SAS For Procured Items Level 3

GSK VQD-SOP-069195 v: 1.
0 Retrieved: 16 Mar 2022 Effective: 15 Mar 2022

Procedure defining Pakistan Audit Standard level 3 for Procured item
STANDARD OPERATING PROCEDURE
Procedure to Define Segmented Audit Standard

for
Procured Item
(Level 1-3 Requirements)
For
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Local for Local Suppliers
(PAKISTAN PSC)
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Proprietary Information. Do not disclose without consent.

The current version from Veeva QualityDocs must be used. Page 1 of 80.
GSK VQD-SOP-069195 v: 1.0 Retrieved: 16 Mar 2022 Effective: 15 Mar 2022
1. PURPOSE
To define the local requirements in Segmented Audit Standard (SAS) for

procured item applicable for local for local suppliers in Pakistan.
This procedure has been prepared to define appropriate standards of GMP for
the manufacture and supply of active pharmaceutical ingredients (APIs), API
intermediates, excipients, raw materials, packaging components, devices and
quality critical services (Procured Items) under an appropriate system for
managing quality. It is also intended to ensure that all procured items and
services meet requirements for quality and purity which they purport or are
represented to possess.
This Segmented Audit Standard (SAS) is designed as per quality and
regulatory requirements to be used by suppliers of procured items to
GlaxoSmithKline (GSK) to assist them in understanding the GSK Pakistan
expectations for the quality of their products being used by GSK Pakistan sites.
It should be clear that the expected level of quality is based on the risk to the
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patients and consumers of GSK Pakistan products and GSK itself as a
business.
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GSK Pakistan has a large portfolio of products. Depending on the function of
the procured item and in which product / product type it is used, there will be
different levels of risk to GSK and the patient, consumer or customer. For this
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reason, appropriate quality requirements have been updated to developed for

the different levels of risk associated with different procured items and
services, in Pakistan.
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2. SCOPE
This procedure applies to perform local for local supplier audits in Pakistan as per
Segmented audit standards managed by Supplier Quality Audit and Compliance
(SQA&C) organization Pakistan.
In this standard, the term "should" indicates requirements that are expected to apply
unless shown to be not applicable or replaced by an alternative that is demonstrated
to provide at least an equivalent level of quality assurance.
This standard may also be used to assess agents used by GSK Pakistan by applying
appropriate sections (for example Quality Management, Personnel, Buildings and
Facilities) that relate to the operations being performed by the agent (for example
storage, repackaging).
3. ROLES AND RESPONSIBILITIES
Roles Responsibilities
SQA (Supplier  To use revised Segmented audit standard Level 1-3 of procured
Quality Auditor) item for L4L suppliers

4. SAS Standards
1 QUALITY MANAGEMENT
2 PERSONNEL
3 BUILDINGS AND FACILITIES
4 PROCESS EQUIPMENT
5 DOCUMENTATION AND RECORDS
6 MATERIALS MANAGEMENT
7 PRODUCTION AND IN-PROCESS CONTROLS
PACKAGING AND IDENTIFICATION LABELLING OF ‘Procured
8 Items
9 STORAGE AND DISTRIBUTION
10 LABORATORY CONTROLS
11 VALIDATION
12 CHANGE CONTROL
13 REJECTION AND RE-USE OF MATERIALS
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14 COMPLAINTS AND RECALLS
CONTRACT SERVICES (INCLUDING MANUFACTURERS,
15 LABORATORIES, CALIBRATION)
AGENTS, BROKERS, TRADERS, DISTRIBUTORS, REPACKERS,
16 AND RELABELLERS
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17 STERILE APIs
18 PRINTED MATERIALS
MATERIALS STERILISED BY ETHYLENE OXIDE OR BY
19 IRRADIATION
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5. SAS Levels
Medicina
Denture Cleanser
Traditional
Medical device
l product
Supplement
Nutritional
Ayurvedic
Cosmetic
Vaccine
Dietary
GSK Monograp Chinese

Group ↓Procured item API hed Drug
application →
OTC Medicine
product
API / Atypical API 4

Registered API 4
intermediate
Consumer Healthcare 2 2 2 3 3 3
claim associated raw
material
Active Dietary Supplement 3
Ingredient
Excipient 3 3
Adjuvant 3
Critical Raw Material 1 3 3 2 2 2 2 2 2 2
Chemical
(including Registered
Starting Material for API*)

Non-Critical Raw Material 1 1 1 1 1 1 1 1 1 1

(Raw Material – General)
Components of medical Medical M
e
devices di
device c
al
Component
appx d
e
vi
c
e
a
p
p
x
Primary packaging 2 3 3 2 2 3 2 2 2 2
components (printed and
unprinted)
Printed primary or 3
secondary packaging
components containing
critical end user print,
legislative or regulatory
artwork (e.g. GSK
data, product dosage,
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usage or storage, supply
chain information affecting
product quality such as
cold transit required).
High risk ‘line of sight’ to
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end user
Printed primary, secondary 2
or tertiary packaging
Packaging / Labeling
either important print or
registered text (e.g.
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product name, basic

usage instructions and
supply chain information
potentially affecting
product).
Medium risk ‘line of sight’
to end user
Printed Tertiary packaging 2
critical end user print,
artwork (e.g. GSK
data, product dosage,
usage or storage, supply
chain information affecting
product such as cold
transit required).
Medium risk ‘line of sight’
to end user

Packaging Material 1
unprinted or printed with
generic text (e.g. GSK
logo, brand name, supply
chain information not
affecting product with no
registered text). Low risk
‘line of sight’ to end user
Single Use Systems 3 3

(valida
tion
SUS
GAS
4) &
appx
2.
Simple medical devices 3 2 2 3
(v
(cup, spoon, dropper, (validation al
dosing syringe, etc.) GAS 4) & id
appx 3. at
io
n
e G
A
S
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4)
&
a
p
p
x
Device
3
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Complex medical devices. 3 2 2 3

(v
Assembled, sub (validation al
assemblies or components GAS 4) & id
thereof. Delivery System appx 3. at
io
n
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G
A
S
4)
&
a
p
p
x
3
6. Audit Frequencies
SAS Frequency Commodities

Recommended
1 and 2 60month Paper Pack suppliers (no regulatory info)
36 months Excipients and Printed Primary packaging Material

3
60months Secondary and Un printed Primary Packaging Material

36 months Non-Sterile Materials

4
24months Sterile Materials
Approval Recommended status

Status change criteria Recommended Time for follow up audit
Conditional 1 Critical - 5 Major 12 months
Approval
Not 2 or more Critical - 5 Major 12 months
Approval
7. QUALITY MANAGEMENT
7.1 Principles
Level 1
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All quality related activities should be defined and documented.
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All quality related activities should be recorded at the time they are performed.
Any deviation from established procedures should be documented and explained.
Responsible management should be notified in a timely manner of product or service defects and
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related actions.
Records should allow traceability of the final product from raw materials through delivery to initial
customers. The methods used for traceability and identification of raw materials used in end products
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produced by continuous processing should be defined. Documents that facilitate traceability and
COAs or equivalent should be provided for each delivery as agreed with the customer.
Level 2
The system for managing quality should encompass the organisational structure, procedures,
processes and resources, as well as activities necessary to ensure confidence that the product or
service will meet its intended specification.
There should be a quality unit that fulfils both quality assurance (QA) and quality control (QC)
responsibilities. This can be in the form of separate QA and QC units or a single individual or group,
depending upon the size and structure of the organization.
Critical deviations should be investigated, and the investigation and its conclusions should be
documented.
No materials should be released or used before the satisfactory completion of evaluation by the quality
unit(s) unless there are appropriate systems in place to allow for such use (e.g. release under
quarantine as described in Section 9.2 or the use of raw materials or intermediates pending
completion of evaluation).

Procedures should exist for notifying responsible management in a timely manner of regulatory
inspections, serious quality deficiencies, product defects and related actions (e.g., quality related
complaints, recalls, regulatory actions, customer and internal audit findings).
Where appropriate, there should be a documented system for quarantining suspect product
Level 3
The Quality Unit should be independent of production.
7.2 Responsibilities of the Quality Unit(s)
Level 1
The quality unit (or designee) should be involved in all quality related activities.
The main responsibilities of Quality unit(s) should not be delegated. These responsibilities should be
described in writing and should include but not necessarily be limited to:
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Releasing or rejecting materials that may be supplied to GSK.
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 Approving all specifications and master production instructions;
 Approving all procedures impacting the quality of ‘Procured Items’;
 Ensure that quality related complaints are investigated and resolved.

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Level 2
The main responsibilities in writing and should include but not necessarily be limited to: .
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• Ensure that critical deviations and complaints are investigated and resolved.
• Approving changes that potentially impact ‘Procured Item’ quality.
• Ensure that effective systems are used for maintaining and calibrating critical equipment.
Level 3
The main responsibilities of the quality unit(s) should not be delegated. These responsibilities should
be described in writing and should include but not necessarily be limited to:
 Ensuring that there is stability data to support retest or expiry dates and storage conditions on
‘Procured Items’ where appropriate.
 Performing management reviews (as defined in Section 1.5).
 Reviewing completed production records of critical process steps to ensure no errors have
occurred and, if errors have occurred, that they have been fully investigated and satisfactorily
resolved
 Reviewing completed laboratory control records before release of final product.

 Ensuring compliance of outsourced services
 Reviewing of quality agreement where applicable

7.3 Responsibility for Production Activities
Level 1
No specific requirement for this level.
Level 2
The responsibility for production activities should be described in writing, and should include but not
necessarily be limited to:
Preparing, reviewing, approving and distributing the instructions for the production of ‘Procured Items’
according to written procedures;
Producing ‘Procured Items’ and, when appropriate, intermediates according to pre-approved

instructions;
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Reviewing all production batch records and ensuring that these are completed and signed;
Ensure that all production deviations are reported and evaluated and that critical deviations are
investigated, and the conclusions are recorded;
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Ensure that production facilities are clean and when appropriate disinfected.
Level 3
Ensure that the premises and equipment are maintained, and records kept;
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7.4 Internal Audits (Self Inspection)
Level 1
A system should be in place of regular internal audits to determine the implementation and
effectiveness of the internal quality management system and compliance to the industry standard(s).
The organisation shall implement an internal audit program based on the criticality of the operations,
changes affecting organisation, and the results of previous audits.
Audit findings and corrective actions should be documented and brought to the attention of
responsible management. Agreed corrective actions should be completed in a timely and effective
manner and their effectiveness documented and brought to the attention of the responsible
management.
Level 2
In order to verify compliance with the relevant principles of current good manufacturing practice for
‘Procured Items’, regular internal audits should be performed in accordance with an approved

schedule. (at least annually). To be carried out by appropriately trained competent auditors, who are
independent from the audited department.
Level 3
Qualified / trained auditor can perform internal audits.
7.5 Management Review (Level 1-2-3)/ Product Quality Review (Level 4)
Level 1
Level 2
Top management shall review the organization’s quality
1) Nonconformities and corrective actions.
2) Audit results.
3) Customer complaints and its CAPA
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Level 3

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7.6 Contract Review and Order Processing
Level 1
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The supplier should not employ sub-contractors for product-related activities without prior written
approval from GlaxoSmithKline.
The supplier should have agreed to the relevant current GlaxoSmithKline specification(s), with
exceptions as appropriate
Level 2
The supplier should have a documented system to seek approval from GlaxoSmithKline for the
substitution of raw materials or any deviation to the manufacturing process, including site of
manufacture or use of sub-contractors.
Level 3
Appropriate change control notification periods and/or safety stock levels should be agreed with
critical materials suppliers commensurate with the supplied materials’ function and its criticality within
the GSK end product.

7.7 Quality Risk Management
Level 1
No specific requirement at this level
Level 2
No specific requirement at this level
Level 3
An appropriate quality risk management system to enable a systematic process for the assessment,
control, communication and review of risks to the quality of the product should be in place. The extent
of the Quality risk management (QRM) should reflect the operations performed.
Additional requirements for medical devices - See Appendix 3 – Assessments of Medical Device
suppliers
8. PERSONNEL
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8.1 Personnel Qualifications
Level 1
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There should be an adequate number of personnel qualified by appropriate education, training and /
or experience for the effective implementation of its quality management system and for the operation
and control of its processes.
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Personnel should have a defined training program with respect to their role, including gowning
requirements (as applicable) for the working environment prior to carrying out the assigned duties.
Level 2
The responsibilities of all personnel whose role has an impact on quality of product or service should
be specified and understood in writing (as job description or contract)
Physical aspects such as eyesight and colour blindness should be routinely assessed, as appropriate
to responsibilities.
cGMP and Good Distribution Practices induction training and refresher courses should be in place
and documented.
Level 3
Training should be regularly conducted by qualified individuals and should cover, at a minimum, the
operations that the employee performs and quality as it relates to the employee's functions.
Training should include:

 the potential risks and consequences of contamination to the quality of the product or service
and potential impact to the end-users.
 the potential impact on product or service quality as result of deviations from procedures and
the reporting of significant failures and deviations from procedures.
8.2 Personnel Hygiene
Level 1
Personnel should practice good sanitation and health habits.

Personnel should wear clean clothing suitable for the manufacturing or service activity with which they
are involved, and this clothing should be changed when appropriate. Additional protective apparel,
such as head, face, hand, and arm coverings, should be worn, when necessary, to protect ‘Procured
Item’ from contamination.
There should be adequate control of personnel loose items, including those in pockets to prevent
contamination risk.
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Smoking, eating, drinking, chewing and the storage of food, personal medication, and tobacco
products, should be restricted to certain designated areas separate from the manufacturing areas.
The consumption of water adjacent to manufacturing equipment is allowed under adequate control.
Any person shown at any time (either by medical examination or supervisory observation) to have an
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apparent illness or open lesions should be excluded from activities where the health condition could
adversely affect the quality of the ‘Procured Items’
Level 2
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The organisation should conduct a risk assessment to identify areas in which the product or service
is at risk of contamination from personnel or their activities.
Level 3
Personnel should avoid direct contact with ‘Procured Items’.
A written procedure should be in place describing gowning requirements
Personnel suffering from an infectious disease or having open lesions on the exposed surface of the
body should not engage in activities that could result in compromising the quality of ‘Procured Items’
Personnel should also ensure hands and clothes are kept clean during operations to avoid any
contamination or visual defect on procured item (e.g., oil/ ink spots) in accordance with the
specification and / or defect library.
8.3 Consultants
Level 1

Level 2
In case of consultants advising on development of quality management systems or the manufacture

and control of ‘Procured Items’, should have sufficient education, training, and experience, or any
combination thereof, to advise on the subject for which they are retained.
Records should be maintained stating the name, address, qualifications, and type of service provided
by these consultants
Level 3
No additional requirements for this level.
9. BUILDINGS AND FACILITIES
9.1 Design and Construction
Level 1
No additional requirements for this level. e

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Level 2

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Level 3
Where required, clean-room facilities should be demonstrated to perform to a recognised standard,

e.g., ISO 14644 – Clean-rooms and associated controlled environments
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The organization should conduct a risk assessment of the facility to identify areas in which the product
or service is at risk of contamination.
The flow of materials and personnel through the building or facilities should be designed to prevent
mix-ups or contamination.
There should be defined areas or other control systems for the following activities:
• Receipt, identification, sampling, and quarantine of incoming materials, pending release or rejection.
• Quarantine before release or rejection of ‘Procured Item’.
• Holding rejected materials before further disposition (e.g., return, reprocessing or destruction).
• Storage of released materials.
• Production operations.
• Packaging and labelling operations
• Laboratory operations.

Where microbiological specifications have been established for the ‘Procured Item’, facilities should
also be designed to limit exposure to objectionable microbiological contaminants as appropriate.
9.2 Utilities
Level 1
Permanently installed pipework should be appropriately identified. This can be accomplished by

identifying individual lines, documentation, computer control systems, or alternative means. Pipework
should be located to avoid risks of contamination of the ‘Procured Item’.
Level 2
Adequate ventilation, air filtration and exhaust systems should be provided, where appropriate.
These systems should be designed and constructed to minimise risks of contamination and cross-
contamination and should include equipment for control of air pressure, micro-organisms (if
appropriate), odour, visible contaminants, insects, humidity, and temperature, as appropriate to the
stage of manufacture.
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Level 3
Where risk assessment has identified the need for an air handling system, it shall be designed and
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maintained to assure adequate protection of the product or service. The effectiveness shall be
demonstrated.
Where an inert atmosphere is required, the gas shall be treated as a quality critical raw material or
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intermediate
Permanently installed pipework should be appropriately identified. This can be accomplished by
identifying individual lines, documentation, computer control systems, or alternative means. Pipework
should be located to avoid risks of contamination of the ‘Procured Item’.
All utilities that could impact on product quality (e.g., steam, gases, compressed air, and heating,
ventilation, and air conditioning) should be qualified and appropriately monitored and action should
be taken when limits are exceeded. Drawings for these utility systems should be available
Particular attention should be given to areas where ‘Procured Items’ are exposed to the environment.
If air is re-circulated to production areas, appropriate measures should be taken to control risks of
contamination and cross-contamination.
In areas where the product is exposed to the work environment or stored, drains shall be of adequate
size and should be provided with an air break or a suitable device to prevent back-siphoning, when
appropriate
9.3 Water
Level 1

Level 2
Level 3
Unless otherwise justified, process water should, at a minimum, meet World Health Organization
(WHO) guidelines for drinking (potable) water quality
Purified water should be used for all washing steps
Where microbiological and / or chemical quality of water is considered critical to product quality,
measures should be taken, measures should include system design to prevent microbial build up and
chemical / physical contamination (appropriate materials of construction, valve design, prevention of
dead legs, continuous recirculation), operational procedures (sanitisation where appropriate, point of
use flushing) and monitoring programme (chemical and microbiological). The required water quality
should be defined and specified.
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For excipients used in parenteral product attention should be given to the potential impact of water
used in production on microbiological or chemical aspects of any material specifications defined and
required by GSK
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9.4 Containment
Level 1

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Level 2
Level 3
Dedicated production areas should be considered when material of an infectious nature or high
pharmacological activity or toxicity is involved (e.g., certain steroids or cytotoxic anti-cancer agents)
unless validated inactivation and/or cleaning procedures are established and maintained.
Appropriate measures should be established and implemented to prevent cross-contamination from

personnel, materials, etc. moving from one dedicated area to another.
Any production activities (including weighing, milling, or packaging) of highly toxic non-pharmaceutical
materials such as herbicides and pesticides should not be conducted using the buildings and/or
equipment being used for the production of ‘Procured Items’. Handling and storage of these highly
toxic non-pharmaceutical materials should be separate from ‘Procured Items’.

The organization should conduct a risk assessment considering the risk to product quality from utilities
and process materials (e.g., nitrogen, compressed air, steam, lubricants etc.) used in the production,
storage, or transfer of materials.
9.5 Lighting
Level 1
Adequate lighting should be provided in all areas to facilitate cleaning, maintenance, and proper
operations.
Where the product is exposed to the work environment or stored, lighting should be shatter-proof or
otherwise protected.
Level 2
Where specified by GSK there should be controlled lighting, e.g., Natural daylight for quality
evaluation of component or printed colour.
Level 3
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9.6 Sewage and Refuse

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Level 1
Sewage, refuse, and other waste (e.g., solids, liquids, or gaseous by-products from manufacturing)
in and from buildings and the immediate surrounding area should be disposed of in a safe, timely,
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and sanitary manner. Containers and/or pipes for waste material should be clearly identified.
Level 2
Level 3
The handling of waste material should be controlled to prevent the risk of cross- contamination and
unauthorised use; in particular:
 All waste or scrap material should be securely contained, clearly identified, and removed from
processing and storage areas in accordance with documented procedures
 Waste or scrap material should be stored in a secure area pending disposal. If interruptions
occur, adequate evidence and rationale should be documented to show that such interruptions
have not compromised the quality of procured item. Such concern is increasingly important
following purification of the procured item.
 Secure waste disposal practices should be enforced to avoid risk of ‘counterfeit’ products
reaching the market, e.g., where the supplied material is identifiable to a GSK final product, or

is GSK intellectual property, e.g.: - rendering unusable before disposal, defacing scrap, or
obsolete printing plates.
 Unless printed materials are shredded or incinerated on site, they should be disposed of via
an approved waste merchant. The waste merchant’s systems for handling, controlling, storage
and secure disposal for recycling or other method of destruction should be inspected prior to
agreement and regularly reviewed by auditing. Where required by GSK (documented
requirement in a specification, contract, or quality agreement) a certificate of
destruction/recycling and method applied for printed and / or other waste should be requested.
 The incorporation of waste or scrap material is inherent in the manufacture of some materials
(plastics, glass, aluminium, board etc.). If reprocessing is allowed, parameters should be
defined and agreed with GSK.
9.7 Sanitation and Maintenance
Level 1
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Buildings used in the manufacture of ‘Procured Items’ should be properly maintained and repaired
and kept in a clean condition.
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Appropriate pest control should be in place giving protection from rodents, crawling, and flying insects,
any other pests prevalent in the area.
Effectiveness of pest control should be assessed through regular, documented surveys.

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Traps, bait stations and other associated equipment should be clearly labelled, securely positioned,
and positioned in such a way that it presents no risk to production, materials, or product.
Level 2
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There should be an effective cleaning and maintenance system in place including:
 Appropriate planned preventative maintenance.
 Written procedures assigning responsibility for sanitation and describing the cleaning
schedules, methods, equipment, and materials to be used in cleaning buildings and facilities.
 Records of the above.
An individual should be assigned responsibility for establishing and maintaining schedules for
cleaning and general housekeeping within the facility and for maintenance of associated records.
Level 3
When necessary, written procedures should also be established for the use of suitable rodenticides,
insecticides, fungicides, fumigating agents, and cleaning and sanitizing agents to prevent the
contamination of equipment, raw materials, packaging/labelling materials, and ‘Procured Items’.

10. PROCESS EQUIPMENT
10.1 Design and Construction
Level 1
Equipment used in the manufacture of ‘Procured Items’ should be of appropriate design and adequate
size, and suitably located for its intended use, cleaning, sanitization (where appropriate), and
maintenance.
Equipment should be constructed so that surfaces that contact raw materials, intermediates, or
‘Procured Items’ do not alter the quality of the ‘Procured Items’ beyond the official or other established
specifications.
Any substances associated with the operation of equipment, such as lubricants, heating fluids or
coolants, should not contact ‘Procured Items’ to alter their quality beyond the official or other
established specifications. Any deviations from this should be evaluated to ensure that there are no
detrimental effects upon the fitness for purpose of the material. Wherever possible, food grade
lubricants and oils should be used.
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Closed or contained equipment should be used whenever appropriate. Where open equipment is
used, or equipment is opened, appropriate precautions should be taken to minimize the risk of
contamination.
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Level 2
Where equipment is located outdoors there should be suitable controls to minimise the risk to material
quality from the environment (for example processing within a closed system).
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Production equipment should only be used within its qualified operating range
Level 3
Some of the procured item categories especially ‘Agri’ based raw material (e.g., wheat flour, malted
barley, skimmed milk powder, malt extract etc) and other procured items which inherently harbour,
and support insect / pest hence controls measures including fumigation of premises, material as
appropriate should be in place and adequate records to be maintained.
Major equipment (e.g., reactors, storage containers, mould tools, cutters and dies) and permanently
installed processing lines used during the production of a ‘Procured Item’ should be appropriately
identified.
10.2 Equipment Maintenance and Cleaning
Level 1
Schedules and procedures (including assignment of responsibility) should be established for the
preventative maintenance of equipment.
Written procedures should be established for cleaning of equipment.

Level 2
There should be an effective cleaning and maintenance system in place including:
Cleaning procedures should contain enough details to enable operators to clean each type of
equipment in a reproducible and effective manner. These procedures should include:
• Assignment of responsibility for cleaning of equipment.
• Cleaning schedules, including, where appropriate, sanitizing schedules.
• A complete description of the methods and materials, including dilution of cleaning agents
used to clean equipment
Level 3
Equipment and utensils should be cleaned, stored, and, where appropriate, sanitized or sterilized to
prevent contamination or carry-over of a material that would alter the quality of the ‘Procured Item’
beyond the official or other established specifications.
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Where equipment is assigned to continuous production or campaign production of successive batches
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of the same ‘Procured Item’, equipment should be cleaned at appropriate intervals to prevent build-
up and carry-over of contaminants (e.g., degradants or objectionable levels of micro-organisms).
Non-dedicated equipment should be cleaned between production of different materials to prevent

cross-contamination.
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Equipment should be identified as to its contents and its cleanliness status by appropriate means.
10.3 Calibration
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Level 1
Control, weighing, measuring, monitoring and test equipment that is critical for assuring the quality of
‘Procured Items’ should be calibrated according to written procedures and an established schedule
across the operating range used.
Equipment calibrations should be performed using standards traceable to certified standards, if

existing.
Records of these calibrations should be maintained.
The current calibration status of critical equipment should be known and verifiable.
Instruments that do not meet calibration criteria should not be used.
Measuring equipment should be safeguarded from adjustments, damage or deterioration that would
invalidate the calibration status and subsequent measurement results.

Deviations from approved standards of calibration on critical instruments should be investigated to

determine if these could have had an impact on the quality of the ’Procured Items’ manufactured using
this equipment since the last successful calibration.
Level 2
Level 3
10.4 Computerised Systems
Level 1
Computerised systems should have sufficient controls to prevent unauthorized access or changes to
data. There should be controls to prevent omissions in data (e.g., system turned off and data not
captured).
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If system breakdowns or failures would result in the permanent loss of records, a back-up system
should be provided. A means of ensuring data protection should be established for all computerised
systems.
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Level 2
Level 3
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Appropriate installation qualification and operational qualification should demonstrate the suitability of
computer hardware and software to perform assigned tasks. Any data back-up and recovery
processes should be qualified.
Commercially available software that has been qualified does not require the same level of testing.
Written procedures should be available for the operation and maintenance of computerised systems.
Where critical data are being entered manually, there should be an additional check on the accuracy
of the entry. This can be done by a second operator or by the system itself.
Incidents related to computerised systems that could affect the quality of ‘Procured Items’ or the
reliability of records or test results should be recorded and investigated.
Changes to the computerised system should be made according to a change procedure and should
be formally authorized, documented and tested. Records should be kept of all changes, including
modifications and enhancements made to the hardware, software, and any other critical component
of the system

10.5 Tooling
Level 1
Level 2
Tooling (e.g., injection mould, blown plastic, cutter dies) should be uniquely and indelibly identified.
Tooling condition should be inspected prior to use. If appropriate the supplier should perform
inspections of samples from each cavity or position as part of the pass to run controls at the
commencement of a production run.
Records of cavity blanking should be maintained.
If tool refurbishment is required during a production run, then samples should be re-checked.
Samples manufactured after major tooling modification should be provided to GSK.
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Tooling usage records and maintenance should be maintained.
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Tooling should be stored securely and adequately protected.
Tooling awaiting repair or destruction should be segregated and appropriately labelled.

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Level 3

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11. DOCUMENTATION AND RECORDS
11.1 Documentation System and Specifications
Level 1
Documentation System and Specifications
All documents related to the manufacture of ‘Procured Items’ should be prepared, reviewed, approved
and distributed according to written procedures.
All production, control, and distribution records should be retained for an appropriate defined period.
When entries are made in records, these should be made indelibly in spaces provided for such entries,
directly after performing the activities, and should identify the person making the entry. Corrections to
entries should be dated and signed and leave the original entry still readable with an explanation of
the reason for the change if not immediately evident.
Level 2

Level 3
The issuance, revision, superseding and withdrawal of all documents should be controlled with
maintenance of revision histories.
An individual should be assigned responsibility for establishing and maintaining schedules for
cleaning and general housekeeping within the facility and for maintenance of associated records.
All production, control, and distribution records should be retained for at least 1 year after the expiry
date of the batch or retained as defined within any quality assurance or other formal agreement.
Typically, retention periods are related either to the shelf life of the finished product or to appropriate
regulatory expectations (in the instance of data used to support regulatory submissions).
Where no expiry date is assigned, records should be retained for 5 years. For ‘Procured Items’ with
retest dates, records should be retained for at least 3 years after the batch is completely distributed.
Machine/tool validation should be expected to be retained for life of tool or until revalidated.
Qualification, validation, and related stability documents should be retained until lifetime or until
requalification / revalidation. During the retention period, originals or copies of records should be
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readily available at the establishment where the activities described in such records occurred.
Records that can be promptly retrieved from another location by electronic or other means are
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acceptable.
All quality related documentation such as specifications, instructions, procedures, records and
qualification and validation protocols and reports can be retained either as originals or as true copies
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such as photocopies, microfilm, microfiche, or other accurate reproductions of the original records.
Where reduction techniques such as microfilming or electronic records are used, suitable retrieval
equipment and a means to produce a hard copy should be readily available.
Specifications should be established and documented for raw materials, intermediates where
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necessary, ‘Procured Items’, and labelling and packaging materials. In addition, specifications may
be appropriate for certain other materials, such as process aids, gaskets, or other materials used
during the production of ‘Procured Items’ that could critically impact on quality. Acceptance criteria
should be established and documented for in-process controls.
If electronic signatures are used on documents, they should be authenticated and secure
11.2 Equipment Cleaning and Use Record
Level 1
Records of major equipment use should be maintained.
Level 2
Level 3

Records of major equipment cleaning, sanitization and/or sterilization and maintenance should show
the date, time (if appropriate), product, and batch number of each batch processed in the equipment,
and the person who performed the cleaning and maintenance.
If equipment is dedicated to manufacturing one ‘Procured Item’, then individual equipment records
are not necessary if batches of the ‘Procured Item’ follow in traceable sequence. In cases where
dedicated equipment is employed, the records of cleaning, maintenance, and use can be part of the
batch record or maintained separately
11.3 Records of Raw Materials, ‘Procured Items’ Labeling and Packaging Materials
Level 1
Records should be maintained including:
• The name of the manufacturer, identity and quantity of each shipment of each batch of raw materials,
intermediates or labelling and packaging materials for ‘Procured Items’; the name of the supplier; the
supplier's control number(s), if known, or other identification number; the number allocated on receipt;
and the date of receipt.
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The final decision regarding rejected raw materials, intermediates or ‘Procured Items’ labelling and
packaging materials
Level 2
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Level 3
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 The results of any test or examination performed and the conclusions derived from this.
 Supplier C of A’s received along with the material should be verified by QA/QC of the receiving
organisation.
Records should be maintained including:
 Supplier assessment and approval records.
 Records tracing the use of materials.
 Documentation of the examination and review of ‘Procured Item’ labelling and packaging materials
for conformity with established specifications
11.4 Master Production Instructions (Master Production and Control Records)
Level 1
Master production instructions should include:

• The name of the ‘Procured Item’ being manufactured and an identifying document reference code,
if applicable.
Level 2
Level 3
A complete list of raw materials and intermediates designated by names or codes sufficiently specific
to identify any special quality characteristics.
• An accurate statement of the quantity or ratio of each raw material or intermediate to be used,
including the unit of measure. Where the quantity is not fixed, the calculation for each batch size or
rate of production should be included.
• The production location and major production equipment to be used.
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Master production instructions should also include:
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• Variations to quantities should be included where they are justified.
• Detailed production instructions, including the:
o Sequences to be followed,
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o Sampling instructions and in-process controls with their acceptance criteria, where appropriate,
The instructions for storage of the ‘Procured Item’ to assure its suitability for use, including the labelling
and packaging materials and special storage conditions with time limits, where appropriate.
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Master Production instructions should be independently checked, dated, and signed by a person in
the quality unit(s).
Production instructions should also specify ranges of process parameters to be used
11.5 Batch Production Records (Batch Production and Control Records)
Level 1
Batch production records should be prepared for each ‘Procured Item’.
These records should be numbered with a unique batch or identification number, dated, and signed
when issued. In continuous production, the product code together with the date and time can serve
as the unique identifier until the final number is allocated.
Recording of the completion of each significant step in the batch production records should be
performed as and when activity is started / completed.

Written procedures should be established and followed for investigating critical deviations or the
failure of a batch of ‘Procured Item’ to meet specifications. The investigation should extend to other
batches that may have been associated with the specific failure or deviation.
Level 2
Records should be witnessed as appropriate to indicate materials used, process parameters and
applicable controls were adequate and confirming that traceability was maintained
Level 3
Batch production records should include complete information relating to the production and control
of each batch.
If the batch production record is produced from a separate part of the master document, that document
should include a reference to the current master production instruction being used.
These records should also include:
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• Quantities of packaging and labels issued/used for ‘Procured Item’.
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• Any deviation noted, its evaluation, investigation conducted (if appropriate) or reference to that
investigation if stored separately; and
• The identity of any mobile, multi-purpose equipment (for example pumps) used, should be recorded
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where required for traceability.
11.6 Laboratory Control Records

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Level 1
Level 2
Laboratory Control records should also include
• A statement of or reference to each test method used.
• A statement of the weight or measure of sample used for each test as described by the
method; data on or cross-reference to the preparation and testing of reference standards, reagents,
and standard solutions.
• A complete record of all raw data generated during each test, in addition to graphs, charts,
and spectra from laboratory instrumentation, properly identified to show the specific material and
batch tested.
• A record of all calculations performed in connection with the test, including, for example, units
of measure, conversion factors, and equivalency factors; **

• Where spreadsheets are used to perform automated calculations, they should be secure and
checked to ensure accuracy.
• Raw data produced by the laboratory equipment or computerized system must be reviewed
as per companies’ procedures to ensure data validity and integrity. The raw data to be reviewed, as
well as the related review task, must be defined in the system management definition or in a
corresponding standard operating procedure (SOP).
Level 3
Laboratory Control Records
Laboratory control records should include complete data derived from all tests conducted to ensure
compliance with established specifications and standards, including examinations and assays, as
follows:
• A description of samples received for testing, including the material name or source, batch number
or other distinctive code, date sample was taken, and, where appropriate, the quantity and date the
sample was received for testing.
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• A statement of the test results and how they compare with established acceptance criteria.
• Data must be attributable to the person generating the data, legible permanent, contemporaneous,
and accurate. The identity of the person who performed each test and the date(s) the tests were
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performed should be included.
Complete records should also be maintained for:
• Any modifications to an established analytical method.

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• Periodic calibration of laboratory instruments, apparatus, gauges, and recording devices.
• Out of specification (OOS) investigations.
Laboratory records to be completed as and when an activity/ step has been started / performed or
witnessed to ensure traceability is maintained.
A documented system should be in place to ensure that data records are accurate, complete, without
deletion and maintained within their original context, including their relationship to other data records.
Laboratory Control records should also include
• A statement of or reference to each test method used.
• A statement of the weight or measure of sample used for each test as described by the method;
data on or cross-reference to the preparation and testing of reference standards, reagents, and
standard solutions.
• A complete record of all raw data generated during each test, in addition to graphs, charts, and
spectra from laboratory instrumentation, properly identified to show the specific material and batch
tested.

• A record of all calculations performed in connection with the test, including, for example, units of
measure, conversion factors, and equivalency factors
• Raw data produced by the laboratory equipment or computerized system must be reviewed as per
companies’ procedures to ensure data validity and integrity.
11.7 Batch Production Record Review
Level 1
Batch production and laboratory control records of critical process steps should be reviewed before a
‘Procured Item’ batch is released or distributed.
Level 2
Level 3
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Written procedures should be established and followed for the review and approval of batch
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production and laboratory control records, including packaging and labelling, to determine compliance
of the ‘Procured Item’ with established specifications before a batch is released or distributed.
All deviation, investigation, and OOS reports should be reviewed before the batch is released.
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The Quality unit must approve release of product. The quality unit(s) can delegate to the production
unit the responsibility and authority for release of intermediates, except for those shipped outside the
control of the manufacturing company.
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Batch production and laboratory control records of critical process steps should be reviewed and
approved by the quality unit(s) before a ‘Procured Item’ batch is released or distributed. Production
and laboratory control records of non-critical process steps can be reviewed by qualified production
personnel or other units following procedures approved by the quality unit(s).
All deviation, investigation, and OOS reports should be reviewed as part of the batch record review
before the batch is released.
When release testing is not performed on a representative sample, defects identified during the IPC
should be reviewed and assessed against the AQL before batch release.
12. MATERIALS MANAGEMENT
12.1 General Controls
Level 1
Procedures shall define how exceptions are handled, e.g., the use of products or services where audit
or monitoring has not been undertaken.
Availability of approved supplier list at ‘appropriate location.

Where incoming product could produce defects, an assessment should be in place to document what
(if any) control and detections should be in place.
Level 2
Manufacturers of ‘Procured Items’ should have a system for evaluating the suppliers of critical
materials.
Level 3
There should be written procedures describing the receipt, identification, quarantine, storage,
handling, sampling, testing, and approval or rejection of materials.
Materials should be purchased against an agreed specification, from an approved supplier.
Usage of Pallets:
In the case of wooden pallets:
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Pallets should comply with the requirements of any GSK purchase specification, if no specification is
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in place, then the following should apply:
• Source of wooden pallets should be known.
• Treatment of wooden pallets with 2, 4, 6-tribromophenol (TBP) is prohibited.

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• Determine if wooden pallets are treated (fumigated/heat treated). Heat treated wooden pallets are
preferred however Methyl bromide (MB) treatment in accordance with international standard ISPE 15
is permissible, but not preferred.
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• Pallets conform to International Standards for Phytosanitary Measures No. 15 (ISPM15), including
recycled / refurbished pallets
12.2 Receipt and Quarantine
Level 1
Upon receipt and before acceptance, each container or grouping of containers of materials should be
examined visually for correct labelling (including correlation between the name used by the supplier
and the in-house name, if these are different), container damage, broken seals and evidence of
tampering or contamination.
Level 2
Level 3
Materials should be held under quarantine until they have been sampled, examined, or tested as
appropriate, and released for use.

Before incoming materials are mixed with existing stocks (e.g., solvents or stocks in silos), they should
be identified as correct, tested, if appropriate, and released. Procedures should be available to
prevent discharging incoming materials wrongly into the existing stock.
If bulk deliveries are made in non-dedicated tankers, there should be assurance of no cross-
contamination from the tanker. Means of providing this assurance could include one or more of the
following:
• Certificate of cleaning
• Testing for trace impurities
• Audit of the supplier.
A system should be in place to identify the status of each batch.
Large storage containers, and their attendant manifolds, filling and discharge lines should be
appropriately identified.
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Each container or grouping of containers (batches) of materials should be assigned and identified
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with a distinctive code, batch, or receipt number. This number should be used in recording the
disposition of each batch
12.3 Sampling and Testing of Incoming Production Materials

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Level 1
Visual examination of containers, labels, and recording of batch numbers should help in establishing
the identity of these materials.
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Level 2
Level 3
Processing aids, hazardous or highly toxic raw materials, other special materials, or materials
transferred to another unit within the company’s control do not need to be tested if the manufacturer’s
Certificate is obtained, showing that these raw materials conform to established specifications.
Samples should be representative of the batch of material from which they are taken.
Sampling should be conducted following procedures designed to prevent contamination of the

material sampled and contamination of other materials.
Containers from which samples are withdrawn should be opened carefully and subsequently reclosed
Samples should be clearly labelled with the input material code/description and batch identifier.

Product contact utilities such as nitrogen, compressed air, steam etc. should follow the same controls
as quality critical materials and should be assessed and appropriate action taken to control the risk
of contamination and cross-contamination.
Sampling methods should specify the number of containers to be sampled, (individual or composite
sample), which part of the container to sample, and the amount of material to be taken from each
container. Containers from which samples are withdrawn should be marked to indicate that a sample
has been taken.
Sampling should be conducted at defined locations
Supplier approval, for quality critical materials, should include an evaluation that provides adequate
evidence (e.g., past quality history) that the manufacturer can consistently provide material meeting
specifications.
The number of containers to sample and the sample size should be based upon a sampling plan that
takes into consideration the criticality of the material, material variability, past quality history of the
supplier, and the quantity needed for analysis
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12.4 Storage
Level 1
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Materials should be handled and stored in a manner to prevent degradation, contamination, and
cross-contamination.
Certain materials in suitable containers can be stored outdoors, provided identifying labels remain
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legible and containers are appropriately cleaned before opening and use.
Rejected materials should be identified and controlled under a quarantine system designed to prevent
their unauthorised use in manufacturing.
Level 2
Level 3
Materials should be stored under conditions and for a period that have no adverse affect on their
quality and should normally be controlled so that the oldest stock is used first. The storage conditions
of the area where the materials are stored should be aligned with the storage conditions stated on the
material labels.
Quarantine systems may involve; electronic segregation within qualified systems which have been
designed and certified to prevent the use of rejected or ‘Out of Specification’ materials; physical
labelling and physical segregation, or a combination of the above.

Materials stored in fibre drums, bags, or boxes should be stored off the floor and, when appropriate,
suitably spaced to permit cleaning and inspection.
For GSK supplied materials ensure appropriate control of old stock, returned stock and destruction of
stock
12.5 Re-evaluation
Level 1
Level 2
Level 3
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Materials should be re-evaluated as appropriate to determine their suitability for use (e.g., after
prolonged storage or exposure to heat or humidity, or near retest or expiry date)
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12.6 Control of Transmissible Spongiform Encephalopathy agents (TSE), Viral and Biological
Risks from Animal Sources
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Level 1
Control of Transmissible Spongiform Encephalopathy agents (TSE), Viral and Biological Risks from
Animal Sources
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Control of TSE is required for all materials that are:
• Input directly to GSK’s manufacturing process for - an excipient, primary or secondary product,
including materials that are not present in the final excipient or product.
• Reagents and solvents.
• Enzymes and catalysts.
• Process aids e.g. charcoal, celite etc.
• Media components and cell banks.
• Purification columns.
• Used as primary packaging components for materials and products or product contact. For
components of medical devices falling under the remit of MDR 2017/745, both product contact AND
non-product contact components.
• Have the potential to come into direct contact with product contact processing or packaging
equipment e.g. lubricants, cleaning agents, water softeners, media fills.

The supplier must have procurement controls in documented form in place that specify the grade of
material to be supplied and any permitted use of animal derived materials or must confirm that no
animal derived materials are used. Routine receipt procedures must confirm that the correct grade is
received. The supplier must confirm that they are able to apply the necessary controls over animal
derived materials. The supplier must conform to applicable local regulations (e.g. EU Directive
92/46/EEC for milk and milk derived products).
Any change in the certification must be immediately communicated and agreed with GSK.
Agents should be requested to provide information on their control and supply arrangements and to
ask the manufacturers to supply information directly to GSK.
Level 2
Level 3
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12.7 Aflatoxins
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Level 1
Level 2
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Level 3
For ingredients that may be at risk of carrying aflatoxins and intended for use in the manufacture of
nutritional products adequate control and verification of compliance with maximum permitted level
should be in place.
12.8 Nitrosamines
Level 1
No requirements for this level.
Level 2
No requirements for this level.
Level 3

Control of Nitrosamines is required for all materials that are:
• Input directly into GSK’s manufacturing process and become part of the finished product (i. e.
excipients and APIs).
• For materials input directly into excipient and API suppliers’ manufacturing process (including
materials that are not present in the final excipient or API) including:
o Reagents
o Solvents.
• Used as primary packaging components for materials and products or product contact
components of delivery devices
Suppliers should investigate their supply chain so that any nitrosamine contamination risks are
identified, and appropriate controls established.
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The potential for contamination of supplied products (excipients and APIs) with nitrosamines must be
subject to a documented assessment. The assessment should include whether or not nitrosamines
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are or can be introduced at any stage during the production of the material or product, including
supplied materials and how the supplier controls these risks.
A formal Nitrosamine risk assessment should be in place at the supplier for the excipient / API sourced
to GSK. Appropriate testing protocols should be in place based on results of risk assessment.
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A completed nitrosamines questionnaire is expected to be completed by suppliers of excipients and

APIs.
Process or raw material changes that could impact the Nitrosamine Risk Assessment should be
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notified to GSK via change control.
Virgin and recovered/recycled solvents in particular should be assessed for potential Nitrosamine
risks and appropriately managed to reduce the risk of nitrosamines in the finished supplied materials
to GSK.
The supplier must conform to any applicable local regulations
13. PRODUCTION AND IN-PROCESS CONTROLS
13.1 Production Operations
Level 1
The processing status of major units of equipment should be indicated either on the individual units
of equipment or by appropriate documentation, computer control systems, or alternative means.
Level 2

Critical weighing, measuring, or subdividing operations should be witnessed or subjected to an

equivalent control. Prior to use, production personnel should verify that the materials are those
specified in the batch record for the intended ‘Procured Item’.
Any deviation should be documented and explained. Any critical deviation should be investigated.
Materials to be reprocessed or reworked should be appropriately controlled to prevent unauthorized

use.
Where production of moulded components includes the use of ‘re-grind’ this should be controlled in
line with any defined GSK specification.
Where a GSK generated and agreed defect catalogue is in place, the Supplier should ensure that
process capability mapping is carried out including defect generation and mitigation activities.
Level 3
Raw materials for intermediate and ‘Procured Item’ manufacturing should be weighed or measured
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under appropriate conditions that do not affect their suitability for use. Weighing and measuring
devices should be of suitable accuracy for the intended use.
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If a material is subdivided for later use in production operations, the container receiving the material
should be suitable and should be so identified that the following information is available:
• Material name and/or item code;

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• Receiving or control number;
• Weight or measure of material in the new container; and

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• QC release status & Re-evaluation or retest date if appropriate.
Other critical activities should be witnessed or subjected to an equivalent control.
Where there is no defined specification, the use of regrind should be controlled to minimise the risk
of extraneous contamination, should only be from a closed loop system and the proportion of re-grind
should remain within the defined validated limits. Where the level of re-grind is changed this should
be notified to GSK
For chemical processes actual yields should be compared with expected yields at designated steps
in the production process. Expected yields with appropriate ranges should be established based on
previous laboratory, pilot scale, or manufacturing data. Deviations in yield associated with critical
process steps should be investigated to determine their impact or potential impact on the resulting
quality of affected batches.
The critical quality attributes of the ‘Procured Item’ supplied should be defined and the associated
quality critical process parameters should be identified and controlled. The adequacy of these controls
should be known, and process limits defined

13.2 Time Limits
Level 1
Level 2
Level 3
Intermediates held for further processing should be stored under appropriate conditions to ensure
their suitability for use.
13.3 In-process Sampling and Controls
Level 1

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Level 2

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Level 3
In-process Sampling and Controls
Critical in-process controls (and critical process monitoring), including the control points and methods,
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should be stated in writing.
All tests and results should be fully documented
In-process sampling should be conducted using procedures designed to prevent contamination of the
sampled material and other ‘Procured Items’.
Out-of-specification (OOS) investigations are not normally needed for in-process tests that are
performed for the purpose of monitoring and/or adjusting the process.
The acceptance criteria and type and extent of testing can depend on the nature of the ‘Procured
Item’ being manufactured, the reaction or process step being conducted, and the degree to which the
process introduces variability in the product’s quality. Less stringent in-process controls may be
appropriate in early processing steps, whereas tighter controls may be appropriate for later processing
steps (e.g., isolation and purification steps).
Written procedures should describe the sampling methods for in-process materials, and ‘Procured
Items’.
In-process controls can be performed by qualified production department personnel and the process
adjusted without prior quality unit(s) approval if the adjustments are made within pre-established limits

approved by the quality unit(s). All tests and results should be fully documented as part of the batch
record.
Procedures should be established to ensure the integrity of samples after collection.
Samples should not be returned to the batch where this may be detrimental to product quality, e.g.
where the samples have been removed from the immediate area or subjected to invasive testing,
Samples that are destined for GSK incoming control should not be subjected to any visual, analytical
or dimensional testing, stratified throughout the manufacturing batch that they are supplied from
(where possible and applicable).
When a defect library or Acceptance Quality Level is in place, In Process Control should be performed
using them as a reference.
When a defect library is in place, it should be updated including complaints sample received from the
customer.
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Where automatic test equipment, such as camera inspection systems, automatic weighing stations
and code readers, is used there shall be periodic documented challenge tests
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13.4 Blending Batches of ‘Procured Items’
Level 1
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Level 2
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Level 3
Blending Batches of ‘Procured Items’
For the purpose of this document, blending is defined as the process of combining materials within
the same specification to produce a homogeneous ‘Procured Item’. In-process mixing of fractions
from single batches (e.g., collecting several centrifuge loads from a single crystallization batch) or
combining fractions from several batches for further processing is considered to be part of the
production process and is not considered to be blending.
Out-Of-Specification batches should not be blended with other batches for the purpose of meeting
specifications. Each batch incorporated into the blend should have been manufactured using an
established process and should have been individually tested and found to meet appropriate
specifications prior to blending. (Note: exceptions to this requirement may be accepted for non–critical
raw materials. In this type of productions it is industrial practice to do so).
Acceptable blending operations include but are not limited to:
• Blending of small batches to increase batch size

• Blending of tailings (i.e., relatively small quantities of isolated material) from batches of the same
‘Procured Item’ to form a single batch.
Blending processes should be adequately controlled and documented and the blended batch should
be tested for conformance to established specifications where appropriate.
The batch record of the blending process should allow traceability back to the individual batches that
make up the blend.
The expiry or retest date of the blended batch should be based on the manufacturing date of the
oldest tailings or batch in the blend
13.5 Contamination Control & Line Clearance
Level 1
Level 2
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Level 3
Residual materials can be carried over into successive batches of the same ‘Procured Item’ if there
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is adequate control. Examples include residue adhering to the wall of a microniser, residual layer of
damp crystals remaining in a centrifuge bowl after discharge, and incomplete discharge of fluids or
crystals from a processing vessel upon transfer of the material to the next step in the process. Such
carryover should not result in the carryover of degradants or microbial contamination that may
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adversely alter the established ‘Procured Item’ impurity profile.
Production operations should be conducted in a manner that will prevent contamination of ‘Procured
Items’ by other materials.
Precautions to avoid contamination should be taken when ‘Procured Items’ are handled after
purification.
Foreign matter detectors should be used where appropriate. As appropriate depending upon supply
chain of raw material used, material of construction of process equipment, and other process aids
where there is reasonable probability of contamination evident, provision of metal detector or other
suitable means of elimination, reduction of contamination risk to an acceptable level as per updated
specification should be considered. Applicability of HACCP and/ or FMEA tool can be considered for
identification of control and critical control points.
To prevent cross-contamination (mix-ups) during production there should be a recorded line clearance
at the end of each production run (including removal of production documents)

14. PACKAGING AND IDENTIFICATION LABELLING OF ‘Procured Items’
14.1 General
Level 1
Packaging and labelling materials should conform to established specifications from a supplier or
suppliers approved by the quality unit(s). Those that do not comply with such specifications should
be rejected to prevent their use in operations for which they are unsuitable.
Level 2
Level 3
There should be written procedures describing the receipt, identification, quarantine, sampling,
examination and/or testing and release, and handling of packaging and labelling materials.
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Records should be maintained for each shipment of labels and packaging materials showing receipt,
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examination, or testing, and whether accepted or rejected.
14.2 Packaging Materials

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Level 1
Containers should provide adequate protection against deterioration or contamination of the

‘Procured Item’ that may occur during transportation and recommended storage.
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Containers should be clean and, where indicated by the nature of the ‘Procured Item’, sanitized to
ensure that they are suitable for their intended use. These containers should not be reactive, additive,
or absorptive so as to alter the quality of the ‘Procured Item’ beyond the specified limits.
If containers are re-used, they should be cleaned, any liners replaced, and all previous labels should
be removed or defaced.
Packaging material must be agreed formally and in written with each user sites for each SKUs
Level 2
Level 3

14.3 Label Issuance and Control
Level 1
Level 2
Procedures should be used to reconcile the quantities of labels issued, used, and returned and to
evaluate discrepancies found between the number of containers labelled and the number of labels
issued. Such discrepancies should be investigated, and the investigation should be approved by the
quality unit(s).
Returned labels should be maintained and stored in a manner that prevents mix-ups and provides
proper identification.
Printing devices used to print labels for packaging operations should be controlled to ensure that all
imprinting conforms to the print specified in the batch production record
Level 3
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All excess and out dated labels bearing batch numbers or other batch-related printing should be
destroyed.
Printed labels issued for a batch should be controlled and carefully examined for proper identity and
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conformity to specifications in the master production record.
14.4 Packaging and Labelling Operations

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Level 1
Labelling operations should be designed to prevent mix-ups.
Labels used on containers of ‘Procured Items’ should indicate the name or identifying code, the batch
number of the product, and storage conditions, when such information is critical to assure the quality
of ‘Procured Item’.
Packaged and labelled ‘Procured Items’ should be examined to ensure that containers and packages
in the batch have the correct label.
For bulk shipments, the label content can appear on a combination of the Bill of Lading and the vehicle
placard (where regulations on showing safety information permit such additions).
Level 2
Level 3
There should be documented procedures designed to ensure that correct packaging materials and
labels are used.

There should be physical or spatial separation from operations involving other ‘Procured Items’.
Packaging and labelling facilities should be inspected immediately before use to ensure that all
materials not needed for the next packaging operation have been removed. This examination should
be documented in the batch production records, the facility log, or other documentation system.
‘Procured Item’ containers that are transported outside of the manufacturer's control should be sealed
in a manner such that, if the seal is breached or missing, the recipient will be alerted to the possibility
that the contents may have been altered
Selection of packaging system (direct product contact) should be justified and documented. It should
have written packaging specification, including any special storage condition and Tamper evident seal
where specified
15. STORAGE AND DISTRIBUTION
15.1 Warehousing Procedures
Level 1
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Facilities should be available for the storage of all materials under appropriate conditions (e.g. closed
and clean with controlled temperature and humidity, when necessary). Records should be maintained
of these conditions if they are critical for the maintenance of material characteristics. There should be
procedures detailing appropriate actions to be taken if the stated conditions are exceeded.
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Unless there is an alternative system to prevent the unintentional or unauthorised use of quarantined,
rejected, returned, or recalled materials, separate storage areas should be assigned for their
temporary storage until the decision as to their future use has been taken.
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Special attention should be given to the design, use, cleaning and maintenance of all equipment for
bulk handling and storage, such as tanks and silos.
Level 2
Conditions should prevent contamination from objectionable microorganisms, pests, toxic chemicals,
pesticides and sources of flavour and odour taint.
Level 3
Temperature Control
Where the monitoring of temperatures of storage premises is a requirement temperature profile
studies should be carried out to identify problem areas and to confirm that the warehouse meets the
requirements. There should be a regular recording of the warehouse temperature at enough locations
to cover possible temperature variations. Records of monitoring should be regularly reviewed and be
available for examination. There should be a system to alert the customer (manufacturer or agent)
when pre-determined temperature and time limits have been exceeded so that an assessment of the
potential impact on product can be made.

15.2 Distribution Procedures
Level 1
Level 2
Level 3
‘Procured Items’ should only be released for distribution to third parties after they have been released
by the quality representative/unit(s). ‘Procured Items’ can be transferred under quarantine to another
unit under the company’s control when authorized by the quality unit(s) and if appropriate controls
and documentation are in place.
For bulk transport in non-dedicated equipment, verified cleaning procedures shall be applied between
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loadings, and a list of restricted and/or allowed previous cargoes shall be supplied to the transport
companies. Records of cleaning shall be retained.
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Special transport or storage conditions for a ‘Procured Item’ should be stated on the label.
‘Procured Items’ should be transported in a manner that does not adversely affect their quality, e.g.
contamination from objectionable microorganisms, pests, toxic chemicals, pesticides and sources of
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flavour and odour taint. Containers if used in distribution are re-sealed after opening and record
maintained.
The manufacturer should ensure that the contract acceptor (contractor) for transportation of the
‘Procured Item’ knows and follows the appropriate transport and storage conditions and where
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specified product security terms and conditions.
A system should be in place by which the distribution of each batch of ‘Procured Item’ can be readily
determined to permit its recall.
The manufacturer has systems in place to prevent cross contamination and mix-ups with other
materials during distribution
The distribution procedure needs to ensure that both batch disposition at the suppliers facility and
GSK requirements for incoming goods (defined in the specification, cahier de charge or other quality
agreements) are met e.g. Provision of samples, CofA or CofC and delivery documents
16. LABORATORY CONTROLS
16.1 General Controls
Level 1

Level 2
Level 3
The quality unit(s) should have at its disposal adequate laboratory facilities.
There should be documented procedures describing sampling, testing, approval or rejection of

materials, and recording and storage of laboratory data. Laboratory records should be maintained in
accordance with Section 5.6.
All specifications, sampling plans, and test procedures should be scientifically sound and appropriate
to ensure that raw materials, intermediates, ‘Procured Items’, and labels and packaging materials
conform to established standards of quality and/or purity. Appropriate specifications should be
established for ‘Procured Items’ in accordance with accepted standards and consistent with the
manufacturing process. Where applicable, the specifications should include a control of the impurities
(e.g. organic impurities, inorganic impurities, nitrosamines and residual solvents).
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Laboratory controls should be followed and documented at the time of performance. Any departures
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from the above described procedures should be documented and explained.
Any out-of-specification result obtained should be investigated
Reagents and standard solutions should be prepared and labelled following written procedures. “Use
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by” dates should be applied as appropriate for analytical reagents or standard solutions.
Primary reference standards should be obtained as appropriate for the manufacture of ‘Procured
Items’.
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Secondary reference standards should be appropriately prepared, identified, tested, approved, and
stored. The suitability of each batch of secondary reference standard should be determined prior to
first use by comparing against a primary reference standard. Each batch of secondary reference
standard should be periodically re-qualified in accordance with a written protocol.
Where appropriate, there should be a mechanism for ensuring the current status of external standards
e.g. pharmacopoeia.
Test results should not be averaged to mask individual out of specification results.
Analytical data, including electronic data, must not be deleted even if the test determinations or test
results are deemed invalid.
Specifications, sampling plans, and test procedures, including changes to them, should be drafted by
the appropriate organizational unit and reviewed and approved by the quality unit(s).
If the ‘Procured Item’ has a specification for microbiological purity, appropriate action limits for total
microbial counts and objectionable organisms should be established and met. If the ‘Procured Item’
has a specification for endotoxins, appropriate action limits should be established and met.

Out of specification should be documented according to a procedure,
This out of specification procedure should require analysis of the data, assessment of whether a
significant problem exists, allocation of the tasks for corrective actions, and conclusions. Any
resampling and/or retesting after OOS results should be performed according to a documented
procedure. In case there is no assignable cause to invalidate original result, the OOS SOP should
define statistic technique that are to be used and under what situation, criteria for use of retest sample
result and criteria for re-sampling.
Retest sample result can only be used to replace original test result if it is demonstrated that the
original result is erroneous based on a documented investigation. When statistical analysis is used,
both the original and retest data must be included. The same principle applies when the sample is
suspected of not being representative of the material from which it was taken.
The limit for known impurities and objectionable microorganisms should be identified, established and
met. The limit should be based upon appropriate safety data, limit as described in official compendia
or other requirement and sound GMP consideration. Manufacturing process should be adequately
controlled, so that the impurities do not exceed the limit. Many excipients are extracted using organic
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solvents. These solvents are normally removed by drying. It is important that excipient specification
include test and limit for solvent residue and nitrosamines, where appropriate
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16.2 Testing of ‘Procured Items’
Level 1
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For each batch ‘Procured Item’, appropriate laboratory tests should be conducted to determine
conformance to specifications.
Level 2
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Level 3
Appropriate microbiological tests should be conducted where microbial quality is specified.
Microbial testing using specific media should be verified to ensure that, for example, any preservative
present in the ‘Procured Item’ are inactivated by the media, and that suspected organisms (including
those known to be slow growing) grow on the media being used during the incubation period set.
Purchased media should be supplied with a certificate and each batch should be given a growth
promotion test
16.3 Validation of Analytical Procedures - see Section 11.
16.4 Certificates of Analysis
Level 1

No additional requirements for this level
Level 2
Level 3
Authentic Certificates of Analysis should be issued for each batch of ‘Procured Item’ on request.
Information on the name of the ‘Procured Item’ including where appropriate its grade, the batch
number, and the date of manufacture should be provided on the Certificate of Analysis. For ‘Procured
Items’ with an expiry date, the expiry date should be provided on the label and Certificate of Analysis.
For ‘Procured Items’ with a retest date, the retest date should be indicated on the label and/or
Certificate of Analysis. Where procured items are repackaged there should be documented evidence
that their stability has not been adversely affected and specified expiry dates or retest intervals are
justified.
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The Certificate should list each test performed in accordance with compendial or customer
requirements, including the acceptance limits, and the numerical results obtained (if test results are
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numerical).
Certificates should be dated and signed by authorised personnel of the quality unit(s) or generated
from a secure system and should show the name, address and telephone number of the original
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manufacturer. Where the analysis has been carried out by a repacker or reprocessor, the Certificate
of Analysis should show the name, address and telephone number of the repacker/reprocessor and
a reference to the name of the original manufacturer.
If new Certificates are issued by or on behalf of repackers/ reprocessors, agents or brokers, these
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Certificates should show the name, address and telephone number of the laboratory that performed
the analysis. They should also contain a reference to the name and address of the original
manufacturer and to the original batch Certificate, a copy of which should be attached.
It should be made clear on the certificate if the results are for analysis of that particular batch or are
results taken from a monitoring programme or are a predicted (if tested) result
16.5 Stability Monitoring
Level 1
Level 2
Level 3
Where special storage conditions and/or restricted shelf-life applies to the ‘Procured Item,’ the limits
for these should be justified.

16.6 Expiry and Retest Dating
Level 1
Where special storage conditions and/or restricted shelf-life applies to the ‘Procured Item,’ an expiry
date or retest date should be assigned and provided on the Certificate of Analysis.
Level 2
Level 3
An expiry date or retest date should be assigned to each procured item and included on the Certificate
of Analysis. The assigned date should be based on a formal stability study or documented review of
historical data. Where excipients are repackaged there shall be documented evidence that their
stability has not been adversely affected and specified expiry dates or retest intervals are justified.
16.7 Reserve/Retention Samples
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Level 1
A representative sample should be taken for the purpose of performing a retest.
Level 2
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For ‘Procured Items’ with retest dates, similar reserve samples should be retained for three years
after the batch is completely distributed by the manufacturer or as agreed with GSK.
Level 3
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The packaging and holding of reserve samples is for the purpose of potential future evaluation of the
quality of batches of ‘Procured Item’ and not for future stability testing purposes.
Appropriately identified reserve samples of each ‘Procured Item’ batch should be retained for one
year after the expiry date of the batch assigned by the manufacturer, or for three years after
distribution of the batch, whichever is the longer.
The reserve sample should be stored in the same packaging system in which the ‘Procured Item’ is
stored or in one that is equivalent to or more protective than the marketed packaging system.
Retention/ reserve sample shall be stored in secured location, readily retrievable and in storage
condition consistent with procured item.
Enough quantities should be retained to conduct at least two full compendial analyses or, when there
is no pharmacopoeia monograph, two full specification analyses

17. VALIDATION
17.1 Validation Policy
Level 1
Level 2
Level 3
17.2 Validation/Qualification Documentation
Level 1
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Level 2
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Appropriate qualification of critical equipment and ancillary systems should be completed and
documented.
Level 3
Suitable qualifications for the process and testing equipments (internal or through third part) with cross
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reference URS should be prepared and available
17.3 Qualification
Level 1
Level 2
Appropriate qualification of critical equipment and ancillary systems (including those in any testing
laboratory) should be completed and documented. This should verify that these critical equipment
and systems perform as intended across the anticipated operating range to consistently achieve the
quality specification. Process control limits should be established to provide the approved
manufacturing operating range.
Level 3
Suitable qualifications for the process and testing equipments (internal or through third part) with cross
reference URS should be prepared and available

17.4 Approaches to Process Validation
Level 1
Level 2
Level 3
17.5 Process Validation Program
Level 1
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Level 2
Level 3
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17.6 Periodic Review of Validated Systems

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Level 1
Level 2
Level 3
17.7 Cleaning Validation
Level 1
Level 2

Level 3
17.8 Validation of Analytical Methods
Level 1
Level 2
Methods should be validated to include consideration of characteristics included within the ICH
guidelines on validation of analytical methods. The degree of analytical qualification performed should
reflect the purpose of the analysis and the stage of the ‘Procured Item’ production process.
Appropriate qualification of analytical equipment should be considered before starting validation of

analytical methods.
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Complete records should be maintained of any modification of a validated analytical method. Such
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records should include the reason for the modification and appropriate data to verify that the
modification produces results that are as accurate and reliable as the established method.
Level 3
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Analytical methods should be validated unless the method employed is included in the relevant
pharmacopoeia or other recognised standard reference.
If the procured item is claimed to be in compliance with a pharmacopoeia or other official compendium,
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any non-compendial analytical method shall be demonstrated to be at least equivalent to those in the
compendia, the method shall comply with applicable general chapters and notices, and the
responsibility for monitoring the current pharmacopoeia or official compendium shall be assigned.
17.9 Qualification of Test Methods and Equipment
Level 1
Level 2
Level 3
Test methods and equipment should be qualified to demonstrate suitability to confirm specification
requirements. Where variable data is obtained the qualification should consider precision, accuracy,
range and robustness e.g. R&R study

18. CHANGE CONTROL
Level 1
No Additional requirement
Level 2
Written procedures should provide for the identification, documentation, appropriate review, and
approval of changes in raw materials, specifications, analytical methods, facilities, support systems,
equipment (including computer hardware), processing steps, labelling and packaging materials, and
computer software. Procedures should also cover changes identified by suppliers of critical materials.
Any proposals for changes with potential impact on quality should be drafted, reviewed, and approved
by the appropriate organisational units, and reviewed and approved by the quality unit(s).
The potential impact of the proposed change on the quality of the ‘Procured Item’ should be evaluated.
A classification procedure may help in determining the level of testing, validation, and documentation
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needed to justify changes to a qualified or validated process.
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Level 3
A formal change control SOP should be available to record changes and assess impact of the change
on the products.
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Notifications for changes should be done to customers prior to implement changes
Changes can be classified (e.g. as minor or major) depending on the nature and extent of the
changes, and the effects these changes may impart on the process. Scientific judgement should
determine what additional testing and validation studies are appropriate to justify a change in a
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validated process.
After the change has been implemented, there should be an evaluation of the first batches produced
or tested under the change
19. REJECTION AND RE-USE OF MATERIALS
19.1 Rejection
Level 1
‘Procured Items’ failing to meet established specifications should be identified as such and
quarantined. These ‘Procured Items’ can be reprocessed or reworked as described below (unless
otherwise specified). The final disposition of rejected materials should be recorded.
Level 2
Level 3

19.2 Reprocessing (Raw Materials/Excipients/Intermediates & APIs only)
Level 1
Level 2
Level 3
Introducing a material including one that does not conform to standards or specifications, back into
the process and reprocessing by repeating a crystallization step or other appropriate chemical or
physical manipulation steps (e.g., distillation, filtration, chromatography, milling) that are part of the
established manufacturing process is generally considered acceptable. However, if such
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reprocessing is used for a majority of batches, such reprocessing should be included as part of the
standard manufacturing process.
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Continuation of a process step after an in-process control test has shown that the step is incomplete
is considered to be part of the normal process. This is not considered to be reprocessing.
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Introducing un-reacted material back into a process and repeating a chemical reaction is reprocessing
unless it is part of the established process. Such reprocessing should be preceded by careful
evaluation to ensure that the quality of the ‘Procured Item’ is not adversely impacted due to the
potential formation of by-products and over-reacted materials
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19.3 Reworking
Level 1
Level 2
Level 3
Before a decision is taken to rework batches that do not conform to established standards or
specifications, an investigation into the reason for non-conformance should be performed.
Batches that have been reworked should be subjected to appropriate evaluation, testing, stability
testing if warranted, and documentation to show that the reworked product is of equivalent quality to
that produced by the original process
Concessions/ reworking protocols to be agreed by GSK using reference samples of acceptable/ not
acceptable materials.

19.4 Recovery of Materials and Solvents
Level 1
Level 2
Level 3
Recovery (e.g. from mother liquor or filtrates) of reactants, intermediates, or the final product is
considered acceptable, provided that approved procedures exist for the recovery and the recovered
materials meet specifications suitable for their intended use.
Solvents can be recovered and reused in the same processes or in different processes, provided that
the recovery procedures are controlled and monitored to ensure that solvents meet appropriate
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standards before reuse or co-mingling with other approved materials.
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Fresh and recovered solvents and reagents can be combined if adequate testing has shown their
suitability for all manufacturing processes in which they may be used.
The use of recovered solvents, mother liquors, and other recovered materials should be adequately
documented.
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19.5 Returns
Level 1
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Returned ‘Procured Items’ should be identified as such and quarantined.
Records of returned ‘Procured Items’ should be maintained. For each return, documentation should
include:
 Name and address of the consignee
 ‘Procured Item’, batch number, and quantity returned
 Reason for return
 Use or disposal of the returned ‘Procured Item’
Level 2
Level 3

If the conditions under which returned ‘Procured Items’ have been stored or shipped before or during
their return or the condition of their containers casts doubt on their quality, the returned ‘Procured
Items’ should be reprocessed, reworked, or destroyed, as appropriate
20. COMPLAINTS AND RECALLS
Level 1
All quality related complaints, whether received orally or in writing, should be recorded and
investigated according to a written procedure.
There should be a written procedure that defines the circumstances under which a recall of a
‘Procured Item’ should be considered.
Level 2
Level 3
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A Complaint records should include:
• Name and address of complainant;
• Name (and, where appropriate, title) and phone number of person submitting the complaint;
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• Complaint nature (including name and batch number of the ‘Procured Item’);
• Date complaint is received;

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• Action initially taken (including dates and identity of person taking the action);
• Any follow-up action taken;
• Response provided to the originator of complaint (including date response sent); and
• Final decision on ‘Procured Item’ batch or lot.
Records of complaints should be retained in order to evaluate trends, product-related frequencies,

and severity with a view to taking additional, and if appropriate, immediate corrective action
21. CONTRACT SERVICES (INCLUDING MANUFACTURERS, LABORATORIES,

CALIBRATION)
Level 1
Level 2

Level 3
All contract services should comply with the standards defined in this document (to the appropriate
level). Special consideration should be given to the prevention of cross-contamination and to
maintaining traceability.
Records should be kept at the site where the activity occurs and be readily available.
There should be a written and approved contract or formal agreement between the contract giver and
the contract acceptor that defines in detail the Quality responsibilities, including the quality measures,
of each party.
Where subcontracting is allowed, the contract acceptor should not pass to a third party any of the
work entrusted to him under the contract without the contract giver's prior evaluation and approval of
the arrangements.
Changes in the process, equipment, test methods, specifications, or other contractual requirements
should not be made unless the contract giver is informed and approves the changes
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Contract services should be evaluated by the contract giver to ensure Quality compliance of the
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specific operations occurring at the contract sites.
The contract should permit the contract giver to audit the contract acceptor's facilities for compliance
with good manufacturing practice.
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Where a sub-contracted activity occurs, the supplier should have a risk assessment/ inspection
criterion that allows for an evaluation/identification of risk introduced to the product/service by the
activity. Examples include (but are not limited to);
• additional printing steps for which electronic comparison of returned product takes place (rationale
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for a statistically relevant stratified sample)
• micronisation of product where contamination control needs to be proven
• printing paraphernalia such as print cylinders, cutting dies where conformance to drawings and
artworks need to be re-confirmed after sub contracted activity
• moulding sub contractors where dimensional and functional stability needs to proven
22. AGENTS, BROKERS, TRADERS, DISTRIBUTORS, REPACKERS, AND RELABELLERS
22.1 Applicability
Level 1
Level 2

Level 3
This section applies to any party other than the original manufacturer who may trade and/or take
possession, repack, relabel, manipulate, distribute or store a ‘Procured Item’. This party directly
supplies GSK.
22.2 Traceability of Distributed ‘Procured Items’
Level 1
Agents, brokers, traders, distributors, re-packers, or re-labellers should maintain traceability of

‘Procured Items’ that they distribute. Documents that should be retained and available include:
 Identity of original manufacturer
 Address of original manufacturer
 Purchase orders
 Receipt documents
 Name or designation of ‘Procured Item’
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 Manufacturer’s batch number
 Transportation and distribution records
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Level 2
Documents that should be retained and available also include:
All authentic Certificates of Analysis, including those of the original manufacturer

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Retest or expiry date as appropriate
Level 3
22.3 Quality Management
Level 1
Agents, brokers, traders, distributors, re-packers, or re-labellers should establish, document and
implement an effective system of managing quality, as specified in the relevant clauses within Section
1.
Level 2
Level 3

22.4 Repackaging, Re-labelling and Holding of ‘Procured Items’
Level 1
Level 2
Level 3
Repackaging, Re-labelling and Holding of ‘Procured Items’
Repackaging, re-labelling and holding of ‘Procured Items’ should be performed under appropriate
controls, as stipulated in this document, to avoid mix-ups and loss ‘Procured Item’ identity or purity.
Repackaging should be conducted under appropriate environmental conditions to avoid

contamination and cross-contamination.
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22.5 Stability
Level 1

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Level 2

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Level 3
22.6 Transfer of Information
Level 1
The agent, broker, trader, distributor, repacker, or relabeller who supplies the procured item to GSK
should provide the name of the original item manufacturer and the batch number(s) supplied.
The specific guidance for Certificates of Analysis included in Section 10.4 should be met.
Level 2
Level 3

22.7 Handling of Complaints and Recalls
Level 1
Level 2
Level 3
Agents, brokers, traders, distributors, repackers, or relabellers should maintain records of complaints
and recalls, as specified in the relevant clauses within Section 14, for all complaints and recalls that
come to their attention.
22.8 Handling of Returns
Level 1
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Level 2

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Level 3
Returns should be handled as specified in Section 13.5. The agents, brokers, traders, distributors,
repackers, or relabellers should maintain documentation of returned items.
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23. STERILE APIs
23.1 General
Level 1, Level 2 & Level 3
No specific requirement for these levels. Applies to GAS Level 4 only.
23.2 Premises - General
23.3 Changing Rooms & Airlocks

23.4 Air Systems
23.5 Equipment
23.6 Cleaning
23.7 Aseptic Preparation of Sterile Products

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23.8 Sterilisation Of Equipment

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23.9 Environment [clean rooms]
23.10 Personnel
General
Clothing required in classified rooms

23.11 Processing
23.12 Aseptic Manufacturing of API’s
23.13 Terminal sterilisation of API’s
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23.14 Finishing of Sterile Active Pharmaceutical Ingredients
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23.15 Validation

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23.16 Quality Unit activities
No specific requirement for these levels.
24. PRINTED MATERIALS
24.1 Security Barcodes
Level 1
Level 2
Each type and variety of carton (and, where appropriate, other board products) produced should
include a unique glue flap security bar code incorporated into the design. The supplier should

document a policy for the issue and allocation of glue flap security bar codes and maintain a register
of the issued codes. If codes are repeated this must not jeopardize the integrity of the system.
A converter’s flap code is commonly included in the design to assist in the prevention of admixtures
with the agreement of GSK. The converter’s flap code is commonly located on a part of the design,
which is subsequently covered when the carton is erected (e.g. on the inner edge of the tuck in flap).
A register of all converter’s flap codes should be maintained.
The converter’s flap code should be visually inspected and verified at appropriate converting
operations (e.g. cut/crease, stripping & gluing).
Where the product design incorporates crease codes, the codes should be visually checked during
the packing operation.
Where the crease codes are incorporated by the supplier, during origination, a register of the codes
should be maintained, and objective evidence shown that the same code cannot be used twice for
similar shaped but different product components.
Level 3
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Where agreed by GSK, the supplier may add its own identification codes to the product design.
Other equipment commonly used are Optical Character Recognition, 2d code readers, partial/full
camera verification and as these can be used and set to scan/read unique area, e.g. item code on
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component they can provide the same assurance as other applications such as pharma codes.
Where security bar codes, included in the design are to be verified during the production process, the
equipment software/controls configuration should be loaded from a source that can be fully traced to
the original GSK supplied one (specification or approved proof). Once a code is checked and entered,
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the scanning equipment should be effectively locked (e.g. remove controlling key to prevent
tampering). Verification should include readability of the code and assurance that the correct product
is being produced.
Where each item is to be verified by online scanning equipment; there should be an effective system
for rejecting any product that fails the scanning process. The ejection process should ensure complete
removal into rejection bins and same cannot be reintroduced into the line.
The online scanning equipment and its associated reject mechanism should be challenged during
production to determine if its operation is effective in detecting incorrect bar coding. Such monitoring
should take place at the start and end of the process, and at regular intervals, and be recorded.
Any product rejected by the online scanning system should be inspected to determine the cause of
rejection and the rejected components subsequently scrapped. These findings should be recorded
and reviewed prior to product release There should be physical barriers in place between production
lines following bar-code scanning in particular where product is to undergo subsequent processing
such as gluing.
Any product produced where electronic scanning is specified (e.g. Paper / leaflet with critical / major
print or other type of printed packaging material) but has not been performed, should be properly

authorised and recorded in the quality records. GSK should be notified, and documented approval
obtained before product release.
In the case of multi-lane production, all lanes should be subject to bar code verification. Where this
cannot be performed (and in agreement with GSK), one lane only may be verified.
Offline measurement and sample verification of all lanes should be carried out.
Scanning of security bar codes on leaflets (including both sides of a double sided leaflet) should be
carried out during the last production process (e.g. folding) to verify the reading of the bar code system
and to ensure that the correct product is being produced. Where scanning of security bar codes is not
possible (e.g. due to positioning of the code) then the supplier should employ automatic visual
scanning to verify the presence of print.
Where an offsite/ offline process e.g. hot foil stamping takes place on product that has already been
bar code read must be re- bar code read to ensure no rogues have been introduced during the extra
step. For product supplied flat/ un-glued all product must be bar code read to prevent rogues.
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Where feasible and where required by local regulatory authorities, each colour of the design
(particularly the legal / critical text) should be included in the bar code.
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Upon request GSK should be provided with a list of unreadable colours and/or a list of carton profiles
that cannot run with the code reader in operation.
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Where “Point of Sale” Bar Codes (EAN, Code 39, PZN etc.) are incorporated into the design, a
documented sample verification check should be carried out during the production process.
With the development in technology other systems can be successfully used; Optical Character
Recognition, 2d code readers, partial/full camera verification as these can be used and set to
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scan/read unique area, e.g. item code on leaflet and still provide the same assurance as pharma code
application.
Any artwork discrepancies should be formally notified to GSK for example using an artwork
discrepancy form (can be obtained via PASS Packaging Artwork Shared Service)

24.2 Reel Fed Materials - General
Level 1
Level 2
Level 3
Splices should be:
• Made as required by GSK specification.
• Verified either side of the splice to ensure identical materials are joined.
The batch identity, reel number and production date should be recorded as agreed with GSK user
site.
Removal and disposal of waste shall be recorded.
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Printed material should not be left in the converting equipment, a plain or suitably identified liner
should be used to re-web.
Full web and full die station should be represented at IPC, batch release and as customer supplied
samples
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Segregation of the good and rejected material to be ensured appropriately
24.3 Reel Fed Self-adhesive Labels

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Level 1
Level 2
Level 3
For reasons of security and admixture control, labels, which are missing or have been removed from
the backing web, should not be replaced unless the replacement is validated by an automated system
and in agreement with the customer.
Production and inspection equipment should operate at a speed that does not prejudice print quality
nor result in label detachment.
Other overprinting processes, agreed as part of the contract, should be subject to the same
verification controls.
samples

Where possible missing labels should not be replaced to prevent admixture, if replacement is required
controls should be in place to ensure there is no mix ups or misalignments
24.4 Leaflets
Level 1
Level 2
Where leaflets are printed on sheet-fed presses mechanical or electronic double sheet detection
should be employed. These should be challenged prior to a print run. The result should be recorded.
Presses should not run where the challenge has failed (without suitable evaluation and action being
applied). Where scanning of security bar codes is not possible (e.g. due to position of the code) then
the supplier should employ automatic visual scanning to verify the presence of print, on printed faces.
These should be challenged prior to a print run. The results should be recorded. Presses should not
run where the challenge has failed, (without suitable evaluation and action being applied).
The supplier should: e

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 Validate the system for ensuring accuracy in counting
 Pack all leaflets in securely sealed outer packaging in quantities determined within accuracy
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limits agreed with GSK and in accordance with the agreed specification.
samples.
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Level 3
24.5 Board Products (cartons, cards, wallets, catch cards etc.)
Level 1
Level 2
Where cartons are printed on sheet-fed presses mechanical or electronic double sheet detection
should be employed. These should be challenged prior to a print run. The result should be recorded.
Presses should not run where a challenge has failed (without suitable evaluation and action being
applied).
Level 3

Carton counting -
The number of cartons in each transit container or shipping outer should be determined within
accuracy limits agreed with the customer and validated.
Carton packing - Folded Cartons should be supplied packed on edge (not flat) within the outer.
Storage methods should ensure that vertical positioning is maintained.
24.6 Combination (e.g. Label/Leaflets, Carton/Leaflets)
Level 1
Level 2
Level 3
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Combination (e.g. Label/Leaflets, Carton/Leaflets)
Where individual printed components are combined, each individual component should be verified by
barcode, or other system that offers a similar assurance of control, at point of combination
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24.7 Digital Printing
Level 1
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Level 2
Level 3
The flexible capabilities of digital printing introduce new activities, which should be controlled and
documented to ensure the accuracy and security of the printed products.
The use of digital printing and any special requirements for the product should be agreed with GSK.
The organisation should establish a secure, validated, file access system, which is designed to
prevent unintentional use of incorrect artwork files.
Unless alternative security is designed, the controlling computer within the digital printing machine
should only have the specific artwork file in its memory for the current print run, and removal of this
file should form part of documented line clearance.

Operational settings to achieve acceptable colours should be established through a formal process
and recorded. The colours should be approved by GSK
Digital print engines should be the subject of a formal validation.
There is a need for subsequent print verification due to an increased risk of random generated defects.
24.8 Origination Procedures
Level 1
Level 2
Level 3
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All origination material should carry a unique identification and be stored in a secure area with a
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documented system for authorised issue and return.
Origination work should be segregated, and jobs progressed individually.
Origination work areas should be subject to a documented procedure that details line-clearance
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including the requirement that all origination files on the active computer have been closed
24.9 Digital/Electronic Artwork

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Level 1
Level 2
Level 3
All digital artwork files should carry unique identification and be stored in a secure area with access
control. A system should exist to back-up or archive digital files. Archive copies should be securely
stored and protected, e.g. in separate locations or fire-proof environment.
The supplier should possess suitable software under license, including fonts where artwork is not
vectorised, to enable them to process GSK artwork.
Incoming artwork should be checked for virus contamination. Software used to check artwork should
be routinely updated. A record of incoming files should be maintained.

Any changes to digital files to enable origination and printing should be agreed with GSK. This
includes the addition of a supplier’s logo.
The supplier should have a validated build status for artwork computer systems.
The supplier should electronically compare artwork provided by GSK to the suppliers own file sent to
the printing press (normally via a validated CTP computer to plate) technology. The use of human
proofreading is discouraged due to the probability and likelihood of errors.
Where a supplier chooses to omit the GMP level 2 EV check and rely solely on the first off printed
component one, then this must be carried out to the GSK provided artwork file
24.10 Origination Process
Level 1
Level 2
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Level 3
Electronic data output should be verified against a customer-approved copy. Critical parameters
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should be verified, and the checks recorded. GSK should be notified of any problems.
Critical parameters should be verified, and the checks recorded by use of validated electronic
comparison system (EV). GSK should be notified of any problems prior to any supply of batches in
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question (using the Artwork Discrepancy Process
24.11 Control of Pictures, Images and Transparencies
Level 1
Level 2
Level 3

A register of transparencies should be maintained, with individual transparencies and sets uniquely
identified. Where images, logos and pictures are held in digital format they should be uniquely
identified with access and usage controlled.
24.12 Print Impression Media
Level 1
Level 2
Level 3
All print impression media should;
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•Be produced from and traceable to a unit master (electronic data or unit films), which contains the
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approved copy from GSK.
•Carry a unique identification, which is traceable to the origination material identification.
•Be stored in a secure area with a documented system for authorised issue and return to store.
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•Rendered unusable at the end of its life.
24.13 Matched Plates
Level 1
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Level 2
Level 3
Where more than one printing plate is required there should be a documented system for ensuring
that all plates within the set are used. Where a set of plates contains the generic design for several
jobs, each individual plate within the set should be clearly, uniquely identified and documented.
24.14 Copy/Design Change
Level 1
Level 2

Level 3
Where a design requires several plates and some of them are to be replaced because of a
copy/design change, there should be a documented procedure to allow for the replacement of the
affected plate(s) and the retention of the other media within the set. The original plates should be
subject to a procedure that allows re-identification
Where a design is changed all obsolete plates should be securely withdrawn and a new set, with the
new item code/version issued.
Where the CTP (Computer to plate) Technology is used to produce printing plates produces the press
unique punch outs prior to image creation, appropriate and regular checks on both the punch
collection tray and visual plate check should take place. These should mitigate the risk posed by
punches laying on the plate surface and leaving a text/image free area being produced
24.15 Verification
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Level 1 Verification of the design on print impression media should be carried out during the printing
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machine make ready and before the approval to run the product is given.
Electronic Verification is not mandated at Level 1

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Level 2
Electronic Verification

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Level 3:
Electronic Verification (traceable to GSK supplied artwork) of the final artwork file to be sent to CTP
(computer to plate or equivalent) should be carried out prior to printing plate (or other printing medium)
preparation
Electronic Verification
For paper / card based printed packaging components confirmation of correct transcription of artwork
through to printed component should be based on Electronic Verification as follows:
• Origination (Pre Press):The supplier should electronically compare artwork provided by GSK to the
supplier’s own file sent to the printing press (normally via a validated CTP computer to plate
technology).
The use of human proofreading is discouraged due to the probability and likelihood of errors
Electronic Verifications / Bar code reader:
Printed Packaging material suppliers should minimum maintain bar code readers if EV is not available
Make Ready:
Level 2
Electronic Verification of printed components is not mandated.

Level 3
The supplier should compare a minimum of one printed component (at a sheet or web level) to the
supplier’s own file sent to the printing press ensuring content and layout is identical to the GSK
artwork. This may the first off (as part of the make ready process) or as part of the formal IPC
procedure and occur later in the run.
Comparison must be made by Electronic Verification.
The repeat of this process at a defined frequency including last off component is encouraged to
provide mitigation against print defects caused by the printing press operation.
The Electronic Verification system should be capable of assessing the following:
• Text accuracy, location, font type, size and colour variation,
• Graphics accuracy, size and colour variation,
• Dimensional accuracy,
• Braille position,
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• Presence of supplier added quality critical content (i.e. barcodes, die station numbers)
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• Absence of print run defects (bleed, blotch, hickey, varnish, security logo),
• Correct glue flap and retail (EAN) / pharmacode barcodes,
• Absence of glue marks, scuff, tear,
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• Absence of skew and, presence of Insert etc.

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24.16 Quarantine and Destruction
Level 1
Level 2
Level 3
The organisation should have:
 A documented procedure which ensures that origination and print media, for a design undergoing
revision, are subject to formal quarantine.
 A documented system detailing the method for disposal of unwanted origination and print
impression media. Origination and print impression media should be rendered unusable and
disposed of in a controlled and secure manner to prevent the risk of counterfeiting.

24.17 Print Machine Set-Up (Make Ready)
Level 1
Prior to make ready paper should be acclimatised to the production environment.
Initial print make ready should be performed using unprinted stock.
Make ready for subsequent print processes may use material from the initial print process of the same
batch.
Initial make ready material may be reused during the make ready process to achieve correct colour.
Suitable controls, e.g. ‘flagging’, must be applied to this make ready material to ensure secure removal
either following make ready or during subsequent processing
Inks should be identified, stored and issued in a controlled manner. Where ink is mixed on the
supplier’s premises documented recipes should be established. Suitable colour standards or other
controls should be applied
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Level 2
Level 3
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24.18 Retained Samples

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Level 1
Printed samples (e.g. first and last off sheets), which are to be retained, should be clearly identified
with a unique identification and securely stored. Braille samples (e.g. first and last off sheets), should
be retained and securely stored.
Samples used for administration purposes should be voided, identified and securely stored.
Level 2
Level 3
24.19 Replacement Print Media
Level 1

If print impression media has to be replaced during a production run, plates shall be made from an
existing fixed approved source, e.g. negatives or computer-to-plate technology from an existing
stepped image
Then a first off sample sheet should be taken from the new printing set-up and subject to the same
controls as for the initial set-up. Quality records should document the introduction of any replacement
print media.
Level 2
GSK should be informed of replacement print impression media.
During a production run, if plates are created from a new source (e.g. recreating from the primary
customer artwork) the existing job shall be lifted and the replacement plates treated as a new
origination and a new batch number assigned.
Level 3
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24.20 Gang Printing
Level 1
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Gang printing (the process of printing more than one design on a substrate at one production run)
may be used provided a risk assessment has been carried out by the supplier and its findings support
the use of gang printing for the target market.
The use of gang-printed labelling for different products, or different strengths or net contents of the
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same product, is prohibited unless the labelling from gang-printed sheets is adequately differentiated
by size, shape, or colour.
In all cases the quality implications must be fully assessed, and appropriate controls documented in
the appropriate operating procedures. The activity must be pre-approved by GSK quality.
For further information and guidance around gang printing approval and requirements refer to the
guideline “Supplier Quality Guideline for the Valuation and Introduction of Gang Printing for Printed
Packaging Components” in Veeva Quality Docs (VQD).
Level 2
Level 3
24.21 Braille and Embossing
Level 1

Where Braille or embossed information is present, there should be a formal documented system for
ensuring that the Braille/embossed symbols are correct, in the correct orientation and comply with the
specifications for size, position and embossed height.
System should include unique references traceable to the individual item code. These references
should be present on Braille/Embossing tooling and screens and any media, e.g. overlays used to
verify Braille integrity.
If outsourced Technical specifications should be agreed between the supplier and the tool maker /
screen manufacturer. The supplier should apply suitable assessment of the supplied tooling / screen
against this specification. If manufactured in house suitable specification should be applied to ensure
consistency.
If changes to tooling/screens are required during the production run, then these can be replaced with
new tooling/screen of the same reference. Any such change should include a formally recorded repeat
make ready check.
Sampling and testing should cover all impressions.
Level 2
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The Supplier should demonstrate that Braille specifications are met. This includes the need for
appropriated dimensional testing via manual or automatic means.
Where the GSK Global Specification for Braille Cell Dot Height has been issued to and agreed by the
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supplier, it should be followed on a batch by batch basis.
Level 3

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24.22 Batched Production and Stock Holding
Level 1
Batched production and holding of product in stock should only be practiced when contractually
agreed.
The organisation should maintain a control system, including secure storage that ensures the integrity
of the product and its traceability.
Level 2
Level 3

24.23 Changeover Systems
Level 1
Changeover systems that are designed to reduce make ready time (e.g. Automatic plate changing)
and which do not permit a total line clearance of all print impression media and materials, should be
subject to a risk assessment and operated with controls to ensure product security.
All print media and other tooling, e.g. cutting dies, from the previous job, should be removed from the
line prior to the formal approval for the print run is given.
Level 2
Level 3
24.24 Line Clearance

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Level 1
To prevent cross-contamination (mix-ups) there should be a recorded check that the equipment and
work area are free from previous starting materials, products, waste and documentation and is fit for
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use, immediately before the start of a new production run.
Level 2
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During origination/artwork, the work area shall be subject to a recorded line-clearance ensuring
samples, proofs and documentation have been removed and those artwork files on the computer
have been closed.
There should be an independent recorded check of line clearance.
Level 3
Bar code reading should be part of line clearance.
24.25 Control of coloured printed materials
Level 1
Supplier should ensure good control of colours.
Level 2

Light source for setting of standards and verification of colour should be controlled, i.e. via light box
with suitable lighting controls applied. Natural daylight for quality evaluation of component or printed
colour should be used where specified.
Pantone books are used by suppliers to follow as an ink recipe and not as a definitive colour
standards. Pantone books are printed on a single substrate and as such are not generally produced
on the same substrate as the supplied material. (in this instance carton board). Suppliers should
ensure ongoing batch by batch colour matching by means of internal reference standards and where
appropriate test using spectrometers/densitometer. These are produced using the same substrate as
the supplied material, are controlled and new versions produced periodically in line with local controls.
These standards or other suitable colour standards are audited by GSK as part of the supplier
capability and control process within the Global Audit Standards to the GMP level of 2.
Level 3
No additional requirements
18.26 Control of Rework
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Where printed product is subjected to re-work the following must be in place.
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 A defined area to be used with;
o adequate lighting for inspection
o adequate space to reduce likelihood of inspected and to-be-inspected product being
mixed up
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o barriers around it to reduce likelihood of rogues/mix ups

o signage to show that re-work is underway in this area
 Line Clearance with second independent checks before and after rework
 Batch record paperwork showing the nature of the rework and full reconciliation
 Clear labelling at a box label showing product inspected and to-be-inspected
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 Trained staff
 Examples of acceptable and not acceptable product clearly displayed
25. MATERIALS STERILISED BY ETHYLENE OXIDE OR BY IRRADIATION
Note 1
This section covers suppliers of materials sterilised by Ethylene oxide or by irradiation, which can be:
 either material sterilised directly by the Procured Item manufacturer,
 or materials sterilised by a Contract service provider and supplying directly to GSK as tier-one
supplier (see also Appendix I) or indirectly via the Procured Item manufacturer as tier-two suppliers
(see also section 15).
Note 2
The demonstrated and required Sterility Assurance Level, as well as the status of the material (sterile
or not) should be defined.

25.1 Quality Management
Level 1
Level 2
Level 3
A system should be in place (e.g. QAA and /or contract) defining roles and responsibilities between
the Contract Giver and Contract acceptor and should cover all GSK requirements.
The following should be agreed between all parties:
 Pack format and content for items to be sterilised
 Cycle parameters, including minimum dose required and maximum acceptable dose. Load
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configuration and position, number and type of dosimeters (Irradiation) and Biological
Indicators (ETO)
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 Sampling requirements and sample handling
 Use of third-party laboratories for any associated testing
 Product packaging and handling both pre and post sterilisation
The whole supply chain and release steps should be clearly defined. Final release must be performed
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after the sterilization by the contract giver.
25.2 Personnel
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Level 1
Level 2
Level 3
Personnel involved in the manufacturing or release of sterile procured items should be appropriately
trained in relevant standards (ISO 11135 for Ethylene Oxide Sterilization and 11137 for Irradiation,
current versions) and relevant clean manufacturing practices.
Personnel involved in assessing sterilization service providers should be familiar with the relevant
standards (ISO 11135 for Ethylene Oxide Sterilization and 11137 for Irradiation, (current versions).

25.3 Documentation and records
Level 1
Level 2
Level 3
There must be a process in place to ensure that the procured item batch review includes the following:
physical parameters and biological data and process deviations, environmental monitoring and
product bioburden data. In case of subcontracted activities, the contract service provider should
provide suitable evidence of the assurance of the sterilisation process including critical process
parameters results.
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Documented review of procured items subject to irradiation should include:
 Procured item manufacturing and packaging process, including any specified environmental
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requirements
 Loading patterns for materials to be processed
 Pre irradiation bio burden data (if applicable)
 Sterilisation process parameters including dose records
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 Process deviations
Documented review of procured items subject to ETO sterilisation should include:

 Procured item manufacturing and packaging process, including any specified environmental
requirements
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 Loading patterns for materials to be processed

 Pre ETO sterilisation bioburden data (if applicable)
 Cycle reference (associated to the qualification PQ report)
 Cycle sequences
 Critical sterilization process parameters (Physical & Biological data)
 BIs incubation results
 Product Sterility test (if applicable)
 ETO and Ethylene Chlorohydrin (ECH) residuals (if applicable)
 process deviations
25.4 Production and In-Process controls
Level 1
Level 2

Level 3
Sterilisation processes (ETO, irradiation) should comply with a recognised standard e.g. ISO 11135-
11137, current versions.
Routine process should be aligned to validated cycle. Procedure should be in place describing
process parameters, cycle specifications, loading configuration, pallet pattern, and descriptions of
physical or biological monitors’ placement. Dosimeters (physical monitors for irradiation) or Biological
indicators (biological monitors for ETO) should be retrieved and processed within a defined period
after sterilisation.
Location of Physical and Biological sterility indicators should be distributed in the load according to a
defined and validated pattern.
Each batch of dosimeters should be calibrated and there is a system in place to ensure that calibrated
status is maintained. Dosimeters should have a unique reference to ensure full traceability.
Where Biological indicators are used (ETO sterilisation), Bacillus atrophaeus BIs (with a minimum
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population defined) should comply with ISO 11138-2 and be tested for population, resistance (D
value). Storage conditions should be clearly defined. Population of BIs should be verified on a regular
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basis by the user. BIs used for validation and routine monitoring should be at least as resistant to
ETO as is the bioburden of product to be sterilized.
Traceability of each BI’s used should be recorded.
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The number of BIs used during routine sterilisation process should not be less than half of the amount
used during validation unless supported by a rationale. A positive control BI must be tested with each
cycle test.
For the ETO sterilization, during the sterilization, physical parameters of the chamber e.g. time,
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temperature, relative humidity, pressure, measures to confirm the ETO admission should be under
defined limits, monitored and recorded.
Where sterilisation indicators are used, they should be placed as agreed with the customer.
For ETO sterilisation, water vapour (steam) should be used to humidify the chamber.
Steam should be produced from water which complies with the standard for Potable water as a
minimum and should be free any contaminants which may impair the sterilisation process, equipment
or load.
Risks of contamination of the steam resulting from the use of boiler additives in steam generation
should be considered.
Direct injection of nebulised water should not be used for humidification (ref. EN 1422 2014).
There should be a procedure in place to ensure continued effectiveness of the sterilisation process.
This should include a periodic pre-sterilisation bioburden monitoring. There should be a procedure in
place defining action to be taken in the event of bioburden action and alert limits being exceeded. The
bioburden limit is established and fixed during the initial validation.

25.5 Laboratory controls
Level 1
Level 2
Level 3
A system must be in place to ensure that any deviations or out of tolerance/specification arising during
laboratory evaluation of samples or monitoring systems (BIs or dosimeters) which have a potential
impact on product sterility assurance, product functionalities and ETO, ECH residues are
communicated to GSK.
Communication of any product sterility failures, BI failures, or failures to comply with the required
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gamma irradiation dose requirement, must be made by supplier to GSK.
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25.6 Validation
Level 1

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Level 2

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Level 3
Sterilisation processes should be validated to applicable standards (ISO 11135 and 11137), current
versions.
The sterilisation validation approach should be clearly defined, and validation results should include
demonstration of process robustness as well as lethality or agreed Sterility Assurance Level.
In case of matrix or product family validation approach, this should be supported by a rationale.
The contract giver of the critical sterile procured items is responsible for review and acceptance of the
sterilisation validation process. Copies of the validation documents should be available on site and
validation summary reports should be made available to the Customer upon request.
A review of Irradiation validation should be performed on a yearly basis. Dose audits should be
performed on a defined frequency. The dose audit period is every three months but could be extended
providing that the control of the bioburden charge and type has been demonstrated without seasonal
variation. The dose audit period should not exceed one year.
There should be as well an annual recalibration of the cobalt source, and consecutively, a dose
mapping exercise should be performed to confirm absence of impact on validation.

For Ethylene oxide, IQ, OQ, PQ should be reviewed annually to determine the extent of requalification
needed.
The annual review should include the equipment, product and the processing history. The frequency
for the revalidation of the sterilisation cycle should be defined and justified by a rationale. However, a
cycle for microbial performance qualification (MPQ) and a physical performance qualification (PPQ)
including load temperature and humidity measurements should be performed at least every two years.
All requalification documents should be available on site for review.
Failures in requalification should be communicated to the customer.
For Ethylene oxide sterilisation, the use of external process challenge devices should be supported
by validation. The continued use of these devices must be reviewed during the yearly validation
review.
Holding times between the different process steps must be defined and supported by a rationale or
validation.
25.7 Storage and Distribution e

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Level 1

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Level 2

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Level 3
There should be an adequate segregation between sterilized and non-sterilized components.
25.8 Contract Services
Level 1
Level 2
Level 3
Sterilisation contract service providers should be audited by the contract giver at a defined frequency
and the standard applied should cover the applicable sections of this PAS.

21. References
GAS for Procured Items Level 1 (v2.0) -( VQD-STD-001293)
GAS for Procured Items Level 2 (v2.0) -(VQD-STD-001311)
GAS for Procured Items Level 3 (v2.0) (VQD-STD-001304)
GAS for Procured Items Level 4 (v2.0) -(VQD-STD-001313)
22. Version History
Date
Version Changes
Approved
1.0 As per New version

VQD
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APPENDIX 1-Assessment Questionnaire

ASSESSSMENT QUESTIONAIRE
Training Attendance for Instructor Led Trainings with Competency Assessment
SOP Revision/ New SOP
Trainee Name & Signature
Date of ILT training:
Department
Trainer Name, Signature &
Date:
For Trainer’s Use Only
Score Out of (passing mark ≥ 80%)
Assessor Name, Sign & Date
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TITLE: GAS FOR PROCURED LEVEL I CURRICULA*:
DOCUMENT NO: AS PER VQD
ITEMS LEVEL 3 YES NO
*In case of any SOP of LI curricula (Quality or EHS), take exam of L&D prior to
provide the answers.
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Repackaging should be conducted under appropriate (True/ False)

I. environmental conditions to avoid contamination and cross-
contamination.
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II. Bar code reading should be part of line clearance. (True/ False)
A system should be in place (e.g. QAA and /or contract) defining

III. roles and responsibilities between the Contract Giver and Contract (True/ False)
acceptor and should cover all GSK requirements.
IV Communication of any product sterility failures, BI failures, or

. failures to comply with the required gamma irradiation dose (True/ False)
requirement, must be made by supplier to GSK.
V Routine process should not be aligned to validated cycle. (True/ False)
Note: The below table is intended to be used at the time of SOP revision and
uploading questionnaire in myL.
Prepared By SOP Author Name: Sign & Date:
Checked By Manager/ SME Name: Sign & Date:


Document Approvals by Electronic Signature
Verdict: Approve Faheem Uddin Bhutto fb298066

(faheem-uddin.x.bhutto@gsk.com)
Quality Assurance Approval
14-Mar-2022 06:34:06 GMT+0000
Verdict: Approve Farrukh Iqbal fmi48940

(farrukh.m.iqbal@gsk.com)
Author Approval
14-Mar-2022 06:34:27 GMT+0000
ve
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SAS For Procured Items Level 3

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GSK VQD-SOP-069195 v: 1.

0 Retrieved: 16 Mar 2022 Effective: 15 Mar 2022

STANDARD OPERATING PROCEDURE

Procedure to Define Segmented Audit Standard

Proprietary Information. Do not disclose without consent.

To define the local requirements in Segmented Audit Standard (SAS) for

reason, appropriate quality requirements have been updated to developed for

3. ROLES AND RESPONSIBILITIES

Proprietary Information. Do not disclose without consent.

GSK Monograp Chinese

API / Atypical API 4

Proprietary Information. Do not disclose without consent.

Non-Critical Raw Material 1 1 1 1 1 1 1 1 1 1

product name, basic

Proprietary Information. Do not disclose without consent.

Single Use Systems 3 3

Complex medical devices. 3 2 2 3

SAS Frequency Commodities

1 and 2 60month Paper Pack suppliers (no regulatory info)

36 months Excipients and Printed Primary packaging Material

Proprietary Information. Do not disclose without consent.

36 months Non-Sterile Materials

Approval Recommended status

Any deviation from established procedures should be documented and explained.

Proprietary Information. Do not disclose without consent.

 Approving all procedures impacting the quality of ‘Procured Items’;

 Ensure that quality related complaints are investigated and resolved.

• Approving changes that potentially impact ‘Procured Item’ quality.

 Performing management reviews (as defined in Section 1.5).

 Reviewing completed laboratory control records before release of final product.

Proprietary Information. Do not disclose without consent.

 Ensuring compliance of outsourced services

 Reviewing of quality agreement where applicable

No specific requirement for this level.

Producing ‘Procured Items’ and, when appropriate, intermediates according to pre-approved

7.4 Internal Audits (Self Inspection)

Proprietary Information. Do not disclose without consent.

No specific requirement for this level.

No specific requirement for this level.

7.6 Contract Review and Order Processing

Proprietary Information. Do not disclose without consent.

7.7 Quality Risk Management

No specific requirement at this level

No specific requirement at this level

Training should include:

Proprietary Information. Do not disclose without consent.

8.2 Personnel Hygiene

Personnel should practice good sanitation and health habits.

Personnel should avoid direct contact with ‘Procured Items’.

A written procedure should be in place describing gowning requirements

No specific requirement for this level.

Proprietary Information. Do not disclose without consent.

In case of consultants advising on development of quality management systems or the manufacture

No additional requirements for this level.

9. BUILDINGS AND FACILITIES

9.1 Design and Construction

No additional requirements for this level. e

No additional requirements for this level.

Where required, clean-room facilities should be demonstrated to perform to a recognised standard,

• Quarantine before release or rejection of ‘Procured Item’.

• Storage of released materials.

• Packaging and labelling operations