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Introduction and Update on ICH Q12

Guideline
Dr Frank Montgomery, Global Head, Reg CMC, AstraZeneca/Medimmune
Q12 EFPIA Expert
CMC Strategy Forum Japan 2016 6th Dec 2016
Outline

• Q12 Scope and Objectives


• Progress in Osaka
• Overview of Q12
• Q12 EWG workplan

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Q12 Scope and Objectives

• Scope
• The proposed guideline will apply to pharmaceutical products,
including marketed products, chemical, biotechnological and
biological products
• Objectives include:
• 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
• Optimization of industry and regulatory resources
• Support innovation and continual improvement and help to
assure drug product supply

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Regulatory Agencies Involved in Q12

• ICH regions
• US FDA, EU, MHLW/PMDA, Health Canada,
Swissmedic
• New Members
• ANVISA (Brazil), MFDS (Korea)
• Observers
• WHO, TFDA (Chinese Taipei), HSA (Singapore),

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Progress in Osaka

• Reviewed and resolved Q12 Issues Log and reach


alignment among Q12 EWG members
• Major Discussion topics:
• Categorization of Changes
• Established Conditions
• Postapproval Change Management Protocols
• Product Specific Lifecycle Management Strategy
• Pharmaceutical Quality System
• Marketed Products

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Table of Contents

1. INTRODUCTION
2. CATEGORISATION 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. POST APPROVAL CHANGES FOR MARKETED PRODUCTS
9. GLOSSARY
10. ILLUSTRATIVE EXAMPLES, CASE STUDIES, AND TEMPLATES

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Categorisation of Changes
• Drug regulatory authorities are encouraged to utilise a system that
incorporates risk-based mechanisms for
• Requesting approval from the regulatory authority,
• Notifying the regulatory authority,
• Recording changes,
• Time frames for evaluation are commensurate with that potential risk
• Important to the efficient use of industry and regulatory resources

• Convergence toward risk-based categorisation of post-approval changes is


encouraged as an important step toward achieving the objectives of this
guidance.

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Established Conditions (EC)

• Established Conditions for manufacturing process include relevant


parameters and attributes that impact product quality or for which an
impact on product quality cannot be ruled out

• Prior approval (Tell and Do): ECs for which a change:


• Could result in a high severity of harm if the control fails
• Is associated with significant risk that is not robustly controlled
• Notification (Do and Tell): ECs for which a change:
• Is associated with moderate or low risks that are robustly controlled
• Non-reportable (Changes made under PQS; notification is not
required):
• Parameters that do not have an impact on product quality
• Information provided only as “complementary” or “supportive”

• Revised EC chapter and illustrative examples


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CTD Sections That Contain Established Conditions
3.2.S.2.2 Description of manufacturing Individual unit operations and their sequence in the manufacturing
process and process controls process
For levels/details of ECs for individual unit operations, in-put and out-put
Reference is made to section 2.2.4.1 – Identification of Established Conditions
for Manufacturing processes
3.2.S.2.3 Control of Materials Starting material specification acceptance criteria and test principle
Raw material/reagent/solvent critical controls
Source of materials (e.g. cell and seed source, raw materials) and specification
of material (e.g. tests, analytical procedures and acceptance criteria (B)
Generation and control of Master - Working Cell Bank / Master, - Working
Seed Virus ect. (B)
3.2.S.2.4 Control of critical steps and Test and acceptance criteria for critical steps and intermediate
intermediates
3.2.S.2.5 Process validation
3.2.S.2.6 Manufacturing process dvt Supporting information
3.2.S.3 Characterisation
3.2.S.3.1 Elucidation of structure and other characteristics
3.2.S.3.2 Impurities Supporting information
3.2.S.4 Control of Drug Substance
3.2.S.4.1 Specification Drug Substance Specification
3.2.S.4.2 Analytical Procedures Reference is made to section 2.2.4.2 – Identification of Established Conditions
for Analytical Methods

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Post Approval Change Management Protocol
(PACMP)

• Currently applicable in US, EU & Switzerland – although limited use


• Intent is that the CPs will be broader and more general in acceptance
criteria to make them much more useful
• Specific change(s) to a single product
• Broader protocols
a) One or more changes to be implemented across multiple products
b) One or more changes to be implemented across multiple products and at multiple sites

• 2 Step process in which the sponsor may propose an accelerated


approval mechanism for step 2
1) Submission of a protocol that describes the proposed change, its rationale,
risk management activities, proposed studies and acceptance criteria
2) After the change if the acceptance criteria in the protocol are met, the firm
submits this information to the regulatory authority according to the
categorisation (classification) in the approved protocol.

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Product Specific Lifecycle Management Strategy

• Reviewed proposals to address issues identified prior to


Osaka
• Agreed on key elements to be included in regulatory
document
• List of EC
• Reporting categories
• PACMPs
• Post-approval CMC commitments

• Anticipated Post-approval Changes section


• At the MAH’s discretion
• Anticipated changes shortly following marketing authorization
e.g. Addition of supplier to ensure product supply
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Pharmaceutical Quality System

• Describe details of change management process


• Deleted section on Corrective Action Preventive Action
(CAPA) due to redundancy with Q10
• Described Relationship between Assessment and
Inspection
• Emphasize importance that inspection information be
available to assessors, and dossier information be
available to inspectors
• Allow for different regional approaches regarding how this
information is communicated between assessors and
inspectors

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Marketed Products

• Reviewed and revised chapter draft in version 6.0


• Q12 regulatory tools are applicable to marketed
products
• Revised draft of changes to analytical methods:
• Existing analytical methods can benefit from analytical
science advances leading to innovation and continual
improvement (Key Theme in Q12 Concept Paper)
• Developed detailed template for the implementation of
changes to analytical methods
• If this template is followed and all criteria are met,
change to analytical method can be made with post-
implementation regulatory notification
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Summary of Key Accomplishments in Osaka

• All remaining issues discussed in detail


• Version 7 was finalized 22nd November, 2016
• Updated Q12 EWG Workplan
• Proposed Interim meeting

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Q12 EWG Workplan

Completion Date Deliverable


November 2016 – • Share ICH Q12 version 7 with constituents
April 2017
April 2017 Interim • Face-to-face meeting to review comments,
Meeting identify and resolve major issues
May/June 2017 • Face–to-face meeting to finalize Step 1 Technical
Document
Nov 2017 • Face–to-face meeting to finalize Step 4 Technical
Document

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Thank You!

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