Regulatory Perspective - Yukio Hiyama
Regulatory Perspective - Yukio Hiyama
Regulatory Perspective - Yukio Hiyama
APEC LSIF ICH Quality Guidelines Q8 and Q9 Challenges of Implementations COEX, Seoul, September 13-14, 2007
Yukio Hiyama Chief, 3rd Section, Division of Drugs National Institute of Health Sciences, Ministry of Health, Labour and Welfare JAPAN
E mail: hiyama@nihs.go.jp
Presentation Outline
Pharmaceutical Affairs Law (PAL) changes, ICH discussion and MHLW studies Quality Regulations under the Revised Pharmaceutical Affairs Law Commitment of Manufacturing Process as Approval Matters and Role of ICH Q8, Q9 and Q10
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Expected Outcome
For Industry Establishment of quality management system from development to post-marketing For regulatory authority Improvement of the approval review system by integration of the review and the GMP inspection To concentrate on higher risk products The establishment of effective, efficient, and streamlined quality regulation
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Includes;
- Risk management - Technology transfer - Change control, etc.
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2004
2005
2006
2007
JAPAN
Revised PAL enforced GMP guidance Approval matters policy PMDA established Inspection policy
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Pharmaceutical Affairs Law(PAL), ICH Q8/Q9/Q10 and MHLW Grant Regulatory Science Studies
PAL regulation changes
2002 Revised PAL published 2004 PMDA established New GMP standards 2005 Approval matters policy Revised PAL enforced Inspection policy published 2006 Product GMP guidance
ICH discussion
2002 CTD Q&A 2003 GMP workshop in Brussels Q8 and Q9 started 2004 Q8 reached step 2 2005 Q9 reached step 2 Q8 and Q9 reached step4 Q10 started 2007 Q10 reached step 2
GQP
Manufacturer A (API) In country X
Market Release
Manufacturers
Marketing Approval
GQP
GMP
Bulk Products
GMP
Final products
Manufacturers
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A Unique System
Contents provided in the NDA application form are dealt with as matters subject to approval. Contents described in approval letter are legal binding approval matters.
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Approval Matters
General name (for drug substance) Brand name Composition Manufacturing process, including control of materialsNEW under rPAL Dosage and administration Indications Storage condition and shelf-life Specifications and analytical procedures
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Manufacturing Process: Principles and end points of the critical manufacturing steps with key operational parameters of commercial scale will become approval matters. Principle and quality end point for each manufacturing step will be subject to pre-approval review. In-process procedure is pre-approval matter if it replaces final specification test.
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Distinctions between Partial Change Approval Application and Minor Change Notification
Partial Change Approval Application
Change in the principle of unit operation of critical process Change in process control criteria as quality endpoint criteria
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CTD-BASED APPLICATION Marketing Application Partial Change (application) Minor change (notification)
Module 2
Application form
Specification Manufacturing (Process Control)
Low
Quality Information
Module 3
Quality Information
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Manufacturing Approval
2-Step process
GMP Requirement
inspection
( Renewal) Every 5 years
inspection
(5 yearly renewal)
Marketing Approval
Start marketing
Partial License
North America
Asia
Others
Total
17 1 10 0 28
21 7 6 6 40
0 0 1 0 1
2 0 3 0 5
0 0 1 0 1
40 8 21 6 75
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Total
Role of Module 2
Module 2 bridges NDA Application Form (approval matters) and Module 3 Module 2 is one of the key review documents
Reviewers evaluate Module 2 and then narrow down into Module 3, 4, or 5 when they need more detailed information. Module 1 and 2 together with reports written by reviewers are evaluated in Pharmaceutical Affairs and Food Sanitation Council.
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Specifications Analytical procedures Pharmaceutical Development Manufacturing Process batch analyses Justification etc. Raw data
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Review
Review
Minor Change
Application form
Approval letter
Commercial Production
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Merely shows an example of description for each module 2 section and just a reference for an applicant to prepare QoS. Not covers all information required for each NDA, nor shows acceptance criteria for each categories. NEED more description on pharmaceutical development and on justification of manufacturing process according to ICH Q8 and the revised PAL.2006-2008 MHLW Approval matters study group
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Opportunities by Q9
Integration to Industrys Pharmaceutical Quality Systems (ICH Q10 will address this area) Integration to Regulatory Authorities work process (e.g. QS for GMP inspectrate) Integration to Guidance Development and Pharmacopoeia Policy (Government and Industry joint effort)
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Formulation knowledge
(Risk Analysis)
Process knowledge
(Risk Review)
(Risk Review)
Risk-based classification
(Risk Evaluation)
CONTROL STRATEGY
(Risk Reduction)
Organization of PMDA
Offices of General Affairs, Planning & Coordination Center for Product Evaluation
-Review: New Drugs, Medical Devices, Biologics, Generics and OTC
PMDA
Office of Compliance and Standards
Office of Safety
-Reviews and Related Operations / Postmarketing Safety
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ns icatio if Spec
Manufacturing
Specifications
Manufacturing
Former
Revised Revised
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