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GLOBAL QUALITY GUIDELINE


08-GQG-108

GQG Page Revision


Section: EQUIPMENT AND UTILITIES
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Title: MANUFACTURING EQUIPMENT QUALIFICATION

1.0 Purpose
1.1 To provide guidelines for the development, review and approval of Manufacturing Equipment Qualification
Protocols.

1.2 This document provides the recommended guidelines for pre-qualification, installation qualification (IQ),
operational qualification (OQ), performance qualification (PQ), and final approval/release phases of the
qualification process.
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2.0 Scope
2.1 This Global Quality Guideline (GQG) applies to the Apotex group of companies engaged in GxP
regulated activities supporting the development, manufacturing and / or distribution of finished dosage
forms, as applicable to the company’s operations.

2.2 This GQG may be used for the assessment and oversight of Apotex Third Party Organizations, as
applicable.

2.3 This GQG is applicable to critical equipment or automation systems supporting GMP manufacturing
areas, including Major Laboratory Equipment (Ovens, Stability Chambers, Freezers and Refrigerators)
and Packaging Equipment /Systems.

2.4 Laboratory equipment qualification is outside the scope of this GQG. Refer to Global Quality documents
related to laboratory equipment qualification.

2.5 Validation of computerized and control systems of an equipment or facility, with CFR Part 11 applicability
is not within the scope of this procedure. These validations are accomplished through either separate
protocol(s) generated by Computer System Validation & Compliance (CSVC) group or test plans supplied
to equipment and facilities qualification protocol(s) by CSVC.

2.6 This GQG establishes guidelines for the minimum requirements of Manufacturing Equipment
Qualification.

2.7 This GQG establishes guidelines to input Equipment Qualification data in SAP PM master databases or
equivalent, as applicable.

3.0 Owner Organizational Unit


GQC-QA-Global Policy and Systems

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Title: MANUFACTURING EQUIPMENT QUALIFICATION

4.0 Process Overview


See Process Overview in Exhibit A.

5.0 General Information / Background


5.1 Validation provides assurance that a given manufacturing process will consistently produce a product
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meeting an expected result. A process can be validated once all the equipment and ancillary systems of
a given manufacturing process have been qualified and linked together.

5.2 The Validation Team shall consist of, at a minimum, the System Owner, department responsible for
Equipment and Facilities Qualification and representatives from other departments such as Engineering,
Production/Packaging Maintenance, etc., as required.

6.0 Process
The process of manufacturing equipment qualification at Apotex is conducted in the following phases:
6.1 Pre-Qualification Phase
- Equipment/System Requirements
- Equipment/System Assessment
- Qualification Project Plan (QPP), (if required)
- Qualification Strategies
- Protocol Development
6.2 Qualification Phase
- Installation Qualification (IQ)
- Operational Qualification (OQ)
- Performance Qualification (PQ)
6.3 Final Approval / Release Phases
Refer to Exhibit A for Equipment Qualification Process Overview.

6.1 Pre-Qualification Phase


Pre-qualification activities include the functional verification (as applicable to operational ranges
appropriate for intended use) and/or testing of equipment/system before qualification; and verification that
documentation required for qualification is available and accurate.
Note: Any verification or acceptance testing prior to qualification agreed to and established by the
Qualification Project Plan (QPP) may be performed as part of Commissioning. Such verification

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Title: MANUFACTURING EQUIPMENT QUALIFICATION

testing and documentation generated in the Commissioning phase when used to support
qualification shall be documented in accordance with GMP expectations and will require QA
approval if it is decided to be used without being attached to a qualification protocol.
Note: The following steps can be done in sequence or parallel.
6.1.1 The System Owner or appropriate function, as per site procedures, will perform the following:
6.1.1.1 Define the project scope and objectives, if applicable.
6.1.1.2 Notify the Engineering Services Department that a qualification project has been
identified.
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6.1.1.3 Change Control


6.1.1.3.1 All changes to equipment/system qualification shall be evaluated to
determine the impact to the qualified state of the process, as well as any
requalification activities required to maintain the qualified state.
6.1.1.3.2 As per site, new, modified, relocated or transferred equipment and
automation system will require the submission of a change control.
6.1.1.3.3 Change management shall be performed in accordance with Apotex
Global Quality documents related to change control.
6.1.1.4 Equipment/System Requirements
6.1.1.4.1 Generate a comprehensive set of business, and compliance
requirements to ensure that the resulting equipment/system meets
intended purpose or use.
6.1.2 Equipment/System Assessment
6.1.2.1 Risk Assessment of the equipment/system is required for all validations and
qualifications. The Validation Team at each manufacturing facility shall establish the
risk assessment suitability based on individual product/process expectations as per
Global Quality documents related to Quality Risk Management.
6.1.2.2 The Validation Team shall assess equipment/system information to ensure that the
equipment/system meets business and compliance requirements and is fit for
purpose or use.
6.1.3 The Validation Team Lead will be responsible for the following:
6.1.3.1 Ensuring all instrumentation and equipment are entered into the Apotex Management
System for Reliability & Maintenance.
6.1.3.2 Ensuring the availability of the required Vendor information (e.g. list of spare parts,
lubricants, material of construction of product contact parts, operational manuals,
drawings) to support qualification activities for the system.
6.1.3.3 FAT, Commissioning or SAT activities performed by the vendor / supplier or internally
by Apotex, may be used for qualification testing, as appropriate. When used for that
purpose, the information shall meet the following:
- Requirements of this GQG
- Good Documentation Practices

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- Good Engineering Practices


Note: Any system verification or testing performed during FAT, Commissioning or
SAT that is found to be inadequate by Quality may not be used for
qualification testing.
6.1.3.4 Assuring all applicable commissioning activities are completed and delivered to the
Engineering Services Department.
6.1.3.5 Ensuring all critical instruments and equipment are entered into the Apotex
Management System for Reliability & Maintenance per Global Quality documents
related to equipment calibration and preventive maintenance program.
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6.1.3.6 Qualification Project Plan (QPP)


6.1.3.6.1 A Qualification Project Plan (QPP) may be prepared to provide an
overview of the qualification activities and deliverables required for a
specific project. QPPs are optional elements and are normally created as
deemed necessary depending upon the complexity of the
equipment/system or project with multiple system or qualification phases.
Note: The originator of the QPP will be determined by the Validation
Team.
6.1.3.6.2 The QPP will provide an overview of all activities to be executed as part
of the efforts to deliver the equipment and manufacturing automation
system in a qualified state.
6.1.3.6.3 The QPP will provide a high level of description of testing and
verifications needed to achieve an adequate verification or qualification
for its intended purpose.
6.1.4 Qualification Strategies: “Modular” vs. “Holistic”
Note: The Validation Team, including the System Owner, Engineering and QA, are
responsible for determining the Qualification Strategy.
6.1.4.1 The “Modular” approach strategy to Equipment Qualification implies that the
equipment function(s) and process performance are verified separately, as follows:
6.1.4.1.1 The Installation Qualification verifies that equipment is correctly installed.
6.1.4.1.2 The Operational Qualification verifies that the equipment performs as
intended over a process parameter range that is equal to or greater than
the process requires.
6.1.4.1.3 The Performance Qualification assures that equipment consistently
performs as intended under “production like” operation.
6.1.4.2 The “Holistic” approach strategy to Equipment Qualification / Process Validation
assumes that the manufacturing process can be divided into discrete modules
consisting of one (1) or more pieces of manufacturing equipment and the
corresponding process step. Each module has one (1) or more inputs and at least
one (1) output. The module operates within certain key parameters (process
conditions) that assure the output will meet the established requirements. The output
of one (1) module may be the input of the next. (Refer to Figure 1.)

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Title: MANUFACTURING EQUIPMENT QUALIFICATION

For this approach, the equipment function(s) and process performance are verified,
as follows:
6.1.4.2.1 The Installation Qualification verifies that the module is correctly
installed.
6.1.4.2.2 The Operational Qualification combines some aspects of equipment and
process to establish or verify (if previously established) that process
control limits produce the anticipated output.
6.1.4.2.3 The Performance Qualification assures that under anticipated conditions
(nominal parameters), the process (all modules together) produce
acceptable product. In the following illustrated model, the PQ may
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incorporate the PV requirements.


6.1.4.3 The facility shall identify and document the qualification/validation approach chosen
(strategy “Modular” or “Holistic”).

Figure 1: Holistic Qualification Strategy

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Title: MANUFACTURING EQUIPMENT QUALIFICATION

6.1.5 Protocol Development


6.1.5.1 The designated Validation Team member shall be responsible for developing
Manufacturing Equipment qualification protocols or test scripts from applicable
approved specifications.
6.1.5.2 The Manufacturing Equipment qualification protocols or test scripts must be approved
by all signatories (at minimum to include, Validation Team Lead, System Owner /
Subject Matter Expert (SME), Quality) prior to the initiation of protocols or test
execution and data collection.
6.1.5.3 Vendor supplied protocols and reports may be used to leverage or in lieu of an
Apotex generated document. These documents are not required to have the same
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format as Apotex generated documents provided that:


- The general contents are the same.
- The information obtained from vendor is accurate and suitable to meet the
purpose of verification.
- The vendor-supplied documents are subject to the same approvals as an Apotex
generated document for the same topic.
The vendor-supplied documents may be augmented with any additional verification
checks or other controls rather than replicating vendor documentation.
6.1.5.4 Verification or acceptance testing to support qualification requirements may be
performed during the pre-qualification or commissioning process; and shall follow the
requirements as per Section 6.1.3.3.
6.1.5.4.1 The decision and justification for this shall be documented in the QPP,
protocol or any appropriate document, approved by all protocol
signatories including the Quality Unit.
6.1.5.4.2 The Commissioning is intended to complement (and not repeat) the
documentation or testing in the qualification process.
6.1.5.5 If vendor documentation or commissioning is leveraged, these documents shall be
referred to in the protocol, or test scripts. Their use must be approved by Quality.
6.1.5.6 All revisions to the approved Protocol shall be documented via Apotex Change
Control system including the initial document.
6.1.5.7 The IQ, OQ and/or PQ may be combined in a single protocol.
6.1.5.8 Completion of IQ, OQ, and PQ requirements is dependent on the qualification
strategy (“Modular” or “Holistic”) chosen by each Validation Team. Early completion
of qualification requirements identified on IQ, OQ, and PQ matrices is acceptable.
6.1.5.9 All stated requirements shall be fulfilled or justified prior to release of the equipment
or system for use. Any requirements that are not fulfilled shall be justified with written
technical rationale and approved by the Quality Representative.
6.1.5.10 The qualification activity shall be directed and driven by the Validation Team Lead
and supported by a multi-function team of competent individuals. Typical members
shall include technical advisors/engineers and quality representatives.

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Title: MANUFACTURING EQUIPMENT QUALIFICATION

6.1.6 The manufacturing equipment shall be evaluated and understood by the Validation Team. To
ensure adequate equipment and process knowledge, documented planning is required prior to
execution of equipment qualification activities. The following are the recommended elements to
be considered for review during the planning stage of equipment qualification:
- Multi-function team responsibilities
- Material(s)/component(s) specifications and qualification
- Product design specifications and pre-determined acceptance criteria
- Product characteristics and method(s) for monitoring
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- Process flow diagram(s)/map(s)


- Operating parameters (equipment, process) input, desired outputs, and monitoring
- Process capability and stability studies
- Utilities/critical systems/equipment identification
- Equipment capacity and safety
- Equipment documentation
- Equipment maintenance and calibration
- Process operating documentation (manuals, operating procedures, SOPs)
- Personnel Competency (e.g. training)
- cGMP (Current Good Manufacturing Practices) training
- Validation approach (strategy Modular, strategy Holistic)
- Vendor selection/assessment/approval and PO (Purchase Order)
- Computerized systems validation status
- Microbiological validation status
- Assay (method) validation status
- Facility/Utilities/Ancillary Systems validation status
- PLA (Product License Application)
- Load capacity analysis for utilities
- Equipment regulatory compliance requirements
- System User Requirements
6.1.7 If qualification is performed on equipment similar to an existing piece of equipment (same
operational parameters, same safety feature, etc.), with appropriate technical justification, the
documentation can be leveraged to support the new equipment qualification. Copies of
documents and/or reference to the location of the qualification original documentation shall be
included as part of the new equipment qualification documentation.

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Title: MANUFACTURING EQUIPMENT QUALIFICATION

6.2 Qualification Phase


Note: The Validation Team Lead is responsible for generating protocols and final reports.
6.2.1 Qualification consists of the following phases, IQ, OQ, and PQ, if required, as per the Site
Validation Master Plan.
6.2.2 IQ, OQ, PQ (if required) shall meet the following requirements or an approved, documented
justification to indicate that qualification is not required shall be provided.
6.2.3 Installation Qualification (IQ)
Note: Refer to Exhibit B for Process Overview of Installation Qualification.
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6.2.3.1 The IQ objective is to demonstrate by approved documentation that equipment and


ancillary systems are installed according to written and pre-approved specifications.
6.2.3.2 IQ provides documented evidence that the system has been assembled, installed,
and configured as specified by the equipment manufacturer and Apotex
requirements.
6.2.3.3 The IQ is developed based on information from the following (as applicable):
6.2.3.3.1 Pre-approved Functional Specifications or Design Specification
6.2.3.3.2 Applicable Apotex installation and configuration requirements
6.2.3.3.3 Applicable vendor installation documentation, operational manuals,
drawings, etc.
6.2.3.3.4 Testing of system power and connectivity, physical security, access
controls, proper software and hardware installations, applicable system
configuration
6.2.3.3.5 Evidence that the utilities, facility, environment and security controls have
been adequately applied
6.2.3.3.6 Qualification Project Plan (QPP)
6.2.3.3.7 Pre-qualification activities:
- Where applicable, equipment/system has been labelled with “Out of
Service” or similar.
- As per site requirements, Change Control has been issued and
approved.
6.2.3.4 Refer to Exhibit C for typical test sections found within the IQ protocol.
Note: The test scenarios and lists cited within Exhibit C are not all inclusive as no
piece of manufacturing equipment are exactly the same; it is the
responsibility of the protocol owner/study director to ensure that all aspects of
the equipment/system is tested appropriately and fit for its intended use.
6.2.3.5 Verification documentation may be attached to the executed equipment IQ protocol,
as applicable, and shall address the review of the attributes, as applicable.
Examples of IQ attributes are identified in Table 1.

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6.2.3.6 The final report(s) shall provide a summary of the IQ protocol execution and the
results.
Table 1: Examples of Installation Qualification Attributes

Existing
IQ Attributes New Equipment
Equipment
Equipment identification and X A/R
installation verification
Engineering Drawings and Documents X X
Verification (wiring diagram(s))
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Major Components Verification (prints, X X


drawings, manuals)
Spare part list A/R A/R
Components/Parts list X X
Environmental conditions A/R A/R
Permits/Reports/Certificates X A/R
Utilities Verification X A/R
X = Mandatory
A/R = As Required shall be used as follows:
- If requirement does not apply, a justification statement shall be included
within the qualification documentation.
- If documentation for the requirement exists, the qualification/validation final
report(s) shall include copies of documents and/or reference to the original
document(s) location.
6.2.3.7 IQ acceptance criteria are usually based on Design Specifications, Configuration
Specifications, vendor/supplier user’s manuals, and/or other vendor/supplier
documentation.
6.2.4 Operational Qualification (OQ)
Note: Refer to Exhibit D for Operational Qualification Process Overview.
6.2.4.1 The OQ phase provides documented evidence that the manufacturing equipment
and automation system functionality and operation meet the approved acceptance
criteria throughout all specified operating ranges, and demonstrates fitness for use.
6.2.4.2 OQ testing will be performed across the planned operational range of the system and
encompasses both system hardware and software.
6.2.4.3 The OQ is developed based on information from the following (as applicable):
- IQ
- User Requirements, Functional and/or Design Specification
6.2.4.4 Refer to Exhibit E for typical test sections found within the OQ protocol.

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Note: The test scenarios cited within this procedure is not all inclusive as no piece
of manufacturing equipment are exactly the same; it is the responsibility of
the protocol owner/study director to ensure that all aspects of the
equipment/system is tested appropriately and fit for its intended use.
6.2.4.5 For OQ objectives, refer to Qualification Strategies section (strategy “Modular” and
“Holistic”).
6.2.4.6 The OQ phase is to be executed following IQ execution. However, OQ can be
completed concurrently with the execution of the IQ phase when there is no overlap
or disruption which could have an impact on subsequent activities. Justification for
the completion of OQ concurrently with the execution of the IQ phase shall be
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documented and approved by Quality.


6.2.4.7 Completion of OQ concurrently with the execution of the IQ phase shall be approved
by Quality.
6.2.4.8 Verification documentation may be attached to the executed equipment OQ protocol,
as applicable, and shall address the review of attributes, as applicable. Examples of
OQ attributes are identified in Table 2.
6.2.4.9 The final report(s) shall provide a summary of the OQ protocol execution and the
results.
Table 2: Examples of Operational Qualification Attributes

Existing
OQ Attributes New Equipment
Equipment
SOP List (may be in draft) for A/R A/R
calibration, maintenance, and cleaning,
operation (e.g., start-up, shut-down)
Test Instrument monitoring key X A/R
parameters is within calibration of
instruments
Software and controls/sequence of A/R A/R
operation is tested.
Equipment safety features X X
Equipment design features (material of X A/R
construction)
Functional testing X X
Boundary testing of operating A/R A/R
parameters
Operational safety features A/R A/R
X = Mandatory
A/R = As Required shall be used as follows:
- If requirement does not apply, a justification statement shall be included on
qualification/validation documentation.

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- If documentation for the requirement exists, the qualification/validation final


report(s) shall include copies of documents and/or reference to the original
document(s) location.
6.2.4.10 OQ acceptance criteria are usually based on Function Specifications, vendor /
supplier user’s manuals, and / or other vendor / supplier documentation.
6.2.5 Performance Qualification (PQ)
Note: Refer to Exhibit F for Performance Qualification Process Overview.
6.2.5.1 The PQ phase provides documented evidence that the system is capable of
performing or controlling the activities of the processes as defined according to
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approved specifications while operating in its specified operating environment or


simulated loaded conditions.
6.2.5.2 The PQ is developed based on information from the following (as applicable):
- IQ and OQ phases
- User Requirements, Functional and/or Design Specification
- Verification that system performs as defined in SOPs not directly related to the
qualification activities
- PQ testing which is designed to verify that critical elements of the process
perform consistently and reliably in the final system configuration according to
approved SOPs
6.2.5.3 Typical PQ tests (see Exhibit G) may challenge the minimum and maximum
operating ranges (e.g., speed, spray rates, temperature, pressure, rotation, volume,
weight, timing, etc.), or when properly justified, a verification of the performance of
the system at operational conditions under load. PQ tests may cover the following
elements:
Note: The test scenarios cited within this procedure is not all inclusive as no piece
of manufacturing equipment are exactly the same, it is the responsibility of
the protocol owner/study director to ensure that all aspects of the
equipment/system is tested appropriately and fit for its intended use.
6.2.5.3.1 An evaluation of a set of conditions encompassing the lower and
upper critical operating parameters.
6.2.5.3.2 A single, operating parameter considered as worst case
(example: maximum speed) may be used to challenge the
equipment/system.
6.2.5.3.3 Test Instrumentation Verification – This test section documents
the calibration information of all instrumentation or
measuring devices used for the PQ execution and
verification that they were calibrated to NIST traceable
standards or equivalent.
6.2.5.4 For PQ objectives, refer to Qualification Strategies section (strategy “Modular” and
“Holistic”) and Exhibit H. PQ can be completed concurrently with the execution of
OQ phase.

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6.2.5.5 The PQ phase is to be executed following OQ execution. However, PQ can be


completed concurrently with the execution of the OQ phase when there is no overlap
or disruption which could have an impact on subsequent activities. Justification for
the completion of PQ concurrently with the execution of the OQ phase shall be
documented and approved by Quality.
6.2.5.6 Verification documentation may be attached to the executed equipment PQ protocol,
as applicable, and shall address the review of the attributes, as applicable.
Examples of PQ Attributes are identified in Table 3.
6.2.5.7 The final report(s) shall provide a summary of the PQ protocol execution and the
results.
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Table 3: Examples of Performance Qualification Attributes

Existing
PQ Attributes New Equipment
Equipment
SOP List (may be in draft) for calibration, A/R A/R
maintenance, and cleaning, operation
(e.g., start-up, shut-down)
Preventive maintenance X A/R
Key equipment operating within critical X A/R
parameters consistency (repeatability
and reproducibility)
Operating parameters within worst case X X
scenario
X = Mandatory
A/R = As Required shall be used as follows:
- If requirement does not apply, a justification statement shall be included on
qualification/validation documentation.
- If documentation for the requirement exists, the qualification/validation final
report(s) shall include copies of documents and/or reference to the original
document(s) location.

6.3 Final Approval / Release Phase


6.3.1 The Validation Team will be responsible for the following:
6.3.1.1 Review of all executed protocol scripts against their acceptance criteria ensuring that
the equipment/system is fit for intended use.
6.3.1.2 Review of final reports for the qualification phases, IQ, OQ, and PQ.
Note: Final reports can be combined, or a sign off page with all appropriate
signatories from the protocol approval page.
6.3.1.3 Confirm that change control initiated for qualification activity has been closed.

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6.3.2 If a QPP was utilized for the qualification exercise, the QPP Final Report and Release for
Operation can also serve to release the system for operational use.

7.0 Documentation Requirements


7.1 The qualification activities related to requirements identified in this procedure shall be documented in
protocol(s) and final report(s) and as applicable, shall include the following elements:
Note: Format/sequence/section(s) and title(s) of these documentation elements are for reference only.
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7.1.1 Document Identification – This section shall include title, document number (unique number
assigned), revision, effective date, and author name.
7.1.2 Purpose - This section shall describe the reason(s) the qualification/validation is being
performed.
7.1.3 Background (Process History/Applicability) - This section shall provide additional pertinent
information including but not limited to identification of equipment process/product
specifications and associated documentation.
7.1.4 Responsibilities - This section shall identify the department(s) and/or individual(s) by the
primary responsibility of each function involved.
7.1.5 System Description (Materials/Equipment) - This section shall provide specific information
describing equipment/ancillary systems, instruments, product, etc., required to complete the
qualification/validation related activities. It is important to maintain traceability information for
the materials used (e.g., machine number, material specifications /requirements).
7.1.6 Test Method and Equipment - This section shall provide information on test methods and
equipment utilized, to include:
- Documentation review.
- Instrumentation verification for current calibration/maintenance status (calibration number,
due date, etc.).
Note: If calibration is not required (due to no quality impact), the technical rationale shall
be provided.
- Verification of the required utilities and components.
- Equipment installation information referencing manufacturing instructions.
- Verification that all test methods/equipment have been validated/qualified.
7.1.7 Data Recording – All pertinent documents (e.g., raw test data) shall be referenced in this
section.
7.1.8 Operator Instructions (Procedures) - This section shall identify all relevant activities/tasks
that shall be performed to complete the qualification/validation and as applicable, reference(s)
to related documentation (e.g., SOPs, vendor installations, operating manuals, etc.).
7.1.9 Sampling (Sample Size Justification) - This section shall include the statistical rationale and
identification of the sampling method(s) chosen to assure a high degree of confidence for the
testing performed.

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7.1.10 Analysis of Data - This section shall:


- Identify any statistical methods used.
- State any assumptions made.
7.1.11 Acceptance Criteria - This section shall reference all predetermined acceptance criteria
including but not limited to acceptance criteria for key equipment/process operating parameters
and product characteristics. Acceptance criteria shall be approved prior to qualification
execution.
7.1.12 Attachments - This section may include, as appropriate:
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- List of relevant documents with identification information (document title, revision, control
number, and/or location).
- Lists of equipment (including model/serial number, classification, attributes, maintenance
strategies, performance ranges) configured for input into Apotex Management System(s)
for Reliability & Maintenance.
- List of instruments (including description, serial/part number, range of operation,
calibration/maintenance status, schedule, due date, etc.).
- Spare parts list with identification information [Part Number (P/N), manufacturer].
- Component list with identification information [Part Number (P/N), description, etc.].
- Approved deviation reports (e.g., addendum/amendments) including deviation description,
resolution (corrective action plan), approval signature and date, listed clearly or
summarized on the appropriate final report(s).
- List of supporting documentation (SOPs, master records, etc.).
- Open issue log, to track validation issues. At minimum, the issue, resolution and closure
date shall be listed.
7.1.13 Qualification Summary Report (executive summary) - This section shall summarize
concisely the protocol outcome regarding:
7.1.13.1 Verification that each protocol requirements are met.
7.1.13.2 Deviation(s), issue log and related corrective action(s), as appropriate.
7.1.13.3 Qualification/validation final disposition (acceptable or non-acceptable).
7.1.13.4 Statement of equipment’s fitness for intended use.
7.1.13.5 Result(s) information location.
7.1.13.6 Release for Operation information or reference/copy of documentation addressing it.
Note: Elements 7.1.6 to 7.1.12 are included in the executed protocol and therefore are not
required to be copied into the Qualification Summary Report.
Note: For simple or low risk systems, a Qualification Summary Report may not be necessary
as the applicable aspects may be captured in another document (i.e. data entries made
within a qualification protocol during execution).
Note: For complex systems Qualification Summary Reports may be issued after the
completion of each Qualification Protocol, as applicable.

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7.1.14 Approvals - This section shall identify the individuals (name, title) reviewing and approving the
protocols and final qualification/validation results, as follows:
7.1.14.1 The manufacturing representative(s) or delegate shall review and approve the
protocol/final report for conformance with the facility objectives and compliance with
the operational procedures.
7.1.14.2 The facility quality management representative(s) or delegate shall review the
qualification/validation documents for compliance with operating procedures and
conformance to CGMP and approve them as follows:
- Protocol(s), prior to qualification/validation execution.
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- Final report(s), prior to qualification/validation closure.


- All justifications for not performing qualifications/validations, prior to using the
equipment/process to manufacture product for distribution.
- Evaluation documentation, attached to final report(s) and affecting product
release documentation for product used to successfully verify the protocol
requirements (e.g., worst case/extreme limits), prior to product release for
distribution.
- Closed/addressed deviation report(s) and issue log, prior to validation closure
7.1.14.3 Other review and approval signatures may be required as deemed necessary by
individual facility.

7.2 Use Table 4 when identifying the documentation requirements of each qualification phase.
Table 4: Documentation Requirements

Documentation Section IQ OQ PQ
Document Identification X X X
Purpose X X X
Background (process A/R A/R A/R
history/applicability)
Responsibilities X X X
SOP List for calibration, maintenance, A/R A/R A/R
and cleaning, operation (e.g., start-up,
shut-down)
System X A/R X
Description(materials/equipment)
Test Method and Equipment X X X
Data Recording X X X
Operator Instructions (procedures) X X X
Sampling (sample size justification) A/R X X
Analysis of Data A/R X X
Acceptance Criteria X X X

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Documentation Section IQ OQ PQ
Attachments X X X
Qualification Summary Report X X X
(Executive Summary)
Approvals X X X
X = Mandatory
A/R = As Required shall be used as follows:
- If requirement does not apply, a justification statement shall be included on qualification/validation
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documentation.
- If documentation for the requirement exists, the qualification/validation final report(s) shall include
copies of documents and/or reference to the original document(s) location.

7.3 QPP Final Report (If applicable)


7.3.1 The QPP Final Report shall identify the equipment/system qualification final package
requirements to ensure documents entirety and integrity.
7.3.2 All document pages shall be numbered and the total number of pages included for each
document set. All pages shall be reviewed for blanks (unnecessary entries or missing data).

7.4 Release for Operation (Certification for Use)


7.4.1 After successful completion of all required Qualification activities, a Validation Certification for
Use shall be issued by the responsible Validation department.
7.4.2 Alternatively, the systems release to operation may be included as part of the QPP Final
Report.

7.5 Qualification related documentation shall be retained in an organized and easy retrievable manner. Each
facility shall establish a written procedure describing how validation documentation is archived and shall
include location, methodology (chronologically, alphabetically) to ensure traceability to each specific
process/equipment.

7.6 Once Equipment Qualification is completed, qualification data shall be entered into the SAP PM
Management System master databases or equivalent system, as applicable.

7.7 All qualification documents shall include date, signature, printed name of the signer (if signature specimen
is not available) and meaning of the signature (review, approval), original data/documents, or copy of the
original data/documents and/or reference to document number/location of original data and shall be in
compliance with the Good Documentation Practices (GDP) elements as defined in division or facility
procedure(s). The facility shall have a system to ensure the security and timely retrieval of validation
documents.

7.8 The ultimate goal of manufacturing equipment qualification is to ensure a qualified facility, with qualified
systems and equipment meeting all requirements to manufacture product. Non-qualified equipment will
be tagged out of service and will not be used to manufacture product.

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7.9 The commissioning and qualification documentation will follow the approach and practices summarized in
the Site Validation Master Plan.
7.9.1 A Site Validation Master Plan provides a comprehensive, coordinating document that structures
the information used to define the site’s validation program.
7.9.2 Identification of the qualification activities that are to be completed by Apotex will ensure that
the site facilities and equipment are in full compliance with cGMPs for manufacture of products.
7.9.3 The Site Validation Master Plan includes how the facilities, utilities and equipment will be
validated to ensure current GMP compliance.
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8.0 Traceability Matrix


8.1 The Validation Team Lead shall be responsible for the development of a Traceability Matrix during
system specification and maintaining the Traceability Matrix throughout the equipment/system
qualification process.

8.2 The Traceability Matrix shall be used for the following:


- To link equipment/system requirements and specifications, as applicable. This linkage shall be used
to perform Design Review activities to ensure the system is designed and configured to meet the
original user’s requirements.
- To document the linkage of relevant system specifications to testing performed and / or procedural
controls.
- To provide a method to ensure that all applicable elements of specifications, including
equipment/system requirements, have been properly verified during qualification testing or provide
cross-reference to the appropriate procedural controls in place.

8.3 The Traceability Matrix shall be completed and approved after all qualification testing activities are
completed.

9.0 Qualification Maintenance


9.1 The System Owner shall be responsible for managing any changes/requalification required for a qualified
equipment/system.
9.1.1 Change management of qualified equipment/system shall be performed in accordance with the
Global Quality documents related to change control.
9.1.2 Requalification may be necessary in the following circumstances:
- Changes to qualified system’s hardware that are not “like for like” changes
- Changes to the qualified system’s software version
- Changes to the qualified system’s configuration of settings, parameters, and/or function
- Changes to validated upstream utilities supplied to the system

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- Changes to other systems related to the validated system


9.1.3 The degree of requalification required depends on the nature of the changes and shall be
evaluated according to documents related to Apotex Change Control Program. Certain other
changes may require requalification as well.

9.2 The System Owner shall be responsible for ensuring the implementation of a Calibration, Preventive
Maintenance and Training Program for a qualified equipment/system as per site procedures.
9.2.1 A Calibration Program is implemented to assure accuracy and reproducibility of all critical
instrumentation associated with the equipment/system.
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9.2.2 A Preventive Maintenance Program is implemented to continuously monitor and maintain


equipment/system.
9.2.3 A Training Program for operators is implemented to assure the maintenance of skills and
education of those operating the equipment/system.

9.3 For Automation Systems, the following systems to support operation may apply, and as applicable they
may be verified as part of the qualification process:
- Security and System Administration
- Record Management (Retention, Archival and Retrieval)
- Continuity Management (Backup and Restore, Business Continuity Planning, Disaster Recovery)

9.4 Once qualification has been established, the status of equipment qualification should be periodically
assessed based on information from routine monitoring, maintenance and calibration activities. Based on
this information the maintenance and/or calibration frequencies may be adjusted and the need for re-
qualification established.

10.0 Equipment / System Decommissioning


10.1 The System Owner shall inform the Validation Team Lead of the equipment/system decommissioning.

10.2 The Validation Team Lead shall execute the decommissioning process for an associated
equipment/system’s computerized system and document it in a System Decommissioning Plan. The
System Decommissioning Plan shall address the following items, at a minimum:
- Migration, archival and destruction requirements for historic data or records
- Identification of the current software and hardware configurations, as well as interfaced systems,
equipment, or instrumentation
- Identification of any external processes or systems that rely on data or records from the system
- If the system will be replaced, include a plan for the transition to the new system
- Decommissioning of manufacturing equipment shall include an “as found” calibration verification, as
well as an operational / performance check via validation periodic review and / or revalidation
activities to bracket the use of the system since the last calibration and validation activities were

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performed. If the “as found” system is not within system specifications, an investigation shall be
performed to determine system impact.

10.3 After system decommissioning, the Validation Team Lead shall create a System Decommissioning Report
to address the following, at a minimum:
- Description of the execution of the plan
- Summary of the results of any testing or verification activities that were executed
- Discussion of any deviations and their associated resolution
- An index of all documentation, data, and records related to the decommissioned system, and where
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they are stored.

11.0 Definitions
Term Definition
Acceptance Criteria Pre-defined and measurable criteria under which a test result may be considered
acceptable.
Attachment A document/drawing/manual/raw data required to be collected by the execution of
the protocol.
Automation System A computer system which is responsible for localized control of manufacturing or
packaging equipment/systems (e.g. tablet press, pan coaters, fluid-bed dryers,
filler machine, etc.) and utility systems (e.g. Building Management System (BMS),
Purified Water, etc.)
Commissioning A well planned, documented, and managed engineering approach to the start-up
and turnover of facilities, systems, and equipment to the end-user, that results in a
safe and functional environment that meets established design requirements and
stakeholder expectations.
Critical System A system whose performance has a direct and measurable impact on the quality of
the intermediate or final product.
Datasheets Data collection forms that are developed, approved, and issued with the
validation/qualification protocol for the purpose of capturing results and
documentation of the validation in a consistent fashion.
Design Reviews Planned and systematic reviews of specifications, design development and
continuous improvement changes performed as appropriate throughout the life-
cycle of the manufacturing system. Design reviews evaluate deliverables against
standards and requirements, identify problems, and propose required corrective
actions.
Deviation A departure from an approved practice or parameter that may or may not have
impact upon product quality.
Directed Review Review and subsequent approval of Protocols and Summary Reports by limiting
the reviewer appraisal of the documents to the reviewer’s field of expertise.
Engineering Study The evaluation of parameters and their effect on equipment or system functionality.

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Term Definition
Factory Acceptance Acceptance Testing performed at the vendor / supplier site prior to delivery to the
Testing (FAT) customer (Apotex) site.
Installation Documented verification that a system is installed according to written and pre-
Qualification approved specifications.
Management System(s) System to manage sustainability of process and equipment functionalities by
for Reliability & utilizing documented qualification data.
Maintenance
Manufacturing Systems Elements of pharmaceutical manufacturing capability, including manufacturing
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systems, facility equipment, process equipment, supporting utilities, associated


process monitoring and control systems, and automation systems, that have the
potential to affect product quality and patient safety.
Operational Documented verification that a system operates according to written and pre-
Qualification approved specifications throughout all specified operating ranges.
Performance Documented verification that a system is capable of performing or controlling the
Qualification activities of the processes it is required to perform or control, according to written
and pre-approved specifications, while operating in its specified operating
environment.
Portable Equipment Equipment that, by design, facilitates movement from one room to another or from
one building to another without qualification impact. It is generally on wheels,
movable, or has a plug (rather than hard wired) if it has a power supply.
Pre-Qualification Phase that encompasses all engineering and documentation activities from the
time a qualification project has been identified through the time it is turned-over to
the Qualification Department.
Qualification Action of proving and documenting that equipment or ancillary systems are
properly installed, work correctly, and actually lead to the expected results.
Reliability Data Delivery Process to ensure qualification data is collected for entry into the Management for
Reliability & Maintenance databases.
Site Acceptance SAT is Acceptance Testing performed after the system is properly installed and
Testing (SAT) commissioned in its intended operating environment at the customer (Apotex) site.
User The department that operates or interacts directly with the equipment/system. User
is typically the system owner.
Worst Case Conditions A set of conditions encompassing upper and lower processing limits and
circumstances, including those within standard operating procedures, that pose the
greatest chance of process or product failure (when compared to ideal conditions).
Such conditions do not necessarily induce product or process failure.
Validation A documented program that provides a high degree of assurance that a specific
process, method, or system will consistently produce a result meeting
predetermined acceptance criteria.

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Term Definition
Verification A systematic approach to verify that Critical Systems, acting singly or in
combination, are fit for intended use, have been properly installed, and are
operating correctly. This is an umbrella term that encompasses all types of
approaches to assuring systems are fit for use such as qualification,
commissioning and qualification, verification, system validation, or others.
Validation Team A multidisciplinary team responsible for planning, authoring, executing, and
reviewing tasks associated with qualifying equipment and facilities. The team
includes:
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- Department responsible for Equipment and Facilities Qualification


- System Owner
- Representatives, as needed, from other departments such as Engineering;
Production/Packaging Maintenance or Technical Services; Computer System
Validation &Compliance (CSVC); Safety, Health & Environment (SH&E), and
QA as subject matter experts (SMEs).
Validation Master Plan The establishment of a dynamic written plan that defines the overall approach to
Validation at a site. It will define the governing procedures and terminology to be
used by all subsequent documentation, outline descriptions of the facility site, the
manufacturing processes and the scope and implementation of the Validation
activities. This document is maintained current as a living document.

12.0 Exhibits
Exhibit Title
Exhibit A Equipment Qualification Process Overview
Exhibit B Installation Qualification Process Overview
Exhibit C Typical Test Sections of an Installation Qualification (IQ) Protocol
Exhibit D Operational Qualification Process Overview
Exhibit E Typical Test Sections of an Operational Qualification (OQ) Protocol
Exhibit F Performance Qualification Process Overview
Exhibit G Typical Test Sections of a Performance Qualification (PQ) Protocol
Exhibit H Operational and Performance Qualification Overview – Holistic Strategy

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13.0 Revision History


Revision No. Effective Date Change Control No. Author of Revision
0 Current 500633 Allanna Papaioannou,
Manager, QA Global Policy & Standards

Description/Reason for Change:


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New Global Quality Guideline, 08-GQG-108, ‘Manufacturing Equipment Qualification’ GSOP-008-009


‘Manufacturing Equipment Qualification’.

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Exhibit A: Equipment Qualification Process Overview

Initiation
System Retirement
(New System Required)

Apotex User
Vendor - Supplier Audit /
Qualification Maintenance
System Categorization / Release to Operation
(Change / Configuration
System Risk Assessment / (Certification for Use)
Management)
System Procurement
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Qualification Planning Compared to Planned Qualification Reporting

Primary Responsibility
User Requirements
Performance Qualification
Specification Tested Against
(PQ)
(URS)

ting
Tes
Spe

Functional Specification Operational Qualification


cifi

tion
Tested Against
(FS) (OQ)
cat

ica
ion

alif
Qu

Equipment/System Vendor
Installation Qualification
Design specification (DS) Tested Against
(IQ)

Testing and Commissioning


(FAT / TOP / SAT)

Vendor / Supplier Quality System

Traceability, Document / Record Management

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Exhibit B: Installation Qualification Process Overview


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Exhibit C: Typical Test Sections of an Installation Qualification (IQ) Protocol


Section Description
IQ Purpose Documents why the qualification is being performed.
IQ Objective Documents what will be accomplished upon completion of executed IQ phase.
Equipment Identification and Installation Documents the identification of the room/equipment/manufacturing system to be
Verification qualified along with its location. This includes the verification that it is assembled or
installed/constructed in a safe manner and in accordance with manufacturer’s
specifications and Apotex requirements.
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Engineering Drawings and Documents Verifies and documents the availability, location and, as appropriate, the version of all
Verification general documentation, drawings or manuals associated with the operation, and
maintenance of the equipment/system. As built and/or GMP drawings related to
schematics and/or Piping and Instrumentation Drawings (P&ID) will be verified to be
accurate and represent as-built conditions. Inconsistencies observed on any of the as-
built and/or GMP drawings shall be red-lined, initialled and dated. A copy of the red-
lined drawing will be submitted to engineering for inclusion to the appropriate
engineering documentation(s) and/or update through the change control process.
Note: For modified existing drawings, approved red-lined drawing submitted to
change control must be used during field verification.
Utilities Verification Verifies and documents information regarding all utilities supplied to the
equipment/system components.
Major Components Verification Verifies and documents that all major components (e.g., motor, variable frequency
drive, transformer, fans, hardware, etc.) of the equipment/system are installed in
accordance with the manufacturer’s and Apotex requirements.
Critical Instrumentation Calibration Identifies all critical instruments or control and monitoring instrumentation associated
Verification with the equipment/system and documents their calibration dates. All standards used in
calibration must be traceable to the National Institute of Standard and Technology
(NIST) or equivalent. This also verifies that the instrument is logged into the calibration
program. Calibration forms or certificate shall be attached to the protocol.
Material of Product Contact List Documents the material of construction for each part with potential product contact. If
passivation is required, certification will be attached. Material for coating contact parts
(if applicable) will also be documented.
Spare Parts List Verifies the availability of any spare part lists needed to assure maintenance of the
(As Applicable) system.
Software Verification Verifies the correct Programmable Logic Controller (PLC) / Human Machine Interface
(As Applicable) (HMI) with name and version of software are installed. If a copy of the installed software
is available, verify that it is labelled properly and location is identified. If a copy is not
available, ensure that vendor support is current and available via suitable escrow
agreement.
Control Device Configuration Verification Documents the system configuration parameters or set-points considered critical for
(As Applicable) system functionality.
Input/Output Verification Verifies that digital and analog input and output connections are installed in accordance
(As Applicable) with wiring diagrams. Verification will include all I/Os connected to critical for system
functionality.
Installation Qualification Closeout Verifies that all IQ test sections have been completed and ensure that the next
(As Applicable) qualification phase can commence.

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Exhibit D: Operational Qualification Process Overview


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Exhibit E: Typical Test Sections of an Operational Qualification (OQ) Protocol


Section Description
Operational Qualification Execution Verifies and documents that all prerequisites, in regard to the qualification of the
Pre-requisite Verification equipment/system, have been met prior to the start of OQ activities. This section is not
required when there is a close-out section of previous qualification phase.
SOP List Verifies that the SOPs for the operation, cleaning, and preventive maintenance and related
applicable SOPs (security, backup and restore, maintenance of password, etc.) for the
equipment/systems are available. These SOPs may be draft documents as a need for
changes may be necessary in order to executed or as a result of the execution of the OQ
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protocol. If changes are necessary they shall be managed in accordance with Good
Documentation Practices.
Controls/Sequence of Operation Verifies and documents the proper operation of the Control Panel, as well as the sequence
(As Applicable) of operation for the equipment/system, under normal operating conditions. Complete
cycle/process is executed including start-up and shutdown (per design) to achieve end
results.
Operator Interface Verification Verifies that all interface features are functional and as designed. Typical tests include:
(As Applicable) Screen navigation, screen data, screen controls (i.e. buttons), sub-screens.
Boundaries Verification Data entry fields must be tested within and outside of each boundary limit specified to
(As Applicable) ensure that only valid entries are allowed.
Security Testing Verifies and documents that security levels for the equipment/system provides access as
(As Applicable) detailed in the user requirements or specifications. This may include testing of
administrative functions such as add, delete or modify users, passwords, or privileges.
Alarms and Interlocks Verification Verifies equipment/system alarms are functional and produce the expected results. All
(As Applicable) interlocks operate as designed.
Recipe Builder Verification Verifies that a recipe can be created, modified, deleted, and loaded per specifications.
(As Applicable)
Data Collection and Report Generation Verifies that data are archived and applicable screens or reports are printed appropriately.
Verification
(As Applicable)
Functional Testing Verifies the equipment/system functions as specified in the user requirements and/or as
intended for use by Apotex.
Loss of Power Verification Verifies that power loss and recovery present no danger to personnel and/or product. This
may also include verification that data and/or settings are retained or that sequence of
operation resumes as per design specifications.
Frequency / Electromagnetic Verifies that the Radio Frequencies (RF) and Electromagnetic (EM) fields do not adversely
Interference Verification affect the operation of the system.
Test Instrumentation Verification Documents the calibration information of all instrumentation or measuring devices used for
the OQ execution and verification that they were calibrated to NIST traceable standards or
equivalent.
Operational Qualification Close-Out Verifies that all OQ test sections have been completed and ensure that the next
qualification phase can commence.
Note: This section is not required if next phase is the Final Report.

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Exhibit F: Performance Qualification Process Overview


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Exhibit G: Typical Test Sections of a Performance Qualification (PQ) Protocol


Section Description
Process Qualification Execution Pre- Verifies and documents that all prerequisites, in regard to the operational qualification of
requisite Verification the equipment/system, have been met prior to the start of PQ activities. This section is not
required when there is a close-out section of previous qualification phase.
SOP List Verifies that the SOPs for the operation, cleaning, and preventive maintenance and related
applicable SOPs (security, backup and restore, maintenance of password, etc.) for the
equipment/systems are available. These SOPs may be draft documents. These SOPs
shall be in approved status with an assigned effective date when the equipment change
control or equipment release is complete.
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Controls/Sequence of Operation Verifies and documents the proper operation of the Control Panel, as well as the sequence
of operation for the equipment/system, under normal operating conditions. Complete
cycle/process is executed including start-up and shutdown (per design) to achieve end
results.
Operator Interface Verification Verifies that all interface features are functional and as designed. Typical tests include:
(As Applicable) screen navigation, screen data, screen controls (i.e. buttons), sub-screens.
Boundaries Verification Data entry fields must be tested within and outside of each boundary limit specified to
(As Applicable) ensure that only valid entries are allowed.
Security Testing Verifies and documents that security levels for the equipment/system provides access as
(As Applicable) detailed in the user requirements or specifications. This may include testing of
administrative functions such as add, delete or modify users, passwords, or privileges.
Alarms and Interlocks Verification Verifies equipment/system alarms are functional and produce the expected results. All
(As Applicable) interlocks operate as designed.
Recipe Builder Verification Verifies that a recipe can be created, modified, deleted, and loaded per specifications.
(As Applicable)
Data Collection and Report Generation Verifies that data are archived and applicable screens or reports are printed appropriately.
Verification
(As Applicable)
Functional Testing Verifies the equipment/system functions as specified in the user requirements and/or as
intended for use by Apotex.
Loss of Power Verification Verifies that power loss and recovery present no danger to personnel and/or product. This
may also include verification that data and/or settings are retained or that sequence of
operation resumes as per design specifications.
Test Instrumentation Verification Documents the calibration information of all instrumentation or measuring devices used for
the PQ execution and verification that they were calibrated to NIST traceable standards or
equivalent.
Operational Qualification Close-Out Verifies that all OQ test sections have been completed and ensure that the next
qualification phase can commence.
Note: This section is not required if next phase is the Final Report.

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Number
GLOBAL QUALITY GUIDELINE
08-GQG-108

GQG Page Revision


Section: EQUIPMENT AND UTILITIES
30 of 30 0

Title: MANUFACTURING EQUIPMENT QUALIFICATION

Exhibit H: Operational and Performance Qualification Overview - Holistic


Strategy
Uncontrolled Copy After: September 13, 2018 11:59:59 PM ET

08-GQG-108 rev. 0 Effective Date: 10/24/2017 Page incl. Approval: 30 of 31


APPROVALS AND SIGNATURES

UserName: Elizabeth Bagshaw (apotex\ebagshaw)


Title: Associate Dir, Global Policy & Systems
Date: Tuesday, 04 April 2017, 04:15 PM Eastern Time
Meaning: Approval
================================================

UserName: Meseret Jimale (apotex\mjimale)


Title: Manager, Global Field & Market Response
Date: Wednesday, 05 April 2017, 04:11 PM Eastern Time
Meaning: QA Approval
Uncontrolled Copy After: September 13, 2018 11:59:59 PM ET

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08-GQG-108 rev. 0 Effective Date: 10/24/2017 Page incl. Approval: 31 of 31