The document provides an overview of implementing a pharmaceutical quality system according to ICH Q10 guidelines. It discusses establishing the foundation through following procedures and defining a quality policy. It then outlines a "simple process" to implement key elements like quality objectives, continual improvement plans, and management reviews. The goal is to enhance quality and facilitate innovation using a risk-based approach throughout the product lifecycle.

1. A Practical Approach to
Implementing ICH Q10
Pharmaceutical Quality Systems
Chris Masterson
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2. A Practical Approach to Implementing
ICH Q10 Pharmaceutical Quality Systems
Table of Contents:
 Foundation
 “Simple” Process
 Quality Manual and Quality Policy
 GMP Lifecycle Policy
 Quality Objectives / KPIs
 Continual Improvement Plan/Report
 Management Review
 Conclusion
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3. The Foundation
 The Foundation:
 Have procedures! (21CFR 211.100 (a))
 Follow them! (21CFR 211.100 (b))
 What is a “Pharmaceutical Quality System” (PQS)?
 A comprehensive model of an effective quality “system”, including
ISO concepts and GMP regs using a product life cycle approach to
enhance the quality of medicine.
 ICH Q10 Objectives: Section 1.5
 Establish, Implement and Maintain PQS
 Monitor and Control PQS
 Continually Improve PQS
 (Note:Time doesn’t permit hitting everything in ICHQ10.)
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4. Foundation Toolbox: “HOW” You Do It
 Moral “Compass”
 Tenacious/Fearless
 Continuous Improvement
 Candor
 Discovery
 Big Picture View
 Wisdom/Knowledge (Culture shock)
Place the tools in your toolbox…and let’s go.
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5. “Simple” Process
Slide format will describe:
 ICH Q10 Section Reference
 Brief description (simplified from ICH Q10)
 Interpretation / Advice
 Example(s)
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6. Quality Manual and Policy (1.8; 2.2)
 Section 1.8: Quality Manual
 (a) Quality Policy (Refer to Section 2.2)
 (b) Scope
 (c) Processes, including linkages and interdependencies
 (d) Management Responsibilities
 Section 2.2: Quality Policy
 (a) Sr Mgt to establish Quality Policy to provide direction
 (b) Comply with reg. reqs. and continually improve PQS
 (c) Communicate to all; all should understand.
 (d) Review periodically for continued
effectiveness.
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7. Quality Manual and Policy
 Interpretation / Advice
 Quality Manual: NMT 10 pages long
 Embed Quality Policy in Quality Manual
 Simple and easy-to-read
 Very high level
 Endorsed / Signed by QMRC
 “Example” Quality Manual can be shared individually.
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8. Quality Policy Example
 The Quality mission is to assure that COMPANY X
commercial and clinical products are manufactured, tested and
released to meet the highest standards for quality, safety,
identity, strength and purity, while facilitating innovation and
improvement and adding value to COMPANY X.
 We are committed to successful collaboration with internal
and external customers to ensure our customers are educated
on COMPANY X Quality expectations, assuring GXP
regulations are met or exceeded, best practices are
incorporated and robust and efficient Quality processes are
developed, followed and continuously improved.
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9. Quality Manual and Policy
 Quality System Processes
 The Quality System is comprised of the following
systems. Documented policies/procedures shall be
established, maintained and continuously improved.
 Written Procedures
 Written procedures will be generated and followed to control and
maintain documentation. The magnitude of control is dependent on
the type of document ranging from level 1 (least specificity) through
level 4 (greatest specificity) as follows:
 Level 1: Quality Manual
 Level 2: Policy Documents
 Level 3: Procedural Documents
 Level 4: Detailed Instructional Documents/Records
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10. Quality Manual and Policy
 ID/include Quality Systems needed.
 Document System
 Deviation, Investigation
 CAPA, Change Control
 Customer Complaint, Recall
 Quality (Technical) Agreement, Product Discontinuation
 Product Disposition, Annual Product Quality Review
 Out of Spec (OOS), Risk Management, Self Inspections
 External Audits, Nonconforming Product Control,
 Inspection, Sampling and Testing
 Etc.
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11. GMP Lifecycle Policy (1.3, 1.7(b), 3.1)
 1.3: The regional GMPs do not explicitly address all product lifecycle stages.
This guideline encourages the use of science and risk based approaches at
each lifecycle stage, promoting continuous improvement.
 1.7(b): Elements should be applied in a manner that is appropriate and
proportionate to the lifecycle stage, recognizing the goals and knowledge of
each stage.
 3.1Lifecycle Stage Goals:
 3.1.1 Development (Preclinical, Ph 1, Ph 2, Ph 3): “Design” a product and process to meet
intended performance and meet customer needs. Refer to ICH Q8.
 3.1.2 Technology Transfer: Transfer product and process knowledge between development
and manufacturing and within/between manufacturing sites. Forms basis for the Mfg
process, control strategy, PV approach and continuous improvement.
 3.1.3 Commercial Mfg: Achieve product realization, establish and maintain a state of
control and continuously improve.
 3.1.4 Discontinuation: Planned approach to ending the product life. (E.g. Stability tests,
complaints, doc retention, sample retention, etc.)
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12. GMP Lifecycle Policy
 Interpretation / Advice:
 Create a “GMP Lifecycle Policy” to provide direction to
company. (Resource: PDA)
 Define in “SOP” the hand-off from Development to Mfg. (E.g.
PD handles Ph 1/2; Mfg handles Ph 3 and Comm.
 Define in “SOP” the hand-off from Analytical Development to
QC. (E.g. AD handles Ph 1/2; Mfg handles Ph 3 and Comm.
 Quality Unit GMP oversight is required for all product
intended for human use.
 Discontinuation “SOP” needed. (low priority until unprepared)
 “Example” GMP Lifecycle Policy can be shared individually.
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13. Product Lifecycle
Development
Discontinuation
Tech Transfer
Commercialization
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14. Product Lifecycle from ICH Q10
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15. Quality Objectives (2.3)
 2.3 Quality Planning
 2.3(a) Sr Mgt should ensure Quality Objectives are defined and
communicated.
 2.3(b) Quality Objectives are supported by all levels.
 2.3(c) Quality Objectives should align with company strategy and be
consistent with quality policy.
 2.3(d) Mgt should provide appropriate resources and training to meet
quality objectives.
 2.3(e) Performance Indicators that measure progress against Quality
Objectives should be established, monitored, communicated regularly and
acted upon. (See “Management Review”)
 Interpretation / Advice
 Communicate QOs to Sr Mgt, with industry news. (E.g. Quarterly update
from Quality Head to CEO and staff on KPI’s and 1 page “newsletter” with
links.)
 Bump up One Goal to HIGHEST Level
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16. Quality Objectives / KPIs
Advice:
 Develop 4-6 that will help show “Company GMP
Compliance”. (Measuring compliance, not Quality group)
 Focus on areas of “opportunity” or “pain points”
 If you could improve only a few areas, what would they be?
 A. Define “As Is”. Where you are.
 B. Define “To Be”. Where you want to be at year end.
 Define how to get from A to B. Build “Road Map”.
 Define what to measure, formulae and process / people to
measure them.
 Must be SMART: Specific, Measurable, Achievable, Relevant
and Time-bound.
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17. EXAMPLE of Quality Objectives: KPIs
2012 Quality Objectives: Tier 1 by Month - All Departments
Target January February March April May June July August September October November December YTD YTD Presenter NOTES
KEY PERFORMANCE INDICATOR (KPI)
Cumul. Total
1 On time closure of Quality Systems
> 80% 50% 14% 45% 100% 54% 37 QS
1a Deviations (Internal)
> 80% 25% 50% 80% 80% 63% 16 QS
1b CAPAs
> 80% 100% 100% 100% 100% 100% 69 QS
1c Complaints
> 80% N/A N/A 100% 100% 100% 3 QC
1d OOSs (Internal Laboratory Investigations)
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18. Continual Improvement (1.5.3; 2.4)
 1.5.3 Facilitate continual improvement by identifying and implementing
product quality improvements. Use Quality risk Mgt.
 2.4 Management should determine and provide resources (people, cash,
fac/equip, materials) to implement, maintain and continually improve the
PQS.
 4.2 Monitor regs, guidance and industry trends.
 Interpretation / Advice:
 Tie to Corporate/Department GOALS! Cultural.
 Brainstorm Systems’ Gaps
 Do you have all Quality Systems (SOPs, Policies, etc)?
 Document System, Deviation, Investigation, CAPA, Change Control, Customer Complaint, Recall,
Quality (Technical) Agreement, Product Discontinuation, Product Disposition, Technology
Transfer, Annual Product Quality Review, Out of Spec (OOS), Risk Management, Self Inspections,
External Audits, Nonconforming Product Control, Inspection, Sampling and Testing
 Prioritize Gaps (E.g. Ranking)
 Fill Gaps (E.g. Use tool such as CI Plan/Report)
 Speak up if a group lacks resources; Quality’s responsibility to ID resource needs.
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19. Continual Improvement
 Examples
 Continuous Improvement Plan: Q1
 Continuous Improvement Report: Q1 of next year
 Quality intranet site; Monthly Quality Newsletter
“Example” Continuous Improvement Plan and Report can
be shared individually. Keep Simple and SMART!
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20. Management Review (2.1; 2.4; 2.6; 3.2.4;
4.1; 4.3)
 Section 2.1: Management Commitment
 (a) Senior Mgt must assure a PQS is in place to achieve “Quality Objectives” which are
communicated to all.
 (b) Mgt assists in PQS design and implementation and visibly/strongly supports efforts.
Assures quality issues are escalated. Assures “independent” Quality authority is
communicated to all. Performs “Management Reviews”. Advocates “Continuous
Improvement”. Commits resources.
 2.4 Resource Management: Management should determine and provide resources
(people, cash, fac/equip, materials) to implement, maintain and continually improve
the PQS.
 2.5: Internal Communication: Management should assure communication processes
are established, used and include escalation of issues and broad communication
throughout org.
 2.6: Management review
 (a) Senior Mgt must be responsible for PQS governance through Management Review to
assure continued PQS suitability and effectiveness.
 (b) Mgt must assess conclusions of periodic reviews of process performance and product
quality of the PQS.
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21. Management Review
 3.2.4: Management Review of Process Performance and
Product Quality: Management review should assure process
performance and product quality are managed over the
lifecycle. How you set up reviews depends on org. complexity.
Management should assure communication processes are established,
are timely, are used and include escalation of issues to Sr Mgt. for review.
Include:
 (1) Reg. Authority inspections and commitments, audit findings and
other org. assessments.
 (2) Periodic Quality reviews that may can include:
 Complaints and Recalls
 Process performance and product quality monitoring conclusions
 CAPA effectiveness for process and product changes
 (3) Previous Management Review follow-up actions
Identify:
 (1) Improvements to Mfg. processes and products
 (2) Provision, training and realignment of resources
 (3) Capture and dissemination of knowledge
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22. Management Review
 4.1 Management review of the PQS: Mgt. should have a
formal review process for the PQS periodically, to
include:
 Quality System Objectives and KPIs (e.g. Complaint, CAPA,
Dev, Change control, CMO activities, internal audits,
trending, risk assessments, reg inspections and customer
audits
 4.3 Outcomes can include:
 Improvement of PS and related processes.
 Resource (re)allocation and training
 Revisions to Quality Policy or Quality Objectives; Escalate
results to Sr Mgt
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23. Management Review
 Interpretation / Advice:
 Quality reporting structure is important!
 Independence needed (E.g. Report/Dotted line to CEO)
 Quality Unit Approval/Rejection responsibility/authority shall not be
questioned. (21CFR 211.22(a))
 Develop a Quality Council or Quality “Management Review”
Committee (QMRC) who is responsible for fulfilling the
“Management Review” role. Choose senior managers, but those
who are engaged in the business (recommend at the Director level).
Depending on the company size, a corporate QMRC may be formed,
with local Quality Councils. Regardless, a group must perform this
function which fits into your org structure.
 Develop a Quality Specifications Committee to review and
approve test specifications and testing standards. Likely a separate
team with analytical testing experts. In young companies, may want
to merge with QMRC.
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24. Management Review
 Example(s)
 Management Review : (Embed in Quality Manual)
 Management review of the Pharmaceutical Quality System will be
ongoing via the QMRC
 Quality Management Review Committee (QMRC)
 Senior management will review the suitability and effectiveness of the Cubist
Quality Systems periodically to ensure Quality Objectives are met. This Quality
Management Review Committee (QMRC) will have a charter defining its
responsibilities.
 Quality Specifications Committee (QSC)
 Specifications will be approved and endorsed by a Quality Specifications
Committee (QSC). The QSC meets to review proposed new and revised quality
policies, procedures, specifications and standards. Meeting minutes from all QSC
meetings are required to be recorded and are maintained in Quality department
files.
 “Example” QMRC and QSC Meeting Charters can be shared individually.
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25. Conclusion:
 Read ICH Q10!
 Write a Quality Policy
 Write a Quality Manual
 Educate colleagues to create “Quality Culture”
 Start/Maintain “Management Review” meetings
 Define SMART “Quality Objectives”
 Write a “GMP Lifecycle” Policy
 Create a “Continuous Improvement” culture
 Write a CI Plan in Q1
 Write a CI Report in Q1 of following year
 Keep it Simple.
 (Catch me afterward if you’d like specific questions answered.)
 Available for review: 2012 Q. Obj; Q. Manual; 2011 CI Plan and Report; 2012
Goals; QSC Charter; QMRC Charter
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26. Backup Slide
 Network with colleagues; share best practices
 Use the concept of continual improvement; “Rome wasn’t
built in a day”.
 Use Operational Excellence (Lean) tools to assist (E.g.
Brainstorming, Narrowing, Selection, Ranking and
Prioritization)
 Use corporate tools (e.g. OLEx)
 Don’t restrain yourself; look outside pharma
 Partner Education / Build Relationships
 Industry should Lead (develop Quality Principles)
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