CE Conformite Europene
CFR Code of Federal Regulation
DQ Design Qualification
DV Design Verification (Some with DQ, but without regulatory approval)
EP European Pharmacopoeia
EPDM Ethylene Propylene Diene Monomer
EU European Union
FAT Factory Acceptance Test
FDA Food and Drug Administration
FMS Facility Management System
FS Functional Specification
GAMP5 ISPE Good Automated Manufacturing Practice Revision 5
GEP Good Engineering Prctice
GMP Good Manufacturing Practice
HDS Hardware Design Specification
HMI Human Machine Interface
IQ Installation Qualification
IV Installation Verification (Same as IQ, but without regulatory approval)
MHRA Medicines and Healthcare products Regulatory Approval
NDT Non Destructive Testing
OQ Operation Qualification
OV Operation Verification
PED Pressure Equipment Directive
PLC Programmable Logic System
PQ Performance Qualification
PV Performance Verification
PTFE Polytetrafluoroethylene
SAT Site Acceptance Test
SDS Software Design Specification
URS User Requirements Specification
USP United State Pharmacopoeia
TERM DEFINITION
Shall/will The word shall or will denotes that the requirement is mandatory
Should The word should denotes that the requirement is good practice / highly
recomended, but not mandatory
May The word May is used to indicate an acceptable option

6. REQUIREMENTS

No. 1 System Requirement

6.1.1 There will be a dedicated Pure Steam Generation and Distribution system to supply the
process sterilization with autoclave
6.1.2 The material of construction shall be
 316 L stainless steel for welded prduct contact parts
 316 0r 316 L stainless steel for non welded product contact parts.
6.1.3 Non metallic material in contact with the product such as elastomers ( e.g. silicone
rubber, etc ) or polymers ( e.g. PTFE or EPOM ) shall be of pharmaceutical grade sanitary
construction and shall be in conformance with 21CFR 177.2600.
6.1.4 All pure steam contacting heat exchangers shall be double sheet shell and tube heat
exchangers
6.1.5 All pipework and product contacting parts shall be designed as per ASME BPE 2012
6.1.6 All product tubing on the PS Generation skid to slope to ≥ 1: 100
6.1.7 All product tubing on the PS Generation Header to slope to ≥ 1 : 200
6.1.8 The system shall be designed to minimize product contacting dead legs, as per ASME BPE
2012 i.e 2D is a target rather than an absolute requirement
6.1.9 All process contact valves shall be sanitary ball, diaphragm valves or sanitary sampling
valves
6.1.10 The following parameters shall be logged in the Fascility Management System (FMS)
 Pure steam condensate temperature ( at the discharge from the pure steam
generator)
 Pure steam condensate conductivity ( at the discharge from the pure steam
generator
 Signal to confirm Pure steam Generator (PSG) is being supplied to distribution
system
 Pressure in Pure steam distribution loop
6.1.11 A common alarm signal shall be roted to the Building Management system (BMS) from
the PSG. The pure steam pressure shall be monitored and alarmed within the PSG
6.1.12 Instrument supplied shall be suitable for the operating conditions specified in section 2.14
6.1.13 Instrumentation shall be selected such that their accuracy is sufficient to achieve the
process control loop accuracy wihin stated parameters i.e. it shall be possible to calibrate
all instruments to an accuracy greater than that required of the associated measurement
or control loop
6.1.14 Process contact temperature transmitters shall be installed in thermowells ( only
thermowells shall contact the process )
6.1.15 Process contact stailess steel surfaces shall be polished to Ra ≤ 0.5 µm
6.1.16 System components including gasket , seal, etc. Shall be suitable for the complete range
of temperatures specified in section 2.14
6.1.17 The pure steam generation and distribution system shall be controlled by a PLC based
control system, with a human machine interface (HMI)
6.1.18 When fully implemented the control system software shall be compliant with EU and US
 regulations, including the following :
 GAMP, Good Automation Manufacturing Practice
 US Code of Federal Regulations (CFR) Title 21 part 11

6.1.19 There will be a restriction of maximum combined take off 500 kg/hr from all user points.
This will controlled by procedure and alarm monitoring the pressure in the pure steam
header. The PSG , pure steam header and the user points to be sized so that the system
can maintain pressure and flowrate within the maximum combined take off.
6.1.20 The control system software shall be designed, developed, tested, supplied and maintai
. ned in accordance with a documented Quality Management System.

2. Operational Requirements
6.2.1 Pure steam shall be produced by the generator at minimum operating pressure of 3 barg
and the pure steam generator shall keep the distribution header pressured to 3 barg ±
0.25 barg at all times
6.2,2 The system shall generate and distribute Pure Steam with WFI quality condensate as
defined by the current USP and EP, with the exception of the aerobic bacterial levels,
which are not monitored
6.2.3 Automatic temperature compensation shall not be allowed on the conductivity probes
6.2.4 User flowrates shall be established during detailed design and finalised during
commissioning
6.2.5 Expected flowrates of pure steam for use points
 Sterilising Autoclave for rubber stopper 100 kg/cycle about 30 minutes
 Sterilising Autoclave for products 100 kg/cycle about 30 minutes
6.2.6 The pure steam design flow shall be rated for not less than 250 kg/hr from th pure steam
generator to the pure steam distribution user points
6.2,7 Where possible, valves for pure steam service shall be designed for optimum drainability
and in all cases shall have minimal fluid hold-up volumes
6.2.8 All components of the pure steam service shall be suitable for continuous steam service
6.2.9 The pure steam distribution system should have adequate provision to remove air during
start-up and normal operations
6.2.10 Connection to the product , feed water, or condensate/blowdown produced by the units
shall be made by the use of hygienic design fittings
6.2.11 Pure steam distribution system shall not be directly connected to any unhygienic systems,
air breaks of at least 50 mm shall be used
6.2.12 The pure steam distribution system shall be continuously self sanitising
6.2.13 The system shall be designed to compensate for pressure fluctuations in the Pure Water
distribution loop
6.2,14 The feed water ( pure water ) distribution system shall be periodically heated to greater
than 85°C during sanitisation. The pure steam generator shall be capable of operating
with inlet feed water temperatures of up to 90°C
6.2.15 All components within the pure steam distribution system shall be self draining
6.2.16 It shall be possible to take pure steam condensate samples at or upstream of critical
product contacting users ( Autoclave and SIP user points)
6.2.17 User points that are not as critical do not have to be sampled at the point use. For these
userss, end of header sampling is sufficient
6.2.18 It shall be possible to test the steam quality for compliance with EN 285 & HTM 2010
close to the sterilising Autoclave, SIP and PSG outlet
6.2.19 The following steam quality parameters can be manually tested at these points according
to EN 285
  Dryness ( dryness level ≥ 0.95 )
 Superheat ( ≥ 25°C )
 Non-condensable gases ( Maximum 3.5 % V/V )
6.2.20 It shall be possible to sample pure steam condensate directly from the pure steam
generation unit
6.2.21 Process and non – sanitary relief vents shall be directed to a safe location
6.2.22 All vertical vents to be fiited with a weep hole on the open side of the vent
6.2.23 In the event of the Pure Water storage and distributions system being shut down and
drained prior to steam sanitisation, there be a capability to connect the outlet of the pure
water generator direct to the feed inlet of the pure steam generator ( by removable
spool pieced or hose ), to enable pure steam to be generated to steam sanitise pure
water loop
6.2.24 Steam traps shall be located at all low points
6.2.25 The control system shall be implemented in compliance with FDA regulation 21 CFR Part
11. Pertaining to electronic records and electronic signatures (using a combination of
technological and procedural solutions) in relation to the following
 Access Control
 Data Integrity
 Audit Trail
6.2.26 The control system shall not generate Electronic Records or Electronic Signatures

3 Documentation Requirements

6.3.1 Bursting Disc/Relief stream certificate

6.3.2 CE Certificate ( Certificate of incorporation/conformance as appropriate
6.3.3 Cleaning/flushing procedure & certificate
6.3.4 GA Drawing & section
6.3.5 Installation Operation & Maintenance Manual
6.3.6 Lubrication Instruction & schedule
6.3.7 Performanc curve & NPSH curve
6.3.8 Technical Data Sheets
6.3.9 Alarm list
6.3.10 Loop Diagram
6.3.11 Control panel schematic & GA diagrams
6.3.12 Wiring diagrams
6.3.13 List of Instrumentation
6.3.14 Certificate of compliance that all wetted parts & elastomers are FDA compliant
6.3.15 Degreasing & Passivation report ( including method statement and report)
6.3.16 Material Certificates
6.3.17 NDT results Certificate ( X-ray graphs, boroscope pictures and reports )
6.3.18 PED Certification
6.3.19 Pressure Test / Leak Test Certificate
6.3.20 Riboflavin Wetting Test certificate
6.3.21 Surface Finish Certificates
6.3.22 Weld Samples ( taken at the beginning of each shift, once per welder & for equipment
adjusment )
6.3.23 Weld Logs
6.3.24 Weld Maps ( Isometric )
6.3.25 Welder qualifications, weld procedures and specifications, weld reports
6.3.26 Filter Certificates (0.22 µm filters only )
6.3.27 QA Inspection and Test Plan
6.3.28 Quality and Project Plan ( QPP )
6.3.29 Functional specification ( FS )
6.3.30 Hardware Design Specification ( HDS )
6.3.31 Software Design Specification ( SDS )
6.3.32 Requirements Traceability Matrix ( RTM )
6.3.33 Factory Acceptance Test ( FAT ) Protocols
6.3.34 Factory Acceptance Test ( FAT ) Reports
6.3.35 Site Acceptance Test ( SAT ) Protocols
6.3.36 Site Acceptance Test ( SAT ) Reports
6.3.37 Design Verification ( DV ) Protocols
6.3.38 Design Verification ( DV ) Reports
6.3.39 Installation Verification ( IV ) Protocols
6.3.40 Installation Verification ( IV ) Reports
6.3.41 Operational Verification ( OV ) Protocols
6.3.42 Operational Verification ( OV ) Reports
6.3.43 QA-Manager of ARF shall pre and post approve all test and qualification protocols

4. Testing Requirements

6.4.1 Factory Acceptance Test ( FAT )

6.4.2 Commissioning
6.4.3 Site Acceptance Test
6.4.4 Design Verification ( DV )
6.4.5 Installation Verification ( IV )
6.4.6 Operational Verification ( OV )
6.4.7 A representative of ARF ( Aditamaraya Farmindo ) will have to witness all commissioning
and qualification testing

5. Training

6.5.1 The vendor shall be required to provide sufficient training for operators and maintenance
personnel to operate and maintain the equipment