ICH Q12 : A Unique Opportunity to Realize 21st

Century Quality Vision

Moheb M. Nasr

3rd FDA/PQRI Conference March 22, 2017

Disclosures

• The speaker is solely responsible for the content of this presentation

• The views presented here do not necessarily represent the views of GSK or ICH

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Outline

• Background • ICH Q12: Scope and Objectives • Q12: Potential Benefits • Q12 Version 7 Draft

• Key Sections and Enabling Tools • Critical Issues to Address

• Implementation at Regional Level • Next Steps • Conclusions • Acknowledgments

ICH Quality Strategy Workshop (1)

• June 2014 in Minneapolis, Minnesota, USA

• Purpose: To reflect on progress made since 2003 and develop a future vision and strategy

• Assessment of ICH Quality Vision and Needs • Implementation of ICH Q8, Q9, Q10 and Q11 provides

opportunities for more science and risk based approaches to assessing changes across the lifecycle

• Main emphasis of these guidelines was on development stage of lifecycle

• Opportunities and benefits have not been fully realized/enabled, and the envisioned “operational flexibility” has not been achieved

• Need for more focus on the Commercial Manufacturing phase of the lifecycle

ICH Quality Strategy Workshop (2)

• Agreement on vision and needs • Developed 5-year workplan • Priorities Identified:

ICH Q12: “Technical and Regulatory Considerations of Pharmaceutical Product Lifecycle Management”

API Starting Materials (ICH Q11 IWG) Quality Overall Summary Enhanced Approaches for Development and

Utilization of Analytical Procedures (AQbD) Continuous Manufacturing of Pharmaceuticals

ICH Q12: Scope and Objectives

• Concept Paper and Business Plan developed and endorsed by the ICH Steering Committee in September 2014

• Scope The proposed guideline will apply to pharmaceutical

products, including currently marketed chemical, biotechnological and biological products

Objectives Intended to work with ICH Q8 to Q11 Guidelines to

provide a framework to facilitate the management of post-approval Chemistry, Manufacturing and Controls (CMC) changes in a more predictable and efficient manner across the product lifecycle

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Q12: Potential Benefits • Help assure supply reliability by enabling strategic and

efficient management of post-approval changes which could mitigate drug shortages related to manufacturing and quality issues

• Optimization of resources for both regulators and industry • Facilitate continual improvement and encourage the

adoption of innovative technologies • Q12 will:

• Develop harmonized approach to define regulatory commitments (Established Conditions)

• Introduce regulatory tools for prospective change management, including Post Approval Change Management Protocols (PACMP) Product Specific Lifecycle Management (PSLCM) Strategy

Q12 Expert Working Group (EWG)

• Large team representing regulators (FDA, EC, MHLW/PMDA, HC, Swissmedic, ANVISA, MFDS, HSA, WHO, TFDA) and industry ( PhRMA, EfPIA, JPMA, IGBA, BIO, APIC, WSMI)

• Diverse technical, quality and regulatory expertise

• Excellent collaboration and dedication

• Commitment to develop a transformational guideline

• Willingness to discuss and resolve difficult technical and regulatory issues

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Q12 Version 7 Draft

Table of Contents 1. Introduction 2. Categorization of Changes 3. Established Conditions 4. Post-Approval Change Management Protocol (PACMP) 5. Product Specific Lifecycle Management (PSLCM) Strategy 6. Pharmaceutical Quality System (PQS) and Change Management 7. Relationship Between Assessment and Inspection 8. Approaches to Streamline Changes to Marketed Products 9. Glossary 10. References 11. Illustrative Examples, Case Studies and Templates

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Key Sections of Q12 v7.0 document (1) Categorization of Changes

• Considers a risk based system for categorization of changes and regulatory communications

• System does exist in some markets • Global implementation will allow timely and efficient introduction of

CMC changes and enable effective use of industry and regulatory resources

Established Conditions • Describes a harmonized approach to defining “Regulatory

Commitments” i.e. those elements in the regulatory submission which are subject to regulatory change control

• Clear and unambiguous identification of these elements will be critical to the uniform implementation of ICH Q12 across regions

• Concept exists and/or is evolving in some regions Japan: MHLW ‘Approved Matters’ USA: Draft FDA Guidance on ‘Established Conditions’

Key Sections of Q12 v7.0 document (2)

Post-Approval Change Management Protocol (PACMP) • Describes the change(s) a firm would like to implement during the

lifecycle of a product and proposed reporting categories • Provides predictability and transparency • PACMP exists in EU and US

Product Specific Lifecycle Management (PSLCM) Strategy • Serves as a central repository of the ECs, reporting category for

making changes to approved ECs, PACMPs, planned major post-approval CMC changes (if known), and post-approval CMC commitments

• Provides a framework to facilitate and encourage a more strategic approach to lifecycle management

• Enables transparency and facilitates continuous improvement

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Key Sections of Q12 v7.0 document (3)

Pharmaceutical Quality System (PQS) and Change Management • ICH Q10 describes principles for the effective management of

CMC changes under the PQS • This section elaborates on Q10 principles and describes how

the PQS can be utilized effectively in the application of Q12 concepts

Relationship Between Assessment and Inspection • Confirms that changes to GMP related information (e.g.

facilities, equipment and utilities) is held on site and managed and documented in accordance with GMP

• Availability of information to assessors and inspectors both • Less reliance on add hoc communication among individuals

• Enhanced communication between assessors and inspectors a key to successful implementation of Q12

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Q12 Version 7: Critical Issues to Address (1)

Established Conditions • A well developed and understood section on ECs will be

critical to achieve alignment across the ICH regions and beyond

• Further clarification of Decision Tree for identification of and reporting of ECs for a manufacturing process is needed

• Elaborate on performance based approach for defining ECs

• Identify appropriate illustrative examples to facilitate understanding and ensure harmonized implementation

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Q12 Version 7: Critical Issues to Address (2)

Product Specific Lifecycle Management Strategy • Benefits need to be more clearly articulated • In addition to postapproval changes, how to ensure value and

utility across entire product lifecycle? • Use illustrative examples for PSLCM (chemical entities and

biologics) • Agreement on single location in CTD e.g. in Module 1 • Further clarification on maintenance aspects and relationship

with CTD sections needed

PACMP Protocols • Clarify the opportunity of the “broader protocol” for multiple

changes to a single product • Consideration of a streamlined regulatory process to submit

an amendment to a protocol

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Q12 Version 7: Critical Issues to Address (3)

Biotech products and Vaccines • Further guidance and/or examples should be developed

to enable the principles and regulatory tools outlined in Q12 to be more easily applied for these types of products (e.g. Analytical methods)

Marketed Products • Q12 regulatory tools are applicable to marketed products • In addition, Q12 can provide specific guidance to

implement post-approval manufacturing changes (Do and Tell) e.g. changes to analytical methods for chemical entities and biologicals

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Implementation at Regional Level

• Revisions to existing variation/supplement regulations and guidelines is needed to ensure successful implementation

• Particular attention will be needed to introduce key principles and regulatory tools: Categorization of Changes (in some regions) Established Conditions Product Specific Lifecycle Management Strategy Post-Approval Change Management Protocols

• Extent of revisions will depend on if/how Q12 regulatory tools are already in place in the region

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Implementation: Training Materials

• Throughout the development of the Q12 guideline, constituents and interested parties have communicated the expected complexity of the implementation of Q12

• Development of a comprehensive training program and supporting documentation sponsored by ICH is highly recommended to ensure the proper interpretation and effective utilization and implementation by industry and regulators This is important not only for ICH, but also for non-ICH

regions

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Next Steps • Q12 version 7 document under informal review Q12 EWG interim meeting, April 4-7, 2017 to review

comments and address remaining issues

• Q12 EWG to reach step 1/2A in June 2017 Step 2B document expected to released for public

consultation Q3 2017 Step 4 expected Q2 2018

Conclusions

• Significant progress has been made with the development of Q12 • Opportunity for Q12 to be a transformational guideline

• There are still a number of critical issues and gaps to address • Q12 EWG Team is committed to reach Step 1/2a in Montreal (May

28-June 1, 2017) • Some revisions to existing Variation/Supplement regulations

and guidelines will be needed to successfully implement • It is desirable to initiate these discussions soon after Q12 reaches step

1/2a in June 2017 • Training materials will also be needed to facilitate a

harmonized interpretation and global implementation

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Acknowledgements

• Mike James, GSK

• Ashley Boam, FDA, EWG Regulatory Chair

• Q12 EWG Team

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Q12 EWG Team

Questions?

22 January 26, 2017