Client: Centre for Process Innovation (CPI) Validation Doc Number: na Project: National Biologics Manufacturing Centre (NBMC) Validation issue: na Title: URS – Isolators and Safety Cabinets Version: 2.0 Page:1 of 31CPI – NBMC URS – ISOLATOR and SAFETY CABINETS Ab st rac t Centre for Process Innovation (CPI) is setting up the National Biologics Manufacturing Centre (NBMC) in Darlington. This will undertake process development projects for the UK biopharmaceutical industry. Although this will not be a licenced GMP Facility, it will use international ly recognised standards for operation to ensure that t he processes and results of experiments are transferable elsewhere. Two types of Isolator and Safety Cabinets are required as follows: Negative pressure Safety Cabinets f or operator & environment protection from cytotoxics Postive pressure Isolator for product protection for mimicking final finishing operation This URS defines the performance requirements for both Isolator and Safety Cabinets and will enable the vendor to design, specify, f abricate, install and commission the equipment. Au th or Organisation & Responsibilit y Signature Date Andrew Provan Process Consultant – eXmoor Pharma 20 th Dec 2013 Ap pr ov ed By Organisation & Responsibil ity Signature Date Robert Haugh Project Manager – eXmoor Lucy Foley Project Engineer - CPI Harvey Branton Process and Technical Manager-CPI Jerry Cooper Project Manager - CPI DOCUMENT HISTORY Version Verification Issue Reason for Issue Date 1.0 n/a For Client Review 12 th Dec 2013 2.0 n/a Inc client comments – ready for ITT 20 th Dec 2013
Client: Centre for Process Innovation (CPI) Validation Doc Number:
na
Project: National Biologics Manufacturing Centre (NBMC)
Validation issue: na
Title: URS – Isolators and Safety Cabinets Version: 2.0
Page: 1 of 31
CPI – NBMC
Abstract
Centre for Process Innovation (CPI) is setting up the National
Biologics Manufacturing Centre (NBMC) in Darlington. This will
undertake process development projects for the UK biopharmaceutical
industry. Although this will not be a licenced GMP Facility, it
will use internationally recognised standards for operation to
ensure that the processes and results of experiments are
transferable elsewhere.
Two types of Isolator and Safety Cabinets are required as
follows:
Negative pressure Safety Cabinets for operator &
environment protection from cytotoxics
Postive pressure Isolator for product protection for
mimicking final finishing operation This URS defines the
performance requirements for both Isolator and Safety Cabinets and
will enable the vendor to design, specify, fabricate, install and
commission the equipment.
Author Organisation & Responsibility Signature Date
Andrew Provan Process Consultant – eXmoor Pharma
20th Dec 2013
Approved By Organisation & Responsibility Signature
Date
Robert Haugh Project Manager – eXmoor
Lucy Foley Project Engineer - CPI
Harvey Branton Process and Technical Manager-CPI
Jerry Cooper Project Manager - CPI
DOCUMENT HISTORY Version Verification
1.0 n/a For Client Review 12th Dec 2013
Client: Centre for Process Innovation (CPI) Validation Doc Number:
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Project: National Biologics Manufacturing Centre (NBMC)
Validation issue: na
Title: URS – Isolators and Safety Cabinets Version: 2.0
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CONTENTS 1. INTRODUCTION
...................................................................................................................
3
1.2 Definitions
....................................................................................................................
4
2 REGULATORY REQUIREMENTS
.........................................................................................
5
6 SCOPE OF SUPPLY
............................................................................................................
11
7 GLOSSARY AND REGULATORY FOCUS
..........................................................................
12
7.3 Health and Safety
......................................................................................................
12
7.4 Glossary
....................................................................................................................
12
Appendix 1 –Layout of the Isolators 1st Floor Process
CPI-NBMC .............................................. 13
Appendix 2 - SPECIFIC REQUIREMENTS
.................................................................................
14
A2.1 Isolator and Safety Cabinets Operation and Performance
........................................ 14
A2.2 Isolator and Safety Cabinets Controls and
Instrumentation ...................................... 17
A2.3 Isolator and Safety Cabinets Ancillaries
....................................................................
19
A2.4 Isolator and Safety Cabinets Construction
................................................................
19
A2.5 Isolator and Safety Cabinets Air Handling Units
........................................................ 22
A2.6 Isolator and Safety Cabinets Sterilisation
..................................................................
23
A2.7 VHP Generator Operation and Performance
.............................................................
25
A2.8 Cleanroom Sterilisation
.............................................................................................
26
APPENDIX 3 –3-WAY VALVE OPERATION
...............................................................................
31
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1. INTRODUCTION
1.1 Background
The Centre for Process Innovation (CPI) is setting up the National
Biologics Manufacturing Centre (NBMC) in Darlington UK to support,
develop and progress the biopharmaceutical manufacturing industry
in the UK. It will be involved in process development, analytical
methods, training, new equipment, new technologies, showcasing
equipment and technology, funding, advisory support and act as a
centre of collaboration and cross fertilisation of ideas in the
UK.
The NBMC comprises 5,000m² flexible laboratory facility for
process, analytical and technology
development, small scale production areas for process demonstration
and pre-clinical requirements, clean rooms for GMP simulation of
process and equipment and flexible, open-plan areas where new
facility design concepts can be developed and tested.
In addition to the technical facilities, the Centre will provide
training and conferencing facilities together with office and
meeting spaces.
The NBMC will not be a licenced GMP facility, and therefore will
not be producing pharmaceutical material for Clinical Trials nor
for sale. Therefore none of the equipment nor processes
needs to be qualified or validated according to standard
practice in the pharmaceutical industry.
However it is a requirement that any experiments or process
development work is undertaken to internationally recognised
standards, so that the processes can be transferred to
manufacturing sites, and the experiments and results are
reproducible elsewhere.
This will employ the same design, specification, installation and
commissioning standards as that for a licenced GMP facility.
However it will not be qualified (IQ/OQ) but instead will undergo a
process of Documented Commissioning (DocCom), and DV, IV, OV and PV
(Design, Installation, Operation and Performance
Verification).
This will employ many of the standards and technique as for
Installation Verification (IV) and Operational Verification (OV),
but will not be subject to review by regulatory agencies.
The building design, construction and commissioning will be
undertaken by others on a separate contract, and will include the
shell, clean room and laboratory fit out, HVAC, mechanical
services, electrical and other services.
The process equipment package (of which the Isolator and Safety
Cabinets are part of) will be specified and purchased separately by
CPI.
1.2 Scope and Purpose of this Document This specification covers
the design, manufacture, installation, testing and documentation of
the Isolator and Safety Cabinets for the CPI-NBMC Centre. A total
of two 4-glove Isolator and Safety Cabinets are required as
follows;
1 negative pressure Safety Cabinets for cytotoxic
production
1 positive pressure Isolator for final finishing and
formulation.
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Appendix 2 of this User Requirement Specification (URS)
contains requirements, which relate to current Good Manufacturing
Practice (GMP) and hence will be qualified according to the
requirements of Section 2. User requirements in other sections and
appendices relate to Good Engineering Practice (GEP) and safety or
provide information and so will not be qualified but will become
contractual requirements.
This URS will provide a basis for:
Manufacture of the Isolator and Safety Cabinets by
Supplier.
Definition of performance testing requirements to be
undertaken by the Supplier.
Technical basis of contractual arrangements between the
Supplier and the Purchaser
1.3 Definitions
Purchaser Centre for Process Innovation
Project Manager Jerry Cooper, CPI
Main Contractor A design and build contractor, to be
appointed
Process and GMP Consultant
eXmoor Pharma Concepts, appointed by the Purchaser to carry out
process design and oversee GMP compliance and qualification.
Supplier The designer and manufacturer of the Isolator and Safety
Cabinets
Must/Will The word “must” or “will” denotes that the requirement is
mandatory.
Should The word “should” denotes that the requirement is good
practice/highly recommended, but is not mandatory. Where the
Supplier does not meet this requirement it must be agreed with the
Purchaser.
May “May” is used where information is provided to assist the
Supplier, and no requirement is implied.
The Supplier of the Isolator and Safety Cabinets is required to
adhere to the content of this document; any deviations proposed
must be clearly identified and justified by the Supplier.
Compliance with the agreed contents must be a contractual
requirement of the purchase order and any costs associated with
meeting the agreed requirements must be included in the purchase
price.
Not withstanding anything to the contrary in this specification,
the Supplier must be responsible for ensuring that the Isolator and
Safety Cabinets are “fit for purpose” and in particular for
achieving the performance set forth in this specification.
1.4 Purpose of the Isolator and Safety Cabinets
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maintain a Grade A micro-environment in which the various ‘open’
processing stages of individual aseptic batches can be carried out
and which is continuously particle monitored. The specific User
Requirements detailed in Appendix 2 of this document have been
derived from the documents stated above
The Isolator and Safety Cabinets are to be used for both aseptic
and contained bio processing of microbial fermentation, mammalian
cell cultures, purification and conjugation. These activities
support the development of CPI-NBMC processes and product
developmemt for clinical use, however no clinical material will be
generated at the CPI-NBMC Centre and therefore any products
manufactured within the Isolator and Safety Cabinets will not be
used for human application.
The VHP necessary to sterilise the Isolator and Safety Cabinets
will be generated by an individual mobile VHP Generator
system.
The processes to be carried out in the Isolator and Safety Cabinets
are manual, may be repetitive and may involve frequent material
transfers in and out of the Isolator and Safety Cabinets, thus
ergonomics is a major design factor.
Hydrogen Peroxide Vapour (VHP) is hazardous to health, so the
Isolator and Safety Cabinets must incorporate appropriate
safeguards for CPI-NBMC, maintenance and engineering
personnel.
2 REGULATORY REQUIREMENTS
2.1 Design
2.1.1. The Isolator and Safety Cabinets will be used in a GMP-like
environment, therefore, design, construction and installation does
not have to comply with current Good Manufacturing Practice, as
referenced in Section 7, but should try to meet requirements where
possible.
2.1.2. The Isolator and Safety Cabinets must be designed, tested,
supplied and commissioned in accordance with a documented quality
assurance system implemented by the Supplier
2.2 Qualification Requirements
2.2.1. All qualification activities must conform to the
requirements set out in the Facility and Equipment Verification
Plan, ####
2.2.2. The Isolator and Safety Cabinets have been assessed as
‘Direct Impact’ systems requiring the following qualification
stages. This qualification is required even though the unit does
not have to comply with cGMP because the gassing cycle development
will not be able to be completed without the unit being
verified.
Functional Design Specification (FDS)
Factory Acceptance Test (FAT)
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Installation Verification (IV)
Operational Verification (OV)
Performance Verification (PV)
2.2.3. To support qualification the Supplier must provide a cross
reference matrix (Verification Traceability Matrix (VTM)) between
this URS document, the Functional Design Specification and specific
tests to be carried out during Installation and Operational
Qualification. Appendix 2 is set out in the format of the
VTM.
2.2.4. The qualification process will follow the principles set out
in the ISPE Baseline Guide Vol. 5, Commissioning and
Qualification.
2.2.5. All Supplier testing of critical items will be carried out
following pre-approved protocols and test sheets and witnessed by
the Purchaser.
2.2.6. The Supplier is responsible for providing all necessary
documentation. Where test sheets need to be completed, the Supplier
must follow pre-approved documentation procedures, according to
pharmaceutical industry standards and take responsibility for the
correct completion of the test sheets, follow up actions and
close-out of the testing
2.2.7. The Supplier must, at the DV/VTM stage, complete a copy of
the matrix given in
Appendix 2 in the following way.
Where “Required” is entered in the DV row, the Supplier must
replace this with a statement which confirms design compliance or
not with the URS and gives a documentary reference to the Suppliers
Functional Design Specification which relates to the subject.
Where “Required” is entered in the IV row, the Supplier must
replace this with a test reference from their IV protocol.
Where “Required” is entered in the OV row, the Supplier must
replace this with a test reference from their OV protocol.
Where N.A. is entered in any row, this may be ignored. Note:
Appendix 2 is set out to be printed and used as A3 landscape.
2.2.8. The following table summarises the responsibilities for
Supplier qualification services.
Responsibilities for Qualification
n.a. n.a. n.a.
Supplier Purchaser
Supplier Purchaser
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(i) Purchaser to witness
Supplier Purchaser
Supplier Purchaser
Supplier Purchaser
Purchaser Purchaser
(i) Correctly documented FAT and / or Commissioning results may be
leveraged into IV and OV by agreement, if FAT and commissioning is
undertaken to pre-approved Procedures and included in the
Supplier’s Quality Assurance System
3 DOCUMENTATION REQUIREMENTS
3.1 Documentation General
3.1.1. All documentation, including software printouts, must be in
English.
3.1.2. Documentation must meet, as a minimum, the following
requirements:
Providing all the details necessary so that the Isolator and Safety
Cabinets can be qualified
Providing ‘as built’ records and drawings.
Providing information so that operating and maintenance procedures
can be prepared.
3.1.3. Plant items must be uniquely identified on schematic
diagrams.
3.1.4. All documentation must be identifiable by the
Purchaser item number, which is ZNNN.
All validation documentation must be numbered as follows:
NBMC.ZNNN.Vnn.XX, where nn = version number and XX = document type
(FD = Functional Design Specification, DV = Design Qualification,
IV = Installation Qualification, OV = Operational Qualification
etc.)
3.1.5. The final issue by the Supplier of any piece of
documentation is to be marked and certified as the “As-built” or
“As installed” version. The “As-built” and “As-installed” document
is defined as the document which accurately represents the system
at Handover, having passed through FAT, DV, Commissioning, IV and
OV with all documentation discrepancies cleared and final data
verified.
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3.2 Documentation Pre-Delivery
3.2.2. General arrangement drawings and schematics
3.2.3. Parts list with component specifications
3.2.4. Material certificates for all product contact parts or
certificates of conformity to the specification for all parts not
provided with individual material certificates or other quality
assurance documents
3.2.5. Control schematics with control panel layouts and wiring
diagrams
3.2.6. Instrumentation list with calibration certificates for
critical instruments
3.2.7. Operating and Maintenance manuals
3.2.8. Preventative maintenance schedule and recommended spares
list for 2 years
3.2.9. Executed FAT protocol and qualification protocols for
approval, as noted in Section 2
3.2.10. Commissioning Procedure for comment and approval prior to
execution
3.2.11. Qualification protocols for approval, as noted in Section
2
3.3 Documentation Post-Delivery
3.3.1. Any documentation which was issued as “preliminary”, “draft”
or “for construction” or any other documentation which requires
revision as a result of commissioning and qualification must be
certified “As Installed” and re-issued.
3.3.2. Executed Commissioning Procedure approved by the Purchaser
with a list of commissioning spares replaced.
3.3.3. Calibration certificates for all test equipment used at any
stage.
3.3.4. Executed qualification protocols and qualification reports
for approval, as noted in Section 2.
4 GENERAL REQUIREMENTS
4.1 Design Codes/Standards
4.1.1. The Isolator and Safety Cabinets must be permanently CE
Marked to confirm compliance with all relevant EU Directives, and a
suitable conformance certificate must be provided.
4.1.2. The Isolator and Safety Cabinets s must be safe to operate
and comply with the Provision & Use of Work Equipment
Regulations, 1998.
4.2 Mechanical Design
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HEPA filters), VHP connections, controls (with intuitive HMI),
powered height adjustment, sleeves and gloves.
4.2.2. The Isolator and Safety Cabinets must be ergonomically
designed to allow ease of use, cleaning and maintenance.
4.2.3. Sensing devices must be easily accessible and removable for
calibration and maintenance purposes.
4.2.4. Supplier to confirm automated valves are equipped with
open/closed limit switches as standard.
4.2.5. The Isolator and Safety Cabinets must have adequate
temporary protection suitable for transporting to site and for on
site storage and protection once installed up to and including the
commissioning stage.
4.3 Electrical Design
4.3.1. All electrical equipment, documentation and installation
must comply with all local regulations in the UK (the current
edition of BS7671, IEE Wiring Regulations) and EN60204 Safety of
Machinery.
4.3.2. Electrical equipment must only be connected to a single
source of supply. The machine must be equipped with an isolation
switch that completely isolates the machine from the mains
electricity supply. Any other voltages and frequencies must be
produced from within the equipment. Power supply for
instrumentation and control must be 24V DC.
4.3.3. All electrical components and connectors must be compatible
with those used in the UK
4.3.4. All electrical components must be contained in protective
enclosures, having Ingress Protection suitable for cleanroom which
are frequently cleaned with lIVuid products and also sterilised
with VHP.
4.3.5. Access to electrical enclosures must only be permitted by
use of a key or tools. Panel doors must be interlocked to
disconnect power from exposed equipment when the door is opened. It
is permissible to allow low voltage (24V) circuits to remain
powered when the door is open if mains voltage equipment is
strictly segregated and effectively protected from accidental
contact.
4.3.6. All Isolator and Safety Cabinets metalwork must be securely
earthed and an earth continuity test carried out.
4.3.7. Adequate short circuit protection must be installed to guard
against failure of individual electrical circuits.
4.3.8. Clear labelling must be fitted to each fixed component and
termination, labelling must correspond to that used on wiring
diagrams and parts lists.
4.3.9. An Electrical Safety Test must be carried out and documented
to confirm safe installation.
4.4 Site Safety
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the Main Contractor and GSTT must be followed and Risk Assessments
and Method Statements for the work must be submitted and approved
before starting work. All Supplier’s staff working on site will be
required to undergo Site Induction by the Main Contractor.
5 LOCATION, UTILITIES AND CONNECTIONS 5.1. The Isolator and Safety
Cabinets will be located in the following location at
CPI-NBMC;
Negative contained Safety Cabinets – Cytotoxic laboratory –
Room 1.20
Positive pressure Isolator – GMP Simulation – Room 1.33 or
Room 1.34
5.2. The Isolator and Safety Cabinets will be floor standing, the
ceiling is 2700 mm above FFL.
5.3. The room temperature is controlled at 20 ± 3 oC and humidity
will not be controlled
5.4. The route from the goods unloading area is via a goods lift
and internal corridors constrained by doors with an effective
opening of 1800 mm wide and 2500 mm high, with restricted turning
space.
5.5. Utility Parameters Connection
Power 13 A, 230 V, 1 Phase, 50Hz 13A UK type socket
CO2 Vacuum
6 SCOPE OF SUPPLY
6.1. Detailed design, manufacture, installation, commissioning and
qualification of the Isolator and Safety Cabinets
6.2. Packing and delivery to site, including insurances and customs
duties etc.
Offloading, unpacking and moving into position.
6.3. Re-assembly and installation, including connection to
services, which will terminate approximately 2m away from the
machines.
6.4. Commissioning including supply of all consumables, spare
parts, labour and calibrated test equipment used in the tests. Note
that commissioning and qualification may be scheduled several weeks
after installation.
6.5. Qualification services listed in Section 2
6.6. Comprehensive training in both operation and maintenance, with
Training Certificates issued to Purchaser’s staff who have
completed the course.
6.7. Documentation, as listed in Section 3.
6.8. Handover will be achieved when a Handover Certificate
(prepared by the Supplier) is signed by the Purchaser.
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DV, IV and OV protocols have been executed and
unconditionally approved
GCD has been completed and unconditionally approved
Training has been completed and training certificates
issued
All other documentation listed in Section 3 has been
delivered
Spare parts ordered with the contract have been
delivered
6.9. Minimum 12 months Warranty from date of Handover, covering
on-site repair and replacement of defective parts with
re-qualification, if necessary 48 hour maximum response time
required.
6.10. One year’s on-site planned maintenance contract, with defined
rates for labour and parts. Tenderer to provide an option to extend
the planned maintenance contract, including a 48 hour maximum
response time breakdown service, for years 2 to 3.
6.11. Supplier must provide a minimum of 1 spare HEPA filter for
each model number of filter used in the Isolator and Safety
Cabinets. For example should an Isolator or Safety Cabinets use 1
off 300 x 300mm H14 and 1 off 600 x 600mm H14 and there are 6
Isolator and Safety Cabinets all the same then commissioning
consumables must be 6 off 300 x 300mm H14 and 6 off 600 x 600mm
H14.
The commissioning spares are to be shipped with the equipment and
identified as an individual line item for costing purposes.
7 GLOSSARY AND REGULATORY FOCUS
7.3 Health and Safety
o Control of Substances Hazardous to Health (COSHH)
Regulations Schedule 3 2002
o Genetically Modified Organisms (Contained Use) Regulations
2000 (GMO(CU))
o Genetically Modified Organisms (Contained Use) (Amendment)
Regulations 2002
o Advisory Committee on Dangerous Pathogens (ACDP) Approved
List of Biological Agents 2004
o Pressure Systems Safety Regulations 2000
7.4 Glossary
o HMI – Human-Machine Interface
o N.A. – Not applicable
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Appendix 1 –Layout of the Isolators 1 st
Floor Process CPI-NBMC
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Appendix 2 - SPECIFIC REQUIREMENTS
Requirement Fulfilment Sign / Date
A2.1.1. The Isolator and Safety Cabinets must accommodate the
following ‘generic’ process steps (Note that specific loads and
operations will be defined by individual processes and the two
typical loads, identified by the batch sequence diagrams, will be
used to inform VHP gas cycle development):
a) Preparation
Manual cleaning
Glove testing
b) Loading
Load initial single-use disposable tubing sets’or well-plates or
centrifuge tubes or transfer bags or culture flasks
Load ‘tools’ and static equipment (eg battery powered balance, tube
welder) to be used in the process
c) Pre-Process VHP Cycle
Sterilisation of all internal surfaces and items placed inside the
Isolator and Safety Cabinets
d) Transfers
Load extra WFI, media and buffer solutions via Transfer Hatch
Introduce blood-bag, cell culture bag, tube or culture flask
containing cells
e) Processing
Remove wastes via Transfer Hatch.
Return tubing sets via Transfer Hatch.
Introduce new reagents and disposable equipment via the Transfer
Hatch
f) Processing and Transfers
Steps (d) – (e) may be repeated several times, with subtle
variations
g) Remove Final ‘Product’
h) Open, Clean and Tidy
(Note: If viral vectors have been used, it will be necessary to run
a VHP sterilisation cycle before opening)
Remove wastes
Manually clean
DV Required
OV N.A.
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A2.2 Isolato r and Safety Cab inets Controls and Instrumentat
ion
Requirement (applies to all Isolator and Safety Cabinets unless
indicated) Fulfilment Sign / Date
A2.2.1. The Isolator and Safety Cabinets control panel (HMI)
must indicate:
Isolator and Safety Cabinets and Hatch Pressures
(digital)
Air Flowrate or Velocity in the Isolator and Safety
Cabinets, annotated in Air Changes per Hour or m/s.
Terminal and exhaust HEPA filter pressure-drops (Magnahelic
or digital).
Gassing cycle status
Hatch door status
DV Required
IV Required
OV Required
A2.2.2. The HMI requirements of the built-in equipment have
been listed in A2.3. These controls should be incorporated in the
same panel as the Isolator and Safety Cabinets controls, if this is
not possible, they must be mounted close- by.
DV Required
IV Required
OV N.A.
A2.2.3. Settable high and low alarms must be fitted for
Pressure (independent chamber and hatch)
Flow/velocity
Alarms must be annunciated by audible and visible
means.
Alarms must be latched, ie. alarms can only be cleared by
manual intervention once the excursion has been corrected.
Additionally, the Isolator and Safety Cabinets must receive,
display and annunciate a common VHP Generator alarm and a particle
counter.
Alarm noise to be noticeable, but not with a disturbing or
distracting intonation or volume.,
DV Required
IV Required
OV Required
A2.2.4. The control system must log all alarms (alarm type,
time of alarm, time acknowledged and time cleared) and retain these
for operator information at the end of a batch. These alarms are
independent of any EMS alarms.
DV Required
IV Required
OV Required
A2.2.5. The required range and accuracy of the
instrumentation is given in the table below. DV Required
Instrument Range Accuracy Precision
Air Flow 0 – 900 Ach/h + 5 Ach/h 5 Ach/h IV Required
Air Velocity 0 – 10 m/s + 0.1 m/s 0.1 m/s
Pressure -300 to +600 Pa + 5 Pa 10 Pa
HEPA filter DP 0 – 500 Pa + 5 Pa 10 Pa OV N.A.
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A2.2.6. The Isolator and Safety Cabinets control system must
monitor an ‘extract healthy’ signal either from the BMS or directly
and display and annunciate it.
Furthermore, the Isolator and Safety Cabinets control system must
not allow a VHP cycle to start if this signal is not present and it
must go into a ‘safe-hold’ state if the signal drops out during the
aeration phase of a gassing cycle.
DV Required
IV Required
OV Required
A2.2.7. The control system must manage and report automatic
leak tests:
leak test on demand
A pre-gassing leak test as part of the VHP sterilisation
cycle
Glove leak test.
The Isolator and Safety Cabinets must be supplied with a glove
leak-test device for semi-automatic operation.
DV Required
IV N.A.
OV Required
A2.2.8. Control systems must be protected from power failure
by a dedicated UPS with capacity for 30 minutes operation. UPS to
be alarmed for failure or low battery. The UPS must also include
power surge protection.
The Isolator and Safety Cabinets will be connected to a
‘maintained’ supply, therefore power interruptions are anticipated
to be momentary.
In the event of power failure, the Isolator and Safety Cabinets
must restart automatically to its previous set point, with no
operator intervention.
DV Required
IV Required
OV Required
A2.2.9. The inner door of the Transfer Hatch must be
controlled so that a variable delay is applied after the outer door
is closed until the inner door may be opened. This is to allow
alcohol vapour to be swept away and Grade A conditions to
re-establish.
DV Required
IV N.A.
OV Required
A2.2.10. The control system must be password protected, with
at least three levels of entry (Operator, Supervisor and Engineer).
If the selected control system falls within the guidance of Annex
11 (Computerised Systems) of the EU GMP regulations, then password
protection must comply with sections 8 and 10 of Annex 11 of the EU
GMP regulations. This states that all actions carried out under
password control must be logged, with the identity of the person
initiating the actions.
DV Required
IV N.A.
OV Required
A2.2.11. All instruments must be clearly labelled in English
with their function. DV Required
IV Required
OV N.A.
Client: Centre for Process Innovation (CPI) Validation Doc Number:
na
Project: National Biologics Manufacturing Centre (NBMC)
Validation i ssue: na
Title: URS – Isolators and Safety Cabinets Version: 2.0
Page: 25 of 31
A2.7 VHP Generator Operati on and Per formance
Requirement Fulfilment Sign / Date
A2.7.1. A minimum total of one mobile VHP Generator must be
supplied to produce a stream of Hydrogen Peroxide Vapour in
conditioned air (“gas”) to match the stated sterilisation
requirements of the Isolators.
DV Required
IV Required
OV N.A.
A2.7.2. Mobile VHP Generators must be used to sterilise both
Isolators and Safety Cabinet. DV Required
IV Required
OV N.A.
A2.7.3. Mobile VHP Generators (if chosen) will be used to
sterilise the following rooms and suites of rooms;
1.18 – Viral Vectors 122m³ room volume
1.20 – Cytotoxics 97m³ room volume
1.33 – GMP Simulation – Grade D 200m³ room volume
1.34 – GMP Simulation – Grade C 144m³ room volume
DV Required
IV Required
OV N.A.
A2.7.4. A VHP Generator must draw air from the room in which
it is located. DV Required
IV Required
OV Required.
A2.7.5. A VHP Generator must produce concentrations of
hydrogen peroxide and vapour temperatures and H202humidities within
their set-point ranges.
DV Required
IV N.A
OV Required
A2.7.6. The VHP Generators must produce the required
environmental conditions and hydrogen peroxide vapour at a
sufficient rate so that the total Isolator sterilisation cycle
times stated in Section A2.6
If a VHP Generator alone cannot achieve the required cycle time
then the following equipment must be included if required
Catalytic H2O2 destruction units. Such units may be included
in the VHP Generator cabinet or be separate mobile or fixed units
incorporating appropriate circulation or exhaust fans.
Separate distribution fans if appropriate.
DV Required
IV N.A
OV Required
A2.7.7. The VHP Generators must use 30% H2O2 solution to
produce VHP. DV Required
IV Required
OV N.A.
Client: Centre for Process Innovation (CPI) Validation Doc Number:
na
Project: National Biologics Manufacturing Centre (NBMC)
Validation i ssue: na
Title: URS – Isolators and Safety Cabinets Version: 2.0
Page: 28 of 31
A2.9.5. The VHP Generators must be equipped with the
following instruments/sensors
H2O2 solution weight or volume
H2O2 vapour concentration
H2O2 vapour temperature
Alarms
H2O2 solution weight or volume
H2O2 vapour concentration
H2O2 vapour temperature
Batch No.
Operator ID
H2O2 solution weight or volume used
H2O2 vapour concentration and temperature at phase
transitions, with time
Alarms during the cycle, with time
Summary, i.e. “Cycle Successful” or “Cycle Aborted”
DV Required
IV Required
OV Required
A2.9.8. The HMI system must be password protected at least
three levels
Operator,
Supervisor,
Administrator/Engineer/Validator
Out of H2O2 solution
DV Required
IV Required
OV Required
A2.9.10. The controller must provide the following interlock
systems, which must be both hardware and software
implemented.
VHP generation must not start if Isolator leak test
fails
VHP generation must not start if room dampers are not
closed
DV Required
IV Required
OV Required
Client: Centre for Process Innovation (CPI) Validation Doc Number:
na
Project: National Biologics Manufacturing Centre (NBMC)
Validation i ssue: na
Title: URS – Isolators and Safety Cabinets Version: 2.0
Page: 30 of 31
OV N.A
A2.10.4. The mobile VHP Generator be supplied with two “gas”
hoses; one for supply to the Isolator and the other for return from
the Isolator.
All “gas” hoses shall be armoured platinum crosslinked
silicone tubing with ends to match the nozzles on the isolator/ and
Room Nozzle
DV Required
IV Required
OV N.A
A2.10.5. Each major component or sub-assembly in the system
must be identified with a permanently fixed tag, the tag having an
engraved or embossed number corresponding to its identification on
the P&ID.
1 Required
IV Required
OV N.A
Client: Centre for Process Innovation (CPI) Validation Doc Number:
na
Project: National Biologics Manufacturing Centre (NBMC)
Validation i ssue: na
Title: URS – Isolators and Safety Cabinets Version: 2.0
Page: 31 of 31
APPENDIX 3 –3-WAY VALVE OPERATION
Isolator
Isolator