URS-1808 - Rev - 01 - Final - 06.07.2020 Signed

DocuSign Envelope ID: 5D5239DC-5570-4620-80A2-0D3678A620BD
User Requirements Specification for Porton Biopharma

Reconfigured PPC Zones 5-8 for New Limited
Process Solutions and Purification Porton Down UK
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PROJECT: PPC Zones 5-8 reconfiguration

PROJECT NO: 150083
CLIENT: Porton Biopharma Limited
Porton Down, Salisbury
Wiltshire, SP4 0JG
User Requirements Specification for Reconfigured PPC Zones 5-
Document Title:
8 for New Process Solutions and Purification Suites
Document Identification: PBL/URS/1808 rev 01
System Name: PPC B05, Zones 5-8
System Reference: PPC-08-01
Equipment Asset
N/A
Number:
Change Control
CC-0187-19
Reference:
1.0 Document Approval

Role Job Title Name Signature Date
(and affiliation, if
not PBL)
06-Jul-2020
Author Project Manager Jamie Holder
Capital Projects 06-Jul-2020

Validation Peter Reardon
Validation
Process
Engineering Engineering Ian King 06-Jul-2020
Manager
DSP Functional 07-Jul-2020
User Justin Hayzen
Manager
07-Jul-2020
User Unit Manager Caroline Bowditch
Health & Safety 06-Jul-2020

H&S Caroline Langhurst
Manager
Director of
Project 16-Jul-2020
Pharmaceutical Shane Jones
Sponsor
Production
Quality 17-Jul-2020
Qualified Person Paul Bolam
Assurance
Document ID: PBL/URS/1808 rev 01 VAL-TEMP-0025 v: 04

System Name: PPC B05, Zones 5-8 Page 1 of 41

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Contents
1.0 Document Approval .................................................................................... 1
2.0 Revision History .......................................................................................... 3
3.0 Roles and Responsibilities ......................................................................... 4
4.0 Glossary of Terms ....................................................................................... 4
5.0 Introduction ................................................................................................. 6
6.0 Project Scope .............................................................................................. 6
7.0 Codes & Standards ..................................................................................... 8
8.0 Environmental Conditions ........................................................................ 11
9.0 Utilities Available ....................................................................................... 12
10.0 Product and Process Requirements ........................................................ 12
11.0 Operational Requirements........................................................................ 13
12.0 Facility Requirements ............................................................................... 13
13.0 Equipment Requirements ......................................................................... 31
14.0 Testing and Qualification Requirements ................................................. 31
15.0 Health, Safety and Environmental Requirements ................................... 34
16.0 Documentation Requirements and Deliverables .................................... 34
Appendix A – Developed design drawings .......................................................... 39


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2.0 Revision History

Revision Change Details Control Ref Author Date
(Change control or
other record)
0 First Issue CC-0187-19 Jamie Holder 09 DEC 2019

-References to SOP-eENG-0008 and
SOP-eENG-0024 added.
-
-Room numbering updated to match
CAD allocated room numbers and
the change in layout.
-6.2.1 – Added the addition of out of
scope URS for the Clean steam and
WFI generation and new distribution
systems.
- Section 12Updated various
changing requirements from revised
gowning requirements.
- 12.1.16 & 12.2.10 - pressure
cascade modified to suit new layout
and room numbering.
- Processing room 218 only requires
1 x sink.
- Requirement for the UDAFs to form
part of the facility HVAC and
integrated into the facility has been
removed.
01 - All cold room requirements/ CC-0187-19 Jamie Holder 06 JUL 2020
references removed, these will be
captured in separate URSs.
- 6.2.1.5 - clarification that the FMS is
an existing system.
- 12.4.28 - Occasional exposure to
VHP in clean room added.
- 12.7.11.1 - 1 x WFI tundish required
in room 212.
- 12.7.12.1 – Only 1 x sink required in
room 218.
- 12.8.6 – Lighting LUX level
requirements for all ground floor
areas 500LUX.
- 12.9.7 – CCTV viewed from
production office
- 12.9.8 – Inclusion of intercom.
- 12.2.4.11 – Transfer hatch to
transfer 90 x 200L bottles.
- 12.5.5 & 12.5.6 – removed upper
target air change rate.
- 12.5.2 – removed, included in FMS
URS


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- 12.5.10 – HEPAs installed

maintained within clean room
- 12.9.10.5 – Removed TFF 3PH
power requirement.
- 12.3.8 – Interlock to room 208 grade
D corridor.
- 12.6 – All UDAF requirements
removed. Separate URSs to be
produced.
- 12.5.1 – Low relative humidity limit
changed to 10%RH.
- 12.3 – minor updates.
- 12.8 – Socket height requirements
removed.
- 12.1 – Locker requirements defined.
- 12.4 / 12.5 / 14.4 – Minor changes.
- 12.4.6 – Large equipment route into
facility through internal doors.
- 12.1.16 / 12.2.10 – Pressure
cascades adjusted to show desired
design instead of minimum limits.
- 12.5.20 – Minor update
3.0 Roles and Responsibilities

Refer to SOP-eQA-0091 for roles and responsibilities associated with this URS.
4.0 Glossary of Terms

AFFL Above fixed floor level
AHU Air handling unit
ATEX Explosive atmosphere
BMS Building management system
DF Diafiltration
DOP Dispersed oil particulate
DQ Design qualification
FDA Food and Drug Administration
FMS Facility monitoring system
GRP Glass reinforced plastic


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GxP General abbreviation for Good Practice guidelines.

“x” can be substituted with:
• “C” – clinical
• “M” – manufacturing
• “D” or “Doc” – documentation
• “L” – laboratory
HAZOP Hazard and Operation study
HEPA High efficiency particulate air
HMI Human-machine interface
HSE Health & Safety Executive
HVAC Heating, ventilation and air conditioning
IQ Installation qualification
LTHW Low temperature hot water
LV Low voltage
OQ Operational qualification
P&ID Piping & instrumentation diagram
PBL Porton Biopharma Ltd.
PMS Particle monitoring system
PPC Pharmaceutical Production Centre
PQ Performance qualification
QMS Quality management system
SCADA Supervisory control and data acquisition
TFF Tangential flow filtration
UDAF Unidirectional airflow
UF Ultrafiltration
URS User requirements specification
VHP Vaporized Hydrogen Peroxide
VMP Validation master plan
VP Validation plan
WFI Water for injection


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The following Sections 5 to 9 of this user requirements specification 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 (GMP) user
requirements.
5.0 Introduction
This URS describes the requirements of the proposed Pharmaceutical Production Centre
(PPC) Zones 5-8 reconfiguration project for the support of Erwinase manufacture.
The existing PPC building is a steel framed structure with external built up insulated clad
walls and a metal deck insulated mineral torch on felt roof. The ground floor consists of the
cleanroom production areas with a walk on type ceiling above and an open metal deck plant
area above which houses associated plant and equipment such as AHUs, electrical
distribution boards, utilities, etc. Internal walls are constructed in block wall system, laid with
plasterboard and various finishes such as GRP and vinyl walls and ceiling finishes. It was
constructed circa 1978.
This proposal will embark upon a reconfiguration of PPC zones 5-8, in a phased manner,
i.e., zones 7-8 (phase 1) to be executed first, followed by zones 5-6 (phase 2). Zones 7-8 will
be qualified, bought into beneficial use and zones 5-6 current operations (processing
solution manufacture) moved over before zones 5-6 construction activities can begin.
This new layout will support equipment preparation for use in the Erwinase manufacturing
process. Processing solution preparation will be performed in zones 7-8 and used in the
purification process which will relocate from its current location in zones 1-4 to zones 5-6
once zones 5-6 have been reconfigured.
There will be additional URSs required associated with the proposal, mainly associated
around the equipment and utility requirements and individual systems.
5.1 System Impact Assessment Outcome
Reference Revision System Outcome

QRA/1827 01 Facility Direct impact
QRA/1835 01 HVAC Indirect impact
5.2 Computer System Impact Assessment Outcome
Not applicable – no computer systems requiring impact assessment.
6.0 Project Scope

This specification covers the user requirements associated with the design, supply,
installation, commissioning and validation of PPC facility zones 5-8 reconfiguration.
6.1 In Scope
The works are to design, supply, install, commission and validate a GMP and HSE compliant
manufacturing facility to support the manufacture of Erwinase.


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6.1.1 Building
Emphasis must be put on the design strategy with the demolition and construction
works and the on-going normal daily activities within the PPC facility. It is imperative
that the contractor takes this into consideration.
6.1.2 Cleanrooms
6.1.2.1 Walls and finishes
6.1.2.2 Walk-on ceilings
6.1.2.3 Doors
6.1.2.4 Flooring
6.1.3 HVAC
6.1.3.1 Cleanroom air conditioning
New AHUs will replace the old and associated HVAC system in zones 5-8,
including the building management system (BMS), ductwork, chilled water
distribution pipework, steam distribution pipework and all associated valves
and sensors, Hot and cold water services and drainage systems to support
the cleanrooms and plant area above. Drainage will need to be designed to
suit the area to ensure compliance with the relevant cleanroom areas. A
new HVAC system will be designed to support the grade D and Grade C
cleanroom manufacturing areas.
6.1.4 Local extract ventilation
6.1.5 Electrical
6.1.5.1 Main LV distribution
The LV distribution was recently renewed.
6.1.5.2 Main containment
6.1.5.3 Small power
6.1.5.4 Earthing and bonding
6.1.5.5 Lighting
6.1.5.6 Fire alarm
6.1.5.7 Data/telephone
6.1.5.8 Access control
6.1.5.9 Door interlocks
6.2 Out of Scope
6.2.1 The following are captured in separate URSs:

6.2.1.1 Installation of New clean steam & WFI generation system within PPC
basement (B05/110)
6.2.1.2 Installation of new clean steam distribution system
6.2.1.3 Extension to the existing compressed air distribution system
6.2.1.4 Installation of new water for injection (WFI) distribution system
6.2.1.5 Installation of new facility monitoring system (FMS) connected to existing
recorder.


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6.2.1.6 Installation of data points for existing particle monitoring system (PMS)
6.2.1.7 Utilities SCADA
6.2.1.8 Unidirectional airflow units (2 of)
6.2.1.9 Cold store 216 & cold room217
6.2.1.10 Installation of new purified water generation and distribution within PPC
basement (B05/110)
6.2.2 The following utilities are captured in the Scope of Works, which will be supplied to the
principal contractor:
6.2.2.1 Low temperature hot water (LTHW)
6.2.2.2 Compressed air
6.2.2.3 Plant steam and condensate
6.2.2.4 Chilled water
6.2.2.5 Potable water, cold
6.2.2.6 Standalone equipment vents
6.2.3 The following items of equipment will be supplied or moved as part of the configuration.
While their installation will require to be considered as part of the reconfiguration, they
are out of the scope of this URS:
6.2.3.1 Centrifuges (6 of)
6.2.3.2 Large floor Balance
6.2.3.3 Fume cupboard
6.2.3.4 Equipment Washers (2 of)
6.2.3.5 Autoclaves (2 of)
6.2.3.6 Drying Oven
6.2.3.7 AKTA Chromatography Skid
6.2.3.8 Pall Allegro TFF Unit
6.2.3.9 Process room freezers
6.2.3.10 Process solutions UDAF
6.2.3.11 Processing room UDAF
7.0 Codes & Standards

The following Section 7 describes the codes and standards that shall generally apply to all
equipment supplied to meet the user requirements specified in this document.
Where reference to specific sections of these codes and standards is required, these will be
documented in the testable clauses (Section 11-16 of this user requirements specification).
7.1 The equipment shall be in compliance with current CE marking regulations and
requirements.


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7.2 GMP Regulatory Requirements
The equipment shall comply with all current UK and US FDA Good Manufacturing Practices
including, but not limited to, the requirements of:
21CFR Part 210 Current Good Manufacturing Practice in Manufacturing,

Processing, Packing, or Holding of Drugs; General
21CFR Part 211 Current Good Manufacturing Practice for Finished
Pharmaceuticals
21CFR Part 600 Biological Products: General
BS EN ISO 14644-1 Cleanrooms and associated controlled environments – Part 1

Classification of air cleanliness by particle concentration
EMA 410/01 revision 3 Notes for guidance on minimising the risk of transmitting animal
spongiform encephalopathy agents via human and veterinary
medicinal products
EudraLex Vol 4, Annex 1 EU Guidelines for Good Manufacturing Practice for Medicinal
Products for Human and Veterinary Use – Manufacture of
Sterile Medicinal Products
Products for Human and Veterinary Use – Computerised
Systems
Products for Human and Veterinary Use – Qualification and
Validation
EudraLex Vol 4, Annex 19 Reference and Retention Samples
The Orange Guide Rules and Guidance for Pharmaceutical Manufacturers and
Distributors 2015
7.3 Other Regulatory Requirements
The equipment shall comply with other relevant, current UK regulations including, but not
limited to, the requirements of:
PUWER (1998) Provision and use of Work Equipment Regulations

PSSR (2000) Pressure Systems Safety Regulations
Directive 2006/42/EC Machinery Directive
Building regulation Building regulation and planning approval
86/188/CE Protection of Workers from the risks Related to Exposure to
Noise
2003/10/CE Minimum health and safety requirements regarding the
exposure of workers to the risks arising from physical agents
(noise)
ATEX Directive, 94/9/CE Equipment in potentially explosive atmospheres
COSHH Control of Substances Hazardous to Health


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L24 Workplace health, safety and welfare. Workplace (Health,

Safety and Welfare) Regulations 1992. Approved Code of
Practice and guidance
CDM 2015 Construction (Design & Management) Regulations 2015
7.4 Applicable Codes and Standards
2006/95/EC Low Voltage Directive

ASHRAE Handbook Refrigeration Handbook
ASME BPE 2014 Bioprocessing Equipment
BS 7671:2018 Requirements for Electrical Installations. IET Wiring
Regulations 18th Edition
BS 5266-1:2016 Emergency lighting. Code of practice for the emergency
lighting of premises
BS 5499-10:2014 Guidance for the selection and use of safety signs and fire
safety notices
BS EN 60204-1:2006 Safety of machinery. Electrical equipment of machines.
General requirements
BS EN 60598-2-22:2014 Luminaires. Particular requirements. Luminaires for emergency
lighting
BSRIA Building Services Research and Information Association –
current guidelines
CIBSE Chartered Institution of Building Services Engineers – current
guidelines
DSEAR Dangerous Substances and Explosive Atmospheres
Regulations 2002
DW 143 Guide to good practice – Ductwork air leakage testing
DW 144 Specification for sheet metal ductwork
GAMP 5 A Risk Based Approach to Compliant GxP Computerized
Systems
IEC 60529:1989 Degrees of protection provided by enclosures (IP Code)
IEC 61508:2010 Functional safety of electrical/electronic/programmable
electronic safety-related systems
IEC 61511:2018 Functional Safety – Safety instrumented systems for the
process industry sector
7.5 PBL Internal Documents
eCOP-0044 Code of Practice for Security Management of GxP Electronic Systems

eCOP-0045 Code of Practice for Back-up and Recovery of GxP Electronic Systems
eCOP-0069 Code of Practice for Data Integrity
POL-eQM-0001 Quality Manual
POL-eQMP-0001 Porton Biopharma Ltd (PBL) Document Control Policy
POL-eQMP-0009 The Porton Biopharma Ltd Data Governance System
POL-eQMP-0011 Validation Policy


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SOP-eENG-0008 The Preparation and Use of User Requirements Specifications (URS)

SOP-eENG-0024 GMP Capital Projects Procedure
SOP-eENG-0068 Environmentally Control Storage Equipment and Facilities Validation
Procedure
SOP-eQA-0006 Management of GXP Suppliers and Manufacturers
SOP-eQA-0012 Completion of Documentation for GXP Compliance
SOP-eQA-0028 Change Management/Change Control
SOP-eQA-0049 Pest Control at Porton Biopharma Ltd
SOP-eQA-0053 Management of Quality Risks
SOP-eQA-0071 MasterControl 'Quality Events' Module - Issue Review and CAPA
SOP-eQA-0090 Validation Document Management
SOP-eQA-0091 Validation Procedure
SOP-eQA-0102 Facilities Validation Procedure
SOP-eQA-0103 Computer Systems Validation Procedure
8.0 Environmental Conditions

The following Section 8 describes the environmental conditions into which the equipment
supplied to meet the user requirements specified in this document will be installed.
8.1 Cleanrooms on the ground floor of the existing building will consist of EU Grade D & EU
Grade C.
8.2 The outside ambient conditions specified for the site are:
8.2.1 Summer: 35 °C dry bulb, 20 °C wet bulb

8.2.2 Winter: -10 °C saturated
8.3 The HVAC system for zones 7-8 shall be suitable for the heat gains from the following:
8.3.1 2 × autoclaves
8.3.2 2 × Equipment washers
8.3.3 Drying oven
8.3.4 Large walk-in unidirectional airflow unit
8.3.5 Balances
8.3.6 Fume cabinet
8.3.7 Lighting
8.3.8 Up to 12 people
8.4 The HVAC system for zones 5-6 shall be suitable for the heat gains from the following:
8.4.1 Large walk-in unidirectional airflow unit

8.4.2 2 × freezers
8.4.3 6 × centrifuges


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8.4.4 AKTA chromatography skid

8.4.5 Pall Allegro UF/DF System
8.4.6 Lighting
8.4.7 Up to 10 people
8.5 The building and HVAC systems shall be provided with energy reduction options, where
reasonably practicable. Supplier(s) to advise on typical energy and utility consumption
rates
8.6 There shall be ATEX rated areas to support the storage and use of flammable materials,
to be assessed during design.
9.0 Utilities Available

The following Section 9 describes the utilities that shall be made available to serve the
equipment supplied to meet the user requirements specified in this document.
9.1 The project design shall assess any additional utility requirements against the current
system capability to confirm that there is sufficient existing system capacity to meet the
new demand. Vendor to provide utility requirements as specified for this system.
URS Supply
Supply Supply Equipment
Ref Utility Flowrate Connection
Pressure Temperature Requirement
Size
9.1.1 Electrical 240 V, 1ph, N/A N/A Vendor to Vendor to
power 50 Hz advise advise
415 V, 3ph,
50 Hz
9.1.2 Instrument air 7.0 barg -40 ºC Vendor to Vendor to Vendor to
(oil free) dewpoint advise advise advise
9.1.3 Chilled water 3-4 barg <7ºC Vendor to Vendor to Vendor to
advise advise advise
9.1.4 Plant steam ≤ 7 barg Saturated Vendor to Vendor to Vendor to
9.1.5 Potable water ≤ 4.5 barg 10 °C to To suit Vendor to Vendor to
15 °C Advise Advise
9.1.6 Drainage N/A N/A Vendor to Vendor to Vendor to
9.1.7 LTHW ≤5 barg ≤80°C Vendor to Vendor to Vendor to
10.0 Product and Process Requirements

Not applicable – no specific product or process requirements.
The following Sections 11 to 16 of this URS include testable clauses relevant to the specific
equipment that shall be supplied. Clauses specified as ‘GMP’ are highlighted as essential to
the maintenance of product equivalence and regulatory compliance. Clauses specified as
‘HSE’ are highlighted as being critical to health, safety or environmental compliance. Whilst
these must be verified in the testing regime these clauses will not be subject to qualification.


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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.
11.0 Operational Requirements

11.1 Sampling and Monitoring Requirements
Not applicable; while an FMS and extension to the PMS will be installed, they are out of the
scope of this URS.
12.0 Facility Requirements

12.1 Phase 1
Reconfiguration of zones 7-8 will be carried out first.
Proposed layouts and flows for phase 1 are shown in Appendix A .
12.1.1 Room 201
URS Ref. Description Class

12.1.1.1 The following items will be installed in the unclassified Lobby room GMP
201 leading to the entrance to the coats off Room 202 and
Materials airlock in room 207 & external link corridor. This will
facilitate the entrance to the facility and booking in:
• A standing height bench for booking in of materials and
personnel
12.1.2 Room 202

12.1.2.1 The following items will be installed in the unclassified coats off GMP
room 202which is leading to the entrance to the initial change
Room 203, to facilitate changing:
• Lockers for storage of personal effects, wallets, watches,
jewellery, food drink, mobile phones. Any other personal
items will be left outside the unit. Minimum of 30 locker
compartments.
• Coatracks
• Waste bin
• Hand sanitization
12.1.3 Room 203

12.1.3.1 Room 203 will be a personnel initial change area, and shall be GMP
designed to be capable of control to controlled not classified
(CNC). In room 203 personnel will change into a two-piece
scrub.


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12.1.3.2 Room 203 shall be sized to accommodate the following items GMP
and these items will be sized and designed to allow for a
maximum throughput of personnel of 30 people:
• A minimum of 3 cubicles for changing into gowning each
change cubical to contain a bench for putting on clothes,
IPA, wipes and hand sanitiser.
• Bulk storage of gowning
• Storage for outdoor shoes and cleanroom shoes, bags
and safety spectacles
• Lockers for personal clothing
• Storage for mob caps and beard snoods
• Mirror
• Waste bin
• Container for used cleanroom clothing
12.1.3.3 Room 203 will connect to the following spaces: GMP
• Room 202
• Room 204;
• Room 206
12.1.4 Room 204

12.1.4.1 Room 204 will be a waste out unclassified area and will be GMP
connected to the following spaces:
• Room 203
• Room 205
• External space
12.1.5 Room 205

12.1.5.1 Room 205 will be a waste out airlock and shall be classified as GMP
Grade D, in accordance with the requirements of EudraLex 4
Annex 1.
12.1.5.2 Room 205 will be used for the removal of waste from room 209 GMP
and will connect to the following spaces:
• Room 204
• Room 209
12.1.6 Room 206

12.1.6.1 Room 206 will be a personnel change area, and shall be classified GMP
as Grade D, in accordance with the requirements of EudraLex 4
Annex 1.


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12.1.6.2 Room 206 shall be sized to accommodate the following items: GMP
• Individual gown storage
• A step over demarcation.
• Storage racks for gloves, wipes and overshoes
• IPA and hand sanitizing gel
• Bin x 2 for rubbish and used clean room clothes
• Room 203
• Room 208
12.1.7 Room 207

12.1.7.1 Room 207 will be a materials transfer in area, and shall be GMP
classified as Grade D, in accordance with the requirements of
EudraLex 4 Annex 1. Just for phase 1 this will be the materials
transfer In & out until zones 5-6 reconfiguration works (Phase 2)
is operational then material airlock out on 5-6 side will be used.
12.1.7.2 Room 207 will be sized to accommodate: GMP
• Double door width entrance and exit.
• Hydraulically- or power-assisted hinge mounted large
transfer bench to allow for bulk transfer of small items
and the facility for transfer of large equipment.
12.1.7.3 Room 207 shall connect the following spaces: GMP
• Room 201
• Room 208
12.1.8 Room 208

12.1.8.1 Room 208 will be a corridor, and shall be classified as Grade D, GMP
in accordance with the requirements of EudraLex 4 Annex 1.
• Room 206
• Room 207
• Room 209
• Room 210
• Room 211
• Room 220 (as part of 5-6 reconfiguration in phase 2)
12.1.9 Room 209

12.1.9.1 Room 209 will be a room for the cleaning and preparation of GMP
equipment, and shall be classified as Grade D, in accordance with
the requirements of EudraLex 4 Annex 1.


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12.1.9.2 Room 209 to be sized to accommodate the following items: GMP
• 2 × Double ended equipment washers, including
associated trolleys leading into the equipment
preparation room 211;
• Sinks and benches for preparation of used equipment;
• A large drying cabinet (existing) for drying of washed
equipment
• Shelving units/racking for storage of equipment
• A large central bench area for preparation of equipment
• Room 205
• Room 208
• Room 211 via two double ended equipment washers.
12.1.10 Room 210

12.1.10.1 Room 210 will be a personnel change area, and shall be classified GMP
as Grade C, in accordance with the requirements of EudraLex 4
Annex 1.
12.1.10.2 Room 210 shall have sufficient space to accommodate the GMP
following:
• A step over demarcation
• Racking for bulk storage of gowning items (cleanroom
clothing (hoods, oversuit, over boots, goggles, face
mask)
• Racks for shoe and gown storage (gloves, overshoes,
wipes, IPA, hand sanitiser.
• Mirror
• Bin x 2 for rubbish and used clean room clothes
• Clothing hoods (for re-useable cleanroom clothing on
exit).
• Over boot storage (for re-use).
12.1.10.3 Room 210 shall connect with the following spaces: GMP
• Room 208
• Room 212
• Room 218 (Once zones 5-6 (phase 2) have been
reconfigured and implemented)
12.1.10.4 Room 210 will also be connected to the second phase of work, GMP
consideration will be given around the creation of a door within
the spine wall to connect to room 218
12.1.11 Room 211

12.1.11.1 Room 211 will be a room for the packaging and preparation of GMP
equipment, and shall be classified as Grade D, in accordance with


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12.1.11.2 Room 211 will be sized to accommodate the following items: GMP
• 2 integrated double ended autoclaves leading into the
Grade C Storage / staging room
• Shelving units/racking for storage of equipment
• A large central bench area for preparation, assembly and
packaging of equipment with suitable data and power
12.1.11.3 Room 211 will connect the following spaces: GMP
• Room 208
• Room 209 via double ended equipment washers
• Room 213
• Room 215 via two double ended autoclaves
12.1.12 Room 212

12.1.12.1 Room 212 will be used for the preparation of processing solutions, GMP
and shall be classified as Grade C, in accordance with the
requirements of EudraLex 4 Annex 1.
12.1.12.2 Room 212 will be sized to accommodate: GMP
• A walk-in unidirectional airflow unit (UDAF).
• A fume cupboard for the dispensing of powders with top
pan balance within.
• A large floor mounted balance
• Benching to accommodate minor equipment i.e. pH
meters, magnetic stirrers
• Racking for storage of minor equipment.
12.1.12.3 Room 212 will include an ATEX segregated area for use and HSE
short-term storage of corrosive and flammable liquids.
• Room 210
• Room 215
12.1.13 Room 213

12.1.13.1 Room 213 will be an area for transferring materials from Grade D GMP
space to Grade C space, and shall be classified as Grade C, in
accordance with the requirements of EudraLex 4 Annex 1.
12.1.13.2 Room 213 will also include: GMP
• Room 211
• Room 215
12.1.14 Room 214


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12.1.14.1 Room 214 shall be built to allow access to the autoclaves GMP
connecting Rooms 211 and 215 for maintenance without entering
the cleanroom areas. Room 214 will be unclassified.
12.1.14.2 Room 214 shall connect with the maintenance space via a GMP
staircase.
12.1.14.3 Under normal circumstances, room 214 shall NOT connect with HSE
the cleanroom areas; suitable means for escape at ground level
shall be included, e.g. a transparent breakout panel.
12.1.15 Room 215

12.1.15.1 Room 215 will be a storage/staging area, and shall be classified GMP
as Grade C, in accordance with the requirements of EudraLex 4
Annex 1.
12.1.15.2 Room 215 will be sized to accommodate the following items: Non-GMP
consist of:
• Racking for storage of prepared equipment
• Cabinets for bulk flammable & chemical storage
• Storage for large process equipment i.e. process tanks
12.1.15.3 Room 215 shall have an emergency exit to the outside space, HSE
covered by a cleanroom breakout panel.
12.1.15.4 Room 215 will need to consider ATEX segregated area for long- HSE
term storage of flammable liquids
• Room 212;
• Room 213;
• Room 216.
Room 216

12.1.15.6 Room 216 will be captured in a separate URS GMP
12.1.16 Pressure Cascades

Adjacent rooms of different grades should be designed to have a differential pressure of 15
pascal. The differential pressures depicted in the attached drawing represent the desired
pressure cascades. All alarm functions are details in the FMS URS-1817.

12.1.16.1 Room 203 shall be a nominal 5 Pa higher than room 202. Non-GMP
12.1.16.3 Room 206 shall be 15 Pa higher than Room 203. GMP
12.1.16.4 Room 208 shall be a nominal 5 Pa higher than Room 206. Non-GMP
12.1.16.5 Room 207 shall be 15 Pa higher than Room 201 GMP


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12.1.16.8 Room 208 shall be a nominal 10Pa higher than room 209. Non-GMP
12.1.16.9 A pressure differential is not required between Rooms 208 and Non-GMP
211
12.1.16.12 Room 213 shall 15 Pa higher than Room 211. GMP
12.1.16.13 Room 212 shall be nominal 5 Pa higher than Room 210. Non-GMP
12.1.16.15 A pressure differential is not required between Rooms 212, 215 Non-GMP
and 216.
12.2 Phase 2
The second phase will involve a reconfiguration of the existing zones 5-6, and some further
alterations to zones 7-8 to accommodate the extended production area.
Proposed layouts and flows for phase 2 are shown in Appendix A (p.38).
12.2.1 Changes to Zones 7-8

The following changes will be made to zones 7-8 as part of phase 2:

12.2.1.1 A door will be added to room 208 to connect with room 220. GMP
12.2.1.2 A door
A will be added to room 210 to connect with room 218. GMP
12.2.1.3 A door will be added to room 215 to connect with room 218. GMP
12.2.2 Room 217

12.2.2.1 Room 217 will be captured in a separate change control. GMP
12.2.3
12.2.4 Room 218

12.2.4.1 Room 218 will be a processing room, and shall be classified as GMP
Grade C, in accordance with the requirements of EudraLex 4
Annex 1.


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12.2.4.2 Room 218 shall be sized to accommodate the following: GMP
• Walk-in UDAF
• Six centrifuges
• Two ATEX rated freezers (-3.5°C)
• 1 x sinks
• Benching to accommodate minor equipment, e.g. top
pan balances, pH meters, magnetic stirrers
• Room 44 (existing facility, zones 1-4) via a transfer
hatch;
• Room 210;
• Room 215;
• Room 217;
• Room 219.
12.2.4.4 Room 218 shall connect to existing room 44 for the transfer of GMP
drug Substance (DS) into zones 1-4. DS will be transferred into
the area via a transfer hatch of cleanroom standard. It will have
extract from low level and supply air bleed from the grade C
room side (218) via a vent.
12.2.4.5 Transfer hatch to be made from 304 or 316L polished stainless GMP
steel.
12.2.4.6 Transfer hatch will be fixed using concealed stainless steel GMP
fixings.
12.2.4.7 Transfer hatch to be fully sealed into the wall & at the doors. GMP
12.2.4.8 The transfer Hatch doors will be mechanically interlocked to GMP
ensure only 1 door can be opened at any one time.
12.2.4.9 The exposed surface of the transfer Hatch will be crevice & GMP
Ledge free and will be easy to clean.
12.2.4.10 The transfer hatch door will have glazing for visibility into the Non-GMP
hatch and adjacent area.
12.2.4.11 The transfer hatch will be capable of transporting 90 x 200L Non-GMP
bottles of drug substance.
12.2.5 Room 219

12.2.5.1 Room 219 will be an area for transferring materials out of the GMP
Grade C space, and shall be classified as Grade C, in accordance
with the requirements of EudraLex 4 Annex 1.
• Room 218;
• Room 220.
12.2.5.3 Room 219 shall be sized to accommodate the following items: Non-GMP
and the facility for transfer of large equipment


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12.2.6
12.2.7 Room 220

12.2.7.1 Room 220 will be an area for transferring materials out of Grade GMP
D space, and shall be classified as Grade D, in accordance with
12.2.7.2 Room 220 will be sized to accommodate: Non-GMP
• Double door width entrance and exit through to room
222.
• Room 219
• Room 222
• Room 208
12.2.8 Room 221

12.2.8.1 Room 221 will be used as an office area, and shall be an Non-GMP
unclassified area.
12.2.8.2 Room 221 will be sized to accommodate at least two desks with Non-GMP
PCs.
12.2.8.3 Room 221 shall connect with the entrance corridor 225. Non-GMP
12.2.9 Room 222

12.2.9.1 Room 222 will be an area for transferring waste out of the CNC GMP
area, it shall be designed to be capable of control to controlled
not classified (CNC).
12.2.9.2 Room 222 shall be sized to accommodate the following items: Non-GMP
and the facility for transfer of large equipment
• Room 220;
• Room 225
12.2.10 Pressure Cascades

The following pressure differentials are required in addition to those identified in section
12.1.16. Adjacent rooms of different grades should be designed to have a differential
pressure of 15 pascal. The differential pressures depicted in the attached drawing represent
the desired pressure cascades. All alarm functions are details in the FMS URS-1817.


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12.2.10.4 Room 218 shall be a nominal 5 Pa higher than the transfer hatch Non-GMP
to room 44.
12.2.10.5 The transfer hatch to room 44 will be 15Pa higher than room 44 GMP
12.2.10.6 A pressure differential is not required between Rooms 215, 217, Non-GMP
218 and between 220 & 208
12.2.10.8 Room 218 shall be a nominal 5Pa higher than room 210. Non-GMP
12.3 General Facility Design Requirements

12.3.1 Facility design shall maximise the segregation of personnel GMP
and material/waste flows. There should be no cross-over
between inward and outward flows.
12.3.2 Flow diagrams will be produced and approved by PBL at the GMP
design phase of the project.
12.3.3 Lines of sight across production areas shall be maximised. Non-GMP
Where possible, glass shall be used to improve visibility.
12.3.4 The facility is to be fitted with an access controlled door entry GMP
system (extension of the existing) to control access to the initial
change areas. Access to rooms beyond this threshold will not
be access controlled.
12.3.5 Doors for the materials transfer areas are to be hold-open, HSE
motorised doors and operated by proximity sensors, to allow
easy movement of materials. Where doors are not motorised
hold open door closers will be used.
12.3.6 Doors for the materials air locks are to have configurable delay GMP
timers to allow for differential pressure recovery when materials
are moved through the air locks.
12.3.7 All cleanroom ceiling fittings (for example loudspeakers etc) GMP
shall be of flush mounted and cleanable design.
12.3.8 All airlocks will have interlocking doors so that only one set of GMP
doors can be opened at a time. Status indicators will be
present either side of each airlock door to show if the door is
ok to open.
12.3.9 Room 208 grade D corridor will be interlocked with room 206, GMP
207, 210 and 220 with an adequate time delay to mitigate
personnel and materials crossing path in corridor 208.
12.3.10 Change area doors to be fitted with transparent windows to GMP
allow the availability of the change area to be determined
before entry.


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12.3.11 The building internal layout shall allow for all maintenance to GMP
be carried out from outside the cleanroom envelope (this is to
include light fittings, filters, autoclave skids, etc.), without
compromising the cleanroom integrity. Where this is not
possible the design must be agreed with PBL PM.
12.3.12 All areas shall have maintenance areas above ceiling level. It GMP
shall be possible to walk on and access the ceilings above the
cleanrooms.
It must not be possible to access these areas from the

cleanroom areas.
12.3.13 Maintenance area will have suitable clearance for access and Non-GMP
egress.
12.3.14 The areas being modified are to be compliant to current fire HSE
regulations/standards.
12.3.15 A chemical safety station will be required in room 212 to HSE
protect operatives in case of a chemical spill. This will be in the
form of a Diphotine skin & eye wash station
12.4 Facility Construction and Fabric Requirements

12.4.1 The design should not introduce any new penetrations through Non-GMP
the roof of the existing building. Where new penetrations cannot
be avoided they must be identified in the design documents
12.4.2 All cleanroom internal finishes shall be smooth, impervious and GMP
unbroken to minimise the shedding or accumulation of
particulate matter, durable, cleanable and crevice/ledge free.
12.4.3 All cleanrooms shall have floor-to-wall, wall-to-wall and wall-to- GMP
ceiling coving.
12.4.4 Walls and ceilings are to be constructed using a proprietary GMP
clean room panelling system.
12.4.5 All cleanrooms shall have heavy duty (2.5mm) vinyl floors that GMP
are suitable for frequent movement of mobile trolleys and pallet
trucks (approximate weight 500 kg). They shall be hard wearing,
smooth and level. Building expansion joints to be outside
cleanroom envelope where possible. Vendor to advise the detail
of any building expansion floor joints to ensure suitability for
approval by PBL at the detailed design stage.
12.4.6 Cleanrooms shall be designed to allow equipment HSE
installation/removal with as minimal disruption to the cleanroom
environment as possible. This will be done through the main
entrance to the facility. Door heights will be increased through
the route from corridor 225 to 211 through rooms 201 to 207 and
208.
12.4.7 All cleanroom external corners are to have angle edge strips Non-GMP
fitted to protect against potential damage from trolleys/pallet
trucks.


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12.4.8 Low-level rail wall protection shall be fitted on all trolley routes Non-GMP
throughout the facility.
12.4.9 All hinged cleanroom doors shall be provided with triple hinges, GMP
adjustable drop-down seals along their bottom edge and door
closures. Door will be of a suitable cleanroom door standard
12.4.10 All furniture located in grade C and D cleanroom areas should GMP
be 316/304 stainless steel with smooth impervious and
unbroken finishes.
12.4.11 All surfaces shall be assessed for clean ability. GMP
12.4.12 At the design phase the supplier shall supply documented GMP
evidence that the materials are resistant to the following
cleaning solutions:
• Klercide amine (N,N-Bis(3-aminopropyl)laurylamine

<0.5%)
• Actril cold sterilant (0.08% peracetic acid and 1.0%
hydrogen peroxide)
• 2500 ppm available chlorine solution
• Klercide Neutral
Further information on the purchase and/or preparation of these

cleaning agents will be supplied by PBL on request.
12.4.13 Wood shall not be used in the construction of the cleanroom GMP
fabric.
12.4.14 Doors will be fitted with kick plates on material airlock doors 201, Non-GMP
207, 222, 220, 219, 213 and on the direction of travel into rooms
209, 211, 212, 218. No required on personnel change room
doors.
12.4.15 Rooms must be free of steps or changes in floor levels to allow HSE
pallet truck movement
12.4.16 Condensation must not occur at interfaces between cold rooms GMP
and areas of ambient temperatures.
12.4.17 Hot pipework, fittings and equipment shall be insulated to Non-GMP
achieve a heat loss of less than 150 W m-2, based on indoor
conditions and an ambient temperature of 20 °C.
12.4.18 If personal contact is likely under normal operating conditions, HSE
hot surfaces greater than 55 °C shall be fully insulated. Where
insulation is not possible, practical or desirable, these surfaces
shall be suitably guarded.
12.4.19 Pipework, fittings and equipment operating at less than 15 °C Non-GMP
shall be insulated to achieve a heat gain of less than 40 W m-2,
assuming indoor conditions and an ambient temperature of
20 °C. Surface temperatures shall be maintained above the dew
point to avoid condensation, and a vapour barrier (free from
holes) included.
12.4.20 Flexible ‘bag’ type insulation, attached by means of Velcro or Non-GMP
string ties, is acceptable for valves, flanges etc.


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12.4.21 No insulation shall be applied to any part of the work until that Non-GMP
particular part has undergone successful inspection and
pressure testing. All tested pipes shall be clean, dry and grease
free before the installation of insulation.
12.4.22 Where services pass through fire compartment walls, HSE
regulatory approved standards and solutions shall be applied.
12.4.23 All insulation materials shall be appropriately selected and Non-GMP
subject to the following minimum requirements:
• Non-flammable to BS 476-7:1997 Class 1 (or
equivalent).
• Non-corrosive and odourless at operating temperatures
• Shall not contain substances that initiate the growth of
moulds or support vermin.
• Must not suffer deterioration on contact with moisture
• Moulded sections and slabs shall be mechanically
robust such that they do not suffer damage during
transportation and handling.
• The design and installation of insulation shall not
compromise the maintenance operability and safety of
plant and equipment.
• Polystyrene, polyurethane and isocyanate materials are
not permitted.
12.4.24 All pipework insulation shall be clad with stainless steel riveted Non-GMP
in place.
12.4.25 Windows are to be non-opening. GMP
12.4.26 Doors are to have viewing panels (except for change cubicles). GMP
Glazing is to be flush mounted within the cleanroom.
12.4.27 Penetrations are to be fully sealed, crevice and ledge free. GMP
12.4.28 All materials used within the cleanrooms must be able to Non-GMP
withstand occasional exposure to VHP.
12.5 HVAC Requirements

12.5.1 All production spaces shall be held at the following conditions: Non-GMP
• 18 °C ± 2 °C
• 10 %RH – 70 %RH
With the exception of cold rooms 216 and 217, which will be
held at the conditions identified in the specific separate URSs.
12.5.2 Grade C and Grade D areas will be served by separate air GMP
handling units. The use of recirculated filtered air with fresh air
make-up is acceptable.
12.5.3 All Grade D areas shall have a minimum of 10 air changes per GMP
hour.
12.5.4 All Grade C areas shall have a minimum of 20 air changes per GMP
hour.
12.5.5 All HVAC systems design must include N+1 redundancy with Non-GMP
automatic and seamless switch over.


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12.5.6 All HVAC systems, instruments, valves, equipment etc. shall be Non-GMP
designed and located for ease of maintenance.
12.5.7 The air pattern shall show a general downward direction of GMP
airflow with the air extracted from the room via the low level
extract grilles; airflow patterns shall not show “dead zones” or
static airflow within the rooms. Air flow visualisation (smoke) tests
will be carried out to prove airflow requirements.
12.5.8 HEPA filters must be Camfil H14 in standard sizes. All HEPA GMP
filters must be installed & maintained from within the cleanroom
envelope. Hinges and fittings shall facilitate the smooth,
impervious and continuous finish associated with the clean room
design
12.5.9 All HEPA filters shall be capable of being integrity tested in place GMP
by means of a dispersed oil particle (DOP) challenge, as
specified in PD6609:2007.
12.5.10 Where possible AHU duty/standby fans shall be belt free (direct Non-GMP
drive preferred)
12.5.11 All AHU fan motors shall be installed to allow one motor to remain Non-GMP
running and maintain the required room conditions whilst the
other motor is maintained.
12.5.12 All AHU fan motors shall be of variable speed type with variable Non-GMP
speed drives.
12.5.13 All AHUs shall be fitted with 20% extra fan capacity over as-built Non-GMP
design values. Vendor to advise on fan efficiencies at design @
maximum (including 20% extra capacity).
12.5.14 All AHUs shall be fitted with an air gap (minimum 300 mm) Non-GMP
between the unit air inlet ducts and the louvres on the outside
building skin to reduce the effects of the wind.
12.5.15 All AHUs shall be provided with viewing ports and appropriate Non-GMP
lighting to allow inspection of components without the need to
turn off the ventilation system.
12.5.16 All AHUs shall be fitted with efficient pre-filtration with differential Non-GMP
pressure indication to minimise the loading on terminal HEPA
filters.
12.5.17 All HVAC system parts shall be standard availability (i.e. off the Non-GMP
shelf).
12.5.18 Smoke injection points are to be 1½ inch male Camlock type with Non-GMP
R type threads and stainless steel cam levers and pins, and glass
filled polypropylene bodies.
12.5.19 Ductwork to be leak tight in accordance with DW 144, the Non-GMP
designer to specify ductwork pressure class & tested to DW 143.


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12.5.20 All HVAC systems shall be provided with an alarm system which Non-GMP
shall be based on a trend controls as per the site wide system.
The system will report all faults and adverse operation, including
over/under pressure, temperature and air flow rate. The control
system must be capable of generating pressure differential
alarms between adjacent rooms.
The alarm values must be configurable. An alarm schedule will
be developed during the design phase with, and approved by,
PBL.
The system will be connected to the site head end.
12.5.21 Fans to be provided with Danfoss VLT HVAC drive type inverter Non-GMP
for seamless/stepless inverter. Where the supplier proposes an
alternative to the Danfoss VLT it must be pre-approved in writing
by the PBL project engineer.
12.5.22 Ductwork to be kept clean at all stages of fabrication, transport Non-GMP
and installation by capping & sealing ductwork ends.
12.5.23 All parts of all HVAC systems shall auto-restart in a controlled Non-GMP
manner after power failure.
12.5.24 All HVAC systems shall be provided with automatic constant Non-GMP
volume control on the extract.
12.5.25 Variable speed control will be provided on all HVAC AHU fan Non-GMP
motors.
12.5.26 AHU will have sufficient frost protection to protect filters, sensors, Non-GMP
water systems and valves
12.6 Drainage and Waste Handling Requirements

12.6.1 All drainage in Grade D and Grade C cleanrooms are to be of GMP
suitable cleanroom standard and construction.
12.6.2 Drains which may contain hot WFI, autoclave condensate, Non-GMP
washer discharge of 60 °C or more to have heat resistance rated
pipework.
12.6.3 Where fitted, drainage traps need to be constructed from 304 GMP
stainless steel, and designed with access for regular cleaning,
disinfecting and maintenance.
12.6.4 The building design shall minimise underground drainage routed Non-GMP
under the building. Existing drains shall be rerouted where
possible (to minimise disruption to existing production), to
outside of the footprint of the existing building.
12.6.5 The building internal layout shall minimise the risk of flood Non-GMP
damage from pipework or other equipment leaks. Where
reasonably practicable, pipework and equipment which could
potentially leak is not to be located above cleanrooms.
Where this is not practicable, items which may leak shall be
located in appropriate leak trays/bunds, which are piped to drain
and fitted with leak detection alarms. The drain pipework above
cleanrooms is to be lagged to prevent surface condensation
where drain discharge temperature could cause condensation.


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12.6.6 All open water supply points shall exit over a sink, tundish or Non-GMP
gully, to assist drainage.
12.6.7 The basement area can be utilised for new drainage runs. N/A Info
only
12.6.8 Air breaks to be fitted between equipment or sinks and the GMP
drains to prevent backflow.
12.6.9 Floor drains to be fitted with traps or water seals to prevent GMP
backflow.
12.6.10 Drainage Schedule – Zones 7-8

12.6.10.1 Drainage shall be provided for the following areas: GMP
• Room 209 – 3 sinks
• Room 209 – 2 washers
• Room 214 – 2 autoclaves
• Room 212 – 1 tundish for WFI point
12.6.11 Drainage Schedule – Zones 5-6

12.6.11.1 Drainage shall be provided for the following areas: GMP
• Room 218 – 1 sinks for WFI point
• Room 217 – closed drainage points
12.7 Lighting Requirements

12.7.1 The use of natural light shall be maximised. Non-GMP
12.7.2 Lighting is to be of a cleanroom type light fitting. Flush fit to GMP
ceiling, sealed and easy to clean.
12.7.3 Maintenance access for the lighting will be from the walk-on Non-GMP
ceiling; light fittings will not be accessible from within the
cleanroom.
12.7.4 Activation of all lighting shall be via PIR motion sensors, with a Non-GMP
1-hour switch-off delay.
12.7.5 All ground floor areas shall have a light level of no less than Non-GMP
500 Lux, measured at a height of 900 mm AFFL:
•
12.7.6 Emergency lighting in all areas to meet current British HSE
Standards.
12.8 Electrical Requirements

12.8.1 Separate earthing systems are to be provided for power and HSE
for instrumentation.


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12.8.2 Critical control systems (as advised by PBL) shall be GMP
connected to the PPC building B05 uninterruptible power
supply.
12.8.3 Electrical containment within the clean rooms shall be GMP
minimised. If electrical containment must be placed in
cleanrooms, it shall be constructed of cleanroom material, and
subject to the certification requirements outlined in Section
12.10
12.8.4 All electrical sockets in GMP production areas shall be a HSE
minimum of IP55 rated.
12.8.5 All electrical sockets in technical and service areas shall be a HSE
minimum of IP44 rated.
12.8.6 Wall, flush mounted digital clock with NTP server Non-GMP
synchronisation will be installed in rooms209, 211, 212, 215,
217, 218 as a minimum.
12.8.7 CCTV camera system is required for visibility of rooms 209, Non-GMP
211, 212, 215, 217 & 218. The cameras will be of 360 degree
rotating controlled type. The CCTV will be viewed from outside
the clean room within the unclassified Production office.
12.8.8 Intercoms to be installed for quick connection to rooms 209, Non-GMP
211, 212, 215, 217, 218. They will be connected to the site
wide phone system.
12.8.9 Zones 7-8

12.8.9.1 All areas shall be supplied with at least one single-phase Non-GMP
electrical socket.
The following change areas shall be supplied with at least 2

single-phase sockets, to be able to be used either side of the
stepover/transfer bench as appropriate:
• Room 201;
• Room 202;
• Room 203;
• Room 204;
• Room 206;
• Room 207;
• Room 210;
• Room 213;
12.8.9.2 Two-gang single-phase sockets shall be supplied at 900 mm Non-GMP
AFFL in the following areas, to be constructed:
• Room 209, minimum 9 off;
12.8.9.3 Ceiling-mounted single-phase sockets shall be supplied at the Non-GMP
centre of rooms 209 and 211, as required.


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12.8.9.4 Single-phase 13 A sockets shall be supplied at 450 mm AFFL Non-GMP
in all production areas. Minimum socket requirements to be
determined. Dedicated supplies for equipment with local
isolation
12.8.9.5 Production areas shall be supplied with 415 V three-phase Non-GMP
electrical power. .
12.8.10 Zones 5-6

12.8.10.1 All areas shall be supplied with at least one single-phase Non-GMP
electrical socket.
The following change areas shall be supplied with at least 2

single-phase sockets, to be able to be used either side of the
stepover/transfer bench as appropriate:
• Room 219;
• Room 220;
• Room 222
12.8.10.2 Two-gang single-phase sockets shall be supplied at 900 mm & Non-GMP
450mm AFFL in the following areas:
• Room 217; minimum 9 off
• Room 221, minimum 3 off
12.8.10.3 Ceiling-mounted single-phase sockets shall be supplied at the Non-GMP
centre of rooms 218 as required.
12.8.10.4 Single-phase 13 A sockets shall be supplied at 450 mm AFFL Non-GMP
in all production areas. Minimum socket requirements to be
determined. Dedicated supplies for equipment with local
isolation.
12.8.10.5 Production areas shall be supplied with 415 V three-phase Non-GMP
electrical power for equipment.
12.9 Data Requirements
12.9.1 Zones 7-8

12.9.1.1 RJ45 sockets shall be installed at 900 mm AFFL in the Non-GMP
following areas:
• Room 216, minimum 1 off.
12.9.1.2 Ceiling-mounted RJ45 sockets shall be supplied at the centre Non-GMP
of rooms 209, 211 and 212 as required.


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12.9.2 Zones 5-6

12.9.2.1 RJ45 sockets shall be installed at 900 mm AFFL in the Non-GMP
following areas:
• Room 221, minimum 2 off.
12.9.2.2 Ceiling-mounted RJ45 sockets shall be supplied at the centre Non-GMP
of room 218 as required.
12.10 Materials of Construction Requirements

12.10.1 All materials used in the construction of the production areas GMP
shall be suitable for use in cleanrooms, and appropriate
certification shall be supplied
13.0 Equipment Requirements

13.1.1 Ingress Protection rating of equipment panels shall be: HSE
• Technical areas ≥ IP44
• Process (GMP) areas ≥ IP55
14.0 Testing and Qualification Requirements

14.1 Pre-Delivery Inspection (PDI) Requirements

14.1.1 Where PDI’s are carried out it will be against written test scripts. Non GMP
14.1.2 The PDI document will be reviewed by PBL prior to execution Non GMP
14.1.3 The PDI document will be supplied to PBL 2 weeks prior to Non GMP
execution
14.2 Factory Acceptance Test (FAT) Requirements

14.2.1 The vendor shall FAT all equipment against approved protocols GMP
14.2.2 FAT documentation shall be approved by PBL representatives GMP
before execution.
14.2.3 FAT documentation must be supplied to PBL 4 weeks prior to Non-GMP
execution
14.2.4 All FAT testing will be witnessed by PBL GMP


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14.3 Commissioning and Site Acceptance Test (SAT) Requirements

14.3.1 The vendor shall SAT/commission against approved GMP
protocols
14.3.2 SAT and commissioning documentation shall be approved by GMP
PBL representatives before execution.
14.3.3 SAT/Commissioning documentation must be supplied to PBL Non-GMP
4 weeks prior to execution.
14.3.4 All SAT/commissioning testing will be witnessed by PBL.. GMP
14.3.5 Vendor to supply commissioning and instrumentation Non-GMP
calibrations.
14.3.6 Vendor to supply commissioning consumables. Non-GMP
14.3.7 Commissioning must include full loop calibration of all critical Non-GMP
instrumentation and controls in accordance with procedures
pre-approved by PBL and those specified in CIBSE
Commissioning Code C (Automatic Controls) BSRIA codes.
14.3.8 Pre-Commissioning Tests Non-GMP
Specific testing details shall be agreed in consultation with
PBL via a process of SAT/commissioning document review
cycles but shall include the tests documented below as a
minimum:
• Schematic/P&ID verification
• Panel wiring diagram verification
• BMS display verification
• Ductwork leak testing
• Ductwork cleanliness inspection
• Filter integrity testing (from factory manufacture)
• Equipment maintenance access verification
• Supplied utilities verification
• Instrument calibration verification
• Room balancing
14.3.9 All instruments shall be selected and installed such that they Non-GMP
are fit for purpose and easily accessible for regular calibration.
14.3.10 All AHU instrument calibration and general maintenance Non-GMP
activities shall be performable from outside the cleanroom.
14.3.11 All instrument calibrations shall be performed to 3 points as a Non-GMP
minimum, and shall include complete control loop verification.
14.3.12 The vendor shall provide a quotation for the ongoing support Non-GMP
and maintenance of all equipment provided.
14.3.13 All equipment items (valves, instruments, inline items etc.) Non-GMP
shall be suitably and uniquely tagged/identified. Tag numbers
shall be subject to approval by PBL.


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14.3.14 Operational tests GMP
Shall include the tests documented below as a minimum:
• Filter integrity testing of HEPAs (as SAT)
• Room temperature verification
• RH verification
• Airflow rate verification
• Room air change rate calculation
• Room differential pressure verification
• Room particulate/air cleanliness verification (room
classification)
• Equipment noise level verification
• Lighting level verification
• Room balancing
14.3.15 BMS control system functionality tests shall include the tests Non-GMP
documented below as a minimum:
• Control system and hardwired interlocks operation
verification
• Control system alarm verification
• Control system output/interface verification
• Power failure response verification
• Disaster recovery testing
14.4 Qualification Requirements

14.4.1 The facility shall be subject to a full validation lifecycle in GMP
accordance with SOP-eQA-0091 and SOP-eQA-0102., and
shall include the following:
• GMP design reviews
• Design qualification (DQ) and generation of a
requirements trace matrix (RTM)
• Installation qualification (IQ)
• Operational qualification (OQ)
• Equipment summary report
• Performance qualification (PQ)
• Validation summary report (VSR)
14.4.2 All documentation shall be approved by PBL representatives GMP
before execution.
14.4.3 All documentation must be supplied to PBL 4 weeks prior to Non-GMP
execution
14.4.4 All testing will be witnessed by PBL GMP
14.4.5 Facility validation shall be performed in two stages: N/A for
• Upon completion of phase 1 (zones 7-8) information
• Upon completion of phase 2 (zones 5-6) only


Suites
15.0 Health, Safety and Environmental Requirements

15.1 Health and Safety Requirements

15.1.1 Noise level in the cleanrooms is to be below NR60 with no HSE
process equipment running.
15.1.2 Equipment shall not exceed 75 dBA during normal operations HSE
when measured 1 m away from any part of the equipment.
15.1.3 The equipment shall meet all applicable safety regulations, HSE
including the UK Provision and Use of Work Equipment
Regulations, and the Manual Handling Operations Regulations
15.1.4 The vendor shall provide all Health & Safety regulatory HSE
compliance documentation, to support CE marking or as
required by the Pressure Equipment Directive, for the equipment
within the vendor scope of supply.
15.1.5 All emergency stops shall be protected by a shroud to prevent HSE
accidental operation (if applicable).
15.1.6 The building design shall ensure that appropriate emergency HSE
escape routes are maintained and/or incorporated. Fire strategy
drawings will be provided. building control approval will be
required.
15.1.7 The building design shall ensure that emergency lighting is HSE
maintained and/or incorporated to meet current regulation.
15.1.8 The facility is to include an extension of the existing fire alarm HSE
system designed to a minimum of a L2 standard.
15.1.9 All interlocked doors shall be provided with manual override to HSE
release the door in the event of an emergency or power failure.
15.1.10 DSEAR assessment shall be undertaken in rooms 202, 203, HSE
206, 210, 212, 215, 216, 217, 218, technical space (service
floor) above manufacturing room and basement for the use and
storage flammable materials.
15.1.11 The vendor will comply with the relevant pressure systems HSE
safety regulation and provide any related safety documentation.
16.0 Documentation Requirements and Deliverables

16.1 Documentation and Vendor Requirements

16.1.1 The documentation deliverable list (see section 16.3) identifies GMP
GMP documentation that will be tested as part of equipment
qualification.


Suites

16.1.2 The vendor shall have a demonstrable quality management GMP
system (QMS) that:
• Provides a documented set of procedures and
standards
• Ensures activities are performed by suitably competent
and trained staff.
• Provides evidence of compliance with the documented
procedures and standards.
• Enables and promotes continuous improvement.
Within the tender, the vendor must define how the QMS will be
implemented for this supply.
16.1.3 The vendor shall allow for a quality audit, by representatives GMP
from PBL, prior to signature of the supply contract.
16.1.4 The vendor equipment Packages shall use their own tag Non-GMP
numbering system throughout all documents and control
system programs on agreement from PBL. The tag numbering
system shall be approved by PBL. At the outset of the project,
the vendor shall issue the equipment and instrumentation list to
the Project Manager, for review. Main distribution and
equipment items will undergo an assessment by PBL to see if
they’re required to adopt the PBL tagging system.
16.1.5 The vendor shall identify any recommended standard (one- Non-GMP
year operation) and critical spare parts to be held by PBL. The
vendor shall provide a fully detailed list (to include reference
numbers, suppliers, ordering details and costs for all spare
parts).
16.1.6 The vendor shall provide hard copies and electronic copies of Non-GMP
the Documentation Deliverables, as identified Section 16.3 of
this document.
16.1.7 All vendor documentation shall be provided in English. Non-GMP
16.1.8 The vendor shall issue drawings in AutoCAD 2017 MEP format Non-GMP
suitable to be placed onto a PBL CAD drawing frame by
others.
16.1.9 The vendor shall comply with the terms of PBL non- Non-GMP
disclosure/confidentiality agreement(s).
16.1.10 The vendor shall provide adequate evidence of testing GMP
including but not limited to the documents defined in the next
requirement.
16.1.11 Any qualification documentation (FAT, SAT, commissioning, GMP
IQ, OQ, PQ) supplied by the vendor will be reviewed by PBL
for suitability and may not be used without prior approval by
PBL QA and/or validation staff.
16.1.12 The vendor shall be available for installation instruction. GMP
16.1.13 The vendor shall supply a computer system hardware and GMP
software specification to enable PBL to source suitable
hardware and software to support the system.
16.1.14 The vendor will develop the business processes in conjunction GMP
with PBL and write specification documents.


Suites

16.1.15 A list of all software configuration items (operating systems, GMP
application software and configuration files) shall be provided,
together with installed versions for each item.
16.2 Training Requirements

16.2.1 The vendor and/or principal contractor shall provide Non-GMP
familiarisation training for the HVAC & BMS systems.
16.3 Documentation Deliverables
Quality Document
Document
(Y/N)
Equipment
Process, materials, personnel, waste flow diagrams Y
Equipment list Y
Process P&IDs (as built) Y
Electrical & pneumatic schematics (as built) Y
Piping isometric drawings – non-critical pipework (as built) N
GA/layout drawings (as built) Y
Equipment data/specification sheets Y
HEPA filter test & material certification Y
Filter integrity test & material certification Y
Vessel pressure certificates/CE certification N
Installation and commissioning method statements/risk assessments Y
Installation & commissioning test reports Y
Validation IQ protocol(s) & report(s) (if required) Y
Validation OQ protocol(s) & report(s) (if required) Y
HVAC Utilities, Piping & Inline Items
Line list N
Valve list N
Inline item list N
Valve & inline item data/specification sheets N
Piping, fitting & gasket specifications N
Safety valve certification (including relief calculations) N


Suites
Quality Document
Document
(Y/N)
Pipework pressure test certification N
HVAC Ductwork and Inline Items
HVAC schematics/P&IDs (as-built) Y
HVAC ductwork damper list Y
HVAC ductwork in-line item list Y
HVAC ductwork damper and inline item data/specification sheets Y
Ductwork test sheets Y
Ductwork balancing sheets Y
Ductwork leak rate test Y
Instrumentation
Instrument list Y
Instrument data/specification sheets Y
Instrument calibration method Y
Instrument calibration certificates Y
Test instrument calibration certificates Y
Control wiring drawing Y
Cleanroom items
Material certification and Certificates of Conformity (EN 10204 3.1b
Y
type certification, preferred)1
Room data sheets Y
Electrical
Fuse/breaker testing N
Panel & equipment identification N
Wire type/size/termination check N
Distribution board schedules N
Control System
Automatic sequence details N
Control diagram(s) N
Input/output schedule N
Logic flow diagram N
1 Material certification shall be provided for all process contact equipment, piping, components, inline
items and instruments (including seals and gaskets).


Suites
Quality Document
Document
(Y/N)
Description of operation N
Hardware design specifications N
All
Quality plan Y
Functional Design Specification(s) (FDS/HDS/SDS) Y
O & M manuals Y
Lubricant schedule & specification Y
Spare parts lists2 Y
HAZOP report(s)3 N
Training materials & certification4 Y
2 The vendor shall provide comprehensive spares lists for one year’s equipment operation.
3 The vendor shall attend HAZOP and SWIFT study meeting.
4 The vendor shall perform all necessary operator and engineer training. The training programme shall
include assessment and certification.

User Requirements Specification for

Reconfigured PPC Zones 5-8 for New Porton Biopharma
Process Solutions and Purification Suites Limited
Porton Down UK
APPENDICES
Appendix A – Developed design drawings
Pressure regime drawing
225
202
204 203
201
205
222 221
0
206 207
220
209 219
208
210
218
211
212
213
215
217
216
2** = Room number


Porton Down UK
APPENDICES
Area classification drawing


Porton Down UK
APPENDICES
Meterials and people flows drawing


URS-1808 - Rev - 01 - Final - 06.07.2020 Signed

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DocuSign Envelope ID: 5D5239DC-5570-4620-80A2-0D3678A620BD

User Requirements Specification for Porton Biopharma

PROJECT: PPC Zones 5-8 reconfiguration

1.0 Document Approval

Capital Projects 06-Jul-2020

Health & Safety 06-Jul-2020

Document ID: PBL/URS/1808 rev 01 VAL-TEMP-0025 v: 04

User Requirements Specification for Porton Biopharma

1.0 Document Approval .................................................................................... 1

2.0 Revision History .......................................................................................... 3

3.0 Roles and Responsibilities ......................................................................... 4

4.0 Glossary of Terms ....................................................................................... 4

5.0 Introduction ................................................................................................. 6

6.0 Project Scope .............................................................................................. 6

7.0 Codes & Standards ..................................................................................... 8

8.0 Environmental Conditions ........................................................................ 11

9.0 Utilities Available ....................................................................................... 12

10.0 Product and Process Requirements ........................................................ 12

11.0 Operational Requirements........................................................................ 13

12.0 Facility Requirements ............................................................................... 13

13.0 Equipment Requirements ......................................................................... 31

14.0 Testing and Qualification Requirements ................................................. 31

15.0 Health, Safety and Environmental Requirements ................................... 34

16.0 Documentation Requirements and Deliverables .................................... 34

Appendix A – Developed design drawings .......................................................... 39

Document ID: PBL/URS/1808 rev 01 VAL-TEMP-0025 v: 04

User Requirements Specification for Porton Biopharma

2.0 Revision History

0 First Issue CC-0187-19 Jamie Holder 09 DEC 2019

Document ID: PBL/URS/1808 rev 01 VAL-TEMP-0025 v: 04

User Requirements Specification for Porton Biopharma

- 12.5.10 – HEPAs installed

3.0 Roles and Responsibilities

4.0 Glossary of Terms

Document ID: PBL/URS/1808 rev 01 VAL-TEMP-0025 v: 04

User Requirements Specification for Porton Biopharma

GxP General abbreviation for Good Practice guidelines.

Document ID: PBL/URS/1808 rev 01 VAL-TEMP-0025 v: 04

User Requirements Specification for Porton Biopharma

5.1 System Impact Assessment Outcome

Reference Revision System Outcome

5.2 Computer System Impact Assessment Outcome

Not applicable – no computer systems requiring impact assessment.

6.0 Project Scope

Document ID: PBL/URS/1808 rev 01 VAL-TEMP-0025 v: 04

User Requirements Specification for Porton Biopharma

6.2 Out of Scope

6.2.1 The following are captured in separate URSs:

Document ID: PBL/URS/1808 rev 01 VAL-TEMP-0025 v: 04

User Requirements Specification for Porton Biopharma

7.0 Codes & Standards

Document ID: PBL/URS/1808 rev 01 VAL-TEMP-0025 v: 04

User Requirements Specification for Porton Biopharma

7.2 GMP Regulatory Requirements