PRINCIPLES-BASIC-IN-PHARMA-_-Uche-Afoekelu.ppt

qc

1. Basic Principles of
PHARMACEUTICAL QUALITY
SYSTEM (PQS)-ICH Q10
Pharm (Mrs). Uche Sonny-Afoekelu,
M.Sc.(PH), MPCPharm
Assistant Director, Compliance Division
Drug Evaluation and Research
Directorate, NAFDAC
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2. OUTLINE
•Introduction- What is quality?
•Relationship between different levels of quality
•What is ICH Q10?
•Philosophy and essential elements of the quality
system in pharmaceutical manufacturing
•Objectives of Pharmaceutical Quality System (PQS)
•Applications of PQS
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3. INTRODUCTION
•What is Quality?
Degree to which a set of inherent characteristics
fulfills requirements- ISO
Degree- refers to a level which a product or
service satisfies.
So depending on the level of satisfaction, a
product may be termed as excellent, good or
poor quality product
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4. INTRODUCTION…..2
•Inherent characteristics: Those features that
are a part of the product and are responsible
for achieving satisfaction
•Requirements: Refers to the needs of the
customer, needs of the organization, and
those of other interested parties eg
Regulatory Bodies

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5. INTRODUCTION…..3
Examples of quality components
•AREA
•Airlines
•Healthcare
•Food services
•Pharmaceutical Quality
System
•QUALITY COMPONENTS
•On-time, comfortable, low-
cost service
•Correct diagnosis, minimum
wait time, low cost
•Good taste, free from
contamination, fast delivery,
good environment
•????????????
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6. INTRODUCTION….4
•Every Pharmaceutical product has established
identity, strength, purity and other quality
characteristics designed to ensure the
required levels of safety and effectiveness.
•In this Presentation, achieving quality means
achieving these characteristics for a product.
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7. Relationship between different levels of
quality
•Quality management, defining the overall policy of the
organization towards quality, is over everything else.
•Next comes quality assurance, which is the concept
that ensures the policy is achieved.
•GMP is part of quality assurance. It deals with the risks
that cannot be tested. It builds quality into the
product.
•Quality control is a part of GMP. It is that part of GMP
that is focused on testing of the environment and
facilities, as well as the testing of the materials,
components and product in accordance with
standards.
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8. Quality relationships

Quality Management / PQS
Quality Assurance
GMP
Production and Quality Control

9. QUALITY
MANAGEMENT
GMP – PICs Guide
PRODUCTS
&
MATERIALS
FACILITIES
QUALITY
UNIT
EQUIPMENT
PRODUCTION
MANAGEMENT
PEOPLE

10. FDA – 6 Systems Approach of PQS
Quality System
Production System
Facilities &
Equipment
System
Laboratory Controls
System
Materials System
Packaging & Labeling
System

11. New Era With New Challenges
“risk-based”
concepts and
principles of ICH
Q8
Q9
Q10Ref: ICH

12. How did ICH Q10 Originate?
•ICH Q10 was created from aspects of regional GMPs, ICH Q7 “GMP
Guide for APIs”, and ISO 9000 (and related guidelines). ICH Q10
augments GMP by describing specific quality system elements and
management responsibilities.
•ICH Q10 provides a harmonized model for a pharmaceutical quality
system throughout the product lifecycle and is intended to be used
together with regional GMP requirements.
•GMPs don’t explicitly address all stages of product lifecycle (e.g.
Development). The quality system elements and management
responsibilities described in Q10 promote the use of science and risk
based approaches at each lifecycle stage, thereby encouraging continual
improvement across the entire product lifecycle.

13. •ICH Q10 describes a comprehensive approach to
Pharmaceutical Quality System
•It includes Good Manufacturing Practice (GMP) regulations
•It is harmonized with ICH Q8 “Pharmaceutical Development”
and ICH Q9 “Quality Risk Management”
•It allows Industry & Regulatory to enhance the Quality and
Availability of medicines around the Globe in the interest of
Public Health
to IHow did ICH Q10 Originate?......2CH
Q10 Conti...
19

14. What is ICH Q10?
•ICH Q10 is not intended to create any new
regulatory requirements
•It only helps in maintaining product quality and
compliance at all stages of product life cycle
•It helps innovation and continual improvement in
pharmaceutical manufacturing
•GMPs do not explicitly address all stages of the
product life cycle (e.g., development) and ICH
Q10 is intended to encourage the use of science
and risk based approaches at each lifecycle stage
thereby promoting continual improvement across
the entire product life cycle.

15. Scope of ICH Q10
ICH Q10 can be implemented throughout the different stages of a
product lifecycle.
I.Development Stage
II.Technology Transfer Stage
III.Manufacturing Stage
IV.Discontinuation Stage

16. ICH Q10 I(PQS
Pharmaceutical
Development
Investigational products
GMP
Commercial
Manufacturing
Discontinuation
Technology
Transfer
Management Responsibilities
Process Performance & Product Quality Monitoring System
Corrective Action / Preventive Action (CAPA) System
Change Management System
Management Review
Knowledge Management
Quality Risk Management
PQS
elements
Enablers
33

17. Objectives of PQS
(1)Achieve Product Realization: To establish, implement &
maintain a system that allows the delivery of products with
quality attributes appropriate to meet the needs of patient &
other stake holders.
(2) Establish & Maintain a State of Control: To develop & use
effective monitoring & control systems for process
performance & product quality, thereby providing assurance
of continued suitability and capability of processes. Quality
Risk Management (QRM) can be useful in identifying the
monitoring and control systems
(3) Facilitate Continual Improvement: To identify and
implement appropriate product quality improvements,
process improvements, variability reduction, innovation &
quality system enhancements, thereby increasing the ability
to fulfill quality needs consistently. QRM can be useful for
identifying & prioritizing areas for continual improvement.

18. Objectives of PQS
•What is the Objective of any System?
•(Using ICH Q10 as an example)
Development + Tech transfer + Commercial + Discontinuation
Product
Realization
State of
Control
Continual
Improvement
Compliance
ORGANIZATIONAL OPTIMIZATION
System Boundaries ie full Life Cycle
“Quality is a side effect of a system that is running well”

19. GMPs without a Modern Framework will Limit
Improvements
•GMPs provide guidance on the manufacturing
and control of pharmaceutical product
•GMPs do not drive lifecycle approach to
quality
•GMPs do not specifically address proactive
continual improvement
•GMPs only briefly mention management
responsibility
•GMPs are reactive, PQS is more proactive

20. Philosophy of the Quality System in
Pharmaceutical manufacturing
•The overarching philosophy is that
•Quality should be built into the product, and
testing alone cannot be relied on to ensure
product quality !
•Implies QUALITY BY DESIGN (QbD)
(Build Quality into your products, design risk out of
your processes)!
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21. Philosophy of the PQS…2
•The PQS (formerly referred to as Quality
management system) is described in ICH Q10
•It is based on ISO (International Organization
for Standardization ) quality concepts.

•It includes the concepts of QA, GMP, QC,
QRM- which are interrelated aspects of
Quality Management.
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22. Philosophy of the PQS…3
•Quality Management is a management
function
•It determines and implements the quality
policy which is the overall intention and
direction of an organization regarding quality
•It is formally expressed and authorized by top
(senior) management
•Senior management has the ultimate
responsibility to ensure an effective PQS
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23. Philosophy of the PQS…4
•Quality Manual
•A quality manual should be established and
should contain the description of the PQS. The
description should include:
The quality policy
Scope of the PQS
Identification of the PQS system processes, their
linkages and interdependencies. Process maps
and flow charts can be useful.
Management responsibilities within the PQS
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24. Philosophy of the PQS…5
•Paradigm shift in Quality
(ICH Q8, ICH Q9, and ICH Q10)
•ICH Q10 is a model for a Pharmaceutical
Quality System that can be implemented
throughout the different stages of a
product life cycle.
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25. Philosophy of the PQS…6
•Implementation of ICH Q10
throughout product life cycle should
facilitate innovation and continual
improvement and strengthen the link
between pharmaceutical
development and manufacturing
activities
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26. Product lifecycle
Pharmaceutical Development:
Goal: To design a product and its manufacturing
process to consistently deliver the intended
performance and meet the needs of the patients,
healthcare professionals, regulatory authorities.
oDrug Substance development
oFormulation Development
oManufacture of investigational products
oDelivery system development
oManufacturing process development and scale up
oAnalytical method development
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27. Product Lifecycle… 2
Technology transfer
Goal: To transfer Product and Process knowledge
•Between development and manufacturing,
• Within manufacturing sites
•Between manufacturing sites
……. to achieve product realization.
This knowledge forms the basis for the
manufacturing process, control strategy, process
validation approach, and on-going continual
improvement
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28. Product Lifecycle…3
Commercial manufacturing
Goal: To achieve product realization, establish and
maintain a state of control and facilitate continual
improvement
oAcquisition and control of materials
oProvision of facilities, utilities, and equipment
oProduction (including packaging and labeling)
oQuality control and assurance
oRelease
oStorage
oDistribution
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29. Product lifecycle…. 4
Product discontinuation
Goal: To manage the terminal stage of the
product life cycle effectively.
oRetention of Documentation
oSample Retention
oContinued product assessment (complaints
handling and stability)
o Reporting in accordance with Regulatory
requirements
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30. ELEMENTS OF THE PQS
1) Process performance and product quality
monitoring system
2) Corrective action and preventive action
system
3) Change management system
4) Management review of process performance
and product quality
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31. Elements of the PQS….2
•These elements should be applied in
a manner that is appropriate and
proportionate to each of the product
lifecycle stages, recognizing the
differences among the stages and
the different goals of each stage
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32. 1) Process performance and product
quality monitoring
Pharmaceutical companies should plan and
execute a system for the monitoring of
process performance and product quality to
ensure a state of control is maintained.
An effective monitoring system
• provides assurance of the continued
capability of processes and controls to
produce a product of desired quality
•Identifies areas for continual improvement
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34. Application of Process Performance and Product
Quality Monitoring System throughout Product
Lifecycle
Pharmaceutical Development
•Process and product knowledge
generated and process and product
monitoring conducted throughout
development can be used to establish
control strategy for manufacturing
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35. Application of Process Performance and Product
Quality Monitoring System throughout Product
Lifecycle
•Technology transfer
•Monitoring during scale up activities can
provide a preliminary indication of process
performance and the successful integration
into manufacturing
•Knowledge obtained during transfer and scale-
up activities can be useful in further
developing the control strategy
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36. Application of Process Performance and Product
Quality Monitoring System throughout Product Lifecycle
•Commercial manufacturing
•A well defined system for process
performance and product quality
monitoring should be applied to
assure performance within a state of
control and to identify improvement
areas
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37. Application of Process Performance and Product
Quality Monitoring System throughout Product
Lifecycle
•Product discontinuation
•Once manufacturing ceases, monitoring
such as stability testing should continue
to completion of the studies.
•Appropriate action on marketed products
should continue to be executed
according to regional regulations
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38. 2) Corrective Action and Preventive
Action System
•The Pharmaceutical company should have a
system for implementing corrective and
preventive actions resulting from the
investigation of complaints, product
rejections, non conformances, recalls,
deviations, audits, regulatory inspections and
findings, and trends from process
performance and product quality monitoring
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39. Correction, Corrective and Preventive Action
•Correction: Any action taken to eliminate a
non-conformity
•Corrective Action: Action to eliminate the cause
of a detected non-conformity or other
undesirable situation.
Note: Corrective action is taken to prevent
recurrence whereas preventive action is taken
to prevent occurrence (ISO 9000:2005)
•Preventive Action: Action to eliminate the
cause of potential non-conformity or other
undesirable potential situation.
Note: Preventive action is taken to prevent
occurrence whereas corrective action is taken
to prevent recurrence (ISO 9000:2005)

40. Corrective Action and Preventive
Action System…2
•A structured approach to the investigation
process should be used with the objective of
finding the root cause
•CAPA methodology should result in product
and process improvements and enhanced
product and process understanding
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42. Application of Corrective Action and
Preventive action system throughout the
product lifecycle
•Pharmaceutical Development
•Product or process variability is
explored. CAPA methodology is useful
where corrective actions and
preventive actions are incorporated
into the iterative design and
development process
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43. Application of Corrective Action and Preventive
action system throughout the product lifecycle
•Technology Transfer
•CAPA can be used as an
effective system for feedback,
feedforward, and continual
improvement.
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44. Application of Corrective Action and Preventive
action system throughout the product lifecycle
•Commercial Manufacturing
•CAPA should be used and the
effectiveness of the actions
should be evaluated
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45. Application of Corrective Action and Preventive
action system throughout the product lifecycle
•Product Discontinuation
•CAPA should be continued after the
product is discontinued.
•The impact on product remaining on
the market should be considered, as
well as other products that might be
affected
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46. Change Management
•Change Management : A systematic
approach to proposing, evaluating,
approving, implementing & reviewing
changes.
It Should Include
•Quality risk management to evaluate
proposed changes. The level of effort and
formality of the evaluation should be
commensurate with the level of risk

47. Change Management….2
•Innovation, continual improvement, the
output of process performance and product
quality monitoring, and CAPA drive change.
•To evaluate, approve and implement these
changes properly, a company should have an
effective change management system (CMS)
•The CMS should provide a high degree of
assurance that there are no unintended
consequences of the change
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48. Change Management…3
•Proposed changes should be evaluated
relative to the marketing authorization
including design space, to determine
whether a change to regulatory filling is
required under regional requirements
•Proposed change should be evaluated by
experts in contributing their experience
and knowledge

49. Change Management…4
•After implementation, evaluation of change
should be under taken to confirm that the
change objectives were achieved and
there was no deleterious impact on
product quality

51. Application of Change Management
System throughout Product Lifecycle
•Pharmaceutical Development
•Change is an inherent part of the
development process and should be
documented
•The formality of the change management
process should be consistent with the
stage of pharmaceutical development
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52. Application of Change Management System
throughout Product Lifecycle
•Technology Transfer
•The change management system
should provide management and
documentation of adjustments made
to the process during technology
transfer activities
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53. Application of Change Management System
throughout Product Lifecycle
•Commercial Manufacturing
•A formal CMS should be in place for
Commercial Manufacturing.
•Oversight by the Quality unit should
provide assurance of appropriate
science and risk- based assessments
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54. Application of Change Management System
throughout Product Lifecycle
•Product Discontinuation
•Any change after product
discontinuation should go
through an appropriate change
management system
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55. Management Review of Process
Performance and Product Quality
•Management review should provide assurance
that process performance and product quality are
managed over the lifecycle.
•Depending on the size and complexity of the
company, management review can be a series of
reviews at various levels of management and
should include a timely and effective
communication and escalation process to raise
appropriate quality issues to senior levels of
management for review.
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56. Management Review of Process
Performance and Product Quality
•The Management Review should include
Results of regulatory inspections, audits,
commitments made to regulatory authorities
Periodic quality reviews that can include
measures of customer satisfaction such as
product quality complaints and recalls
Any follow-up actions from previous
management reviews
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57. Application of Management Review of
Process Performance and Product Quality
throughout Product Lifecycle
•Pharmaceutical Development
•Aspects of Management Review
can be performed to ensure
adequacy of the product and
process design
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58. Application of Management Review of Process
Performance and Product Quality throughout Product
Lifecycle
•Technology Transfer
•Aspects of Management Review
should be performed to ensure the
developed product and process can
be manufactured at commercial
scale
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59. Application of Management Review of Process
Performance and Product Quality throughout Product
Lifecycle
•Commercial Manufacturing
•Management review should be
a structured system, and
should support continual
improvement
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60. Application of Management Review of Process
Performance and Product Quality throughout Product
Lifecycle
•Product Discontinuation
•Management review should
include such items as product
stability and product quality
complaints
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61. Continual improvement of the PQS
A)Management should have a formal
process for reviewing the PQS on a
periodic basis. The review should
include:
•Measurement of achievement of the
PQS objective
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62. Continual improvement of the PQS…2
•Assessment of performance indicators that
can be used to monitor the effectiveness of
processes within the PQS such as:
Complaints, deviations, CAPA, and Change
Management processes
Feedback on outsourced activities
Self assessment processes including risk
assessments, trending, and audits
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63. Continual improvement of the PQS…3
B) Monitoring of internal and external factors
that can have an impact on PQS
Factors monitored by management may include:
Emerging regulations, guidelines
Innovations that might enhance the PQS
Changes in product ownership
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64. Outcomes of management review
•Improvements to the PQS
•Allocation or re-allocation of resources
•Personnel training
•Revisions to quality policy and quality objectives
•Documentation and timely and effective
communication of the results of the management
review and actions, including escalation of
appropriate issues to senior management
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65. ICH Q10: POINTS TO NOTE
•It introduces the involvement and role of
senior management
•It introduces a product life cycle
perspective
•Quality Risk Management and Knowledge
Management are enablers for the PQS
•Implementation of PQS provides to
enhance assurance of product quality

66. ICH Q10: POINTS TO NOTE
•ICH Q10 requires an understanding of
FDA for the 21st Century, ICH Q8
(Design), ICH Q9 (Risk) as well as ISO
9000 (2005) to maximize benefit
•ICH Q10 is an ISO SYSTEMS approach to
GMP
•NOT additional to GMP but integral to
GMP

67. ICH Q10: POINTS TO NOTE
•Covers full life Cycle of a Product
•Objectives: Product Realization, Control &
improvement
•Demands Management Team to lead
Quality System and which protects public
health in respect of product lifecycle.

68. What are the benefits of implementing a
Pharmaceutical Quality System (in accordance with ICH
Q10)?
•The benefits are:
•Facilitated robustness of the manufacturing
process, through facilitation of continual
improvement through science and risk-based
post approval change processes;

69. What are the benefits of implementing a
Pharmaceutical Quality System (in accordance
with ICH Q10)?
•Consistency in the global pharmaceutical
environment across regions;
•Enable transparency of systems, processes,
organizational and management
responsibility;
•Clearer understanding of the application of a
Quality System throughout product lifecycle;

70. What are the benefits of implementing a
Pharmaceutical Quality System (in accordance
with ICH Q10)?
•Further reducing risk of product failure and
incidence of complaints and recalls thereby
providing greater assurance of pharmaceutical
product consistency and availability (supply)
to the patient;
•Better process performance;

71. What are the benefits of implementing a
Pharmaceutical Quality System (in accordance
with ICH Q10)?
•Opportunity to increase understanding
between industry and regulators and more
optimal use of industry and regulatory
resources. Enhance manufacturer’s and
regulators’ confidence in product quality;
•Increased compliance with GMPs, which
builds confidence in the regulators and may
result in shorter inspections.

72. How does a company demonstrate
implementation of PQS in accordance with ICH
Q10?
•When implemented, a company will
demonstrate the use of an effective PQS
through its documentation (e.g., policies,
standards), its processes, its
training/qualification its management its
continual improvement efforts, and its
performance against pre-defined Key
Performance Indicators.

73. How does a company demonstrate
implementation of PQS in accordance with ICH
Q10?
•A mechanism should be established to
demonstrate at a site how the PQS operates
across the product lifecycle, in an easily
understandable way for management, staff and
regulatory inspectors, e.g., a quality manual,
documentation, flowcharts, procedures.
Companies can implement a program in which
the PQS is routinely audited in-house (i.e.,
internal audit program) to ensure that the system
is functioning at a high level.

74. What are potential sources of information for
Knowledge Management?
•Some examples of knowledge sources are:
•Prior knowledge based on experience
obtained from similar processes (internal
knowledge, industry scientific and technical
publications) and published information
(external knowledge: literature and peer-
reviewed publications);

75. What are potential sources of information for
Knowledge Management?
•Pharmaceutical development studies;
•Mechanism of action;
•Structure/function relationships;
•Technology transfer activities;
•Process validation studies;

76. What are potential sources of information for
Knowledge Management?
•Manufacturing experience e.g.:
•- Internal and Vendor audits;- Raw material
testing data;
•Change management activities;
•Stability reports;
•Product Quality Reviews/Annual Product
Reviews;

77. What are potential sources of information for
Knowledge Management?
•Technical investigations and/or CAPA reports;
•Suppliers and Contractors;
•Product history and /or manufacturing history;
•Ongoing manufacturing processes information
(e.g., trends).

78. What are potential sources of information for
Knowledge Management?
•Complaint Reports;
•Adverse event reports (Patient safety);
•Deviation Reports, Recall Information;

79. Pharmaceutics
Profile
API Salt Selection
Integrity
Uniformity
Weight Control
In vitro
Dissolution
Chemical
Purity
API, Excipients, Manufacturing Process
API Particle Size
Chemical
Compatibility
Degradation
Pathway
Prediction
Material Property
Characterization
Process Simulation
Design
Christopher Sinko, Ph.D.Christopher Sinko, Ph.D.
Pfizer Global Research & Pfizer Global Research &
DevelopmentDevelopment
Knowledge Management Example:
Quality By Design

80. Summary
•ICH Q10 requires an understanding of FDA for the 21
st

Century, ICH Q8 (Design), ICH Q9 (Risk) as well as ISO
9000 (2005) to maximize benefit
•ICH Q10 is an ISO SYSTEMS approach to GMP
•NOT additional to GMP but integral to GMP
•Covers full life Cycle of a Product
•Objectives: Product Realization, Control & Improvement
•DEMANDS Management Team to lead Quality System
•Seek compliance only and you will get compliance only
•The toughest implementation battles are internal so look
for internal Allies before going outside for support

81. References
•NAFDAC cGMP Regulations 2009
•WHO- Quality Assurance of Pharmaceuticals 2015
•GMP for the 21
st
century
www.fda.gov/cder/gmp/gmp2004/GMP_finalreport2004.htm
•International Conference on Harmonisation, ICH Q8:
Pharmaceutical Development, November 2005.
http://www.ich.org/
•International Conference on Harmonisation, ICH Q9: Quality Risk
Management, November 2005. http://www.ich.org/
•International Conference on Harmonisation, Draft Consensus
Guideline, ICH Q10: Pharmaceutical Quality System, May 2007.
http://www.ich.org/
•FDA, Guidance for Industry: Quality Systems Approach to
Pharmaceutical CGMP Regulations, September 2006.
http://www.fda.gov/
•Dr Onyenoha Chukwumerije- Training slides 2016

82. THANK YOU
•QUESTIONS ??
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83. 1. Case study
Group session
Imagine you are being inspected by NAFDAC for
compliance with GMPs.
•Consider the situations in the next slides which
may have impacts on your company’s quality
management programme
•Describe the action(s) you would take in each
case to avoid regulatory citations. (CDs)

84. Issues 1
•Quality Management manual not established in writing
•Limited human resources
•Lack of qualified people
•Processes not properly validated
•Poor SOPs or standard batch documentation
•More consideration to cost than quality
•Family members in key positions of authority

85. Issues – II
•Substandard materials deliberately purchased
•Technical staff not involved in purchasing
•Inability to re-export substandard materials
•Owner insists on selling rejects
•Corruption
•No commitment to training