Commissioning and Qualification From Traditional

Commissioning and Qualification:
From Traditional Approach

to
Verification Approach
(Science & Risk Based)
Ricardo Girão
Tiago Pires
Reunião Anual do Colégio de Indústria

Farmacêutica da Ordem dos Farmacêuticos
Batalha
06 Abril 2019
www.telstar-lifesciences.com
Contents
▪ Basic Concepts
▪ Traditional Approach (Commissioning and Qualification)
▪ Guidelines for a more efficient approach
▪ The Verification Approach – Science & Risk Based
▪ New concepts and fundamentals
▪ (Examples)
▪ Final considerations
OBJECTIVE
Demonstration of fitness for intended use
Traditional Verification
Approach Approach
(Science & Risk
(IQ;OQ;…) Based)
You may stay here …just stop here …or here ..and want to get here…
What is the most appropriate approach?
Traditional Approach - Basic Concepts
• Qualification
As per FDA’s January 2011 Process Validation Guideline: “…qualification refers

to activities undertaken to demonstrate that utilities and equipment are suitable
for their intended use and perform properly”
As per ISPE Good Practice Guide: Applied Risk Management for Commissioning
and Qualification: “Qualification: is the demonstration of suitability for
intended use which has been formally documented and approved”
Qualification of a system shall be understood as set of activities that will provide

documental evidence that its design, construction, installation and operational
mode are in accordance with predefined specifications.
Traditional Approach - Basic Concepts
• Commissioning
As per ISPE Baseline Guide Volume 4, Commissioning and Qualification:

“A well planned, documented, and managed engineering approach to the start-up
and turnover of facilities, systems, and equipment to the End-User that results in a
safe and function environment that meets established design requirements and
stakeholder expectations.”
Physical Testing and

Setting to Regulation and
Completion Performance
Work Adjustment
and Inspection Testing
Planning and preparation associated with managing the above activities
Commissioning has historically been viewed as an engineering activity that was

early in the process where Q-Unit involvement was not necessary.
Qualification Traditional Approach
TRADITIONAL APPROACH: QUALIFICATION
▪ Quality Assurance/Quality Unit approves each and every protocol test

▪ Organization refused to leverage commissioning
▪ Automated systems and controlled equipment were qualified separately and inefficiently
▪ Deviations from trivial items diluted Q-Unit attention
▪ Disqualifying verification documentation made by suppliers because they occurred prior to
Quality unit pre-approval protocol
▪ Separate Commissioning from Qualification and establishing not added value thresholds
between different qualification
TRADITIONAL
TRADITIONAL QUALIFICATION
QUALIFICATION
RIGID PROCESS
RIGID PROCESS
Qualification
Issuing of Approval of Approval of Release for
IQ Testing OQ Testing Activities
IQ/OQ IQ OQ PQ/PV
Finished
Qualification consists of a series of IQ, OQ and PQ Protocols (following

competition of construction and start-up).
- Diluting efforts and resources across documental formalities.
- Focus on all system features instead of on quality-critical aspects related to
the product.
- Inefficiency practices.
- The goal is mostly concentrated on the release of the system for use
- Undervalues a life cycle approach.
Example 1: Reactor / Tank Verification to open It is verified that it is
Qualification a certain valve another one that opens
The deviation is evaluated and approved by the Q-Unit.

The Q-Unit designee who handles the deviation might not have the proper
process equipment knowledge to evaluate it.
Is this the most efficiency approach?
Example 2:
Vendor: Implements a Verifies the motor Reports under

HVAC AHU motor rotation direction Commissioning
Q-Unit: Approves Protocol

Verifies the motor Reports on Qualif.
and Acceptance
rotation direction Protocol
Criteria
Repeat that verification (already knowing the “answer”).

Opportunity for minor deviations due to erroneous test description.
Are we properly using our resources?

Example 3:
It is verified during the IQ that one instrument is not calibrated.
Option 1:
- Open a deviation to be evaluated and approved by the Q-Unit.
Option 2:
- Stop the Qualification / Project and wait for the instrument to be calibrated.
Shall we concentrate our efforts merely formal issues?
• What is the added value of:
- Discrepancies without product-quality impact being approved by the Q-unit.
- Repetition during Qualification of verifications performed during commissioning.
- Interrupt a project due to documental formal issues.
Efficiency (cost)
Product Quality
NO ADDED VALUE
(Risk Control)
Patient Safety
A more efficient approach is needed!
GUIDELINES FOR A MORE EFFICIENT APPROACH
ASTM E2500 - Standard Guide for

Specification, Design, and Verification of
Pharmaceutical and Biopharmaceutical
Manufacturing Systems and Equipment
https://www.astm.org/Standards/E2500.htm
Key Concepts
▪ Describes a risk-based and science-based approach to specification, design,
and verification of manufacturing systems
▪ Intended to ensure that systems are fit for intended use, and to satisfy
requirements for design, installation, operation, and performance
▪ Encompasses all types of approaches - commissioning and qualification,
verification, system validation, or other.
▪ Applies concepts and principles introduced in the FDA initiative, Pharmaceutical cGMPs
for the 21st Century—A Risk-Based Approach
▪ Supports, and is consistent with, the framework described in ICH Q8, ICH Q9, ICH Q10,
and ICH Q11.
Science & Risk Based Verification Approach
Fundamentals of S&RB Approach

▪ Risk-based - applied to specification, design, and verification – QRM principles aligned
with ICH Q9
▪ Science-based – use of product and process information, such as Critical Quality Attributes
(CQA) and Critical Process Parameters (CPP) – in line with ICH Q8
▪ Identify Critical Aspects of the systems - functions, features, abilities, and performance or
characteristics to ensure consistent product quality and patient safety.
▪ Verification documentation shall be sufficiently flexible to be synchronized with the project
progress rather than to rigidly dictate the project execution
▪ Use Good Engineering Practices (GEP) to verify installation and operation, including vendor
documentation, and to address discrepancies not related with Critical Aspects
▪ Identify Subject Matter Experts (SME) and emphasize their role as key through all phases
▪ Re-focus the role of the Q-Unit to the approval of requirements, specs, test plans and
deviations related only with Critical Aspects for product quality and patient safety
▪ Design Reviews and Change Management to assure fitness for use through the system life-
cycle
▪ All activities must bring value
Science & Risk

Based Verification
Approach
(as defined in ASTM E2500)
SUBJECT MATTER EXPERT
▪ Defines or oversees:
– The verification strategy
– The verification deliverables
QA
– The verification activities
QRM
– The acceptance criteria
– The evaluation of deviations
– The release for use
SME
CQA; CPP GEP
Operations Engineering
HOW TO GET THERE
Provides a roadmap for the transition of traditional IQ/OQ

approach to science and risk-based approaches, including
practices and terminology.
https://ispe.org/publications/guid
ance-documents/good-practice-
guide-applied-risk-management-cq
▪ Adopting practices which are lean and efficient is optional

▪ Ensuring that practices provide verification of aspects related with
product quality and patient safety is compulsory
▪ Recommends elimination of wasteful practices for development of IQ and
OQ documentation.
▪ There is a business case as well as a quality case for implementing these
approaches.
• Verification Process Flow Chart
CQA List of Critical Approved by

CPP Aspects Quality Unit
Verification Approved by
Plan Quality Unit
Subject Matter Experts
Verification Testing (Design to Performance) Review all completed

to confirm Critical Aspects and meet verification test by a
Acceptance Criteria second, independent SME
Acceptance Approved by
and Release Quality Unit
Operation,
Continuous
Improvement
• Verification Process Application
Defines the Tests and Developed by SME and

Verification Plan
Acceptance Criteria Approved by Q-Unit
All testing methodology procedures development and protocol issuance,

as well as their execution and revision are performed by the proper SMEs.
Example 1: Reactor / Tank Verification to open It is verified that it is
Qualification a certain valve another one that opens
The deviations is treated by equipment and process SMEs.

The corrective actions can be controlled through an Engineering Change
Management System.
Addressed prior to Q-Unit Acceptance & Release.
Example 2:
Vendor: Implements a Verifies the motor Reports under

HVAC AHU motor rotation direction Commissioning
Evaluated as non critical aspect for product-quality or patient safety.
The verification can be documented on commissioning activities.
Example 3:
It is verified during the IQ that one instrument is not
calibrated.
There is no definition of which activity is included

during “IQ,” or which should only be included during
“OQ.” The logical sequence of testing is more
important than which activity is included during “IQ,”
or which should only be included during “OQ,” e.g., the
calibration of measuring loops needs to be performed
successfully before functional tests are executed
utilizing the measured results.
Suggested Tools:
Use of Red-Lined documentation
Open Deviation (Usage of
Quality Unit Resources)
Ex:
Traditional
Testing: Verification of Missing a non-critical
P&ID instrument on an P&ID
Verification
Use of Red-Lined
documentation
- Applicable to P&ID drawing or SOPs.

- Changes document by hand, initialed, dated
and controlled.
- At an appropriate point these red lined
documents can be transferred to the next
updated version of the document and re-
approved.
- Available for use by SMEs for review and
approval or in the execution of C&Q testing
plans.
• Quality Risk Management Trends

These trends are already being considered in reference practices.
EU GMP Annex 1 - Manufacture of Sterile Medicinal Products (Under Consultation / Revision)
Example – For room classification (Maximum permitted Non-viable Airborne Particles)
▪ Initial Qualification – The particles equal to or greater than 0.5 μm should be measured.
▪ For Monitoring – The particles equal to or greater than 0.5 μm and 5 μm should be measured.
Approach Approach
• Quality Risk Management Trends
These trends are already being considered in reference practices.
EU GMP Annex 15 – Qualification and Validation – In force since October 2015

▪ The QRM principles were introduced.
Curiosity – Did you know how many times does the word “Risk” appears?
Version from July 2001 Version from October 2015

3 23
Approach Approach
Why change our work

Significantly
cultures, & regulatory reduce
costs/time
framework to move from
More consistent Adopting
the traditional and reliable practices which
qualification approach to achievement of are lean and
URS efficient
a value added model?
Provide
clarification of QRM and Alignment with
roles and
responsibilities,
Science post-ICH Q8,
Q9 and Q10
with more Base regulatory
efficient use of
SMEs
Approach expectations
Improve
process
knowledge as Decrease
basis for projects
subsequent complexity and
operations and “bureaucracy”
life cycle Ensure focus is
maintenance on quality-
critical system
features
FINAL CONSIDERATIONS
Risk Assessment Risk Management (QRM)
Departmental Approach Process Approach
Functional Roles Expertise and Knowledge
Predefined Steps Added Value Activities
Conservative Flexible and Efficient
Being In Conformity Being In Control
…just stop
here ...or may want
You may
stay here …or here to get there!
REFERENCES
▪ ASTM E2500-07 “ Standard Guide for Specification, Design, and Verification of

Pharmaceutical and Biopharmaceutical Systems and Equipment” (2007)
▪ ISPE Guide: Science and Risk-Based Approach for the Delivery of Facilities, Systems and
Equipment (ISPE FSE Guide) (2011)
▪ ISPE Baseline® Guide: Volume 5 –Commissioning and Qualification (2001)
▪ European Good Manufacturing Practice (EU GMP) Part I - Basic Requirements for Medicinal
Products
▪ EU GMP Annex 1 – Manufacture of Sterile Medicinal Products
▪ EU GMP Annex 15 – Qualification and Validation
▪ EU GMP Annex 20 – Quality Risk Management
▪ FDA 21 CFR Part 210 – Current good manufacturing practice in manufacturing, processing,
packing, or holding of drugs; general.
▪ FDA 21 CFR Part 211 – Current good manufacturing practice for finished pharmaceuticals.
▪ ICH Q9 – Quality Risk Management
▪ ICH Q10 – Pharmaceutical Quality System
Questions?
Thank you for your attention

rgirao@telstar.com
tpires@telstar.com

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Commissioning and Qualification:

From Traditional Approach

Reunião Anual do Colégio de Indústria

Demonstration of fitness for intended use

What is the most appropriate approach?

As per FDA’s January 2011 Process Validation Guideline: “…qualification refers

Qualification of a system shall be understood as set of activities that will provide

As per ISPE Baseline Guide Volume 4, Commissioning and Qualification:

Physical Testing and

Planning and preparation associated with managing the above activities

Commissioning has historically been viewed as an engineering activity that was

TRADITIONAL APPROACH: QUALIFICATION

▪ Quality Assurance/Quality Unit approves each and every protocol test

Qualification consists of a series of IQ, OQ and PQ Protocols (following

The deviation is evaluated and approved by the Q-Unit.

Is this the most efficiency approach?

Vendor: Implements a Verifies the motor Reports under

Q-Unit: Approves Protocol

Repeat that verification (already knowing the “answer”).

Are we properly using our resources?

Shall we concentrate our efforts merely formal issues?

- Discrepancies without product-quality impact being approved by the Q-unit.

- Repetition during Qualification of verifications performed during commissioning.

- Interrupt a project due to documental formal issues.

A more efficient approach is needed!

ASTM E2500 - Standard Guide for

Fundamentals of S&RB Approach

▪ All activities must bring value

Science & Risk

Provides a roadmap for the transition of traditional IQ/OQ

▪ Adopting practices which are lean and efficient is optional

CQA List of Critical Approved by

Verification Testing (Design to Performance) Review all completed

Defines the Tests and Developed by SME and

All testing methodology procedures development and protocol issuance,

The deviations is treated by equipment and process SMEs.

Vendor: Implements a Verifies the motor Reports under

Evaluated as non critical aspect for product-quality or patient safety.

The verification can be documented on commissioning activities.

There is no definition of which activity is included

- Applicable to P&ID drawing or SOPs.

• Quality Risk Management Trends

EU GMP Annex 1 - Manufacture of Sterile Medicinal Products (Under Consultation / Revision)

Example – For room classification (Maximum permitted Non-viable Airborne Particles)

• Quality Risk Management Trends

These trends are already being considered in reference practices.

EU GMP Annex 15 – Qualification and Validation – In force since October 2015

Version from July 2001 Version from October 2015

Why change our work

Risk Assessment Risk Management (QRM)

Departmental Approach Process Approach

Functional Roles Expertise and Knowledge

Predefined Steps Added Value Activities

Conservative Flexible and Efficient

Being In Conformity Being In Control

▪ ASTM E2500-07 “ Standard Guide for Specification, Design, and Verification of

Thank you for your attention

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