ICH Q12 IWG TrainingMaterial Module6 2021 0514

ICH Q12 - Technical and Regulatory Considerations
for Pharmaceutical Product Lifecycle Management
Training Material - Module 6

• Pharmaceutical Quality System (PQS) and Change
Management
• Relationship between Regulatory Assessment
and Inspection
Publication Date: 11 June 2021
International Council for Harmonisation of Technical Requirements
1
for Pharmaceuticals for Human Use
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ICH Q12 Module 6
Overview of the Training Material
Chapters 6 and 7
• Role/importance of a Pharmaceutical Quality System
(PQS)
• Basis for an effective PQS
• Responsibility for the maintenance of an effective PQS
• Inspection and regional requirements
• How is Change Management (Ch Mgt) a critical element of
the PQS?
• Communication between Regulatory Assessment and
Inspection
3
ICH Q12 Module 6
Role/Importance of a PQS
• A Quality System (QS) is defined in ICH Q9 as “The

sum of all aspects of a system that implements quality
policy and ensures that quality objectives are met”
• To complement ICH Q9, Q10 defines the PQS as the

“Management system to direct and control a pharmaceutical
company with regard to quality."
• From ICH Q7 “Quality Assurance (QA): The sum total of

the organised arrangements made with the object of
ensuring that all APIs are of the quality required for their
intended use and that quality systems are maintained.”
4
ICH Q12 Module 6
Role/importance of a PQS
An effective PQS is the foundation for implementation
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ICH Q12 Module 6
What aspects of the PQS should be considered to
support the use of Q12 tools?
• Effectiveness and Compliance?
o PQS should be effective, as described in Q10
o PQS should be in compliance with regional GMP requirements
where the application is filed
• Across the entire Supply chain?

o Including the effective PQS of the stakeholders
• Across the product life cycle?

o Ch Mgt across supply chain and product lifecycle
o Effective Ch Mgt: step-by-step description
o Use of Knowledge Management in Ch Mgt
o Management review to be considered for an effective Ch Mgt 6
ICH Q12 Module 6
Responsibility for the maintenance of an effective
PQS and associated inspection
• PQS maintenance is the responsibility of the company –
this includes:
o Manufacturing sites and/or
- Corporate Quality Management
- MAH where relevant
• Inspections will continue as foreseen by regional
regulatory requirements
o No intent to require a specific inspection assessing the state of the PQS
before the company can use the principles and tools in ICH Q12
o A manufacturing site can be considered to be in general GMP compliance
while resolving deficiencies that do not require regulatory action. In the event
that such deficiency has an impact on the effectiveness of the change
management in the PQS, may there be a restriction on the ability to utilise
flexibility in this guideline. 7
ICH Q12 Module 6
Change Management Across the Supply Chain
Company has to manage
communication of information
and interactions of PQSs across
multiple entities (Internal and
External).
Implementation of robust change

management across multiple
sites (outsourced or not) is
necessary.
The change management

activities should be considered to
support the approaches defined
in the guideline.
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ICH Q12 Module 6
Change Management Across the Supply Chain
Change management activities to be considered:
• Change to ECs: Communicated in a timely manner

o Between MAH and the regulatory authority
o Between MAH and the manufacturing chain
• Timeliness of communication:
o Driven by the impact of any change related to ECs
o Targeting the relevant entities in the supply chain
• Drivers for change : Process knowledge, Continual improvement, QRM outcome
o Example: CMO proposing process improvements (Control and product consistency). Data
generated to be used to revise ECs and associated PLCM documents if necessary
• Communication mechanisms related to MAA changes and GMP issues
o Should be defined in relevant documentation (including contracts with CMOs, e.g., Quality
Agreement) and all communications should be available for management review (see
ICHQ10)
• Critical failure in PQS anywhere in the supply chain may impact the ability to use
the tools in the guidelines
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o Should communicate such failures to affected regulatory authorities
ICH Q12 Module 6
Change Management across

the supply chain
And all along the product life cycle

Change Management all along product lifecycle
Pharmaceutical Technology Commercial Product
Development Transfer Manufacturing Discontinuation
Approval
Pre-Approval Phase
Phase Post-Approval Phase
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ICH Q12 Module 6
How is Change Management a critical element of the

PQS?
As described in Q10, an effective PQS is necessary
o Among the PQS elements, Change Management is critical to
control post-approval changes
o Knowledge Management is a key enabler to provide the signals for
making changes
o The appropriate Management Review is needed to secure the
effectiveness of the change management process
o An Effective Change Management Process is illustrated step by
11
step in the following slides (Ref. Appendix 2)
ICH Q12 Module 6
Change Management:
Stimulus for Change
1. Capture stimuli for change
Effective PQS is capable of
capturing stimuli for post-approval
changes (PAC), e.g., product
performance and process
robustness.
2. Ensure full understanding of the scope of the change and its

implications for all aspects of the process and control strategy
Including:
• The impact on ECs
• Aspects that are not ECs in affected marketing authorisations
3. Leverages existing process performance and product quality
knowledge
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ICH Q12 Module 6
Change Management:
Use of
Knowledge Management
& Management Review
• Active Knowledge Management is part of an effective change management
• Information from multiple sources is integrated, including & not limited to:
o Developmental studies o Product or process trending
o Process understanding documents o Product-specific CAPA outcome
• Active sharing of knowledge (between MAH & relevant manufacturing

Stakeholders)
o Developmental studies o Product or process trending
o Process understanding documents o Product-specific CAPA outcome
• Management Review
o Monitoring the timelines of Change Management & the performance of the change
o Ensuring that the post-implementation verification occurs and reviewing the results as a measure
of Change Management effectiveness 13
ICH Q12 Module 6
Change Management:
Change Evaluation
4. Assess and manage potential

risks for the change based on
science and prior knowledge
and considers the potential
impact if the intended change is
not implemented.
5. Determine data (existing and/or to be newly generated) needed to support the

change
Accordingly develops study protocols describing the methods, acceptance
criteria and post-implementation monitoring
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ICH Q12 Module 6
Change Management: Internal Change Approval
6. Ensure Regulatory
submission when
required
Change
Management
7. Defined change process
used to approve or reject
the intended change
involving appropriate
stakeholders
Steps 6 & 7 are closely linked 15

ICH Q12 Module 6
Change Management: Implement Change
8. Implementation based on:
a) Alignment with study protocols, PLCM
document, PACMP (if applicable)
b) Data generated demonstrating objective and
acceptance criteria met
9. Risk mitigation developed (if deviations or
unanticipated risks)
10. Verify effective outcome, post-
implementation (without unintended
consequences for product quality) Implement
11. Post implementation Change
a) Capture product/process knowledge
b) Ensure regulatory filings and PLCM document (if applicable) are updated
c) Ensure change included and assessed in Product Quality Review (where applicable)
12. Availability for review
a) The change management system should be available for review during 16
audit/inspection.
ICH Q12 Module 6
In summary
17
ICH Q12 Module 6
Regulatory assessment and inspection
relationship and communication
• Regulatory assessment & inspection are complementary activities, and
their fundamental roles remain unchanged. Nevertheless, effective
communication between assessors and inspectors can facilitate
regulatory oversight.
o Appropriate mechanisms to share knowledge and information
through respective activities can facilitate access to necessary
information and mitigate increased submission burden on the MAH
o Example:
- Inspection’s conclusion available for assessor to support oversight of
product lifecycle management
- Most recent PLCM document, when applicable, available to inspectors
providing awareness of the currently approved status of PLCM
elements
• Communication between regulators across regions is encouraged
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ICH Q12 - Technical and Regulatory Considerations

for Pharmaceutical Product Lifecycle Management

Training Material - Module 6

• A Quality System (QS) is defined in ICH Q9 as “The

• To complement ICH Q9, Q10 defines the PQS as the

• From ICH Q7 “Quality Assurance (QA): The sum total of

• Across the entire Supply chain?

• Across the product life cycle?

Implementation of robust change

The change management

• Change to ECs: Communicated in a timely manner

Change Management across

And all along the product life cycle

How is Change Management a critical element of the

2. Ensure full understanding of the scope of the change and its

• Active sharing of knowledge (between MAH & relevant manufacturing

4. Assess and manage potential

5. Determine data (existing and/or to be newly generated) needed to support the

Steps 6 & 7 are closely linked 15

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