1 of 48 Quality System Model ICH Q10. 2 of 48 Agenda What is ICH Q10 History Why do we need a ‘modern effective Quality System’? The elements and enablers.

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Quality System ModelICH Q10

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Agenda

What is ICH Q10

History

Why do we need a ‘modern effective Quality System’?

The elements and enablers of a Quality System

Model of Pfizer’s Quality System

Review the website

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Pharmaceutical Quality System

The ICH Q10 document on Pharmaceutical Quality System was recommended for adoption to the regulatory bodies of the EU, Japan and USA, June 2008.

The document establishes a tripartite guideline describing a model for an effective quality management system; a management system to direct and control a pharmaceutical company with regard to quality.

The specifics of a pharmaceutical quality system vary depending with the stage of the product lifecycle, but the overall principles and components are the same.

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History

Evolution of regional GMPs 1970s

Evolution of ISO 9000 approaches 1980s

FDA 21st Century initiative 2002

ICH Quality Vision / Q8, Q9 2003

Guidance for Industry - Quality System Approach to Pharmaceutical cGMP Regulations

2006

ICH Q10 Pharmaceutical Quality System 2008

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Comprehensive Model

Based on International Standards Organization (ISO) quality concepts

Includes applicable GMP regulations

Complements both– ICH Q8 Pharmaceutical Development,

– ICH Q9 Quality Risk Management

Not intended to create new expectations beyond current regulatory environment

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A ‘Modern Effective Quality System’?

Good business practice! Significant changes in external business

environment– Fewer new products / ‘blockbusters’– Reduced margins / greater competition / low-cost sources– Focus of efficient, effective organizations– Lean processes

Pharmaceutical industry is behind other industries in Quality Management philosophies / practices

– Marketed products ARE safe and efficacious– BUT costs of quality are high– Often reactive, not designed-in / preventative

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Why do we need a ‘Modern Effective Quality System’?

Implementation should – Facilitate innovation and continual improvement

Inflexible regulatory environment Focus on Compliance, not Science and Risk-Based approach Industry margins did not provide drive for change

– Strengthen the link between pharmaceutical development and manufacturing

GMPs do not provide a ‘full modern’ Quality System– Originated in 1970s – incremental additions– ISO Quality Management thinking not embedded– Need to be complemented with Q8 and Q9

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GMP

TechnologyTransfer

PharmaceuticalDevelopment

CommercialManufacturing

Investigational Products

Management Responsibilities

Process Performance & Product Quality Monitoring SystemCorrective Action/Preventive Action (CAPA) System

Change Management SystemManagement Review

Knowledge Management

Quality Risk Management

Quality System

Elements

Enablers

ProductDiscontinuation

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An Effective Quality System

GMPs

Management Responsibility

Elements - Continual Improvement

Enablers – Knowledge and Risk Management

Lifecycle approach

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GMPs




Lifecycle approach

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Essential component of a Quality System

Not just about compliance – Visible leadership to establish and maintain a company wide

culture and commitment to Quality and improvement– Monitor performance of the Quality System for both internal

and outsourced activities

Quality can not be owned only by the ‘Q’ Unit

– Management is accountable– But independent assessments are key

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Management Commitment

Quality Policy

Quality Planning

Resource Management

Internal Communication

Management Review

Outsourced Activities

Change in Product Ownership

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Management Commitment

Signed Quality Commitments are commonplace and are not indicative of Management Commitment

What is Indicative?– Plant Managers aware of the issues– Management Team that works together– Quality as a Trusted Partner

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Clear Roles, Responsibilities, Processes

Quality Policy: Sets the standards and direction of organization

Quality Planning: Converts into objectives & plans

Resources: Allocations and competence

Communication: Quality items to appropriate audience

Management Reviews– Product and Process performance – Quality System performance

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Quality Policies

Comprehensive and Balanced

Flexibility/adaptability defined is consistent

Interconnectivity of a Quality System requires a comprehensive approach in the design

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Quality Plans

Written Quality Plans are becoming more common

What is Indicative?– Quality Planning Process is dynamic

– Defined process for evaluating issues to bring into the quality planning process.

– Tracking progress against an agreed upon Quality Plan

– Adequate resources are made available

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Resource Management

Adequate resources are made available

Resources include time, money, equipment and people

What is Indicative?– Clear prioritization of resources in line with – Reasonable number of projects with – Realistic commitment time frames

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Internal Communication

Issues will occur

Escalation of issues, actions, decisions and impact

What is Indicative?– Trusting relationship between manufacturing & quality

assurance– Understanding of why timeliness is important– Communication uses defined processes and is transparent– Escalation of issue is not viewed as punitive– The Operations Team is wholly accountable– Adequate resources are made available

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Management Review

Grounded in the device regulations, periodic Management Reviews are becoming more common

What is Indicative?– Linkage between Quality Plan and Management Reviews– Linage between Key Quality Indicators– In a hierarchal company, how information flows– Depth and frequency of Reviews– Attendance at the Management Review– How is the information used?

Opportunity to align priorities and resources Not punitive

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Outsourced Activities and Purchased Materials

Pharmaceutical firm (i.e., Management) is ultimately responsible to assure processes are in place

Process must be in place to:– Assess suitability of contractors / suppliers before use– Ensure use of approved suppliers and a defined supply chain– Define responsibilities and communication processes for

quality related activities– Review performance and make improvements

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GMPs


Elements - Continual Improvement– Process Performance and Product Quality– Corrective Action / Preventive Action– Change Management– Management Review


Lifecycle approach

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Continual Improvement

Continuous Improvement of product quality is a key objective of the quality system, irrespective of the stage of the lifecycle.

Four specific elements of the quality system support achieving continuous improvement:– Process performance and product quality monitoring– Corrective action and preventative action– Change management– Management review of process

performance and product quality

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Product Quality and Process Performance

Use knowledge, Quality by Design, Product and Process understanding and QRM to set Control Strategy– What and when to monitor / measure / test– Based on critical product quality attributes and critical

process parameters to deliver them Reduce and control variation to appropriate levels Confirm and maintain a state of control

– Feed-back and Feed-forward loops

Drive continual improvement Continual verification

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CAPA System

Investigation of non-conformances– Reactive → deviations, rejections, complaints, recalls,

observations from audits and inspections– Proactive → feedback from trends

Structured investigations to seek root cause

Use QRM to ensure degree and formality is commensurate with level of risk

Should result in enhanced knowledge and improvement

Not just reacting to non-conformances

Focus on preventative actions

Need effective tracking / follow up processes

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Change Management System

Change can be good!

Proactively driven by outputs from monitoring / trending / improvement / innovation

– Not just by reacting to problems

Use expert teams and knowledge to evaluate and set success criteria

Use QRM commensurate with level of risk

Consider impact on regulatory filings

Undertake in timely and effective way and tracked

Assure no unintended consequences

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Management Review

Process Performance and Product Quality

Results from inspections and assessments

Periodic quality reviews– Customer satisfaction – complaints, recalls– Conclusions of process performance and product quality

monitoring – Effectiveness of process and product changes

Appropriate actions– Improvements to manufacturing processes– Training and/or realignment of resources– Capture and share knowledge

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Continual Improvement of the Quality System

Assessment of the Quality System against– Internal factors (audits, CAPAs, complaints, recalls, etc.)– External factors (regulatory inspectional findings)– Emerging regulations– New technology– Change in business strategies

Outcomes of the Assessment– Improvements communicated throughout a business– Resource reallocation– Changes in policies, practices

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GMPs




Lifecycle approach

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Systematic and lifecycle approach to acquiring, analyzing, storing and disseminating knowledge on products, processes, components

Provides the basis for science and risk-based approaches in the Quality System– Product and process development– Manufacturing– Change management – Continual improvement

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Quality Risk Management (Q9)

Essential, integrated part of Quality System– The evaluation of the risk to quality should be based on scientific

knowledge and ultimately link to the protection of the patient; and– The level of effort, formality and documentation of the quality risk

management process should be commensurate with the level of risk

Proactive use to identify and control risk

Support decision through lifecycle

Integrate into key parts of Quality System

e.g., change management, CAPA, GMPs – Validation, etc.

Help set meaningful specification / control parameters to ensure product quality control requirements are met

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Key to an Effective Quality System

GMPs


Continual Improvement



Lifecycle approach

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Lifecycle Approach

Holistic and cover the product lifecycle– Design and Development– Manufacturing– Withdrawal

Challenges and removes some traditional organizational silos

– Within industry– Within Regulatory Agencies– With outsourcing partners

Application of Quality System Elements at each stage of the Product Lifecycle

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GMP

TechnologyTransfer





Process Performance & Product Quality Monitoring SystemCorrective Action/Preventive Action (CAPA) System

Change Management SystemManagement Review



Quality System

Elements

Enablers


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Pharmaceutical Development Stage


Design a product and its manufacturing process to consistently deliver the intended performance and meet the needs of patients, health-care professionals, and regulatory authorities

Develop knowledge of product and processes

Utilize Quality Risk Management principles to identify and control risk to product quality

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Technology Transfer Stage

Transfer product and process knowledge between development and manufacturing or between manufacturing units.

Develop further knowledge

Refine Quality Risk Management and control strategies

TechnologyTransfer

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Commercial Manufacturing Stage

Provide product with appropriate quality attributes consistently in a state of control and facilitating continual improvement.

Continually expand product and process knowledge

Adjust the Quality Risk Management and control strategy as needed.


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Product Discontinuation Stage

Manage the terminal stage of the product lifecycle using a pre-defined approach – product complaint

management – stability studies

documentation


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GMPs over the Product Lifecycle

Compliance with applicable GMPs is the foundation of the quality system

The intended use and market of any material produced during the lifecycle must be understood and the appropriate GMPs must be met

Applicable GMPs must be incorporated into the quality system for each stage of the lifecycle

– Documentation– Quality Unit Responsibilities– Facilities and Equipment

GMP

TechnologyTransfer





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Management Controls - Product Lifecycle

Essential over all stages of Product Lifecycle

Includes: Management Commitment, Policy and Planning, Resource Management, Review and Communication

Extends to management controls of outsourced operations

TechnologyTransfer




Management Controls

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Monitoring– Use to provide data and knowledge

CAPA– Use methodology to identify and implement

improvements

Change Management– Change is inherent part of this phase– Change must be documented– Increase formality as development progresses

Management Review– Use to ensure the adequacy of product and

process design


Application of Quality System Elements

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Monitoring– Use to provide indication of how process

performs in manufacturing

CAPA– Used to make improvements to development and

to commercial manufacturing

Change Management– Proactively manage change and thoroughly

Management Review– Use to ensure the developed process can be

manufactured at scale


TechnologyTransfer

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Monitoring– Well-defined monitoring of process performance & product

quality to assure performance within a state of control

CAPA– CAPA methodology must be used and the effectiveness

evaluated

Change Management– Formal change management must be used– Must have oversight by the quality unit

Management Review– A structured review which identifies and

supports continual improvement



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Monitoring– Relevant monitoring should continue (e.g., completion of

stability studies, and product compliant analysis)

CAPA– Should be used to determine and address any impact on

product remaining on the market and on any other products

Change Management– Should continue for any appropriate changes– Oversight by quality unit

Management Review– Continue reviews and include such activities as

stability and complaints



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Enablers Over the Product Lifecycle

Knowledge increases throughout the product lifecycle and must be captured, transferred and used systematically

Quality Risk Management provides proactive approach to identifying and controlling risks throughout the lifecycle

TechnologyTransfer






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Framework of a Quality System

Achieve Product Realization– From the start of an idea for a product, to the culmination of

the product available for the patients.– Manufacturing and release of finished goods so that prodcut

is available for patients

Establish and Maintain a State of Control– Effective monitoring & control systems are in place which

assure continued process performance and prodcut quality– A confidence when scheduling production, product will be

available according to planned dates.

Facilitate Continual Improvement– Reducing project and process variability– Looking for areas of improvement not

self-evident but important

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Summary

The Quality System defines our Quality Culture– Defines the responsibilities and authorities– Defines communication models to all levels in the

organization– Provides a clear governance model defining how

quality decisions are made– Monitors to assure necessary resources are available

for completion of quality plans– Assures alignment of the quality

objectives with the business strategy– Makes life easier

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Pfizer Quality System Model

http://ecf.pfizer.com/sites/PfizerQualitySystem/Wiki%20Pages/Home.aspx

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References

International Conference on Harmonization, Harmonized Tripartite Guideline, Pharmaceutical Quality System, ICH Q10, Step 4, 04June2008

Kaufman, Zena G., Divisional VP, Quality Center of Excellence, Abbott, “Considerations for Designing a Pharmaceutical Quality System”, Nov 2008

Allen, Barbara, Director, Global Quality Systems, Eli Lilly and Company, “Quality Systems over the Product Lifecycle”, Nov 2008

Wilkinson, Neil, David Begg Associates, “The Elements of a Modern Effective Pharmaceutical Quality System”, Nov 2008

1 of 48 Quality System Model ICH Q10. 2 of 48 Agenda What is ICH Q10 History Why do we need a ‘modern effective Quality System’? The elements and enablers.

Documents

modern quality system

costs of quality

ich q9 quality risk

outsourced activities

q9 slide

website slide

key slide

preventative slide