Commissioning & Qualification

of Critical Process Systems

David Tomsik
M+W Thailand Limited

June 2017
 Introduction

 Purpose of this presentation is to present an approach for C&Q of critical process

systems
 Nanofiltration will be used as an example of a critical systems
 Review pre-commissioning activities including creation of Commissioning Master
Plans and Qualification Master Plans
 Preparation of Commissioning Test Plans and Commissioning Test Protocols for
Nanofiltration Skid
 Function of URS, Design Review, FAT, Family Approach, Leveraging and Change
Control.

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 Presentation Outline

 Introduction
 References / guidelines
 Commissioning Master Plan
 Qualification Master Plan
 Overview of CQV steps / stages
 Commissioning Test Plan – NF Skid
 Commissioning Test Protocols – NF Skid

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 C&Q References / Guidelines

 ISPE Baseline® Guide Volume 5: Commissioning & Qualification.

 Impact assessments
 Good engineering practice (GEP)
 Design reviews
 Commissioning
 Qualification (IQ, OQ and PQ)
 ASTM E2500: Standard Guide for Specification, Design, and Verification of
Pharmaceutical and Biopharmaceutical Manufacturing Systems and Equipment.
 Risk‐based and science‐based approach.
 Subject Matter Experts (SMEs) to drive the specification, design, and verification.
 Risk assessments to determine verification needs
 Verification list
 Verification test matrix

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 Key Concepts of ASTM E2500

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 Commissioning Master Plan – Contents

Purpose of the Commission Master Plan is to describe the overall approach for the
commissioning of the facility:
 Commissioning and qualification strategy
 Risk assessments
 Test matrix
 Family approach
 Leveraging
 Need for qualification
 Direct Impact vs. Indirect / No Impact
 Direct Impact will be commissioned and qualified
 Indirect and No Impact equipment systems will be commissioned only

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 Impact Assessment

Identify the System

Develop System
Boundaries

Does the System

have Direct Impact YES
on the Product
Quality?

NO

Is the System YES

linked to a Direct
Impact System?

"Indirect Impact "Direct Impact

NO System" System"

"No Impact System" Develop Supporting Rationale

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 Commissioning Master Plan – (continued)

 Engineering design qualification requirements

 Design review
 DQ
 Construction handover to commissioning
 Factory Acceptance Testing
 Equipment / skids receipt and installation verification
 Mechanical & electrical installation verification
 Turnover documentation verification

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 Commissioning Master Plan – (continued)

 Automation and Control System handover to commissioning

 Network verification
 BMS
 E&I panels and wiring checks
 Loop checks
 Motor & electrical devices verification
 Loss or power & UPS checks

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 Commissioning Master Plan – (continued)

 Commissioning Test Plan

 Title Block / Approval Signatures
 System Description
 Pre-Commissioning Check List
 Commissioning Testing Requirements - Installation / verification
 Commissioning Testing Requirements - Operational testing
 Commissioning Testing Deficiency/Deviation Review
 Commissioning Testing Completion Signoff

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 Commissioning Master Plan – (continued)

 Commissioning Test Protocol

 Title Block / Approval Signatures
 Scope of Test Protocol
 Test Case Description
 Test Executed By - List of individuals involved
 Test Protocol Pre-requisites
 Test Case Record – Step by step description with results and acceptance criteria
 Test Results Approval
 Commissioning Test Report
 Commissioning Deficiencies and Deviations
 Handover to owner for validation/operations

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 Qualification Master Plan – Contents

Purpose is to describe the overall approach for the qualification of the facility:
 Qualification strategy
 Direct Impact equipment groups
 Demonstration / verification of the design, installation and operation
 Testing against the URS
 Leveraging strategy
 Commissioning Test Protocols which were pre-approved as Q relevant
 No critical deviation
 Change control in effect
 Family approach
 Equipment groups of similar designs (size, software, location, etc.)
 Testing of one member can support other members
 Reduced testing based on risk assessments

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 Leveraging of Test Results

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 Qualification Master Plan – (continued)

 Supplier audits
 Vendor maintains acceptable quality standards
 Assure that suppliers have acceptable support documentation
 Risk assessment to identify areas of risk and remediation
 System documentation
 URS
 Risk assessments
 Test matrix
 Computer System Validation (included in Qualification)

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 Qualification Master Plan – (continued)

 Qualification
 Design Qualification (DQ)
 Installation Qualification (IQ)
 Operation Qualification (OQ)
 Performance Qualification (PQ) (by owner)
 Qualification Report

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 Overview of CQV Steps/Stages

System
Classification
Approve
CQMP DQ/DR
Profile
Component
Classification
Planning

Design
Construction
QA
Requirements
Procurement Initial Cals

Loops Commissioning
Package
Construction/
Installation
Project

Simulation/
Commissioning IQ OQ PQ
Offline Testing

Qualification
Owner
IV
FT Validation
RV
SAT
FAT Startup
Approve System- Operations/
level Plans Maintenance

*Refer: ISPE C&Q Benchmarking presentation

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 Commissioning Test Plan – Nanofiltration Skid

 Commissioning testing planned for Nanofiltration Skid

 Pre-commissioning check list
 Mechanical completion
 Safety inspection
 Safety training
 Pressure safety devise verification
 Commissioning Testing Requirements – Installation / verification
 Filter installation verification
 Pump installation verification
 Instrument calibration verification (Q)
 P&ID walk down and slope check (Q)

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 Commissioning Test Plan – NF Skid (continued)

 Commissioning Testing Requirements – operational testing

 Automation code testing
 Pressure control verification
 Transfer verification
 Drain Verification
 Alarm verification (Q)
 Spray ball coverage verification (Q)
 Differential pressure control verification (Q)
 CIP verification
 CIP verification (Q)
 Cold sanitization of filter verification (Q)
 SIP verification
 SIP verification (Q)

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 Commissioning Test Plan – NF Skid (continued)

 Deficiency List
 Deviation List
 Post Approval
 Commissioning Lead
 Process Lead
 Qualification Lead
 HSE Lead

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 PFD - Nanofiltration Skid

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 Commissioning Test Protocol – Filter Installation
Verification
 Install / verify installation of filter element and record details
 Manufacturer
 Model number
 Pore size / rating
 Verify filter element is installed in accordance with design
 Highlight filter datasheets to indicate checked and attach to this document

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 Commissioning Test Protocol – Pump Installation
Verification
 Verify installation of pump and record details
 Pump Type
 Manufacturer
 Model number
 Verify pump is installed in accordance with design
 Highlight pump datasheets to indicate checked and attach to this document
 Check motor rotation direction
 Coupling guards are installed
 Run pump to check performance against pump curve
 Record speed, suction pressure, discharge pressure and flow rate at 3 different
operating points
 Confirm that the pump data recorded matches manufacturers pump curve

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 Commissioning Test Protocol – Instrument Calibration
Verification (Q)
 Verify the calibration of critical instruments and record the details
 Tag number
 Interval
 Calibration range
 Calibration tolerance
 Calibration results
 Calibration due date
 Verify the calibration of non-critical instruments and record location of calibration
reports

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 Commissioning Test Protocol – P&ID Walk Down and
Slope Check (Q)
 Perform P&ID walk down and highlight completed items
 Verify all devices and tag number
 Verify all pipe lines and flow paths
 Verify all input and output fluid tags/arrows
 Verify all notes pertaining to hardware/devices
 Mark any discrepancies in red ink and record deficiencies as needed
 Verify the slopes of product critical lines
 Mark the slope measurement on a copy of the P&ID
 Highlight and record deficiencies as needed

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 Commissioning Test Protocol – Automation Code
Testing
 Verify software download and version
 Verify graphic reflect P&ID
 Highlight the attached P&ID and annotate any deviations
 Verify functionality of emergency stop (E-Stop) buttons
 Activate the E-Stop buttons and confirm that all devices go to safe state as per
the failure logic described in the Functional Specification (FS) for the control
system
 Highlight the tested logic in FS and annotate any deviations
 Verify functionality of the Hold states
 Initial the Hold states and confirm that all devices go to safe state as described
in the Functional Specification (FS) for the control system
 Highlight the tested logic in FS and annotate any deviations

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 Commissioning Test Protocol – Automation Code
Testing (continued)
 Equipment Control Module Testing
 Verify that the graphics reflect the P&ID and highlight the attached P&ID
 Verify all control parameters
 Verify the sequence for each operation including all Production, CIP and SIP
operations
 Verify the safety interlocks and failure logic
 Highlight the tested parameters, operations and logic in FS and annotate any
deviations

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 Commissioning Test Protocol – Pressure Control
Verification
 Pressure control setup
 Record PID tuning parameters
 Setup trend recording of pressure and pressure set point
 Pressure control test, empty system, set point 0.5 Barg
 Vent skid to 0.0 Barg
 Change set point to 0.5 Barg
 Wait for stable pressure at 0.5 Barg and record time
 Continue to control pressure for 10 minute hold time
 Record min/max pressures during hold period
 Acceptance criteria is tolerance ± 0.1 Barg

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 Commissioning Test Protocol – Transfer Verification

 Extractable flush of Nanofiltration Skid

 Input test parameters (Ext_flush_vol = 600 L)
 Run automated operation
 Complete automated operation and record final flush volume
 Acceptance criteria is 600 ± 60 L
 Normalized water permeability (NWP) test of Nanofiltration Skid
 Input test parameters (NWP_deltaP, L_NWP and H_NWP)
 Run automated program
 Simulate NWP low limit test failure by restricting flow (with manual valve)
 Record NWP of failed test
 Retry NWP operation with no flow restriction
 Record NWP and NF differential pressure taken during the test period

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 Commissioning Test Protocol – Transfer Verification
(continued)
 Transfer from product feed vessel to product receiving vessel via NF Skid
 Input test parameters (P_flow and P_deltaP)
 Run automated operation
 Confirm flow control at set point of P_flow
 Simulate high differential pressure by throttling filter inlet valve
 Verify that differential pressure control activates and reduces flow to maintain
differential pressure at set point of P_deltaP
 Record trends of flow and differential pressure
 Transfer from chase buffer vessel to product receiving vessel via NF Skid
 Input test parameters (Flush_flow and Flush_volume)
 Run automated program
 Confirm flow control at set point of Flush_flow
 Complete automatic operation and record chase buffer volume
 Acceptance critera is Flush_volume ±10%
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 Commissioning Test Protocol – Drain Verification

 Verify the drainability of Nanofiltration Skid

 Input test parameters (Drain_pressure and Drain_time)
 Fill the system including inlet/outlet transfer lines with WFI
 Run automated drain cycle
 Complete automated operation
 Inspect the system at designated low points to confirm no liquid remaining
 Highlight attached P&ID to indicate areas inspected and results

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 Commissioning Test Protocol – Alarm Verification (Q)

 Verify alarming functionality of quality critical alarms

 For each quality critical alarm, simulate the process value (PV) above or below
the alarm point
 Verify that each quality critical alarm is triggered and recorded by the control
system
 Attach a printout of the alarm data

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 Commissioning Test Protocol – Spray Ball Coverage
Verification (Q)
 Purpose is to verify spray ball coverage within the filter housing during CIP.
 Prepare riboflavin solution at 0.1 ±0.02 g/L
 Apply riboflavin to all surfaces inside the filter housing
 Run automated operation for CIP final rinse
 Record trend of CIP fluid temperature, pressure and flow rate vs time
 Confirm visually that all riboflavin is removed

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 Commissioning Test Protocol – Differential Pressure
Control Verification (Q)

 Verify that the system calculation for differential pressure is correct and meets the
process tolerance
 Simulate the process value for the NF inlet and outlet pressure.
P(inlet) = 1.00 Bar
P(outlet) = 0.95 Bar
 Confirm that differential pressure displayed on control system is 0.05 Bar
 Simulate the process value for the NF inlet and outlet pressure.
P(inlet) = 4.00 Bar
P(outlet) = 0.00 Bar
 Confirm that differential pressure displayed on control system is 4.00 Bar
 Process tolerance is 0.05 Bar

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 Commissioning Test Protocol – CIP Verification

This test covers operational verification of non-quality critical functions

 CIP Circuit flow path verification
 Highlight each path on the attached P&ID
 CIP flowrate verification
 Annotate flowrate on attached P&ID
 Verify that flowrate meets minimum requirement to ensure turbulent flow and
meets spray ball requirement
 Pressure Leak Test verification
 Verify that the pressure leak test is detecting safety relevant leaks and can be
conducted successfully

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 Commissioning Test Protocol – CIP Verification
(continued)
 CIP Recipe Verification
 Pre Rinse
 Chemical Wash
 Final Rinse
 Purge & Drain
 CIP Monitoring Alarm Limit Verification
 Verify that the alarm limits are in accordance to requirements

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 Commissioning Test Protocol – CIP Verification (Q)

This test covers operational verification of quality critical functions

 Verify that the relevant CIP circuit parameter values are documented and configured
in the process control system
 Run the CIP automated operation to verify that all relevant parameters are
maintained and that there are no critical alarms or hold conditions during the CIP
recipe execution.
 Perform post CIP equipment inspection to verify the equipment is drainable and
there is no excessive pooling in the filter housings

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 Commissioning Test Protocol – Cold Sanitization of
Filter Verification (Q)
 Cold Sanitization flow path verification
 Confirm flow path from supply vessel to target Nanofilter
 Highlight the flow path on attached P&ID
 Cold Sanitization recipe verification
 Run automated operation
 Verify priming step and record volume of WFI transferred
 Verify transfer of NaOH and record volume of NaOH transferred
 Verify soaking step and record soak time.
 Verify final rinse and record volume of WFI transferred
 Verify that NaOH was completely removal

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 Commissioning Test Protocol – SIP Verification

This test covers operational verification of non-quality critical functions

 SIP flow path verification
 Highlight all equipment and lines associated to the SIP circuit on the attached
P&ID
 Verify that all measurement devices, which are used for monitoring of
temperature or pressure during SIP are identified.
 Pressure Leak Test verification
 Verify that the SIP pressure leak test is detecting safety relevant leaks and can
be conducted successfully
 SIP Routing and temperature monitoring verification
 Verify that the SIP circuit has been implemented correctly and confirming paths
and associated monitoring devices on DCS screen

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 Commissioning Test Protocol – SIP Verification
(continued)
 Operation Verification for SIP
 Highpoint temperature verification to ensure that air in highpoints (e.g.
manways, filter housing) has been evacuated properly and SIP temperature can
be reached.
 SIP temperature & dwell time verification
 Vacuum break & post-SIP pressure verification
 Hygienic status verification

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 Commissioning Test Protocol – SIP Verification (Q)

This test covers operational verification of quality critical functions

 Verify that the relevant SIP circuit parameter values are documented and configured
in the process control system
 Verify that the SIP cycle reaches the specified temperature during SIP dwell time
with no critical alarms
 Input test parameters (SIP_temperature and SIP_time)
 Run automated operation
 Verify the SIP cycle completion without any critical alarms
 Verify that all TT reading are ≥ SIP_temperature for ≥ SIP_time.
 Attach trend of all TT’s for the entire SIP duration and annotate the start and end
time of SIP dwell

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