ICH Q12 - Technical and Regulatory Considerations
for Pharmaceutical Product Lifecycle
Management
Training Material
Module 7 – Additional approaches
Publication Date: 11 June 2021
International Council for Harmonisation of Technical Requirements
for Pharmaceuticals for Human Use
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ICH Q12 Module 7
Additional approaches
• In addition to the tools explained in previous modules, following
additional approaches are included in ICH Q12
o Chapter 8 - Structured approaches to frequent CMC
changes: Provides guidance for a structured approach for
frequent post-approval changes using analytical methods as
an example
o Chapter 9 – Stability data approaches to support the
evaluation of CMC changes: Provides strategies for
confirmatory stability studies enabling more timely
implementation of the change
• Manufacturers of authorised products can use these additional
approaches to facilitate implementation of change.
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ICH Q12 Module 7
Chapter 8
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ICH Q12 Module 7
Chapter 8 – Structured approaches to frequent
CMC changes
• This chapter of ICH Q12 describes a structured approach for frequent CMC
changes
• This is an alternative approach that does not require necessarily:
oa PACMP or
o ECs
• These approaches may be applied when the following conditions exist:
o The company has an effective and compliant (see Chapter 6) PQS
change management process which incorporates a risk management
system
o The change is within the scope of structured approach and criteria can
be met
• The steps to be followed and data to be generated are defined in the
structured approach 5
ICH Q12 Module 7
Chapter 8 – Structured approaches to frequent
CMC changes (2)
• The strategy is exemplified with a description of an
approach for analytical procedure changes in Annex II
• Similar structured approaches could be developed and
applied for other frequent CMC changes such as scale,
packaging, etc.
• If the approach is followed and all criteria are met, the
change can be made with immediate or other post-
implementation notification, as appropriate, to the relevant
regulatory authorities
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ICH Q12 Module 7
Chapter 8 – Structured approaches to frequent
CMC changes (3)
• It is recommended that MAHs contact regional authorities
for advice before implementing a change according to this
procedure, as this approach might not be available in all
regions and in all situations
• Structured approaches for frequent CMC changes are
typically applicable to lower-risk changes, since they do not
require prior approval by a regulatory agency
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ICH Q12 Module 7
➔ Annexes
Annex II: Structured approach to
analytical procedure changes
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ICH Q12 Module 7
Structured approach to analytical procedure
changes
• The application of “structured approach to analytical
procedures changes” will benefit in smooth
implementation of similar test procedures
• Conditions and exclusion criteria are specified and the
approach can be used if it meets all the prescribed criteria
• With a favourable outcome of regulatory impact
assessment, analytical procedure changes can be
implemented the soonest
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ICH Q12 Module 7
Structured approach to analytical procedure changes
Scope - Exclusion Criteria:
Change to Analytical
Procedures • PQS change management
for chemical/biological process is not effective or
products
compliant
• Procedures where the acceptance
criteria do not adequately reflect
the complex information provided
Procedure in No by the method.
scope?
• Change(s) to a test method based
on a biological/immunological/
Yes immunochemical principle or a
et any of the
Criteria (for analytical exclusion criteria? method using a biological reagent.
procedure changes):
• Changes to models and
• Same physicochemical multivariate methods
basis and high-level Change meets No Structured
Criteria?
Approach does not • Changes to analytical procedures
description apply described in pharmacopoeial
• Same acceptance criteria monographs.
of the validation protocol. Yes
• Equivalent or better Follow steps for Structured
method based on Approach for Analytical
validation results Procedure Changes
• Comparable test results.
Yes
• No change in acceptance Steps 1 to 5: Steps 6 to 10 :
Consideration of impact on safety, No Implementation, verification and
criteria Any Impact?
efficacy, purity, strength, identity, provide post implementation to
• No need for toxicological or potency of the product regulatory authorities
or clinical data.
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ICH Q12 Module 7
Structured approach – General considerations
• Similar structured approaches could be developed and
applied for other frequent CMC changes
• For example:
o Change of batch size/scale
o Extension of shelf life
o Minor changes in manufacturing process
This is not an exhaustive list
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ICH Q12 Module 7
Chapter 9
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ICH Q12 Module 7
Chapter 9 – Stability data approaches to support
The evaluation of CMC changes
• Chapter 9 provides additional science- and risk-based
approaches that can be used to develop strategies for
confirmatory stability studies supporting post-approval
changes to enable more timely filing, approval, and
implementation of the changes
• Such approaches could be included in a PACMP
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ICH Q12 Module 7
Stability data approaches – New application vs
Post approval
• The objective of formal stability studies recommended in
ICH Q1A(R2) is to establish a useful shelf-life and
storage conditions for a new, yet-to-be-marketed drug
substance/drug product
• The purpose of post approval stability studies is to
confirm a previously approved shelf-life and storage
conditions for the product after implementing the CMC
change
• The scope and design of such studies can use the
knowledge and experience acquired since authorization 14
ICH Q12 Module 7
Stability data approaches – design of studies
• Apply risk assessment and previous data to identify the quality
attributes.
• Use of appropriate tools to evaluate the impact:
o Studies on representative material
o Pre- and post-change comparability studies on representative
material
o Statistical evaluation
o Predictive degradation and other models
o Utilisation of prior knowledge and the scientific literature
• Use of confirmatory stability studies post-change
• Where applicable, include a commitment to initiate or complete
ongoing, long-term stability testing post-change 15
ICH Q12 Module 7
Additional approaches – Summary
• Chapters 8 and 9 provide additional approaches to facilitate
changes
• The structured approach for frequent CMC changes (Chapter
8) does not require any regulatory submission before using the
approach for certain changes
o Analytical procedure changes are exemplified
• Science- and risk-based approaches to confirming shelf-life are
described in chapter 9 and could be used in a PACMP, for
example
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