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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

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CMO Compliance Oversight Best Practices

Margit G. Olson, PhD

Group Vice President,

Quality & Compliance Practice Leader

CASSS CMC Forum 21 July 2014

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© 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.

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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

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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

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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

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Quality Culture Key Elements of a Successful / Sustainable Quality Culture

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DRAFT ver1 of 10-May-2011

14

Elements of a Sustainable Quality Culture

9

Elements of a Sustainable Quality Culture

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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

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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

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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

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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

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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

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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

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Questions?