ISPE INDONESIA – WORKSHOP

APPLIED RISK MANAGEMENT FOR

COMMISSIONING & QUALIFICATION

Pierre Winnepenninckx – No deviation Pte. Ltd.

Joon Ng Leong – No deviation Pte. Ltd

21 & 22 November 2018

SESSION 1:
PATIENT CENTRIC
PARADIGM AND QBD
DURATION: 1H
COMMISSIONING AND
QUALIFICATION
EXISTING GUIDANCE AND FUTURE TREND

3
C&Q guidance

ISPE has 3 guidance documents

1. ISPE Baseline Guide: Volume 5 – Commissioning and qualification
Publish in 2001 and introduce the process for conducting SLIA / CCA Direct /
Indirect / No Impact System
Introduction of the V Model

2. ISPE Guide: Science and risk-Based Approach for the Delivery of Facility, System and
Equipment
Issue in mid 2011 and focused on how to deliver a project following ASTM
E2500, Quality Risk Management (QRM/ICHQ9) Based Verification (C&Q)
process.

3. ISPE Good Practice Guide: Applied Risk Management for Commissioning and
Qualification
Issued in 2011 – provide guidance on how to apply transitional approached to
incorporate QRN when moving from baseline guide to risk base approach

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Overview

Connecting Pharmaceutical Knowledge Science & Risk Based Approach

ispe.org

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Overview

Connecting Pharmaceutical Knowledge Science & Risk Based Approach

ispe.org

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 1991 1992 1993 1994 1995 1996 1997 1998 1999 2000 2001 2002 2003 2004 2005 2006 2007 2008 2009 2010 2011 2012 2013 2014 2015 2016

1-Jan-90
31-Dec-16

Jan 06 Jan 07 Jan 08 Jan 09 Jan 10 Jan 11 Jan 12 Jan 13 Jan 14 Jan 15 Jan 16
1-Jan-05 31-Dec-16

©2018

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 Mar 2001 Sep 2004
ISPE baseline guide: FDA - PHARMACEUTICAL CGMPS FOR THE 21ST CENTURY
Commissioning and Qualification A RISK-BASED APPROACH
Today

1991 1992 1993 1994 1995 1996 1997 1998 1999 2000 2001 2002 2003 2004 2005 2006 2007 2008 2009 2010 2011 2012 2013 2014 2015 2016

1-Jan-90
Nov 2000 31-Dec-16
ICH - Q7 Good Manufacturing Practice
Apr 90
Jan 2011 Mar 2015
Birth of ICH
FDA - Process Validation: EU - Annex 15:
General Principles and Practices Qualification and Validation
Sep 14
ICH - Q12 Lifecycle Management
Nov 05
ICH - Q9 Quality Risk Management

Jan 06 Jan 07 Jan 08 Jan 09 Jan 10 Jan 11 Jan 12 Jan 13 Jan 14 Jan 15 Jan 16
1-Jan-05 31-Dec-16

Jan 11
Jan 2007 Jan 2008
ISPE - Applied risk management for Today
ASTM E2500 ASTM E2537 Commissioning and Qualification
© No deviation Pte. Ltd. - 19 July 2016

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PATIENT CENTRIC
PARADIGM

9
ICH Q8 – From a CQV perspective

“By putting the patient

in the centre of
everything we do and
understanding our
process we are able to
identify and control
the risk to fully
implement the risk
based approach”

©2018

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ICH Q8 – From a CQV perspective

Quality Target Product Profile (QTPP):

A prospective summary of the quality
characteristics of a drug product that ideally
will be achieved to ensure the desired quality,
taking into account safety and efficacy of the
drug product.

Critical Quality Attribute (CQA):

A physical, chemical, biological or
microbiological property or characteristic that
should be within an appropriate limit, range, or
distribution to ensure the desired
product quality.

Critical Process Parameter (CPP):

A process parameter whose variability has an
impact on a critical quality attribute
and therefore should be monitored or
controlled to ensure the process produces the
desired quality.

©2018

Connecting Pharmaceutical Knowledge ispe.org

QUALITY BY DESIGN
A TRANSFORMATION FROM QUALITY TO
CONTROL TO QUALITY ASSURANCE

1
2
 What is Quality by Design?

Quality should be built-in to design of products and

processes not tested in the product

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Mindset shift Leading to a Behaviour change

Quality is a
devotion

Accountability

Quality is a
Guidance

©2018

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OVERVIEW OF THE LIFE CYCLE

Quality by Design
ICH Q8:
Quality by Design (QbD): A systematic approach to development that begins
with predefined objectives and emphasizes product and process
understanding and process control, based on sound science and quality risk
management

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OVERVIEW OF THE LIFE CYCLE

Quality by Design
ICH Q8:
Quality by Design (QbD): A systematic approach to development that begins
with predefined objectives and emphasizes product and process
understanding and process control, based on sound science and quality risk
management
Lean Thinking:
Poka-yoke is a Japanese term that means "mistake-proofing" or "inadvertent
error prevention".
A poka-yoke is any mechanism in a lean manufacturing process that helps
an equipment operator avoid (yokeru) mistakes (poka). Its purpose is to
eliminate product defects by preventing, correcting, or drawing attention to
human errors as they occur.
The concept was formalised, and the term adopted, by Shigeo Shingo as part of the Toyota Production
System.[3][4] It was originally described as baka-yoke, but as this means "fool-proofing" (or "idiot-
proofing") the name was changed to the milder poka-yoke.

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OVERVIEW OF THE LIFE CYCLE

QUALITY

Specification Design Verification

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Quality by Design not by Luck

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Quality by Design not by Luck

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ICH Q8 – From a CQV perspective

Input from
Product
development
(Science)

Scope of the
project CQV
(Engineer)

©2018

Connecting Pharmaceutical Knowledge ispe.org

BREAKOUT SESSION
COOKING CLASS
The Hungry Italian

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 The Hungry Italian

Hungry Italian Italian Food

Pizza Crust

Temperature
Heat Up
Bottom Heat
Kitchen
Oven
Recipe + Cooking instruction

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The Hungry French

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 The Hungry French

Hungry French French Food

Brioche Raising

Temperature
Bake
Top + Bottom
Kitchen Heat
Oven Homogenous
Recipe + Cooking instruction

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THE QUALIFICATION
EXPECTED DELIVERABLE
IQ
OQ
PQ
QUALIFICATION SUMMARY REPORTS
Qualification and Validation

1. Qualification and validation is an area of GMP where there are opportunities for more
international harmonization.
2. There is a general agreement on the high-level purpose of validation
3. GMP expectation:
1. There is a systematic approach to generate evidence that a facility, system, process, equipment or activity can
consistently preform according to pre-determined requirements.

2. Those that manufacture, test, store, transport and distribute pharmaceutical products need to have q
qualification and validation program

3. The program need to be formally defined, documented, approved, implemented and preriodically reviewed.

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IQ – Installation Qualification

1. Systems that are determined to have direct product impact are identified in the Validation Master Plan
(VMP) or equivalent document as requiring IQ.
2. IQ verifies that equipment as installed meets the established critical installation requirements.
3. IQ is verification of installation activities, and not the act of installation.
4. Only those critical components of equipment/systems determined to directly impact product quality
through a component-level risk or impact assessment are included in the IQ protocol. Engineering
details which do not directly impact product quality or patient safety may be documented in
Commissioning and need not be repeated in IQ.

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OQ – Operation Qualification

1. OQ tests demonstrate that the system meets all product/process critical operating requirements. This
includes:
1. Control

2. Monitoring

3. Recording

4. Alarming

of critical process parameters and specified critical quality attributes.

2. OQ should be compliance-based and only include system tests which have a potential direct impact on
product quality
3. OQ should include both equipment and automation qualification testing. intent of OQ is to operationally
qualify a unit as an integrated system.
4. OQ is not process specific, but provides documented verification that the equipment/module/system
operates within its intended design parameters and anticipated operational ranges
5. The goal during OQ testing is zero test failures and zero critical exceptions
6. Qualification is typically performed on-site under anticipated operating conditions

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PQ – Performance Qualification

1. PQ demonstrate that all the individual equipment can perform together.

1. Pertinent SOP have been approved

2. Training on SOP is complete and documented

2. PQ integrate Procedure, personnel, system and materials

1. Loads are define and available (autoclaves, oven, washer,…)

2. HVAC Environmental monitoring plan

3. PQ can be product dependant or product independent

4. PQ demonstrate that the system performance consistently achieves acceptance criteria
1. PQ can involve testing over an extended time period or repetitive testing

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Qualification Summary reports – Acceptance and release

1. Brief summary of the qualification test activities

2. Highlights of testing, especially any failures and the corrective action and resolution
3. Any modifications which were necessary to the protocol
4. Summary statements should indicate whether the equipment specifications have been verified for its
intended use in the manufacturing operations
5. Conclusion – Acceptance and release
1. Based on the passing Qualification results, system qualification is determined to be successfully completed
and system xxx and xxxx are now released for GMP use.

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 CQV Model Evolution

• Focus on What • Focus on How • Focus on Why

Lean model
V Model

Risk Based Approach

• Compliance • 10 Years old • Patient Centric
driven • Reduced effort approach
• Emphasis on • Define Critical • Support
Documents – Not • Introduce the Manufacturing
system notion of need
Performances verification • Improve quality
• Quality control • Some outcomes
behaviour Improvement • Quality Assurance
• Protocol possible model
Developed from • Often limited to • Efficient execution
template Leverage • Promote
• No value adding improvement
• No Improvement

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No deviation Pte Ltd 2 Venture Dive #3-27 Vision Exchange Singapore 608526  +65 6592 4573  admin@nodeviation.com  www.nodeviation.com ©2018
THE MANUFACTURING
NEEDS
ICH Q10 – Pharmaceutical Quality System - Objectives

Achieve product realisation

Establish and Maintain a State of Control

Facilitate Continual Improvement

©2018

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THE REGULATORY BACK
GROUND

3
5
FDA - Guidance for Industry Process Validation:
General Principles and Practices

Process Validation:
Stage 1 – Process Design
Stage 2 – Process Qualification (PQ) - This stage has two elements
2.a Design of the facility and qualification of the equipment and utilities
2.b Process performance qualification (PPQ)
Satge 3 – Continued Process Verification

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EU - Annex 15: Qualification and Validation

Section 3 Page 4
QUALIFICATION STAGES FOR EQUIPMENT, FACILITIES, UTILITIES AND SYSTEMS:
Define URS / DQ / FAT / SAT / IQ / OQ / PQ
Installation qualification (IQ)
3.8. IQ should be performed on equipment, facilities, utilities, or systems.
3.9. IQ should include, but is not limited to the following:
i. Verification of the correct installation of components, instrumentation, equipment, pipe work and
services against the engineering drawings and specifications;
ii. Verification of the correct installation against pre-defined criteria;
iii. Collection and collation of supplier operating and working instructions and maintenance
requirements;
iv. Calibration of instrumentation;
v. Verification of the materials of construction.

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EU - Annex 15: Qualification and Validation

Operational qualification (OQ)

3.10. OQ normally follows IQ but depending on the complexity of the equipment, it may be performed as a
combined Installation/Operation Qualification (IOQ).
3.11. OQ should include but is not limited to the following:
i. Tests that have been developed from the knowledge of processes, systems and equipment to
ensure the system is operating as designed;
ii. Tests to confirm upper and lower operating limits, and /or “worst case” conditions.
3.12. The completion of a successful OQ should allow the finalisation of standard operating and cleaning
procedures, operator training and preventative maintenance requirements..

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EU - Annex 15: Qualification and Validation

Performance qualification (PQ)

3.13. PQ should normally follow the successful completion of IQ and OQ. However, it may in some cases be
appropriate to perform it in conjunction with OQ or Process Validation.
3.14. PQ should include, but is not limited to the following:
i. Tests, using production materials, qualified substitutes or simulated product proven to have
equivalent behaviour under normal operating conditions with worst case batch sizes. The frequency of
sampling used to confirm process control should be justified;
ii. Tests should cover the operating range of the intended process, unless documented evidence from
the development phases confirming the operational ranges is available.

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PIC/S - VALIDATION MASTER PLAN
INSTALLATION AND OPERATIONAL QUALIFICATION NON-STERILE
PROCESS VALIDATION CLEANING VALIDATION
September 2007
2.2.2 At the time of issue, this document reflected the current state of the art. It is not intended to be a
barrier to technical innovation or the pursuit of excellence.
2.2.3 The advice in these Recommendations is not mandatory for industry. However, industry should
consider these Recommendations as appropriate.

2.3.1 The premises, the supporting utilities, the equipment and the processes have been designed in
accordance with the requirements of GMP. This normally constitutes Design Qualification or DQ.
2.3.2 The premises, supporting utilities and the equipment have been built and installed in compliance with
their design specifications. This constitutes Installation Qualification or IQ.
2.3.3 The premises, supporting utilities and the equipment operate in accordance with their design
specifications. This constitutes Operational Qualification or OQ.
2.3.4 A specific process will consistently produce a product meeting its predetermined specifications and
quality attributes. This constitutes Process Validation or PV. The term Performance Qualification or
PQ may be used also.

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PIC/S - VALIDATION MASTER PLAN
INSTALLATION AND OPERATIONAL QUALIFICATION NON-STERILE
PROCESS VALIDATION CLEANING VALIDATION

5.2.1 Installation Qualification is an essential step preceding the Process Validation exercise. It is normally
executed by the Engineering group.
5.3.1. The installation of equipment singularly or as a group (plant) should follow well defined plans.
5.4.1 Operational Qualification is an exercise oriented to the engineering function, generally referred to as
commissioning.
5.4.3 It is expected that during the Operational Qualification stage the manufacturer should develop
draft standard operating procedures (SOPs)
5.5.1 The conduct of an Operational Qualification should follow an authorised protocol. The critical
operating parameters for the equipment or the plant should be identified at the Operational Qualification
stage.

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Conclusion

1. Definition is not the primary focus

2. Guidance is not intended to be a barrier to technical innovation or to the pursuit of excellence
3. Qualification is a starting point not an end
4. Qualification and validation provide some key evidence that a process is under control, but it is
in the day to day operation- over time – where evidence of control must be seen

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