Public Health England

Porton Down
Salisbury SP4 0JG UK
SPECIFICATION NO. PHE-PD/URS/865

Project: UF/DF Unit (PPC)

Project Number: 170160
Document Title: User Requirement Specification for UF/DF Unit (PPC)
Document PHE-PD/URS/865
Number:
Revision Number: 0
Date: 19 Sept 2013

Contents

1. Standard Terminology Used ................................................................................ 2

2. Introduction .......................................................................................................... 3
3. Scope of URS ...................................................................................................... 3
4. Codes & Standards.............................................................................................. 3
5. Environmental Conditions .................................................................................... 3
6. Utilities Available.................................................................................................. 4
7. Equipment Requirements ..................................................................................... 4
8. Process & Operational Requirements.................................................................. 6
9. Control and System Requirements ...................................................................... 7
10. Maintenance & Instrument Calibration Requirements .......................................... 8
11. Testing Requirements.......................................................................................... 8
12. Health & Safety Requirements........................................................................... 10
13. Appendices ........................................................................................................ 11
Appendix A: Documentation Requirements .............................................................. 11
Appendix B: FAT, SAT/Commissioning & Validation Testing Details ....................... 13
Appendix C: Outline Validation Protocol................................................................... 15
Appendix D: Floor Layout of PPC Room 8,9 & 10 ................................................... 17

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 Public Health England
Porton Down
Salisbury SP4 0JG UK
SPECIFICATION NO. PHE-PD/URS/865

1. Standard Terminology Used

GMP Good Manufacturing Practice

HAZOP Hazard and Operability Study

HMI Human Machine Interface

IP Rating Ingress Protection Rating

PC Personnel Computer

PLC Programmable Logic Controller

PHE Public Health England

PPC Pharmaceutical Production Centre

SIQ Software Installation Qualification

SOQ Software Operation Qualification

TFF Tangential Flow Filtration

TMP Trans-membrane Pressure

UF/DF Ultrafiltration / Diafiltration

USP United States Pharmacopoeia

Other Data

UF/DF Location UF/DF will be used in Room 05/09, and generally stored in Room
05/10, Zones 1 to 4 of PPC Building, No 05.

Clauses Specified as ‘GMP All user requirements detailed in this document shall be subject to
Critical’ qualification/validation unless specifically stated otherwise.
However, those clauses specified as ‘GMP Critical’ are highlighted as
essential to the maintenance of product equivalence and regulatory
compliance.

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 Public Health England
Porton Down
Salisbury SP4 0JG UK
SPECIFICATION NO. PHE-PD/URS/865

The following Sections 2 to 4 of this URS do not include testable clauses. They are
introductory sections detailing background project information and existing system
conditions that are included to provide context for the testable user requirements that follow
in Sections 5 to 11

2. Introduction

2.1 A new automated UF/DF (Ultrafiltration/Diafiltration Unit) Unit and associated

equipment is required for the Pharmaceutical Production Centre (PPC) at the PHE, (Public
Health England) Porton Down site.

2.2 The new automated UF/DF rig will replace the existing manual M30 units.
These units have become obsolete as the supplier intends to phase out supply of filter
modules by end of November 2014.

3. Scope of URS

This specification covers the user requirements for the design, manufacture, installation,
commissioning and validation of an automated UF/DF Unit for the PPC at Porton.

4. Codes & Standards

The following Section 4 describes the codes and standards that shall generally apply to all
equipment supplied to meet the user requirements specified in this document.

EudraLex - The Rules Governing Medicinal Products in the European Union Volume 4
EU Guidelines to Good Manufacturing Practice Medicinal Products for Human and
Veterinary Use Annex 1 Manufacture of Sterile Medicinal Products (corrected version).
ASME BPE-2009 Bioprocessing Equipment.
BS EN ISO 14644-8:2006 - Cleanrooms and associated controlled environments.
GAMP 5 - A Risk-Based Approach to Compliant GxP Computerized Systems.
FDA 21 CFR Part 11 - Electronic Records & Electronic Signatures.
EudraLex - The Rules Governing Medicinal Products in the European Union Volume 4
EU Guidelines to Good Manufacturing Practice Medicinal Products for Human and
Veterinary Use Annex 11 Computerised Systems.
Pressure Equipment Directive (PED) 97/23/EC.
Machinery Directive – 2006/42/EC

5. Environmental Conditions
The following Section 5 describes the environmental conditions into which the equipment
supplied to meet the user requirements specified in this document will be installed.

5.1 UF/DF will be used in Room 05/09, and generally stored in Room 05/10, Zone, 1 to 4 of PPC
Department in Building, No 05 at PHE, Porton

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 Public Health England
Porton Down
Salisbury SP4 0JG UK
SPECIFICATION NO. PHE-PD/URS/865

5.2 Room 09 measures 5.440mtr x 2.715mtr and operates between a temperatures of +2 ºC to +8 ºC.

5.3 Room 10 measures 8.090mt x 6.210mt and is temperature controlled between 20°C ± 5°C with a
relative humidity controlled to between 10% and 70%.

5.4 The equipment, including (any inboard or outboard) PC Package will be used within a Grade C
clean room and must be to pharmaceutical GMP Standards.

5.5 The equipment, including (any inboard or outboard) PC Package must be able to be operated
within a cold room at a temperature of +2 ºC to +8 ºC.

5.6 The unpackaged equipment must be able to fit through door opening, including archives, of
900mm width and must be able to be used comfortably in a chilled room measuring 5.440 metres x
2.715 metres.

6. Utilities Available

The following Section 6 describes the utilities that shall be made available to serve the
equipment supplied to meet the user requirements specified in this document.
WFI- Ambient Temperature.
Instrument air (Oil Free).
WFI- Chilled 5°C
Electrical – 220/240V 50Hz Single Phase
Electrical- 415V 50Hz 3 Phase

7. Equipment Requirements

The following Sections 7, 8, & 9 of this URS include testable clauses relevant to the specific
equipment that shall be supplied. They are included to provide clear and precise user
requirement statements that shall support traceability through the design and testing of the
equipment supplied to meet them.

7.1 General

7.1.1 The equipment to be an automated TFF (Tangential Flow Filtration) - UF/DF

(Ultrafiltration/Diafiltration) Unit using flat sheet cassettes and disposable/single use parts.

7.1.2 The equipment to be designed to accommodate flat sheet cassettes with a minimum area of 2.5
metres square.

7.1.3 The equipment package must include all parts, vessels, containers, fittings and fixtures, needed
to operate the UF/DF Rig to the Operating and Running Parameters listed in this URS.

7.1.4 The equipment, including any inboard / outboard PC will be used within a Grade C clean room
and must be to pharmaceutical GMP Standards.

7.1.5 The equipment & instruments must be easy to clean externally and resistant to 1% TEGO 2001
and 70% IPA cleaning solutions.

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Public Health England
Porton Down
Salisbury SP4 0JG UK
SPECIFICATION NO. PHE-PD/URS/865

7.1.6 The system to use diaphragm pump for recirculation loop and the pump head to be supplied as
part of the Sterile Flow Path.

7.1.7 The equipment must have a disposable flow path that will eliminate the need for cleaning
validation of product contact parts.

7.1.8 The flow paths must be supplied double bagged and sterile.

7.1.9 The flow paths must be supplied with full certification stating materials of construction, USP
class VI and animal free origin statements.

7.1.10 All wetted components in the flow path must be biocompatible, USP VI, traceable and animal
free.

7.1.11 All wetted components in the flow path must be compatible with solutions containing 50%
alcohol.

7.1.12 The equipment must be able to operate using solutions at a temperature of between +2 ºC to
+8 ºC.

7.1.13 The equipment must be IP45 rated or better.

7.1.14 The equipment must be mobile and easy to manoeuvre. Wheels must be suitable for use in a
GMP grade C cleanroom environment.

7.1.15 The equipment wheels must be fitted with brakes for security.

7.1.16 The unpackaged equipment must be able to fit through a door opening, including architraves,
of 900mm wide and to be able to be used comfortably in a chilled room measuring 5.44 metres x
2.715 metres.

7.1.17 The equipment, including PC must be able to be operated within a cold room at a temperature
of +2 ºC to +8 ºC.

7.2 Spares
7.2.1 A complete set of Commissioning spares, all separately priced, to be included in the tender to
allow the IQ,OQ & PQ to be completed.
7.2.2 Normal Maintenance/ Running Spares are excluded from the scope of this specification.

7.3 Training
7.3.1 The vendor to include for comprehensive Operator Training at the PHE Site; they should also
include for a comprehensive Engineering Training package.

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Public Health England
Porton Down
Salisbury SP4 0JG UK
SPECIFICATION NO. PHE-PD/URS/865

8. Process & Operational Requirements

The following Section 8 of this URS includes testable clauses relevant to the process that shall
be implemented by the equipment that shall be supplied. They are included to provide clear
and precise user requirement statements that shall support full traceability through the design
and testing of the equipment supplied to meet them.

8.1 Function 1.

8.1.1 The equipment to be designed with retentate a tank / bag capacity of approximately 100 litres
and to concentrate to approximately 30 litres.

8.1.2 The equipment to be designed to accommodate flat sheet cassettes with a minimum area of
0.25 to 2.5 metres square

8.1.3 The equipment to be fully automated and be supplied with an integral PC Package, including
touch screen and data down load facilities etc.

8.1.4 The equipment to have the ability to continually weigh retentate tank via an integral balance.

8.1.5 Cassette holders to be suitable for Pall, Omega 2.5m² gamma irradiated cassettes.

8.1.6 The UF/DF System to be designed with automated inlet, retentate and permeate valves.

8.1.7 The equipment to be capable of concentration and diafiltration process operations.

8.1.8 The equipment must be designed with a minimum of two feed lines on the inlet manifold.

8.1.9 The equipment must be designed with sufficient feed lines on the retentate manifolds to allow
for both diafiltration buffer and product batch feed.

8.1.10 The equipment must be capable of performing and monitoring the following parameters:-
Flux rate 1.6 L/min.
TMP 1.0 bar
Recirculation rate 16L/hr.

8.1.11 The system flow path to contain the following disposable sensors:-
Pressure sensors on feed, retentate and permeate Lines
Flow metre
Conductivity sensor on retentate line
Absorbance measurement at 280 n/m on permeate line

8.2 Function 2

8.2.1 The equipment must be able to perform diafiltration to reduce conductivity of the product
between 400 to 1,150µS/cm maintaining a volume of 20 litres.

8.2.2 The equipment to be designed to accommodate a retentate volume of approximately 20 litres

and concentrate to approximately 10 litres.

8.2.3 The equipment to include all functions listed in function 1.

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Public Health England
Porton Down
Salisbury SP4 0JG UK
SPECIFICATION NO. PHE-PD/URS/865

8.3 Function 3

8.3.1 The equipment must be able to perform diafiltration to reduce residual ethanol levels to below
400ppm and maintain a volume of 10 litres. It would be advantageous if the system could be
designed to accommodate, at a later date, a retentate volume of 50 litres and concentrate to 10 litres.

8.3.2 The equipment to include all functions listed in function 1.

9. Control and System Requirements

The following Section 9 of this URS include testable clauses relevant to the control system
requirements. They are included to provide clear and precise user requirement statements
that shall support full traceability through the design and testing of the control system
supplied to meet them.

9.1 Alarm messages shall provide an accurate and unambiguous description of the alarm condition
and shall be displayed on the HMI in plain English.

9.2 The equipment must be computer or PLC controlled and run with software that can be used for
method writing and method development. User access via a local cleanroom compatible HMI.

9.3 All software must be documented & to be compliant with GAMP 5 or greater.

9.4 Analysis of previous UF/DF run data must be available.

9.5 The equipment software must provide real-time control of the UF/DF system.

9.6 The equipment software must be fully 21 CFR Part 11 compliant and meet EU Annex 11 –
Computerised systems.

9.7 The equipment software must have a method writing function to enable easy method generation.
Within the method writing function, there must be the option to input variable parameters IE Starting
Volumne.

9.8 The equipment software must have the ability to perform extensive data evaluation on both
current and historical runs.

9.9 It must have the option for data evaluation and presentation of results in reports with user design
or on predefined templates.

9.10 The equipment software shall have different security access levels with different access rights at
each level (e.g. Administrator, Supervisor, and Operator.)

9.11 The software must have an electronic signature system that utilizes a password confirmatory
and documenting locking scheme.

9.12 The equipment software must be able to provide hard copy reports detailing any of the
monitored parameters in both graphical and numerical formats.

9.13 The equipment must have the ability to be connected to a printer to enable printing of run data
for inclusion in batch manufacturing records. Should that be required?
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Public Health England
Porton Down
Salisbury SP4 0JG UK
SPECIFICATION NO. PHE-PD/URS/865

9.14 The equipment must be able to download data onto an external memory source.

9.15 The vendor shall supply sufficient instruction, documentation, licences, passwords, keys
and software to enable the system to be fully re-installed onto similar hardware in the event of failure
of a configurable component or the complete system.

9.16 On receipt of a (UPS failure imminent) signal from the server UPS, the server shall
shutdown in an orderly sequence, thus preventing corruption to any data or electronic
records.

9.17 In the event of loss of signal or loss of communication, an error message is to be

recorded in the event log/audit trail.

9.18 In the event of power supply failure, the UF/DF system is to automatically restore to its normal
function on power restoration, and system stopped and system restarted messages are to be
recorded in the event log/audit trail.

9.19 The system shall automatically restart to the stage where the powe outage occurred on
restoration of power to the server.

10. Materials of Construction Requirements

The following Sections 10 to 13 of this URS include testable clauses for the equipment that
shall be supplied. They are included to provide clear and precise user requirement
statements that shall support full traceability through the design and testing of the
equipment supplied to meet them.

10.1 The construction of the Equipment shall be of hygienic design suitable for a pharmaceutical
GMP application.

10.2 The equipment shall be of materials suitable for this duty, for which stainless steel 316L is the
material of first choice. Other materials suitable for GMP use may be chosen where stainless steel is
unsuitable.

10.3 All product contact materials shall be supplied with certified and fully traceable materials history
documentation. (Disposable single use items are covered in Section 7)

10.4 A surface finish better than 0.8µm is required for all work surfaces and product contact surfaces.

Maintenance & Instrument Calibration Requirements

10.5 The Vendor to include all required support servicing and maintenance, for the first year,
separately priced in the tender package.

10.6 All instrument calibrations shall be performed to 3 points as a minimum, and shall include
complete control loop verification.

11. Testing Requirements

Refer to Appendix B & C below, for specific details of the minimum requirements for the
11.
testing required of the UF/DF Rig

11.
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11.
 Public Health England
Porton Down
Salisbury SP4 0JG UK
SPECIFICATION NO. PHE-PD/URS/865
12. FAT Requirements

12.1.1 The vendor shall provide detailed mock-ups of the UF/DF Rig and all HMI software to
enable the performance of pre-FAT mock-up testing to be witnessed by the PHE/BPE Ltd.

12.1.2 The vendor shall provide documentary evidence of the performance of pre-FAT testing of
all equipment to the PHE/BPE Ltd at least seven days before the start of any FAT
activities.

12.1.3 The vendor shall FAT all equipment prior to delivery in accordance with their in-house
quality standards. All FAT’s shall be witnessed by the PHE/BPE Ltd.

12.1.4 FAT’s shall replicate, where possible, the utility parameters stated in Section 6, above.
Details of available utilities shall be recorded, where applicable, during execution of the
FAT.

12.1.5 Specific testing details shall be agreed in consultation with the PHE/BPE Ltd via a process
of FAT document review cycles, but shall include the tests documented in Appendix C of
this document as a minimum.

12.1.6 The vendor shall ensure that interface testing with third party equipment is also performed
and witnessed by the PHE/BPE Ltd.

12.1. SAT/Commissioning Requirements

12.2.1 The vendor shall SAT/Commission all equipment in accordance with their in-house quality
standards. All SAT’s/Commissioning shall be witnessed by PHE.

12.2.2 Specific testing details shall be agreed in consultation with PHE via a process of
SAT/Commissioning document review cycles but shall include the tests documented in
Appendix C of this document as a minimum.

12.2.4 Commissioning must include full loop calibration of all critical instrumentation and controls
in accordance with procedures pre-approved by PHE/BPE Ltd.

12.2. Validation Requirements

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 Public Health England
Porton Down
Salisbury SP4 0JG UK
SPECIFICATION NO. PHE-PD/URS/865

12.3.1 The equipment shall be subject to the following Validation activities, executed to pre-
approved protocols prepared according to PHE procedures and format:
GMP Design Reviews
Design Qualification (DQ) – A DQ Meeting will be held at the PHE site, to be
attended by the vendor.
Installation Qualification (IQ)
Operational Qualification (OQ)
Performance Qualification (PQ)
Software Installation Qualification (SIQ)
Software Operational Qualification (SOQ)
Requirements Traceability

12.3.2 The vendor to include in this tender the option to supply a complete IQ, OQ, SIQ &
SOQ Protocol Documentation Package to fully support qualification of the UF/DF Rig.

12.3.3 The vendor to include in this tender the option to conduct all IQ, OQ, SIQ & SOQ
Qualification activities at PHE, Porton, witnessed by PHE.

13. Health & Safety Requirements

13.1 The UF/DF Rig and equipment making up the package shall not exceed 75dBA during normal operations
and technical area equipment shall not exceed 80 dBA during normal operations when measured 1m away
from any part of the equipment.

13.2 The vendor shall provide suitable design information to enable the completion of both HAZOP and SWIFT
analysis processes.

13.3 The equipment shall be in compliance with Machinery, Electrical and Pressure Equipment Directives
97/23/EC and be CE marked.
13.4 The vendor shall provide all health & safety regulatory compliance documentation, to support CE marking
or as required by the directive and associated equipment within the vendor scope of supply.

13.5 All Emergency Stops shall be protected by a shroud to prevent accidental operation.

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Public Health England
Porton Down
Salisbury SP4 0JG UK
SPECIFICATION NO. PHE-PD/URS/865

14. Appendices

Appendix A: Documentation Requirements

The following Appendix A describes the scope of supply of the vendor documentation package for the
UF/DF Package
The vendor shall supply two paper copies and one electronic copy of the following documentation in
English.

Required Documents Responsibility No. of copies

URS PHE 1
Procurement literature VENDOR 1
Purchase Orders PHE 1
Quotations/Proposals VENDOR 1
Equipment
As Built PID’s: pneumatics VENDOR 1 set per O & M
As Built PID’s: electrical VENDOR 1 set per O & M
As Built PID’s: process VENDOR 1 set per O & M
GA / Layout Drawings VENDOR 1 set per O & M
O & M Manual (Electronic Copy) VENDOR 1
O & M Manual (Hard Copy) VENDOR 3
Spare Parts List VENDOR 1 per O & M
Equipment data sheets VENDOR 1 set per O & M
Material Certificates VENDOR 1 set per O & M
Unique Unit Pressure Certificate VENDOR 1 set per O & M
Component Test Data VENDOR 1 set per O & M
As-built drawings VENDOR 1 set per O & M
Installation and Commissioning Method Statements VENDOR 1
Commissioning Report VENDOR 1
Installation Test Reports VENDOR 1
FAT Report VENDOR/PHE 1
SAT Report VENDOR/PHE 1

Filter Integrity Testing (OQ) VENDOR 1

Design Qualification (DQ) VENDOR 1

Validation Protocol & Report IQ VENDOR 1

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Public Health England
Porton Down
Salisbury SP4 0JG UK
SPECIFICATION NO. PHE-PD/URS/865
Required Documents Responsibility No. of copies

Validation Protocol & Report SIQ VENDOR 1

Validation Protocol & Report SOQ VENDOR 1

Validation Protocol & Report OQ VENDOR 1

Validation Protocol & Report PQ PHE 1

Instrumentation
Control Wiring Drawing VENDOR 1 per O & M
Instrument data sheets VENDOR 1 per O & M
Instrument List – critical & non critical VENDOR/PHE 1
Instrument Calibration Method VENDOR/PHE 1
Instrument Calibration Certificates VENDOR 1 set
Test Instrument Calibration Certificates VENDOR 1 set
Controller (PLC)
GAMP compliance certification VENDOR 1
Part 11 compliance certification VENDOR 1
Control Diagram VENDOR 1
Controller data sheets/manuals VENDOR 1
Hardware Configuration VENDOR 1
I/O Schedule VENDOR 1
Logic Flow Diagram VENDOR 1
Operator manual VENDOR 1
Printer operator manual VENDOR 1
Copy of software VENDOR 2
Electrical
Fuse/Breaker Testing VENDOR/PHE 1
Panel & Equipment Identification VENDOR 1
Schematic Wiring Diagrams VENDOR 1
Wire Type/ Size/ Termination Check VENDOR 1
Training
Operator Training VENDOR

Engineering Training VENDOR

Note 1: Material certification shall be provided fall all process contact equipment, piping,
components, inline items and instruments (including seals and gaskets)
Note 2: Software documentation to include module design specifications etc.

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 Public Health England
Porton Down
Salisbury SP4 0JG UK
SPECIFICATION NO. PHE-PD/URS/865
Appendix B: FAT, SAT/Commissioning & Validation Testing Details
The following Appendix B describes the minimum requirements for the various testing stages
associated with the UF/DF Rig.
Documentation & Installation Tests
Documentation Review
Ergonomics Verification
Equipment Dimensional Verification
P&ID Verification
Panel Wiring Diagram Verification
Critical Equipment Verification
Surface Finish Verification
GMP Installation Verification
Equipment Maintenance Access
Verification
HMI Display Verification
Instrument Calibration Verification
Operational Tests
UF/DF Rig Flat Sheet Cassette integrity
Test
FAT TESTING
Inspection for compliance of all documentation listed as Quality
Documents in Appendix A of this document (including copying
and bringing to site all system software)
Field verification of the ergonomics of the installation
(essentially, mock-up tests using, where possible, production
equipment).
Field verification of equipment critical dimensions against GA
drawing
Field verification of equipment against P&ID’s
Field verification of equipment control panels against wiring
diagrams
Field verification of critical equipment items against data sheets
Field verification of selected internal stainless steel surfaces
Field verification of the equipment for GMP compliance
Field verification of levels of access to maintainable equipment
and calibratable instruments
Field verification of HMI displays against FDS
Verification that all supplied instruments have been correctly
calibrated, calibrations are current and valid and calibration
certificates and stickers are available
Field verification of the correct fitting and operation of the flat
sheet cassette unit.
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 Public Health England
Porton Down
Salisbury SP4 0JG UK
SPECIFICATION NO. PHE-PD/URS/865
FAT TESTING (Continued)
Operational Tests (Continued)
UF/DF Rig Single use Flow Path kit
integrity Test
UF/DF Rig Recirculation container and
balance integrity Test
UF/DF Rig Pump cooling plates and
recirculation system integrity Test
UF/DF Rig sensor & valve integrity Test
UF/DF Ultrafiltration process
Verification
UF/DF Diafiltration process Verification
Operation Verification in a cold room
environment
Equipment Noise Level Verification
Control System Functionality Tests
Control System & Hardwired Interlocks
Operation Verification
Control System Alarm Verification
Control System 21 CFR Part 11 &
Eudralex Annex 11 Compliance
Verification
Control System Output Verification
Control System Sequence Verification
Control System Interface Testing
UPS Operation/Power Failure
Response Verification
Other Tests
Test Instrumentation Calibration
Verification
Field verification of the correct fitting and operation of the Single
use Flow Path kit.
Field verification of the correct fitting and operation
Recirculation container, Pump and balance
Field verification of the correct fitting and operation of cooling
plates, system & pump.
Field verification of the correct fitting and operation of sensors &
valves
Field verification of the correct operation of the Ultrafiltration
process verifying operation of sensors, valves, scales and
meters.
Field verification of the correct operation of the Diafiltration
process verifying operation of sensors, valves, scales and
meters.
Field verification of the correct operation in a cold room
environment
Field verification of equipment shall not exceed 80 dBA during
normal operations when measured 1m away from any part of
the equipment.
Field verification of the correct operation of all system interlocks
(software & hardwired)
Field verification of the correct operation of all system alarms
Field verification of the correct operation of the control system in
terms of data access, data security, data protection, data
archiving, data backup, data export, parameter boundary testing
etc.
Field verification of the correct operation of all system outputs to
the DAS
Field verification of correct equipment cycle/recipe/phase
sequencing
Field verification (and simulation) of the correct operation of all
control system interfaces
Field verification of the correct operation of system UPS and
response to power failure
Verification that all test instruments have been correctly
calibrated to a traceable national standard, calibrations are
current and valid and calibration certificates are available
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Public Health England
Porton Down
Salisbury SP4 0JG UK
SPECIFICATION NO. PHE-PD/URS/856

Appendix C: Outline Validation Protocol

C1. UF/DF validation is establishing documented evidence that provides a high degree of assurance that a
specific process will consistently produce a material meeting its predetermined specification and quality
characteristics. Validation provides evidence that the process reliably and reproducibly delivers the
designed process.
C2. Current standards generally expect that validation shall be carried out in three phases: Installation
Qualification (IQ), Operational Qualification (OQ) and Performance Qualification (PQ). Phases One and
Two will be carried out following installation by the Vendor at PHE, Porton in conjunction with PHE
Engineering Department. Phase Three shall be carried out by Production and Quality Assurance
supported by the Engineering Department.
THE UF/DF MANUFACTURER MUST PROVIDE A SEPARATE ITEMISED COST FOR THE IQ AND OQ IN
THE ORIGINAL TENDER
C3. The following procedures are intended to enable the UF/DF manufacturer to demonstrate to PHE that,
in a logical sequence, the UF/DF Rig meets with the current validation requirements.
C4. The following procedures must be incorporated into protocols that specify the necessary objectives,
actions and acceptance criteria. Protocols must be prepared according to PHE’s standard procedures
and be pre-approved by PHE. Full costs for the preparation of these protocols must be included in the
manufacturer’s bid.
Installation Qualification
C5. Check authenticity and status of received documentation (as specified in Appendix A); verify all
documentation is “as built and installed”.
technical specification
schedule of equipment and materials (all components)
welding certification
operating instruction manual
installation drawing
mechanical & electrical drawings
planned maintenance instructions and schedule
list of critical spare parts
materials certification
passivation certificates
C6. Check compliance of installation against specification and drawings; document deviations from
specification.
C7. Check utility services against specification and drawings (i.e. components, size, materials,
identification, etc.). Document deviations to specification and drawings.

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Public Health England
Porton Down
Salisbury SP4 0JG UK
SPECIFICATION NO. PHE-PD/URS/856

Operational Qualification

C8. Check fittings confirm correct assembly and demonstrate full satisfactory operation of:-
The flat sheet cassette unit.
The Single use Flow Path kit.
Recirculation container, Pump and balance
The cooling plates, system & pump.
All sensors, probes & valves
The Ultrafiltration process verifying operation of sensors, valves, scales and meters.
The Diafiltration process verifying operation of sensors, valves, scales and meters.
C9. Check and confirm the Rig will operate satisfactorily in a cold room environment.
C10. Measure and check noise readings do not exceed 80 dBA during normal operations when measured
1m away from any part of the equipment.
C11. Test & verify correct operation of all system interlocks (software & hardwired)
C12. Test & verify correct operation of all system alarms
C13. Operate and confirm satisfactory operation of all the control system in terms of data access, data
security, data protection, data archiving, data backup, data export, parameter boundary testing etc.
C14. Test and confirm in writing, satisfactory operation:-
The correct operation of all system outputs to the DAS
Correct equipment cycle/recipe/phase sequencing
The correct operation of all control system interfaces
The correct operation of system UPS and response to power failure

C15. On satisfactory demonstration of installation/operational qualification in Sections C5 to C14 above, the

UF/DF manufacturer shall ensure all of the relevant documentation is complete and as installed and
qualified. This documentation shall form part of the overall validation package for the UF/DF.
C16. A full written report of the IQ, SIQ, SOQ and OQ results, compliance with acceptance criteria and
fitness-for-purpose statement must be supplied as part of the overall validation package.

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 User Requirement Specification No. PHE-PD/URS/865

Appendix D: Floor Layout of PPC Room 8,9 & 10

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