ICH Q10
Pharmaceutical Quality System (PQS)
© CBE Pty Ltd
This training program is copyright to CBE Pty Ltd and may not be modified, reproduced,
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© CBE – DCVMN 010 V2 Introduc)on
1
Three Day Program – 1st day
Wednesday Morning
§ Introduction to ICH Q10 – Pharmaceutical Quality System
§ Management of Deviations/Investigations and CAPA
Wednesday Morning
§ Change Management
§ Equipment Qualification
Wednesday Afternoon
§ Practical Exercises (Deviations and CAPA)
§ Practical Exercises (Change Management)
§ Practical Exercises (Equipment Qualification)
© CBE – DCVMN 010 V2 2
Three Day Program – 2nd Day
Thursday Morning
§ Controlling Cross Contamination – Biologics Facility
§ Risk Management
Thursday Morning
§ Supplier Assurance Programs (Qualifying Suppliers)
Thursday Afternoon
§ Practical Workshop Exercise
© CBE – DCVMN 010 V2 3
Three Day Program – 3rd Day
Friday Morning
§ Viral Inactivation – Industry requirements
§ Cleaning and Cleaning Validation in a Biologics Facility
§ Microbiological Control
Friday Morning
§ Effective Internal Auditing
Friday Afternoon
§ Practical Workshop Exercise
© CBE – DCVMN 010 V2 4
PQS - Module Outcomes
On completion of this module the participant should be able
to:
§ Interpret ICH Q10 expectations
§ Develop a Quality Manual (QM) template and Quality
Policies (POL)
§ Design a pharmaceutical quality system using the QM
template
§ Strengthen GMP compliance systems
© CBE – DCVMN 010 V2 Compliance by Design 5
PQS Module Topics
Basics
of
Quality
and
Compliance
How
does
a
Pharmaceu9cal
Quality
System
fit
together
?
–
ICH
Q
10
Devia9ons
CAPA
and
Con9nuous
Improvement
© CBE – DCVMN 010 V2 Introduc9on
Major International Codes of GMP
§ PIC/S Guide to Good Manufacturing Practices - PE 009 - 2014
§ EU Guide to Good Manufacturing Practices (Eudralex Ch 4)
§ World Health Organisation (WHO) c GMPs
§ United States - FDA CFRs Part 21
§ CFR 210/211 for Drugs and Biologics - current GMPs
§ CFR 820 Quality Systems for Medical Devices - current GMPs
§ ICH Q7 GMP for Active Pharmaceutical Ingredients
§ Canadian cGMP (aligned with PICs)
§ ISO 13485 : 2003 - Medical Devices
§ ICH Guidance Documents – Technical Standards
© CBE – DCVMN 010 V2 Regulatory
Agencies
Some Useful Reference Documents
§ EU/PICs/TGA cGMPs – Chapter 1 – Quality
Management
§ ICH Q10 - Pharmaceutical Quality System
§ ICH Q8 – Pharmaceutical Product Development
§ ICH Q9 - Risk Management in Pharmaceuticals
§ FDA Quality Systems Approach to Pharmaceutical
CGMP Regulations (9/2006)
§ GHTF - GHTF/SG3/N15R8 - Implementation of risk
management within a Quality Management System
© CBE – DCVMN 010 V2 8
Significant Changes
40 Year History of Pharmaceutical Quality
Management
1972
Quality Control
Sterile Validation 1975
Quality Assurance 1975
General Validation 1980s
Quality Management 1990s
Risk Management 2004+
PQS – ICH Q8/Q9/
Q10
© CBE – DCVMN 010 V2
9
Quality Control and Sampling
Inward
Unit
Op.
Supplier
Goods
QC
#1
C
of
A
QA
Release
Finished
Unit
Op.
Product
QC
#2
Sampling
Plan
Lot
Size
=
1000
Sample
size
=
20
(2%)
© CBE – DCVMN 010 V2 10
Quality and Compliance
§ Quality refers to:
§ Product Quality – meeting agreed specifications
§ Quality Systems – planned and deployed processes
(systems) used to monitor, report and take corrective
actions
§ GMP Compliance refers to:
§ Identification, documentation and deployment of GMP
obligations
§ Ongoing verification that GMP obligations are being
met, or not.
© CBE – DCVMN 010 V2 11
Compliance Programs
Execu9ve
Commitment
Objec)ves
Iden)fy
Obliga)ons
Gap
Analysis
Assign
Responsibility
Competence
&
Compliance
Training
Compliance
Focused
Behaviours
Controls
to
Manage
Iden)fied
Obliga)ons
Performance
Monitored,
Measured,
Reported
Demonstrate
Compliance
(documents,
records
prac)ces)
Con)nuous
Improvement
and
Management
Review
© CBE – DCVMN 010 V2 12
PQS/Compliance Gap Analysis
§ identify and assess compliance obligations and potential
failures - not just GMP
§ Include external and internal obligations in gap analysis
§ Prioritize gaps using use risk principles
§ Establish a compliance register or database
§ Develop a PQS remediation/ improvement plan
§ Establish a system to monitor external changes in PQS
& compliance obligations e.g Legislation, cGMP updates
…
© CBE – DCVMN 010 V2 13
Things to look for in the gap analysis
Element What to look for
Deviation, OOS System How effective are the failure investigations
CAPA System Does the CAPA system look at root causes or just
symptoms
Audit Programs Do the audit look at symptoms or root causes – are
issues effectively resolved
Reviews, Trends and Are management reviews and APQRs detailed enough
Reporting and responsive
Training Do training programs address compliance obligations
Management Is compliance a KPI within position descriptions
Responsibility
Prioritisation and Is there a mechanism for resource prioritization e.g..
Resource Allocation risk based
Change Management Does change management include compliance review
© CBE – DCVMN 010 V2 14
How does a Quality System Fit Together ?
Change
Incidents
&
Quality
Training
Control
Devia9ons
Control
Document
Control
Valida9on
Failure
Inves9gat’n
Lab
OOS
Produc9on
Management
CAPA
Review
Control
Supplier
Assurance
Annual
Product
Monitoring
&
Review
Trend
Analysis
External
Complaints
&
Internal
Audits
Recall
Regulatory
Pharmacovigilance
© CBE – DCVMN 010 V2 15
“Linkage” of the QMS system
elements
§ Each of the major elements are inter - linked to other
elements
§ Elements either drive or feed others or vice versa
§ Linkage of related elements is critical to quality
management oversight
§ Without strong linkage identification of problem root cause is
difficult
§ With linkages, problems and root causes can be traced through
the linked system
§ Linkage enables “escalation” of significant issues
© CBE – DCVMN 010 V2 16
16
FDA Six Control Systems – Inspection 7356.002
• Batch
compounding,
dosage
form
produc)on,
• In-‐process
sampling
and
tes)ng,
Produc9on
System
•
•
Process
valida)on.
Master
batch
records
and
manufacturing
procedures.
• Change
control,
reprocessing,
batch
release,
• Annual
product
review
• Control
of
finished
products,
components,
water,
gases,
containers
and
closures.
• Valida)on
protocols,
• Product
defect
evalua)ons
Material
System
• Valida)on
of
computer
inventory
control
• Drug
storage,
distribu)on
controls,
records.
• Evalua)on
of
returns.
• Buildings
and
facili)es
&
maintenance
Quality
Equipment
/
Facili9es
•
•
Equipment
qualifica)ons
(IQ/OQ);
Equipment
calibra)on;
Assurance
•
•
Cleaning
and
valida)on
of
cleaning
processes.
U)li)es
-‐
HVAC,
gases,
steam
and
water
• Packaging
and
labeling
opera)ons
&
controls
• Label
examina)on
and
usage,
Package
/
Label
System
• Label
storage
and
issuance,
• Valida)on
of
these
opera)ons.
• Laboratory
procedures,
• Tes)ng,
analy)cal
methods
development
Laboratory
System
• Method
valida)on
or
verifica)on,
• Stability
program
© CBE – DCVMN 010 V2
17
An Overview of ICH Q10
Pharmaceutical Quality System
© CBE – DCVMN 010 V2
18
ICH Q10 - Pharmaceutical Quality System
§ Based on ISO 9000/ISO13485/CFR 820 systems model
§ Compliments ICH Q8 and ICH Q9
§ Applies across the product life-cycle
§ Consistent with GMPs - not intended to add new
expectations to regulations and compliance
§ Applies to APIs, drug products and biotechnology
§ Strengthens the link between product development and
manufacturing activities
© CBE – DCVMN 010 V2
19
Pharmaceutical Quality System, Quality
Assurance, GMP and Quality Control
Pharmaceu9cal
Quality
System
(ICH
Q10)
Quality
Risk
Management
(ICH
Q9)
Quality
by
Design
(ICH
Q8)
Supply
è
Manufacturing
è
Distribu9on
è
Customers
© CBE – DCVMN 010 V2 20
ICH Q10 - Some Important Principles
• The size and complexity of the company’s activities
should be taken into consideration when developing a new
pharmaceutical quality system or modifying an existing
one.
• While some aspects of the pharmaceutical quality system
can be company-wide and others site-specific, the
effectiveness of the implementation of the pharmaceutical
quality system is normally demonstrated at the site level.
© CBE – DCVMN 010 V2
21
ICH Q10 - Pharmaceutical Quality System
© CBE – DCVMN 010 V2 22
A Hierarchy QMS/GMP Documentation
QP
Objec)ves
New expectation
Quality
Manual
(Guidance/Policy)
Systems
Quality
Management
SOPs
Opera)ng
SOPs
Master
Batch
Records
Operator
Instruc)ons
Manufacturing
and
Quality
Records
Training
Manuals
and
Records
© CBE – DCVMN 010 V2 23 Compliance
by
23
Design
Expectation of Skills and Knowledge
Development of Personnel
Quality
Knowledge
GMP
Knowledge
Product
and
Process
Knowledge
(Skills
Competency)
GMP
Behaviour
(Minimising
Human
Error)
Training
Manuals,
Records
and
Competency
Assessments
© CBE – DCVMN 010 V2 24 Compliance
by
24
Design
Integration of PQS and GMP Elements in the
Quality System
PQS
GMP
• Knowledge
Management,
Training
• Quality
Management/Quality
and
Educa9on
Assurance
System.
• Monitoring
Systems
• Facili9es
and
Equipment
System.
• Change
Management
• Materials
System.
• CAPA
&
Improvement
• Produc9on
System
• Management
Review
and
Responsibility
• Packaging
and
Labeling
System
• Quality
Planning
&
Resources
• Laboratory
Control
System
• Process
Performance
and
Product
Quality
Monitoring
System
© CBE – DCVMN 010 V2 25
PQS Enablers
Quality Risk Management (QRM)
§ Quality risk management, in
line with ICH Q9, provides an
essential component of the
Quality System.
§ QRM enables both effective and
efficient practices.
§ Application of QRM ensures the
quality system is efficient.
§ Provides a systematic approach
to escalating and prioritising
significant events
© CBE – DCVMN 010 V2 26
Risk Management Maturity
A Guide to Supply Chain Risk Management for Suppliers to the Pharmaceutical, Medical
Device and Allied Industries
Table 2 – Risk Management Maturity
Risk Maturity Risk Processes Attitude Behaviour Skills &
Level knowledge
Risk No Formal Risk Fear of Blame Unconscious
Scepticism Processes Avoidance Culture Incompetence
Awareness Ad hoc use of Suspended Reactive, Fire Conscious
Stand Alone Belief fighting Incompetence
Processes
Understanding & Tick Box Passive Compliance, Conscious
Application Approach Acceptance reliance on Competence
registers
Embedding & Risk Active Risk-based Unconscious
Integration Management Engagement decision making Competence
embedded in
Business
Robust Risk Regular review & Champion Innovation, Expert
Management Improvement Confident Risk
taking
© CBE – DCVMN 010 V2 Compliance by Design 27
PQS Enablers - Knowledge Management
§ Knowledge management means the
systematic accumulation of information
concerning products so that this knowledge
can be leveraged in the future.
§ Knowledge can be stored in systems such
as:
§ Quality Records, including testing, stability studies
and reports
§ Registration Dossiers
§ Contracts and Technical Agreements
§ Validation Protocol and Reports
§ Marketplace Events (Complaints, Recalls, Adverse
Events etc.)
§ Annual Product Quality Reviews (PQRs)
§ Process control, significant deviations and changes.
© CBE – DCVMN 010 V2 28
ICH Q10 – Pharmaceutical Quality Manual
• A Quality Manual or equivalent documentation approach
should be established and should contain the description of the
pharmaceutical quality system.
• The description should include:
i) The quality policy
ii) The scope of the pharmaceutical quality system.
iii) Identification of the processes within the pharmaceutical
quality system, as well as their sequences, linkages and
inter-dependencies.
• Process maps and flow charts can be useful tools to facilitate
depicting these in a visual manner.
© CBE – DCVMN 010 V2
29
Example Chapters of a Quality Manual
§ MANAGEMENT REVIEW AND RESPONSIBILITY
§ DESCRIPTION OF THE QUALITY SYSTEM
§ QUALITY PLANNING AND RESOURCE
MANAGEMENT
§ TRAINING AND EDUCATION
§ PRODUCT DEVELOPMENT AND PRODUCT
REGISTRATION
§ QUALITY ASSURANCE AND COMPLIANCE
PROGRAMS
§ MONITORING PROGRAMS
§ CAPA / QUALITY AUDITS / PRODUCT QUALITY
REVIEWS
§ MARKETPLACE MONITORING: COMPLAINTS AND
PHARMACOVIGILANCE PROGRAMS
§ QUALITY RISK MANAGEMENT
§ KNOWLEDGE MANAGEMENT
© CBE – DCVMN 010 V2 30
Example Chapters of a Quality Manual
§ MATERIAL CONTROL SYSTEM:
§ SUPPLY CHAIN INTEGRITY AND SUPPLIER ASSURANCE
§ PRODUCTION SYSTEM
§ PRODUCT DEVELOPMENT, TECHNOLOGY TRANSFER AND
MASTER INSTRUCTIONS
§ PROCESS PERFORMANCE AND PRODUCT QUALITY
MONITORING SYSTEM
§ PROCESS VALIDATION
§ PACKAGING AND LABELLING
§ DEVIATIONS, INVESTIGATIONS AND NON-CONFORMING
PRODUCT
§ LABORATORY CONTROL SYSTEM
§ CHANGE MANAGEMENT / VALIDATION
§ FACILITIES AND EQUIPMENT SYSTEM / CLEANING/
CONTAMINATION CONTROL AND COMPUTERISED
SYSTEMS
© CBE – DCVMN 010 V2 31
PQS Objectives
§ Set objectives and clear performance metrics;
§ Objectives are reviewed annually
§ Metrics are measured, time-related and indicate the level of
performance required;
§ Metrics are reviewed regularly;
§ Define how compliance obligations are embedded in
operational practices and procedures.
§ Address processes for identifying, reporting and
responding to compliance failures.
© CBE – DCVMN 010 V2 32
FDA View on Quality Metrics
Indicator Metric
Lot Acceptance Rate Number of lots rejected in a year / number of lots produced
Right First Time Rate Number of deviations / lot
Complaint Rate Number valid complaints/number of lots released per year
Invalidated (OOS) Rate Number of OOS test results invalidated /tests performed
Annual Product Review Number of APRs generated within 30 days of annual due date
(APR) on Time Rate
Management Most senior manager that signed each annual product review
Engagement
Process capability or Whether performed for each critical quality attribute as part of
performance index that product’s APR.
Corrective and Number of CAPAs that were initiated due to an APR, divided by
Preventative Action the total number of APRs generated.
(CAPA) Rate
© CBE – DCVMN 010 V2 Reviewing
Metrics
33
ICH Q10 – 4.1 Management Review
• Senior management should be responsible for
pharmaceutical quality system governance through
management review to ensure its continuing suitability and
effectiveness.
• Management should assess the conclusions of periodic
reviews of process performance and product quality and of
the pharmaceutical quality system.
© CBE – DCVMN 010 V2
34
Commitment to Quality by Management
§ Governing Body and CEO are engaged
§ The Quality Policy is aligned with business objectives
§ Compliance and Quality obligations are embedded in
position responsibilities
§ Resources are allocated to Quality / Compliance
§ Top level engagement in compliance/quality metrics and
reviews
© CBE – DCVMN 010 V2 35
PQS, Compliance and Quality Organisation
§ Assign compliance and quality responsibilities to
individual managers – set out in position descriptions
§ Ensure all management “walk the talk”
§ Appoint a senior Compliance/ Quality executive:
§ direct access to the Board/CEO
§ Access to expert advice (internal and external)
§ Establish compliance/quality objectives and KPIs
§ Ensure compliance/quality function has the authority to
act
© CBE – DCVMN 010 V2 36
ICH Q10 - Management Reviews – should include
§ A timely and effective escalation process to senior
management;
§ Measures of customer satisfaction - complaints and
recalls;
§ Conclusions of process performance and product quality
monitoring;
§ The effectiveness of process and product changes
including those arising from CAPA;
§ Any follow-up actions from previous reviews;
© CBE – DCVMN 010 V2
37
Management Reviews, Trend Analysis
and Feedback
Risk Assessment
SOPs & PQRs Conducted
Reports
Management Report KPIs and Quality
Reviews Metrics
Periodic
Meetings Verification of PQS
Effectiveness
Trend Analysis and
Feedback
© CBE – DCVMN 010 V2
38
ICH Q10 Quality System
Section 3 - Continual Improvement of Process
Performance & Product Quality
§ Process performance and product quality monitoring system:
§ Well defined systems
§ Process control
§ Identification of improvement areas
§ Corrective action and preventive action (CAPA) system
§ In place and effectiveness evaluated
§ Focus on Continuous Improvement
§ Change management system:
§ QA oversight
§ Utilizes science and risk-based assessment
§ Management review of process performance and product
quality
§ Periodic reviews of performance against metrics
§ Supports continual improvement
© CBE – DCVMN 010 V2
ICH Q10 Quality System:
Section 4 - Continual Improvement of the QS
§ Management Review of the Pharmaceutical Quality System
§ Measurement of achievement of QS objectives
§ Assessment of Metrics
§ Monitoring of Internal and External Factors impacting the
QS
§ Emerging regulations, guidance and quality issues
§ Innovations
§ Changes in business strategies and objectives.
§ Outcomes of Management Review and Monitoring
§ (Re)allocation of resources and/or personnel training
§ Timely and effective communication of the results
© CBE – DCVMN 010 V2
40
Compliance and Improvement
Element
Compliance
Regula9on
Improved
Integrated
Compe99ve
is
a
cost
$
Driven
Compliance
Compliance
Advantage
Quality
Focus
Tes)ng
(QC)
GMPs
Processes
and
ICH
Q8,
9,
10
ICH
Q8,9,10
Systems
Started
Embedded
CAPA
Correc)on
Correc)ve
Prevent.
Management
Drive
down
(Reac)ve)
Ac)on
Ac)on
(RCA)
Reviews
COQ
Con9nuous
Absent
Event
Driven
QA
Focus
Opera)ons
Company
Improvement
(Reac)ve)
(Predic)ve)
Focus
Wide
-‐
Part
of
Culture
Compliance
QA/QCs
role
Compliance
/
PQS
Systems
Prepare
for
Welcome
-‐
minimal
GMP
Audits
driven
audits
Regulatory
External
Audits
Audits
Feedback
Knowledge
&
Basic
GMP
Knowledge
is
Systema)c
Knowledge
is
Knowledge
is
Training
Training
anecdotal
Training
Documented
Leveraged
Evaluated
&
Organised
© CBE – DCVMN 010 V2 41
