Quality Systems and Risk Management (Q9

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Quality Systems and Risk Management (Q9 Q10)

• Advisory Committee of the Office of
  Pharmaceutical Science,
• Center for Drug Evaluation and Research, USFDA
• October 5, 2006
• Frederick Razzaghi
• CHPA

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Agenda

• Introduction
• Quality Risk Management Q9
• Relation of Q9 to Q10
• The guidance
• Next step

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• Establishing the science to help settle
  questions.
• (developing the knowledge)
• Doing what is important.
• (Can we afford to do everything?)

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Doing what is important(Risk based)

• Non-science and precedence based Requirements
  have an accumulative effect.
• Overwhelm organizations.
• Organizations can not answer the value question!
• Highlighted in part by the current period of
  dwindling resources and demand for faster and
  better outcomes.

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Risk based

• Quality Risk Management
• Using established knowledge to determine what is
  important

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What is Q9

• Q9 is a systemic process oriented approach to
  decision making that is intended to be practical,
  applicable, predictive, flexible, consistent and
  integrated.
• The ICH Q9 document
• Main body explains the What?
• Annex (I) give ideas on the How?
• Annex (II) give ideas on the Where?
• It is designed to be implemented by industry and
  regulators
• Pharmaceutical development (ICH Q8) and Quality
  Systems (ICH Q10) will facilitate the What?,
  How? and Where?
• It helps to simplify and prevent overly
  prescriptive and unnecessary requirements.

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What does Q9 offer

• Quality risk management serves as a foundation to
  support, other ICH Quality documents and
  complement best quality practices, requirements,
  standards, and guidelines within industry and
  regulators. It specifically provides guidance on
  the principles and some of the tools of quality
  risk management to enable consistent risk based
  decisions across the product lifecycle.

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Reasons for writing Q9

• The circumstances affecting regulators industry
• Increasing external requirements
• Increasing demands and costs
• Growing complexity and scope of risks
• Empowerment Flexibility
• Master complexity and streamline decision making
• Proactive disclosure and build trust and
  understanding
• Improve communication through sharing best
  practice and science based knowledge
• Convert data into knowledge

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Reasons for writing Q9

• Establish a common understanding of Quality Risk
  Management (QRM) among industry and competent
  authorities
• Facilitate moving to the Desired State
• By enhancing communication and transparency
• Moving from fire fighting to proactive
  management of risk

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Benefits of risk management

• Enhanced public confidence in decision making on
  pharmaceutical quality
• Promotes more effective use of regulator and
  industry resources
• Establishes systematic and better-informed
  decision making.
• Increases knowledge of risk
• Fosters quality by design and continuous
  improvement

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Benefits of risk management

• Understand the factors that impact regulators and
  industry operations.
• Create awareness and a culture
• Supports pro-active behaviour
• Open factual dialogue
• Make decisions traceable and consistent
• Provide assurance
• Risks are adequately managed
• Compliance to external and internal requirements
• Recognise risks at a desired level
• Zero risk not possible

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Q9 links back to patient safety

• .

Opportunities to impact risk using quality risk
management
Design
Process
Materials
Manufacturing
Facilities
Distribution
Patient
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Q9 was constructed using knowledge gained from
established standards

• ISO/IEC Guide 73 2002 - Risk Management -
  Vocabulary - Guidelines for use in Standards
• ISO/IEC Guide 511999 - Safety Aspects -
  Guideline for their inclusion in standards
• WHO Technical Report Series No 908, 2003 Annex 7
  Application of Hazard Analysis and Critical
  Control Point (HACCP) methodology to
  pharmaceuticals
• GAMP Good Practice Guide ISPE, 2005 A risk-based
  approach to compliant electronic records and
  signatures
• ISO 149712000 - Application of Risk Management
  to Medical Devices

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Developing the knowledge(Science based)

• The Q documents are a part of the knowledge.
• Establishing new knowledge
• Combining basic disciplines practices
• Core Engineering, Pharmaceutical sciences,
• Gap Technology, Economics, Management (risk, .)

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Q9 integrated into Q10
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ICH Q documents

• Q1 Stability
• Q2 Analytical Validation
• Q3 Impurities
• Q4 Pharmacopoeias
• Q5 Quality of Biotechnological Products
• Q6 Specifications
• Q7 Good Manufacturing Practice
• Q8 Pharmaceutical Development
• Q9 Quality Risk Management
• Q10 Pharmaceutical Quality Systems

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Q9 enables quality systems to address the
following problems

• Product may not be available to patients
• Increase the potential for release of
  unacceptable product
• Delay in new product introductions
• Delays in the implementation of changes and
  improvements
• Recall of drugs
• Inefficient allocation of resources

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Q8, Q9 and Q10 are aligned with the new approach

• GMP Workshop in July 2003 5 year vision
• Develop a harmonised pharmaceutical quality
  system applicable across the life cycle of the
  product emphasizing an integrated approach to
  quality risk management and science
• Consequent ICH Expert Working Groups (EWG)
• ICH Q8, on Pharmaceutical Development, doc.
  approved Nov. 2005
• ICH Q9, on Quality Risk Management, doc.
  approved Nov. 2005
• ICH Q10, on Quality Systems, topic accepted 2005

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How Q9 interacts with Q8 and Q10

• envision

Risk from Manufacturing site
High
Q10 Pharm. Quality Systems
Low
Q8 Pharmaceutical Development
Low
High
Product / Process Risk
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New Q distinctions
Pharmaceutical Development (Q8) Past Data
transfer / Variable output Present Knowledge
transfer / Science based / Consistent output
Quality Risk Management (Q9) Past Used, however
poorly defined Present Opportunity to use
structuredprocess and integrated thinking
Pharmaceutical Quality Systems (Q10) Past GMP
checklist Future Quality Systems across product
life cycle
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New Q distinctions
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The Guidance

• Process
• Formula
• Relationship to uncertainty
• Tools
• Application integration

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The process
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Dimensions of a risk based approach

• .

Parameters for evaluating risks
high
probability
medium
detectability
low
risk
severity
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Risk and Uncertainty

• .

Tomorrow ?
Upper Specification Limit (USL)
Process Parameter ?
Lower Specification Limit (LSL)
Time ?
today
RISK Control options are scenarios for risk
management. Note that this scenario shows the
best estimate is below the USL.
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Risk and uncertainty

• Components of uncertainty
• Limitations of human knowledge
• Absence of established science.
• Limitations of Technology

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Some Risk assessment tools

• Failure Mode Effects Analysis (FMEA)
• Failure Mode, Effects and Criticality Analysis
  (FMECA)
• Fault Tree Analysis (FTA)
• Hazard Analysis of Critical Control Points
  (HACCP)
• Hazard Operability Analysis (HAZOP)
• Preliminary Hazard Analysis (PHA)
• Risk ranking and filtering

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Application Integration
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Q9 applies across the lifecycle

• .

Research
Preclinical Phase
Clinical Phases
Launch
Manufacturing Distribution
Safety
GLP
GCP
Efficacy
GMP
Quality
ICH Q9
GDP
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Integrating QRM into product life cycle
Gain experience
Analyse root cause Continuous improvement
(Risk of) Failure ?
Manufacture
Quality Risk Management(QRM)
Do, what you say
Improve it
Update information
Approval
Say, what you do
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Integration into operations industry regulators

• Foundation for science-based decisions
• Degree of rigor and formality commensurate with
  the complexity and/or criticality of the issue
• Implement QRM principles when updating existing
  guidelines

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Application

• Regulatory operations
• Inspection and assessment activities
• Internal systems

• Industry operations
• Development
• Facilities, equipment and utilities
• Materials management
• Production
• Laboratory control and stability testing
• Packaging and labelling

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Application

• Integrated quality management
• Documentation
• Training and education
• Quality defects
• Auditing / Inspection
• Periodic review
• Change management / change control
• Continual improvement

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Application

• Quality risk management is intended to enable and
  enhance compliance with regulatory requirements
  and science-based decisions when integrated into
  quality systems.
• It is also meant to be applied where it is
  practical and feasible.

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Implementation of Q9 can help identify weak links
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Definitions

• Quality Degree to which a set of inherent
  properties of a product, system or process
  fulfills requirements
• Risk combination of the probability of
  occurrence of harm and the severity of that harm
• Quality Risk management Systematic process for
  the assessment, control, communication and review
  of risks to the quality of the drug (medicinal)
  product across the product lifecycle

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Way Forward

• Review
• Implementation

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Implementation

• Work to Adapt existing structures, organizations
  and systems
• Raise awareness of rationales for decision making
• Education Develop training
• Do not create new requirements

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Implementation

• Work to Improve communication and transparency
• More specific projects (e.g. DMFs)
• Academic collaborations

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Review and determine gaps

• Examine need for additional guidance (e.g.
  Excipients, Packaging/Distribution)
• Adapt and update existing requirements using
  quality risk management

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Thank you