Appendix 1 URS for Isolator and Safety Cabinets

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

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

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.

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

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)
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

(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.


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

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

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.

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

Appendix 1 –Layout of the Isolators 1 st
Floor Process CPI-NBMC
Validation i ssue: na
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.
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.

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.
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.

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
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
APPENDIX 3 –3-WAY VALVE OPERATION
Isolator
Isolator

Appendix 1 URS for Isolator and Safety Cabinets

Documents

Transcript of Appendix 1 URS for Isolator and Safety Cabinets