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Confidential and Proprietary ® Tunnell Consulting , Inc. All Rights Reserved
CMO Compliance Oversight Best Practices
Margit G. Olson, PhD
Group Vice President,
Quality & Compliance Practice Leader
CASSS CMC Forum 21 July 2014
Confidential and Proprietary ® Tunnell Consulting , Inc. All Rights Reserved 2
© 2014
All rights reserved. No part of this document may be
redistributed or reproduced in any form or by any
means, without the prior written permission from
Tunnell Consulting, Inc.
Confidential and Proprietary ® Tunnell Consulting , Inc. All Rights Reserved
Concerns Alignment of Purpose and Vision
Focus on Cost
Multiple Quality Systems
Supplier Management
Changeover and Cleaning
Cross-Contamination
Microbial Contamination
Change Control
Regulatory Notifications
Access to Data, Information, and Direct
Observation
Best Practices Organizational Assessment
Quality Culture Assessment
Quality Agreement
Governance and Communications
Structure
Quality Systems Alignment
Person-in-Plant
Comprehensive cGMP Audits
Product Quality Metrics
Supply Reliability Metrics
Inspection Support
3
CMO Compliance Oversight
Confidential and Proprietary ® Tunnell Consulting , Inc. All Rights Reserved
Increasing FDA Focus on Supplier Quality
Recent industry trends:
» API facilities located in emerging markets
» Complete outsourcing of API, excipient, and packaging to third party
suppliers in emerging markets
FDA expectations:
» “Comprehensive and global assessment of cGMP compliance” (WL)
» Statutory requirement “managing the risk of and establishing the safety
of raw materials, materials used in the manufacture of drugs, and
finished drug products” (2012 FDASIA Part 711, section 501(a)(2)(B))
» Owner cannot outsource the responsibility of Quality Unit (QU) to
approve and release drug components and finished pharmaceuticals
(21CFR Paragraph 211.22(a))
4
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CMO Relationship Management
5
Select the Right CMO Partner
Collaborate Communicate
Measure
Check
Observe
Manage Risks
Remember: Changing your CMO is not trivial!
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Purpose (Due Diligence Focus)
Process (Assessment / Audit Focus)
Product (Metrics and Monitoring)
• Organizational Effectiveness
• Quality Culture
• Quality Systems
• Quality Risk Management
• Product Quality
• Supply Reliability
6
CMO Fitness – Overview of Approach
7 Confidential and Proprietary ® Tunnell Consulting , Inc. All Rights Reserved
Leadership
Quality Oversight
Empowerment
Quality Focused
Culture Throughout
Right-1st-Time
Focus on Customer
• Leadership walks the talk
• Clarity of roles and responsibilities
• QA is independent from operations
• Quality management system
• Accountability
• Right resources with right skills and training to perform the task
• Understanding vision, mission and values
• Quality first
• Lean Six Sigma tools utilized
• Meaningful metrics
• Risk based approach
• Understanding customer needs
CMO Purpose – Due Diligence Focus
Confidential and Proprietary ® Tunnell Consulting , Inc. All Rights Reserved 8
Quality Culture Key Elements of a Successful / Sustainable Quality Culture
Confidential and Proprietary ® Tunnell Consulting , Inc. All Rights Reserved
DRAFT ver1 of 10-May-2011
14
Elements of a Sustainable Quality Culture
9
Elements of a Sustainable Quality Culture
Confidential and Proprietary ® Tunnell Consulting , Inc. All Rights Reserved
Change Control
Deviation Management
Documentation
Sterility Assurance
Validation / Qualification
Analytical Methods
• Changes reported as required
• Change implementation managed to prevent supply impact
• Risk severity level appropriately assigned
• Investigations completed in a timely fashion
• Incorporate all applicable regulatory requirements clearly and without gaps
• In use and followed during key operations
• Monitoring
• Continuing validation
• Monitoring
• Continuing validation
• Robustness
• Monitoring
10
CMO Process – Supplier Assessment Focus
Confidential and Proprietary ® Tunnell Consulting , Inc. All Rights Reserved
Quality Systems Alignment – Best Practices
CMO Quality System is harmonized to global regulations and
expectations
Owner assesses CMO Quality System alignment prior to contract
CMO Quality Systems are not in conflict with Owner Quality
Systems
CMO uses one Quality System acceptable to all Owners
Product-specific requirements, if necessary, may be documented
in additional procedures that are managed on a campaign-basis
(including training)
11
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Quality Agreements
Recommended by the FDA as a tool to delineate responsibilities and
assure the quality, safety and effectiveness of drug products:
» Reference: Draft FDA Guidance May 2013. Contract Manufacturing
Arrangements for Drugs: Quality Agreements
Key Elements:
» Quality unit responsibilities
» Facilities and equipment
» Materials management
» Product-specific terms
» Laboratory controls
» Documentation
» Change control, including subcontractors
Quality Agreements DO NOT relieve either party of their responsibilities
under regulations
12
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Managing Changes – Collaborative Approach
13
CMO:
Transparency of Changes
Owner:
Transparency of Regulatory Filings
Important to
jointly manage
change in order
to avoid impact to
supply reliability
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Responsibility and Accountability – Best Practices
14
Owner
CMO
CMO
CMO
CMO
Delegating
responsibilities to a
CMO does not
diminish Owner’s
responsibilities or
accountability
CMO
Confidential and Proprietary ® Tunnell Consulting , Inc. All Rights Reserved 15
Steering Committee
(issues resolution,
management oversight)
Campaign Planning
and Review
(scheduling, capacity,
materials)
Quality Review
(quality metrics,
change control,
audits, inspections)
Business Review
(quality metrics,
supply metrics,
financial / contract)
VP Operations
VP Quality
VP Procurement
Mgr/Dir Supply Chain
External Manufacturing
External Quality
VP Quality
External Quality
External Manufacturing
VP Procurement
VP Operations
VP Quality
VP Site Operations
VP Corporate Quality
VP Procurement
Mgr/Dir Site Supply Chain
Mgr/Dir Site Manufacturing
Mgr/Dir Site Quality
VP Corporate Quality
Mgr/Dir Site Quality
Mgr/Dir Site Manufacturing
VP Procurement
VP Site Operations
VP Corporate Quality
Owner Representative CMO Representative Joint Governance Body
Governance and Communications – Best Practices
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Quality
» Testing
» Deviation
Management
» Change
Management
» Documents
Person-in-Plant – Best Practices
16
Manufacturing
» Materials
» Equipment
» Process
» Batch Record In-Plant Oversight
» Direct Observation
» Document Review
» Coaching and Mentoring
Ow
ner
Location
CM
O L
ocation
During C
am
paig
n
Supply Chain
Management
» Planning
» Scheduling
» Metrics
Confidential and Proprietary ® Tunnell Consulting , Inc. All Rights Reserved
Comprehensive cGMP Audits – Best Practices
17
Production
System Quality
» Identity
» Strength
» Purity
» Safety
» Effectiveness
Quality by Design
CAPA
Change Control
Quality Risk
Management
Responsibilities
of the Quality
Unit Process for Routine
Audits and For-Cause
Audits are Detailed in
the Quality Agreement
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Inspection Support – Best Practices
Owner knows the product, process, methods, and specifications
best
Owner support for inspections can help address issues that may
emerge during the inspection more effectively
Potential conflicts due to multiple owners products involved in
inspection must be managed carefully
How to manage regulatory inspections needs to be anticipated
and detailed in the Quality Agreement
18
19 Confidential and Proprietary ® Tunnell Consulting , Inc. All Rights Reserved
Annual Review
Pharmacovigilance / Complaints
Specifications
Process Performance
Supplier Management
Supply Chain Management
• Timely
• Major / critical / OOS frequency
• Frequency / severity
• Investigation / reporting
• Based on product design
• Meaningful clinical surrogates
• 4 sigma – goal
• Cycle time
• Supplier qualification
• Supplier risk management
• Change control
• CMC management
CMO Product – Metrics and Monitoring Focus
Confidential and Proprietary ® Tunnell Consulting , Inc. All Rights Reserved
Key Success Factors
Selecting the right CMO – for the long term
Effective governance model
Meaningful Quality Agreement
Collaboration
Managing change proactively
Transparency of data and information
An actively engaged owner
Communicate, communicate, communicate
Comprehensive cGMP audits
Inspection support
Ongoing monitoring of metrics
20
Confidential and Proprietary ® Tunnell Consulting , Inc. All Rights Reserved 21
Confidential and Proprietary ® Tunnell Consulting , Inc. All Rights Reserved 22
Questions?