SCGT - QUALITY MANUAL
SYDNEY
CELL AND GENE
THERAPY
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TABLE OF CONTENTS
SECTION 1
INTRODUCTION .........................................................................................
SECTION 2
THE QUALITY SYSTEM ...........................................................................
SECTION 3
ORGANISATION CHART ..........................................................................
SECTION 4
RESPONSIBILITIES AND ROLES ...........................................................
SECTION 5
DOCUMENT CONTROL ............................................................................
SECTION 6
RECORDS .....................................................................................................
SECTION 7
PERSONNEL AND TRAINING .................................................................
SECTION 8
BUILDING AND FACILITIES ...................................................................
SECTION 9
EQUIPMENT ................................................................................................
SECTION 10
QUALIFICATION AND VALIDATION ...................................................
SECTION 11
CONTROL OF MATERIAL .......................................................................
SECTION 12
DONOR SELECTION, DONATION AND TESTING .............................
SECTION 13
PROCESS CONTROL .................................................................................
SECTION 14
STORAGE, PACKAGING AND TRANSPORT .......................................
SECTION 15
AUDITS ..........................................................................................................
SECTION 16
NON-CONFORMANCE MANAGEMENT ...............................................
SECTION 17
CORRECTIVE ACTION/ PREVENTIVE ACTION ...............................
SECTION 18
QUALITY IMPROVEMENT .....................................................................
SECTION 19
MANAGEMENT REVIEW .........................................................................
SECTION 20
ETHICS ..........................................................................................................
SECTION 21
COMPLAINTS ..............................................................................................
SECTION 22
EXTERNAL USERS .....................................................................................
APPENDIX 1
CHANGES TO PREVIOUS VERSION......................................................
APPENDIX 2
RELEVANT STANDARDS AND GUIDELINES......................................
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1
Introduction
Sydney Centre for Cell and Gene Therapies, hereafter abbreviated as SCGT, is based in one of the largest
healthcare and research precincts in the Southern hemisphere which encompasses two Area Health Services
and three Medical Research Institutes. The SCGT provides a seamless integration of the extensive
knowledge, expertise and facilities of the following organisations:





The Children’s Hospital at Westmead (CHW)
Children’s Medical Research Institute (CMRI)
Westmead Hospital (WH)
Westmead Millennium Institute (WMI)
Kids Research Institute (KRI)
The SCGT has the largest clinical and research experience in cell and gene-based therapeutics in Australia,
with capacity to support third party investigators through access to our template for success and in house
facilities. These facilities include fully commissioned state of the art, aseptic and aseptic/ bio-contained gene
and cellular therapeutics manufacturing suites.
The services and research programs currently undertaken by SCGT include:


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

2
The largest blood and marrow stem cell transplantation laboratory in NSW
The first Clinical Islet Transplant Unit in Australia and only facility in NSW to have performed more
than 5 islet transplants for patients with Type I diabetes.
Research program of Xenotransplantation (pig organs into humans)
Active clinical trials involving adoptive immunotherapy of T cells for opportunistic infection.
The largest and most productive gene therapy research program in Australia.
The Quality System
The quality system applies to all processes and functions of SCGT that require quality management control.
This includes but is not limited to activities associated with all stages of the collection, processing, testing,
storage, and release of product, and the training and development of SCGT personnel.
Compliance with the Quality Policies and Procedures of SCGT is mandatory.
These quality policies also apply to all manufacturing processes that are carried out in the facility by external
staff. It is the responsibility of SCGT management to ensure that all external staff members complete the
requisite training in the SCGT policies and procedures before commencing any processing in the facility.
This Quality Manual (QM) describes the quality system of SCGT including the organisational and
management structure. This QM provides “a map” of the policies and procedures covering all of the
manufacturing functions of the SCGT.
The objectives and policy statements contained within the quality manual are implemented through
procedures that describe the operation of the quality system components.
This quality manual is a controlled document and is distributed to authorised holders in accordance with
SCGT document control procedures.
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The SCGT has developed and implemented an effective quality system that is based on the principles of good
manufacturing practice and ensures that wherever possible all products and services meet or exceed the best
practice standards for quality, efficacy and safety.
The SCGT operates in accordance with all applicable Commonwealth and State / Territory policy
frameworks and laws, particularly those pertaining to the regulation of human cellular therapies. The
manufacture of all cell and gene therapies by SCGT is governed by the following applicable standards:



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
Therapeutic Goods (Manufacturing Principles) Determination No 1.
Australian Code of GMP - Human Blood and Blood Components, Human Tissues and Human
Cellular Therapies TGA.
Note for Guidance on Good Clinical Practice TGA
AS ISO 15189 Medical Laboratories – Particular requirements for quality and compliance
AS ISO 15189 Field Application Document Medical Testing Supplementary requirements for
accreditation (FAD)
FACT-JACIE International Standards for Cellular Therapy Product Collection, Processing and
Administration FACT.
Requirements for Procedures related to the Collection, Processing, Storage and Issue of Human
Hemopoietic Progenitor Cells NPAAC.
Quality Policy Statement
SCGT is committed to excellence in research and manufacture of gene and cellular therapies. Our mission is
to be a world leader in this field.
Our quality goal is to meet all relevant TGA regulations and FACT accreditation standards in order to fulfil
and exceed the missions of our collaborative partners (customers).
The SCGT steering committee supports this policy and each staff member is responsible for implementing
this policy in every area of work.
Employees are encouraged to look for improvement opportunities to enhance the performance of the Quality
System.
It is the responsibility of the Facility Director with the assistance of the Quality Manager to ensure that the
quality policy is implemented and complied with by all SCGT staff. At present this position is shared by the
Unit Directors. Arbitration of any conflicting ideas is resolved via the Steering Committee under the direction
of the Chair. The Directors along with the Quality Manager and the Steering Committee will routinely set
measurable quality objectives to be met by all groups. The Quality System is reviewed for effectiveness at
least annually in a formal Management Review meeting.
Vision
The vision of the SCGT is to be a world leader in health and medical research based on globally competitive
research and health outcomes, which directly benefit the community and are linked to the development of a
vibrant regional biotechnology and health services industry.
Values
S Scientific integrity
C Cellular and genetic therapies allowing care for patients beyond the boundaries of established medicine
G GMP Compliance
T Translating high quality research into clinical outcomes for patients
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Chair, Westmead Research Hub Steering Committee: Professor Jeremy Chapman
Signature _______________________
Date __________
Director, BMT and Cellular Therapy: Professor David Gottlieb
Signature _______________________
Date __________
Head, Gene Therapy Research Unit: Professor Ian Alexander
Signature _______________________
Date __________
Director, Westmead Islets Transplantation: Professor Philip O’Connell
Signature _______________________
Date __________
References:
QS-SYS-P002 (Management Review)
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3
Organisational Chart – Structure
Key
Westmead Research Hub
Executive
Westmead Research Hub is BLUE
External users are Orange
See QS-SYS-P006 (Organisational Chart – Personnel)
for staff details
Hospital
Maintenance,
engineering, IT etc
BMT Network
Quality
Manager
Centre
Administrator
Director of BMT and
Cellular Therapy
Unbroken lines represent reporting
relationships.
Steering
Committee
Director of
Westmead Islets
Transplantation
Dotted lines represent interactions
Director of Gene
Therapy Professor
Director
Quality
Manager
Deputy Director of BMT
and Cellular Therapy
Production
Manager TCR
Production
Manager BMT
Production
Manager
MGMT
Production
Manager WIT
Production
Manager
Quality
Officer
Operations
Managers
BMT
Scientist’s x3
Scientist
Scientist
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Non core
Scientist s x 5
Scientist
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Quality Officer
Scientist
SCGT - QUALITY MANUAL
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Roles and Responsibilities
Facility Director
The Facility Director is ultimately responsible for ensuring the quality of product and compliance of SCGT
with its own quality system and relevant international and national requirements.
Directors
Director Gene and Cell Medicine Facility– Prof Ian Alexander
Director of the Sydney Cellular Therapies Laboratory – Prof David Gottlieb
Director of the Westmead Islets Transplantation – Prof Philip O’Connell
Chair, Steering Committee
Prof Jeremy Chapman
Facility Co-ordinator
Margot Latham
Production Nominees
Cancer Gene Therapy Clinical Trial Leader – Dr Belinda Kramer
Islet Laboratory Production Manager – Dr Wayne Hawthorne
BMT Senior Scientist –Vicki Antonenas
T-Cell Clinical Research – Dr Leighton Clancy
Quality Manager
Richard Makin
As defined by the SCGT organisation chart the quality assurance nominee (i.e. Quality Manager) is
independent of the reporting lines of the manufacture of the product but has appropriate authority to ensure
the quality of the product. The Quality Manager reports directly to the Steering Committee.
The production nominee or manager (i.e. the scientific managers of the units) has the necessary authority to
control the manufacture of the product. The production nominee reports directly to the Directors of the units.
In the event that there is conflict between the production activities and the quality policy it is the
responsibility of the Steering Committee to resolve the issue and ensure appropriate records of the decision
are maintained.
Deputies
Position
Facility Director
Unit Director
Chair of Steering Committee
Production Manager
Quality Manager
Deputy
Director of another unit
Production Manager of the Unit
Nominated
Unit Operations Manager or Scientist
Quality Officer
References
See QS-SYS-X001 to QS-SYS-X008 Position Descriptions
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Document control
Policies, procedures, forms, templates, information sheets of the SCGT are managed via Q-Pulse software
following the document control procedures.
All SCGT quality and facility policies and procedures reside in the SCGT Q-Pulse system. The
production documentation for the Westmead Islets Transplantation, MGMT Trial and
T-Cell Clinical Research also reside in the SCGT Q-Pulse system. The production documents of the BMT
laboratory reside in the BMT Network’s quality system. An MOU has been signed by both parties to
allow the Quality Managers of the BMT Network and SCGT to review each other’s documentation to
ensure consistency.
External standards and guidelines are entered into Q-Pulse as external documents. Staff should ensure
these have not been superseded prior to referring to them.
The units are obliged to comply with the policies and procedures of the hospitals and research institutes in
which they reside. These are reviewed via the intranet and internet.
MOUs are established with the organisations (e.g. donor co-ordinators) controlling additional
documentation which mat effect the units to ensure that the documents are reviewed periodically and that
only current versions are available for use.
References
QS-SYS-S003 (Document Control)
QS-SYS-S010 (Document control – Q-Pulse)
SCGT-BMT Network MOU
6
Records
Records provide evidence that what was required to be done was actually done. Records provide the
evidence that the quality system is implemented.
Any record that has a bearing on the quality of a product manufactured at and/or supplied by SCGT, and
which is necessary to ensure traceability or to demonstrate that specific actions were taken in the event of
challenges by outside parties, must be retained for a minimum of 20 years according to the code of GMP.
This period of retention may be greater if specified by other parties such as another regulatory body.
This includes (but not limited to) records for the following:
 Critical materiel
 Purchase orders
 Donor/patient
 Inspection and testing
 Collection and processing
 Equipment checks, calibrations, cleaning
 Equipment and facility servicing and maintenance
 Packaging and labelling
 Product release
 Quality Control
 Training
 Audit
 Validations
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Staff are responsible for:
 Ensuring that procedures incorporate requirements to capture and record data and information;
 Ensuring that hand written entries are clear, legible and any amendments are corrected to allow
legibility of the original data;
 Ensuring that forms used to record data are designed to allow clear entry of data, meet task
traceability requirements and are part of the document control system; and
 Developing procedures for collation and storage of records so that they are secure, readily
retrievable, are protected from deterioration, and are batched prior to archiving.
The Quality Manager is responsible for developing and implementing procedures for storage of archived
records in a form which provides adequate security and confidentiality, and prevents deterioration for at
least the statutory 20 year period and ensures that archived records are readily accessible. Paper records
are protected from environmental and pest damage. Locked cabinets are used to secure records from
unauthorised access.
Records of products not released are stamped with “Quarantined” to distinguish them from those that
conform to specification. Corrective actions to products which do not meet the required specification must
be adequately detailed to demonstrate the resolution of the non-conformance. This detail is recorded in QPulse as a CAPA.
Recorded information includes:
 Traceability of all critical steps in the procedure;
 The identity of the person making the record;
 Date, and where relevant the time of each step performed;
 All original information (e.g. observations and calculations);
 Equipment used;
 Identity of the person authorising steps and checking transcriptions;
 Quality control results;
 Inspection check results;
 Product release authorisation: and
 Any other information specified in the SOP, other contractual documents or relevant statutory
regulations.
Computer records
SCGT records are primarily paper-based however records may also be in the form of microfilm,
microfiche, computer files, or CD-ROM. If computer systems are used to record critical process related
information then the computer system must be properly validated and data must be secure. Data should
not be able to be changed, if changes are made then there must be an audit trail provided by the system.
Records may be scanned and stored electronically; however, it is ensured that all original information is
included in the scan.
Data and information relating to the services and products supplied by SCGT is captured and recorded,
such that evidence is available to demonstrate:
 Achievement of quality requirements;
 Fulfilment of contractual requirements;
 Fulfilment of regulatory requirements;
 Effective operation of systems and procedures;
 Maintenance of inspection and test equipment; and
 A complete history of the product.
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When purchasing or upgrading a computer system it is important that the system is compatible with
current systems. This is assessed prior to a commitment to purchase is made. The data saved from the old
computer systems must be able to be accessed for the required retention time period.
It is the policy of SCGT that vendors have an established quality system e.g. ISO 9001 or an equivalent
standard. A certificate is requested of the vendor to demonstrate compliance.
References:
QS-SYS-S005 (Records)
7
Personnel and Training
Supervision
The Unit Directors are responsible for ensuring that there are sufficient staff resources with relevant
qualifications, experience and competence across the SCGT to ensure that the quality system is maintained
and consistently high quality products are manufactured.
This is achieved by:
 A training protocol for all staff which includes orientation training, training in assigned tasks, ongoing and refresher training and periodic competency assessments;
 Records maintained of SOPs being read by all relevant staff. The acknowledgement of updates and
changes to documents is recorded via Q-Pulse;
 Trainees being signed off by the trainer to demonstrate competencies in assigned tasks;
 Maintaining a register of staff signatures;
 Training in the safety aspects of the laboratory (e.g. fire, MSDS, personnel hygiene);
 Staff being trained in the product requirements e.g. cGMP;
 Staff receiving training in the SCGT quality system;
 Access to internal continuing education activities i.e. journal club;
 Access to external continuing education activities e.g. workshops
 Access to relevant texts, journals and internet; and
 Involvement in relevant professional societies e.g. ISCT.
Supervisory staff have adequate experience in manufacturing the products they oversee and have a
thorough knowledge of the requirements of cGMP, FACT and ISO 15189 to ensure products consistently
meet the specified requirements.
Supervisory staff have adequate authority to discharge their responsibilities, where relevant. Deputies for
key tasks are assigned for all sections.
There is currently no requirement for the facilities to run routinely out-of-hours and have dedicated outof-hours staff. If this case arises it is SCGT policy that these staff must have regular contact with
supervisory staff and work normal hours at least one day per month for personal / professional
development.
Where any part of the manufacture of a product is not performed on-site (e.g. donor collection) a contract
with the provider is set up to ensure that the specification requirements are met and staff are adequately
trained with detailed training records maintained.
The responsibilities of individual staff are defined in the position descriptions along with the deputies for
key tasks.
Roles have been clearly defined so that there is no conflict of interest or overlap in responsibilities which
may hinder the production of a quality product.
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References:
QS-SYS-P005 (Training overview)
QS-SYS-X001 – QS-SYS-X008 Position Descriptions
8
Facilities
Design
SCGT consists of four clean room facilities which have been designed to meet the production
requirements, the safety and comforts of its occupants and the requirements of cGMP. Regular cleaning,
sanitising, monitoring and maintenance are performed to ensure the quality of the products being
manufactured.
Access
The facilities are secure from unauthorised access via swipe card entry. Detail of access control is
provided by the Security SOPs. A list of authorised users is maintained for each of the facilities.
Monitoring
Temperature and humidity are continuously monitored via the building maintenance systems. These
building maintenance systems are alarmed centrally. Where temperature and humidity levels exceed the
acceptable limits corrective action is recorded and a decision on the use of the product is made. The
acceptance or rejection of the product is made by the Director and Production Manager in consultation
with relevant clinicians.
Environmental monitoring (microbial, particulate and viable air sampling) is important in ensuring an
aseptic manufacturing environment for products. The environmental monitoring SOP details the
frequency and extent of environmental monitoring in the facilities.
Cleaning
Cleaning of the facilities is performed as detailed in the Cleaning SOP. This is made available to all
laboratory and cleaning staff. The adequacy of the use of the protocol is assessed via auditing and
environmental monitoring. Training of the cleaners in cGMP building and facility requirements is
provided.
Storage
Purpose built storage facilities are implemented across SCGT. These allow for the suitable storage
conditions for product and segregation of non-conforming product and material. These storage facilities
are continuously monitored by centrally alarmed systems and are routinely environmentally monitored.
Safety
Staff are required to follow the OHS policies of the hospitals and research institutes. These are available
via the intranet of each hospital. Regular training sessions (e.g. fire, hand cleaning) are conducted.
All chemicals stored in the facilities are listed in the Chem Alert MSDS database as per the Westmead
Hospital and Kid Research Institute requirements. Chemical spill kits are available which are relevant to
the chemicals stored in the facility.
Eyewash, hand wash and safety shower facilities are readily available.
References:
RE-SYS-S001 (Environmental Monitoring)
RE-SYS-S003 (Cleaning cleanrooms and associated rooms)
RE-SCT-S002 (SCTL Access and Security)
RE-SCT-S004 (Monitoring of SCTL)
RE-KRI-S010 (GCMF Access and Security)
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Equipment
All equipment is suitably procured and / or designed and built to ensure the reliable manufacture of
product(s) to the specified requirements. Equipment is regularly checked, calibrated and serviced to ensure
reproducibility and consistency in product manufacture. These steps ensure that equipment is fit for the
purpose.
Qualification and validation
All equipment (including computer software used in critical control steps) is commissioned prior to use
according to the Validation Master Plan. A validation report is completed as a record of commissioning. In
addition any major change to the equipment (new software) is validated.
Equipment (including portable equipment) is used in accordance with the manufacturer’s recommendations
unless the change has been validated. All operational checks defined by the manufacturer or equipment SOP
are completed and recorded.
Equipment which was in use prior to the implementation of the quality system and has not been formally
commissioned must have extensive quality control and quality assurance data accumulated and recorded to
demonstrate its reliability and reproducibility. Existing equipment may undergo retrospective validation if
the process it carries out is a critical step.
Preventative Maintenance
All equipment is included on the preventative maintenance schedule. Scheduled maintenance /shutdown
maintenance/servicing are conducted externally following established contracts and records of the service
maintained. Short term preventative maintenance is performed in-house, where possible or where an external
contractor is not available. This is performed in accordance with the maintenance/servicing SOP.
Training of staff in preventative maintenance is provided during initial training.
Calibration, checks and verification
Equipment is calibrated or checked according to the manufacturer’s recommendations or specified standards,
which ever calibration/ check interval is shorter. Where equipment calibration/ check requirements are listed
in Section 4 - Equipment Calibration table of the NATA Medical Testing FAD the timeframes and methods
are followed.
Where a calibration to a reference material / standard has been performed a certificate for this reference
material / standard is obtained. The provider of the service should be NATA accredited and the certificate
provided should include the NATA logo and accreditation number. If this is absent, the accreditation status
should be checked on the NATA website (www.nata.com.au ) and the service contract reviewed.
Equipment which does not meet the manufacturer’s recommendations or specified standards must be taken
out of service and clearly labelled as ‘OUT OF SERVICE’. Following servicing and prior to use the piece of
equipment must be verified to be suitable for its intended use. The verification must be recorded on the
verification worksheet.
Equipment must also to be verified to be suitable for use when it has been moved or major repair work
performed. Revalidation may be required. The protocol for calibration/ checking of equipment must be
included in the equipment SOPs. The minimum information required is:
 Frequency of calibration and/or check;
 Method used;
 Acceptable limits (define by the purpose of the equipment); and
 Action to be taken to non-conforming equipment.
Specific monitoring requirements are included in the specific equipments SOPs.
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Equipment records (e.g. temperature charts) must include the actual results and the acceptable limits.
Action must be taken and recorded to non-conforming results.
References:
RE-SYS-S018 (Validation Master Plan)
QS-SYS-P008 (Contract Management)
10
Qualification and Validation
SCGT facilities, equipment and processes must be designed, installed, operated to meet the product
specifications and to consistently manufacture high quality products. Processes include critical computer
systems as well as facilities and equipment.
Prior to the introduction of a new process, staff initiate a change control to document and cost the planned
process. The change control process allows all responsible managers to review the proposed new process.
The change control process includes a risk assessment which looks at effect on donor / patient safety and
costs of the new or changed process or equipment.
If approved to proceed the new process will be included in the validation schedule.
Existing processes are also considered for requalification and revalidation in the Validation Master Plan.
The Validation Master Plan includes;
 Scope of validation operations;
 Responsibilities, resourcing, costs;
 Product types or description (could cross-reference similar validations);
 Critical considerations;
 Systems, or equipment or test processes to be validated;
 Acceptance criteria;
 Required SOPs;
 Change control;
 Retraining of personnel
 Authorisation
 Validation status of each process or piece of equipment
 Revalidation requirements
Once a validation protocol and/or design specification has been established the validation is conducted and
documented. The process of Installation Qualification (IQ), Operational Qualification (OQ) Performance
Qualification (PQ) is followed.
It is possible that some validations may be assisted/ performed externally. It is, however, the responsibility
of SCGT that these validations are adequately detailed to demonstrate that product specifications will be
met.
Change control
All changes to facilities, equipment, material and processes, including test methods which will affect the
manufactured product must be reviewed, validated and authorised by the relevant supervising staff (e.g.
Unit Director, Production Manager, and Quality Manager). The degree of validation will be determined by
the extent of the change. All significant changes must be notified to relevant staff and client/ clinician.
Detail of the required review, authorisation, re-qualification and notification is included in the change
control and validation procedures.
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The relationship between change control and IQ/OQ/PQ
Change Control
Preapproval
Pre-approval of changes to facility, systems or equipment is required via the
change control system. Complete TE-SYS-F008 (Change control form)
Design Qualification
(DQ) / User
Requirement
Specification (URS)
DQ- Check that the facilities, system and equipment have been designed in
accordance with GMP e.g. equipment is a certain brand, has a service
contract, displays certain data.
Installation
Qualification
Operational
Qualification
Performance
Qualification
Change Control
Verification of the
study and final
approval
URS – Brief provided to prospective manufacturers or service providers
outlining the unit’s requirements.
IQ - The documented verification that the facilities, systems and equipment
as installed or modified, comply with the approved design and
manufacturer’s recommendations.
This information is often provided by the manufacturer, however, a check
should be made against the manufacturers’ requirements and purchase
specifications.
OQ - The documented verification that the facilities, systems and equipment,
as installed or modified, perform as intended throughout the anticipated
operating ranges e.g. running replicates of QC.
Complete:
TS-SYS-S012 (Validation Protocol Template)
TS-SYS-F020 (Validation Report Template)
PQ – Assessment of the facility, systems and equipment to perform its
intended task reproducibly and effectively following relevant SOPs and
product requirements.
Complete:
TS-SYS-S012 (Validation Protocol Template)
TS-SYS-F020 (Validation Report Template)
Change control – formal system for the notification and authorisation of
change including validations. Complete CCF.
References:
RE-SYS-S018 (Validation Master Plan)
QS-SYS-P004 (Change control)
TE-SYS-S002 (Validation Protocol Template)
TE-SYS-F020 (Validation Report Template)
PIC/S Recommendations on validation master plan, Installation and operation qualification, Non-sterile
process, Cleaning Validation
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Control of Material
All critical material is verified to meet required specifications prior to use in manufacturing of product.
Critical material is defined by cGMP as all components, materials or supplies which could have a direct
negative impact on the quality of the end product or a direct negative impact on the patient.
Chemicals used in the manufacture of products are evaluated prior to use against relevant material
specifications. Each chemical/ ingredient has a material specification sheet. Vendors of critical materials
have been assessed via the Vendor Approval process. Critical materials are purchased only from approved
vendors.
Assessment of material
Validation against
Material Specification
Sheet
Production
Manager to
co-ordinate
Nonconforming
material
Director/
Production
Manager to
co-ordinate
Quarantine
Found to
not comply
during
processing
or expired
Material
Receipt
Material receipt
record
Conforming
Material
Discard
procedure
Potential
for unsafe
product TGA
Discard
No
potential
for unsafe
product
Validation
Ready for
production
Product Recall
The product recall procedure is based on the Australian Uniform Recall Procedure for Therapeutic Goods.
The TGA will be notified if product does not conform to requirements.
Storage
Conforming and quarantined material are clearly separated. Quarantined product is stored in a lockable
storage area / container.
Material is stored as per the manufacturer’s recommendations. Storage facilities are monitored for
temperature and humidity, where necessary for maintaining the integrity of the material.
Sterile solutions are labelled as ‘sterile for therapeutic use’. Where sterility is tested externally records of the
sterility testing are maintained. Where sterile packs are used the integrity of the pack is checked prior to use.
It is the policy of SCGT that expired material is not to be used in the manufacture of a product unless
comprehensive validation of the extension to the expiry date is maintained. Expired material is quarantined.
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Transport of material
The transport requirements for material are specified in the Material Specification Sheet. Where material is
transported within the facility or to another facility the specifications are followed.
Labelling
All material is uniquely identified by the product name and batch / lot number. The status of the material is
also included e.g. received, released.
It is SCGT policy that only specifically designed labels (e.g. adhesive, format) be used for products i.e. Meet
TGO labelling requirements. Label batches are checked prior to use to ensure they are not duplicates or do
not include the incorrect information. Labels are only produced by authorised personnel.
When not in use labels are securely stored in a locked Production Managers office in mater folders.
Purchasing and Sub-contracting
A list of suppliers of material and contractors is maintained for each of the units.
Suppliers are assessed against the following criteria prior to entering into a formal contract:
There supplies meet product and material specifications;
They are reliable and consistent;
They provide customer support;
Where relevant, they have a suitable quality system and have evidence of such a system (ISO 9001
certificate, AS ISO15189 accreditation certificate or TGA Licence number); and
They are able to provide adequate service records.
Once these criteria are met contract arrangements are made with the supplier including specification details
and the limits of rejection.
The material is assessed on receipt and any deviations from the specifications are fed back to the supplier via
the Production Manager.
References:
www.tga.gov.au
RE-SYS-S009 (Material Management)
QS-SYS-S008 (Product Recall)
RE-SYS-S019 (Selection, Qualification and monitoring of vendors)
RE-SYS-S017 (Procurement)
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Donor Selection, Donation and Testing
Donor procedures are documented and implemented by the following associated organisations:
Sydney Cellular Therapies Laboratory
Westmead Bone Marrow Transplant Laboratory
BMT Network NSW
Westmead Islet Transplantation
Donor Transplant Co-ordinator
Gene and Cell Medicine Facility
MGMT Trial
CHW Oncology
Contracts are in place with each of the organisations which require their procedures polices and documents to
be compliant cGMP and relevant privacy legislation.
References:
DO-WIT-S001 (Islet Transplantation)
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Process control
The quality of the products is determined by the material, procedures and controls in place, capability of the
equipment used, the competency of staff to manufacture the product to the specifications and the consistent
maintenance of the equipment and facilities.
These fundamental components are monitored and maintained by:
 Regular internal audits;
 Sampling of product (to determine how to do this);
 Monitoring of humidity and temperature;
 Environmental testing;
 Staff training and competency assessment; and
 Equipment checking, calibration, servicing and maintenance.
Quality control
Quality controls are used to demonstrate that processes are under adequate control. Quality controls are
performed in compliance with the documented procedures and results recorded. Any non-conformance in
quality control (QC) results is recorded along with the corrective taken. The Production Manager is informed
where the QC results indicate a problem with the product.
The Production Manager will periodically perform a long term review of QC results and process records to
determine trends. Issues with QC results and processes are discussed with all relevant staff via Unit
meetings. Any significant issues are raised at the Quality and Steering Committee Meetings.
Product release
Products are signed out for release by the Unit Director /Production Manager. The criteria listed in the
Product Release Specification must be fulfilled prior to release of products. Products which do not meet
these criteria are place in quarantine. A review of the batch documentation is performed by the Quality
Manager.
Testing of product
Product testing is performed in compliance with the product specifications. Products are tested using external
laboratories (e.g. ARCBS), internally (e.g. Research Laboratory) and associated pathology laboratories (e.g.
Westmead Hospital Microbiology Department).
References:
PR-SYS-S001 (Review of Batch Documentation)
QS-SYS- P007 (Product Release)
QS-SYS-P009 (CAPA Policy)
QS-SYS-S008 (Product Recall)
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Storage packaging and transport
Storage
Storage conditions of the facilities are monitored via building maintenance systems which are alarmed
centrally and /or externally depending on the parameter being monitored.
Products ready for release are clearly segregated from quarantined product.
Quarantine product is placed in a secured store which is clearly labelled as ‘Quarantined’. The product itself
is also labelled as ‘Quarantined’. A log of quarantined product is maintained which details the production
donation number and the reason for its quarantined status. Quarantined product can only be removed by the
Production Manager.
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If the quarantined product is subsequently transported the ‘Quarantined’ label is checked to be firmly
attached. The transport container is also labelled ‘Quarantined’.
Discard
The disposal procedure for each product is defined in the disposal SOP. All products to be disposed of is
labelled as such and stored in the quarantine area. The product is then disposed of in the timeframe stated in
the disposal SOP. A record of the donation product number, date of disposal, reason for disposal, how it was
disposed of, and the staff member disposing of the product is maintained on the log of discarded product.
Labelling
Product labels are used to identify the status of the product. A label is attached to the product and the
production records to enable reconciliation.
Any product with uncertain status is segregated and accompanied by a record detailing the reason for
segregation and any investigation / corrective action.
The particulars on product labels follow the Therapeutic Goods Order No.69.
Product labels are placed in a locked store when not in use.
Packaging
Product to be transported is packaged and labelled using specified packaging instructions.
The minimum information allowable on the transport container is:
 The address and contact name of the site of origin of the product and its destination; and
 The contents of the container.
A consignment note is accompanied with each container. The minimum allowable information on the
consignment note is:
 SCGT plus the name of unit (e.g. Cancer Gene Therapy);
 Name of the receiving site;
 Container number;
 Name and status of product(s);
 Donation number of product(s);
 Total number of product(s);
 Date/time of dispatch; and
 Signature of staff member authorising the dispatch.
When the product is received by the recipient the date and time is also recorded.
Transport
SCGT is responsible for the transport conditions of the product prior to receipt of the product by the
recipient. If an external courier service is used they are informed of the transport requirements.
Acknowledgement of these requirements is made as part of contract arrangements.
Reference:
www.tga.gov.au/docs/html/tgo/tgo69.htm
Therapeutic Goods Order No.69 General Requirements for Labels for Medicines
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Internal Audit
The internal audit schedule is drawn up at the end of each calendar year for the forthcoming year by the
Quality Manager with input from relevant staff.
Audit management and reporting is performed using the Q-Pulse quality management system. It is the
responsibility of the Quality Manager to maintain the overall use of the system including staff software
training, implementing the audit schedule, timely completion of audits/ corrective actions and reporting the
findings at the Quality Meeting and the Steering Committee Meeting.
Audits are conducted periodically which cover both management and technical aspects of the quality system
including all manufacturing processes. Audits also cover relevant national and international standards.
Non-conformances to national and international requirements identified by internal or external auditors may
require additional auditing of a policies, processes and/or procedures to investigate if the non-conformance is
systematic.
Audits are not to be performed by staff that have direct responsibility for the process they are auditing. This
is/will be achieved by:
 Non-technical aspects of processes audited by the Quality Manager, Quality Officer and quality
consultants; and
 Technical audits conducted by trained auditing staff that have the technical knowledge to understand
a process but are not directly responsible for that process.
References:
QS-SYS-S009 (Internal Audit)
QS-SYS-P009 (CAPA Policy)
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Non-conformance
A non-conformance is any deviation to testing, equipment, product, or quality system which may be
detrimental to the manufacturing process.
Non-conformances may be raised by staff, due to internal or external audits, complaints and client feedback.
Where a non-conformance is raised the following is completed:
 The issue is recorded into Q-Pulse via the CA/PA module;
 The Quality Manager and relevant staff are notified via the email alerts of Q-Pulse;
 Action is taken to initially correct the issue and this action is recorded in Q-Pulse;
 An investigation is undertaken to assess the extent of the non-conformance;
 Where production will be effected, the Director and Production Manager are notified;
 Where necessary, production is ceased until the non-conformance has been investigated;
 Where potentially detrimental to the patient the patient and clinician are notified and product recalled
prior to administration/transplant;
 Where the issue is identified post transplant the patient and the clinician are notified and a patient
management plan established. In addition a IIMS report is completed;
 The root cause of the non-conformance is identified and recorded in Q-Pulse;
 Corrective action is taken and recorded to ensure the resolution of any systematic errors; and
 If necessary new procedures are established and implemented.
Where a non-conformance is identified that casts doubt on the effectiveness of the quality system itself
additional audits are conducted to identify the extent of the issue and to ensure the effectiveness of the
resulting corrective action.
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References:
QS-SYS-P009 (CAPA POLICY)
QS-SYS-S008 (Product Recall)
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Corrective Action/ Preventive Action
Corrective Action
The action taken to address a systemic problem is termed corrective action. Corrective action taken must be
commensurate with the severity of a non-conformance raised.
Corrective actions may be raised due to audits, external assessments, complaints and staff feedback.
It is important that the root cause of the non-conformance is identified and eliminated via corrective action.
This is more than just correction of the non-conformance but correction of any non-conformances of the
systems contributing to the incident. The effectiveness of corrective actions should be monitored via audit to
ensure the effectiveness of eliminating the root cause.
Corrective actions are recorded in Q-Pulse in the CA/PA module.
The responsibility for completion of corrective actions is defined in the Q-Pulse system. It is ultimately
responsibility of the Quality Manager to monitor and ensure completion of corrective actions.
Preventive Action
Systems for proactively looking for potential non-conformances are termed preventive action. This is
achieved by periodically auditing of policies and procedures, trend analysis of processes and reviews of
quality control and facility monitoring data.
All preventive actions are recorded in Q-Pulse and reviewed by the Quality Manager. Action items will be
raised at the Quality Meeting.
The responsibility for completion of preventive actions is defined in the Q-Pulse system. It is ultimately the
responsibility of the Quality Manager to monitor and ensure completion of preventive actions.
References:
QS-SYS-P009 (CAPA Policy)
QS-SYS-S008 (Product Recall)
IIMS procedure -intranet
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Quality Improvement
The quality of the products manufactured by SCGT is ultimately indicated by their success in treating
patients. Feedback from clinicians using the products is proactively sought.
The number of successful and non-successful products, the microbial contamination rate and the number of
series non-conformances is maintained for each unit and each staff member.
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Management Review
The suitability, adequacy and effectiveness of the quality system is assessed at the monthly Quality Meeting
and the Steering Committee Meeting.
Quality Meeting
The Quality Meeting is held once a month. The production nominee or delegate from each unit must be
present along with the Quality Manager and Quality Officer(s).
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The meeting is based on the Quality Meeting Agenda and the minutes and actions are recorded.
The meeting is chaired by the Quality Manager and there is a nominated secretary.
The intent of the meeting is to discuss quality system activities for the month, discuss audit findings, close
out audits/ non-conformance reports/ corrective actions, delegate quality system tasks for the forthcoming
month(s), discuss future needs of the quality system and to discuss issues to be raised with the Steering
Committee.
The last meeting of the year is focused on reviewing the whole quality management system (management
review). SCGTs quality outcomes will be compared to the quality policy, mission and values. A
management review report is provided at the Steering Committee Meeting.
Steering Committee Meeting
The Steering Committee Meeting is held monthly to discuss any issues that relate to the manufacture of
products including expenditure, resourcing, use of the facilities and cGMP compliance. Membership of the
Steering Committee is defined by the Terms of Reference.
A secretary is nominated for the meetings. The minutes and actions of the meeting are recorded.
The meeting addresses strategic, process and quality system issues. Major issues raised at the Quality
Meeting are raised at this meeting for resolution.
A report on the quality system is provided by the Quality Manager prior to each meeting. The action and
prioritisation of the quality system issues are set at this meeting.
Laboratory Meetings
The individual unit all have a monthly minuted meeting. Issues raised at these meetings are tabled at the
Quality Meeting and/or the Steering Committee Meeting.
Email/ Internet
The quality system documents, audits, corrective action and preventive action are accessed via a terminal
internet server. Changes to documents, audit and action requests are made via Q-Pulse and emailed out to the
staff on the distribution list.
Important emails which have the potential to affect the product are recorded and saved on the hospital/
institute server. This information is back-up by the hospital/institute IT.
References:
QS-SYS-P002 (Management Review)
QS-SYS-P003 (Westmead Research Hub Steering Committee TOR)
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Ethics
Accreditation/ Certification/ Licensing
SCGT does not claim accreditation/ certification/ licensing for any process which has not been assessed to
comply with the specified requirements/ regulations. The accreditation/ certification logo must only be used
where the process is covered by the accreditation/ certification. This includes on websites, stationary, reports
etc. Where logos are used the appropriate mandatory statements and logo orientation specified by the
accreditation/ certification bodies must also be used.
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The Westmead Bone Marrow Transplant Laboratory is currently accredited to AS ISO 15189 by NATA. The
scope of accreditation and accreditation status can be viewed at www.nata.asn.au. The rules of NATA
accreditation (including logo use) are stated in NATA Rules which is also available at the website.
Approvals
Ethics approvals for the clinical trials performed by SCGT are reviewed by Human Research Ethics
Committee’s in line with the TGA CTN and CTX approval system. The ethics committee reviewing
approvals must comply with the Therapeutic Goods Act.
References
Human Research Ethics Committees and the Therapeutic Goods Legislation TGA
Note for Guidance on Good Clinical Practice TGA
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Complaints
All complaints, whether received orally or in writing, should be recorded and investigated.
There are five categories in which SCGT may receive a complaint. Each has established policies and
procedures for resolution of the complaint.
Patient /family
The NSW Health Complaints Management Policy and Complaints Management Guidelines GL2006_023 are
followed for all complaints made by patients and/or their families. All complaints are entered into the
Incident Information Management System. This is accessible via the hospital intranet.
Relating to a clinician
The NSW Health Complaint or concern about Clinician Guidelines is followed.
Service
Contracts are set up with organisations using the SCGT facilities which specify the legal framework for
disputes. Both CHW and WH have governance officers which may provide advice in such matters.
Staff member
Any complaint from a staff member should be resolved by the Director of the unit. Unresolved issues should
be addressed by following NSW Health policy.
Product
Any complaint regarding a product manufactured by SCGT is notified on the first instance to the relevant
Production Manager and the Quality Manager. In addition a corrective action report is initiated and the
corrective action procedure followed. All significant complaints are raised with the Director of the unit and
tabled at the Steering Committee meeting.
Where the complaint raises concern about the relevant product or products the recall procedure will be
followed.
References:
CHW and Westmead Hospital intranet
QS-SYS-P009 (CAPA Policy)
QS-SYS-S008 (Product Recall)
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External users
The facilities of SCGT may be leased to other biotechnology organisations. These organisations must
comply with the facility and management requirements of SCGT as well as the policies of the hospital and/or
institutes in which the facility is being leased.
A clear contract of the responsibilities of each party is drawn up prior to use of the facility. Contracts should
conform with the governance systems for each institution. A legal opinion may also be sought for some
contracts.
It is important that activities conducted by an external organisation do not invalidate the ability of SCGT to
attain or maintain a TGA licence. If the organisation leasing the facility has its own quality system a
certificate demonstrating licensing/ accreditation/ certification must be provided and left on file. An audit of
the quality system may also be required.
If the organisation does not have a recognised quality system SCGT may provide assistance in establishing a
system. The external organisation may incur a cost for this service.
Appendix 1
Changes to previous version
Version 1 to Version 2
Included GCP references
Update to document number
Update of organisation chart
Appendix 2
Relevant Standards and Guidelines
AS/NZS ISO 9000 Quality system guide to selection and use
AS/NZS ISO 9001 Quality systems – Model for quality assurance in design, development, production,
installation and servicing
AS1057 Cleanrooms and clean workstations
AS3864 Medical refrigeration equipment – for the storage of blood and blood products
ISO 14644 Cleanrooms and associated controlled environments
Guide to GMP for medicinal products. Annex 1 – Manufacture of sterile medicinal products
Note for Guidance on Good Clinical Practice TGA
TGA Guidelines for sterility testing of Therapeutic Goods
Council of Europe Publishing: Guide to the Preparation, use and quality assurance of blood components
IATA Dangerous Goods Regulations, International Air Transport Association
A WHO guide to good manufacturing practice (GMP) requirements
Pharmaceutical Inspection Co-operation Scheme (PIC/S) Guide to Good Manufacturing Practice for Medicinal
Products
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