Introduction and Update on ICH Q12 Guideline Dr Frank Montgomery, Global Head, Reg CMC, AstraZeneca/Medimmune Q12 EFPIA Expert

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1 Introduction and Update on ICH Q12 Guideline Dr Frank Montgomery, Global Head, Reg CMC, AstraZeneca/Medimmune Q12 EFPIA Expert CMC Strategy Forum Japan th Dec 2016

2 Outline Q12 Scope and Objectives Progress in Osaka Overview of Q12 Q12 EWG workplan 2

3 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 postapproval 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 3

4 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), 4

5 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 5

6 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 2/14/2017 6

7 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. 7

8 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 8

9 CTD Sections That Contain Established Conditions 3.2.S.2.2 Description of manufacturing process and process controls Individual unit operations and their sequence in the manufacturing process For levels/details of ECs for individual unit operations, in-put and out-put Reference is made to section 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 S S.3.2 Characterisation Elucidation of structure and other characteristics 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 Identification of Established Conditions for Analytical Methods 9

10 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. 10

11 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 11

12 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 12

13 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 postimplementation regulatory notification 13

14 Summary of Key Accomplishments in Osaka All remaining issues discussed in detail Version 7 was finalized 22 nd November, 2016 Updated Q12 EWG Workplan Proposed Interim meeting 14

15 Q12 EWG Workplan Completion Date November 2016 April 2017 April 2017 Interim Meeting Deliverable Share ICH Q12 version 7 with constituents Face-to-face meeting to review comments, 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 15

16 Thank You!