Equipment Qualification –
Fit for Intended Use
Karem Y. Monge Sepúlveda
MS Physics, CQA
Senior Scientist-Technical Services
Mylan LLC
10/27-29/15
1
General Information
2
Why Qualify an equipment?
› References
– ASTM E2500-13 Standard Guide for Specification, Design, and Verification
of Pharmaceutical and Biopharmaceutical Manufacturing Systems and
Equipment
– ASTM 2537-08 Standard Guide for Application of Continuous Quality
Verification to Pharmaceutical and Biopharmaceutical Manufacturing
– Pharmaceutical cGMPs for the 21st Century
– Commissioning, Qualification, and Verification: A Review Solving the
Terminology Conundrum by R. Adamson, N. Calnan, R. E. Chew, and S. J.
Wisniewski
– ICHQ8 thru ICHQ11
– ISPEs Guidance Documents for Commissioning and Qualification
– ISPEs Science and Risk-Based Approach for the Delivery of Facilities,
Systems, and Equipment
– ISPEs White Paper on Risk-Based Qualification for the 21st Century, March
2005
– US FDA 21 CFR Part 11, 210 & 211, and 820
– EU GMPs
3
Why Qualify an equipment?
› Design and verify that an equipment that has the potential
to affect product quality and patient safety complies with
specifications that are for its intended use.
› Provide manufacturing capability to support defined and
controlled processes that can consistently produce product
meeting defined quality requirements.
4
What it means “fit for intended use”?
› An equipment identified and designed for a particular task, with
a particular purpose, and performs during the manufacturing
process ensuring consistent product quality and patient safety.
› ASTM E2500 objective:
– Ensure that equipment is “fit for intended use” throughout it’s
lifecycle from concept to retirement in a systematic, efficient, and
effective way.
– Provide manufacturing capability to support defined and controlled
processes that can consistently produce product meeting defined
quality requirements.
– Satisfy international regulatory expectations.
The main objective is to reduce cost while improving
quality and safety.
5
What is the equipment lifecycle
approach?
› The lifecycle of an equipment begins from the time it
is requested through the end of its useful life or
when it is disposed.
› In general, the Site shall establish a lifecycle system
complemented by written SOPs that require the
documentation and testing of an equipment, from
design
through
initial
testing,
qualification,
requalification,
maintenance,
and
eventual
retirement.
6
Identify the need
Impact Assessment
New Equipment
Buy the equipment
Decommissioning
Modify and/or
upgrade
Qualify, Maintain, and
Monitor
7
What is the equipment lifecycle
approach?
› The lifecycle of an equipment consists of:
– Identifying the need for a particular equipment, giving special
attention to applications
› Equipment that do not have a GMP significance and does not
have a direct impact on product quality must be commissioned
following GEP.
– Performing an Impact Assessment
› May be integrated with a risk management process used to
determine product impact and the extent of the
verification/qualification and re-qualification period.
› Defines the boundaries of what to include/exclude from the
verification/qualification.
– Buying the equipment
– Qualifying, Maintaining, and Monitoring
8
– Decommissioning
What is the equipment lifecycle
approach?
› Design phase that sets the equipment requirements.
› Testing phase consisting of evaluation and development
to ensure that the equipment meets the design
specifications.
› Qualification phase to verify that the equipment meets
requirements consistently.
› Maintenance phase that includes calibration, preventive
maintenance, change control, and formal evaluation
documented using SOPs.
› Defining phase of requalification requirements and
period.
› Decommissioning phase (retirement) consisting of final
testing and formal documentation.
9
YES
Identify all utilities,
equipment, and systems
GMP Significance
Define boundaries
NO
Perform Impact Assessment
GEP



Commissioning and
Recertification required
Qualification not required
CC review may be
required
YES
(e.g. Air Quality)
Direct product contact
NO
(e.g. Building
Management System)
YES
Produces data which
impacts product release
NO
YES
(e.g. WFI)
Provides an excipient or
produces an ingredient or
solvent
NO
YES
(e.g. PLC)
Confirm boundaries and
redefine if necessary
Process Control System with
no independent verification
NO
(e.g. Clean Steam)
YES
Used in final Cleaning
or Sterilization
NO
Qualification Process
YES
(e.g. Nitrogen)
Preserves product quality
NO
YES
Failure or alarm has
direct effect on product
NO
YES
BU or SME review
direct impact
NO
YES
GEP



Commissioning and/or
Recertification required
Qualification not required
CC review required
10
New Utilities/Equipment
Qualification Request
Existing Utilities/Equipment
Study Request (Process
and/or Utilities/Equipment
Requalification
Study Request
NO
Re-design or purchase
new Utilities,
Equipment, System
Is Utilities/Equipment
adequate for new
application?
YES
NO
Gather Utilities/Equipment
maintenance records,
or other operational data
Check existing Protocols
and Reports, are they
adequate for new
application?
YES
Are SOPs adequate
for new application?
NO
NO
Review Functional Requirement
Specification, Manufacturer’s
recommendations and drawings
Existing Requalification
SOPs?
Draft Operation SOPs
(if applicable)
YES
Develop, review,
and approve Protocol
YES
Execute Protocols or
Requalification SOPs
NO
Meet Acceptance
Criteria?
Record the deviation(s) and
ensure corrective actions
YES
Finalize Operation SOPs
(if applicable)
Prepare, review, and
approve Final Report
11
What entails the Qualification Process?
› Systematically verify that an equipment, acting singly or in
combination, are fit for intended use, have been properly
installed, and are operating correctly.
› ASTM 2500 describes two approaches to the specification,
design, and verification of the equipment that have the
potential to affect product quality and patient safety.
– Risk-Based Approach
– Science-Based Approach
› ISPE describes the Science and Risk-based Approach (RBA)
as a paradigm.
12
What entails the Qualification Process?
› Risk -Based Approach
– Apply risk management to specifications, design, and verification
– ICH Q9:
› The evaluation of the risk to quality should be based on scientific
knowledge and ultimately link to protection of the patient.
› The level of effort, formality, and documentation of the quality
risk management process should be commensurate with the level
of risk.
– QRM is a systematic process for the assessment, control,
communication, and review of risks to the quality of the drug
(product) across the product lifecycle.
13
What entails the Qualification Process?
› Science-Based Approach
– Use product and process information as the basis for making
science- and risk-based decisions. This ensures that manufacturing
systems are designed and verified to be fir for their intended use.
– Examples:
›
›
›
›
Critical Quality Attributes (CQAs)
Critical Process Parameters (CPPs)
Process Control strategy information
Prior execution experience
14
What entails the Qualification Process?
› ISPEs Science/Risk-Based Approach:
– There is a shift in the global pharmaceutical industry. It is applying
an all-encompassing approach to qualification and toward using
focused methodologies to assess the scope of qualification.
– It consists of:
› The identification and control of risks to product quality
› Formality and documentation commensurate with the risk
› Use of Good Engineering Practices (GEPs) to verify installation
and operation of the system / equipment
› Verification that the system / equipment performance meets
product and process user requirements
“Fit for
Intended
Use”!!!
15
What entails the Qualification Process?
› Risk-Based Qualification Principles1:
– Focus on that which affects product quality
– User requirements, based on the process (not on the equipment or
system) are the key to acceptability.
– Risk assessments and Process Knowledge used to identify critical
elements
– Use of Critical Process Parameters (CPPs) as the basis for the
qualification
– All activities must be value-added. That is, contribute in the
manufacturing capacity.
– Risk-based asset delivery
– Value-added documents based on technical merit.
– Use of supplier documentation
– Test planning (one-time testing)
– Foster innovation
1. ISPE: “A White Paper on Risk-Based Qualification for the
21st
Century” – March 2005
16
Specification, Design, and Review Process
Good Engineering Practice
Product Knowledge
Process Knowledge
Requirements Specifications
and Design
Verification
Acceptance
and Release
Operations and
Continuous Improvement
Regulatory Requirements
Risk Management
Quality
Design Review
Change Management
17 - 13
1. ASTME2500
Equipment Qualification
18
Qualification
› Commissioning, Qualification, and Verification Riddle
– Commissioning
› A planned, documented, and managed engineering approach to the start-up
and turnover of systems (e.g. facilities, equipment, and software) to the enduser that results in a safe and functional environment that meets established
design requirements and stakeholder expectations
– Qualification
› A sub-set of validation that provides documentation that critical components
of direct impact systems (e.g. facilities, equipment, software) are properly
deigned, installed, and tested according to predefined acceptance criteria
› A state, or determination, that the equipment has been found to be suitable
for its intended use
– Verification
› The act of confirming, through objective evidence, that a particular
specification has been met
19
Commissioning – Start-Up, setting to work, physical
adjustment, physical inspection, functional testing,
performance testing
SAT Verification Work
Commissioning Verification
Work
FAT Verification Work
Basis for suitability (process
requirements, risk control)
Qualified as Suitable
for Intended Use
Other Verification Work
Solving the Terminology
20 2 )
Conundrum (Fig.
Qualification Phases
› Functional Requirement Specifications (FRS)
– A document that delineates the operational characteristics of the
equipment as well as any design or construction details that have cGMP
implications. It is utilized as the basis for any design, Factory Acceptance
Test (FATs), Site Acceptance Test (SATs), Commissioning, and Validation
Activities.
› Enhanced Commissioning
– Commissioning documentation used to fulfill field-testing requirements for
the IQ and OQ
› Commissioning
– Systematic challenge that establishes that the equipment is manufactured
and installed properly, and that it operates in normal conditions in
accordance with the design and installation requirements and acceptance
criteria.
– Planned and systematic process for challenging and verifying that a facility,
system and equipment is constructed, installed and functionally operates
through all normal modes and conditions in accordance with the 21user,
design, and installation requirement and acceptance criteria.
Qualification Phases
› Installation Qualification (Verification)
– Documented verification that all key aspects of the equipment have
been properly selected, constructed, and installed in accordance
with the design requirements and established specification.
› Operational Qualification (Verification)
– Documented evidence establishing confidence that the equipment
operates as intended and is capable of consistent operation within
established specifications.
› Performance Qualification
– Documented evidence that the process or system, when operating
in its environment under typical conditions performs as intended in
meeting determined specifications
22
Purpose and Common Tests
›
Enhanced Commissioning
–
Identify requirements for the facility, system, equipment
to be commissioned, such as:
›
Change Control, Factory Acceptance Test (FAT), Functional
Requirements
Specification
(FRS),
User
Requirement
Specification (URS), verification of construction completion,
passivation, system leak test, pressure test, system cleaning,
among others
23
›
Purpose and Common Tests
Enhanced Commissioning
– Test Plan should include:
›
›
›
›
›
›
›
›
›
›
Identification and listing of all equipment, systems/sub-systems,
critical utilities, their specifications, normal operating limits, and
acceptance criteria
Identification of pre-requisites such as FAT, FRS and URS.
Identification of system boundaries.
Commissioning roles and responsibilities
Approval Matrix
Drawings
Area for deficiencies documentation, how they will be managed, and
resolutions
Test conditions (usually manufacturer’s recommendations) and
acceptance criteria
Commissioning Schedule
Unique identification number.
24
›
Purpose and Common Tests
IQ
– Equipment/System Specifications and Installation Verification
›
›
›
–
Equipment Drawing Verification
›
›
–
Compare the equipment/change against the key design specifications.
Fabrication and assembly will be per manufacturer specifications.
Document the equipment/change information and record the required
information, such as model number, serial number, company identification,
etc.
Identify the equipment/change major components, such as motors, valves,
sensors, etc. Inspect the individual system components for proper
installation. Document the inspection results. All equipment must be
installed according to the manufacturer and design specifications.
›
Identify (red lines) the equipment/change drawings that provide the
equipment/system physical location and identify the utilities required.
Verify the accuracy of as-built drawings against the actual installation and
visually compare the system with the manufacturer drawings.
Equipment Change Parts Verification
Identify and document the equipment/change parts and verify that all
change parts are in stock. The change parts should be under custody of
the
25
equipment owner.
›
Purpose and Common Tests
IQ
– General Documentation
›
Review the equipment/system manuals available for
installation, operation and maintenance manuals.
›
Verify the impacted Standard Operating Procedures (SOPs).
›
Store a copy of the equipment/system manual in the
Engineering Department and in the Owner’s Department (make
copies).
›
Verify and document the existence of the equipment/system
Functional Requirements and/or System Specifications that
define the intended application of the system.
›
Verify the equipment/change parts materials that are in direct
contact with the product. Document if the material used is
safe, appropriate, and free of contaminants.
›
Review the construction material documentation such as:
material certification, passivation, welding logs/certifications
and other applicable documents.
›
Verify the critical utilities such as Clean Steam and Water
for
26
Injection (WFI) pipelines.
›
Purpose and Common Tests
IQ
– Instrument Identification and Calibration Verification
›
›
›
Verify and document that the equipment/system instrumentation has been
categorized
as
either
GMP
(critical/non-critical)
or
non-GMP
instrumentation, and calibrated within manufacturer and design specified
ranges.
Verify that all critical instruments (manufacturer supplied) and supplemental
indicators, gauges and/or instrument loops are properly identified with an
instrument number and calibration label, and have been entered into the
Site Calibration Program.
All instruments associated with critical components must be categorized as
critical.
– For example, if a conveyor is identified as a critical component of the
equipment, the tachometer associated with that conveyor is a critical
instrument.
– Assure that all the standards required to verify the calibration of the
equipment are available and instructions or methodologies for the
handling, labeling, receipt, storage and replacement of them are in
place. These procedures should be in accordance with the manufacturer
recommendations and process requirements .
27
›
Purpose and Common Tests
IQ
– Utilities Verification
› Verify (through tests, measurements, etc.) that the required
utilities adhere to equipment/change requirements. The
utilities must be installed and available in conformance with
design and manufacturer specifications.
› Verify that the electrical utility includes an additional source
panel and a breaker. Utilities with product contact, such as
Water for Injection, Clean Steam, etc, must have qualification
packages completed or at least executed.
› A certified electrician must take the electrical measurements.
› Include
a
Wiring
Certification
from
a
qualified
engineer/technician, in order to certify that all field wiring of
the equipment/change has been properly connected and as
specified in the electrical and wiring diagrams.
28
›
Purpose and Common Tests
IQ
– Maintenance/Preventive Maintenance (PM) Review
›
›
–
Recommended Spare Parts List
›
›
–
Review the recommended and required Preventive Maintenance (PM). Verify
that the specified equipment/system items (battery back-up, lubrication,
etc.) and/or critical components (e.g. conveyor, vial rotator, fans, etc.)
either mechanical or controls have been entered in the Site Preventive
Maintenance Program. In addition, methods for recording irregular repair or
unscheduled maintenance should be in place.
Note: Critical components are those which have parameters or ranges that
maintain the performance and qualified state of the equipment/system. The
appropriate PM must assure that this is verified.
›
Review, verify, and document which spare parts are required for operation
and routine maintenance. Include referenced documents and an inventory
parts list.
Verify and document that such list have been submitted to the proper
Department. Include a documented evidence of the transaction.
Filter Installation Verification
Verify the proper identification and installation of filters (e.g., HEPA, ULPA)
related to the equipment and provide evidence of inclusion to the applicable
Certification Program. Include all certification and integrity testing
29
evidence.
›
Purpose and Common Tests
OQ
– Preventive Maintenance (PM) Review
›
–
–
–
›
›
Perform an assessment of the periodic re-qualification of the
equipment/system.
If the equipment/system requires periodic requalification, verify that the re-qualification activity has been entered into
the System. Include copy of the transaction.
Alarms Test
Challenge each alarm of the equipment/system following the established
test procedures and verify the machine response. Identify the alarms that
are not in use and document the reason for being disabled.
Controls Verification
Verify that the equipment operates as described by the manufacturer.
Start-up Sequence and Power Failure Verification
›
›
Verify that all steps following the activation of the equipment (“on” mode)
are satisfactorily achieved according with manufacturer specifications.
Verify that the equipment operates correctly after a power failure, and that
all restart conditions are met as well as the status of any set-up
configuration.
30
›
Purpose and Common Tests
OQ
– Radio Frequency (RFI) and Electromagnetic Interference (EMI)
Verification
›
–
Verify and document that radio frequency and electromagnetic interference
do not adversely affect the operation of the system.
Functionality Test
›
›
Verify the function of each main component of the equipment and
operational sequence functions.
Challenge the boundary limit of the ranges specified in the functional
specifications and verify the system capability (stress) and/or challenge the
machine speed, if applicable.
31
›
Purpose and Common Tests
OQ
– Operational
Qualification
of
Steam
Sterilizers,
Dry
Heat/Depyrogenation Ovens and Tunnels, and component
preparation equipment, additional tests include, but are not
limited to:
›
›
›
›
–
Temperature Distribution: Perform a temperature profile
Chamber Seal Integrity: Verify that the integrity of the door seals to hold
pressure
Door Interlocks: Verify that the door opening sequence is correct and
prevents the aseptic area to be compromised.
Particulate Removal: Determine the level of particulate on components and
closures after processing.
Development consists of, but is not limited to, the following
tests:
›
›
›
›
›
Heat Penetration Study
Machine ability
Sterilization
Humidity
Particulate Removal.
32
›
Purpose and Common Tests
PQ
– Objective:
›
›
›
–
Documented evidence that the equipment/system can consistently and
reliably perform the desired functions under actual or simulated conditions
of use (including environment) within the required process operating ranges
and meeting predetermined specifications.
It is executed at normal production environment (with the inclusion of the
expected load that to be managed by the equipment/system).
The equipment/system will be tested as a unit integrating all its parts and
sub-systems.
Preventive Maintenance (PM) Review
›
›
›
If the equipment/system requires periodic re-qualification, verify that the
re-qualification activity has been entered into the proper system.
Include a copy of the transaction as part of the qualification binder.
Note: For re-qualification date purposes of new equipment, the year will
start counting from the date of finalization of the first worst case successful
run instead of the date of report approval.
33
How to Maintain the Qualified State?
›
Develop a Validation Master Plan stating the overall
philosophy and approach used by the Facility / Functional
Unit for planning, designing, organizing, executing, and
reporting validation / qualification. The plan includes the
current state of validation.
Equipment Qualification - Include the approach to evaluate and perform
the equipment validation, which should include the computerized
control system that controls documents or acquire data for GMP related
activities, when applicable.
–
›
–
“Critical qualified equipment are re-qualified every 12 months.”
Validation Maintenance - Monitoring and Control Program to ensure that
a process once validated continues to operate in a validated state.
Include frequency of re-qualification and quantity of runs and tests.
34
How to Maintain the Qualified State?
›
Generate a List of GMP Equipment to be re-qualified
including the re-qualification schedule
– List should include the following:
Equipment
Type
Equipment
Name
Equipment
No.
Next Due
Date
Current
Report No.
Autoclave
Finn-Aqua
A1
11/15
Report #1
Fedegari
A2
01/16
Report #2
Precision
B1
12/15
Report #3
Thermo
Forma
B2
Hotpack
B3
Incubator
Decommissioned
11/15
Report #5
– List should be complemented with the Preventive
Maintenance System.
35
How to Maintain the Qualified State?
›
Create an SOP for the Re-qualification Program
–
›
Describe how the “periodic” Re-qualification Program is run in the
Facility/Site, to which equipment it applies, frequency of the requalification per type of equipment, and general process of the
re-qualification.
Create SOPs per type of equipment to re-qualify instead of
a Protocol/Test Plan (Pre-approved Protocol/Test Plan)
–
–
–
–
Overall exercise preparation
Execution of Test Runs
Handling of Deviations
Attachments for execution
36
Attachment I: Incubator HOTPACK (B3) - sensors Location Diagram
Place each sensor tip approximately three inches from the shelf surface
Load description: Incubator full of Product A samples in plastic trails (or equivalent to
simulated full conditions).
37
How to Maintain the Qualified State?
›
If it was determined that the equipment requires periodic
re-qualification, make sure that the applicable procedures
and Site Validation Master Plan is updated and
contemplates this requirement in its re-qualification
schedule.
›
Complete the necessary documentation in the proper
system to activate the scheduled re-qualification, to
indicate when the next re-qualification will take place.
›
If there are no procedures to adequately address the requalification requirements, develop a new procedure based
on the original validation exercise and current technical
procedures.
38
39
Documentation
40
How to Write an Effective Protocol?
› The general purpose of all technical writing is to inform the
reader as efficiently as possible.
› The aim of all technical writing is to transfer information.
41
How to Write an Effective Protocol?
› Write for the reader
– Means identifying who the audience for your document is and what
the purpose of your document is
› Write clear concise English
– Means creating clear concise sentences that are easy to read and
understand
– Structure the document in a logical order
› Select relevant appropriate details
– Means to focus on the essentials
› Make writing process effective
– Means to follow essential rules and guidelines in a systematic way
and maintain the focus on these every time a technical document is
written
42
How to Write an Effective Protocol?
› Technical Writing is a 4-phase process:
– Requirements: audience, purpose
› Clarify the audience and purpose (who are we writing
for and what we are trying to achieve)
– Design: organization and structure
› Define the structure that our document will have and
organize the information accordingly
– Implementation: draft
› Write the draft
– Testing: revision
› Review the draft; first by the writer, then it is distributed
for a more formal review
43
How to Write an Effective Protocol?
› Audience (Write for the reader)
– Before writing anything, define clearly:
› Primary Audience: who, what, when, how
– Who is the main person or main group who will read and use this
document?
– Who will perform?
› Secondary Audience: who else will read it
› Level of knowledge: about this specific subject
– Key question: Do they know about X, Or have they done Y
before?
– NOTE: The sign-offs are not the Primary Audience, they are the
Secondary Reader.
– NOTE: The Auditor is not the Primary Reader / Audience. What they
have is a level of knowledge. Thus, no matter time, the document
44
should read effortlessly.
How to Write an Effective Protocol?
› Specific Purpose (Write for the reader)
– The specific question for each document:
› What is this document meant to achieve? It is a tool to do a job,
where you must define exactly what that job is.
› What difference will it make? The document must make a
difference.
› What the reader will be able to do? This is the key question for
instructional material like procedures and work instructions and
protocols and operator’s manuals.
› What the reader understand? This is the key question for
technical reports.
› What action or response do I want? This is a key question for
proposals and or technical correspondence.
45
How to Write an Effective Protocol?
›
Structure (Write Clear Concise English)
– Do’s and Don’ts:
› Do make it brief (1 or 2 sentences).
› Do take time to be precise.
› Do stick to facts known at the time.
›
›
›
›
Don’t be vague.
Don’t include opinions.
Don’t include assumptions.
Don’t give too much or too little information.
46
How to Write an Effective Protocol?
›
Clear Concise English “The Golden Rule”
–
Sentences
› Short sentences – avoid long sentences
› Avoid complicated constructions
› Keep to 1 or 2 ideas
› Average of 15 to 20 words or less
› Break up long sentences
› Ex. The test cycle was restarted because two units were
contaminate. (10 – one idea)
› Ex. The Operations Department compiles inventory forecasts on
Friday and issues them to suppliers on Monday. (15 – two
ideas/use of clauses)
› Caution:
– Do not write telegraphese (like text messaging)
– Do not omit words
47
– Do not abbreviate normal words
How to Write an Effective Protocol?
›
Clear Concise English “The Golden Rule” Cont’d
–
Paragraphs
› The basic building block
› A set of related sentences
› Divide your subject into topics
› Cover each topic in one paragraph
› Keep paragraphs short
› Aim for a maximum of 5 sentences
› Aim for a maximum of 10 lines.
–
NOTE: The main point is to be clear about what the role of the
paragraph is – then the correct use of the paragraph will happen
naturally.
48
How to Write an Effective Protocol?
›
Clear Concise English “The Golden Rule” Cont’d
–
Verbs
› Tenses: past – present – future
– Past: we observed the reaction (this is after the execution)
– Present: we observe the reaction (used mostly for
instructions)
– Future: we will observe the reaction
– Keep the framework of tenses consistent
› Active and Passive
– Active – subject performs the action expressed in the verb
– Passive – subject receives the action expressed in the verb
or action is performed on the subject of the sentence
49
How to Write an Effective Protocol?
Clear Concise English “The Golden Rule” Cont’d
› Verbs
– In Reports:
› Use Passive Voice to
report actions and results
› Use the Past Tense to
report actions and results
› Optionally, use the
Present Tense for
discussion, conclusions,
and recommendations
› Above all, BE
CONSISTENT
› Verbs
– In Instructions:
› Use Present Tense for
instructions
› Pretend everything
happens in the Present
Tense
› Also, describe
processes in Present
Tense
› Use the Imperative, if
possible
› Place the Imperative at the
start of the instruction, if
possible
50
How to Write an Effective Protocol?
›
Clear Concise English “The Golden Rule” Cont’d
–
Verbs (Common Mistakes)
› Open the nozzle until the light flashes.
– Ideal Form: “Open” is the Imperative and is at the start,
instruction is short and self-contained, addresses the reader
directly
› The operator must open the nozzle until the light flashes.
– Most used: reader is not addressed directly because there is more
than 1 person involved; thus, imperative cannot be used.
› The nozzle is opened by the operator until the light flashes.
– Passive Voice: not to be used for instructions; does not even read
like an instruction, it reads like a description of something. Avoid
This.
› The nozzle shall be opened until the light flashes.
– Passive Voice and Future Tense: it is not clear who should carry
out the instruction, and it is not clear if it is an instruction at all.
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Avoid This.
How to Write an Effective Protocol?
›
Clear Concise English “The Golden Rule” Cont’d
–
–
Modifier Stacks
› Is a word which describes a noun or a noun phrase. It acts like
an adjective.
› The guideline: do not place strings of modifiers before nouns.
› Rule of Thumb: use no more than 2 modifiers per noun
› Ex. AVOID: she audited the revised document archive
management procedure
– USE: she audited the revised procedure for managing the
document archive
Vocabulary
› Use words that are familiar, short, concrete – They inform
› Avoid words which are unusual, long, fancy, abstract
› Ensure that the vocabulary is appropriate for your audience
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How to Write an Effective Protocol?
›
Clear Concise English “The Golden Rule” Cont’d
–
–
Deadwood
› Is a meaningless padding in your writing; words and phrases
which either mean nothing at all or are very long-winded.
› Ex. In consequence of the fact…=as a result, because
In the event that… = if
It is to be noted that…=note or “leave out”
In this point in time=now, at the moment
Lean Writing – (Select Relevant Appropriate Details)
› Three rules:
– Omit needless words
– Omit irrelevant information (not relevant to the purpose of
the document
– Omit unnecessary repetition
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How to Write an Effective Protocol?
›
Clear Concise English “The Golden Rule” Cont’d
–
Lean Writing – (Select Relevant Appropriate Details)
Cont’d
› Common Errors, Foreign Words, Copy and Paste
› Technical Jargon
– Only use jargon that the audience understands
– Explain any word that the audience does not understand
– Use footnotes or a glossary
– Use the words consistently
› Abbreviations
– Are convenient for the reader, not the writer
– Avoid abbreviating ordinary words
– Universally understood abbreviations are acceptable
– Expand abbreviations the first time they occur
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How to Write an Effective Protocol?
›
Draft and Revision
–
Review your own draft
›
›
›
›
›
–
Review the Draft thoroughly before distribution
Take a break between finishing the draft and starting your review
Try to see the document as your reader would see it
Get someone else to review it, if possible (peer reviewing)
“print it out, put it aside, revise with fresh eyes”
Review someone else’s draft
›
Make two careful passes to ensure:
–
–
–
The document does what it is meant to do.
The mechanics of the document are correct.
Suggestions for reviewers
›
›
›
›
›
›
Be constructive
●Adopt a standard dictionary
Explain what the problem is
● Adopt a style guide
Suggest alternatives, if possible
●Avoid red ink for markup
Be consistent
Provide templates and Guidelines
Provide a library of model documents
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›
How to Structure a Test?
Develop the equipment qualification protocol using the
following required documents, as applicable:
– Change Control and it’s documentation
– Functional Requirements Specifications and/or Functional
Specifications Documentation.
›
These documents shall define the system boundary, if
necessary. The boundary describes the equipment/system
process and systems operating or the processing limits for
qualification purposes.
– Design/Vendor drawings
– Operation and/or Maintenance Manuals
– Factory Acceptance Test (FAT) documents and/or Commissioning
Documentation.
Change Control
Manual, FAT, SAT
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Commissioning
How to Structure a Test?
› To develop a protocol for new equipment, system or process:
– obtain and review the Change Control documentation, Regulatory
requirements, Technology Transfer Report, Validation Master Plan,
Project Scope document, Functional Requirements Specification,
Factory Acceptance Test, Commissioning Report, Vendor Operating
Manuals, and draft Standard Operating Procedures (SOPs), as
applicable.
› To develop a protocol for a change to existing equipment,
system, process or product:
– obtain the applicable archived Validation Books from previous
qualifications and applicable current PPGs. Identify quality and
operational items affected by the change.
› Generate a protocol following the minimum format
requirements. You should have a procedure and/or template.
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How to Structure a Test?
›
If it is an Existing Equipment:
– Evaluate the “nature of change” (e.g., upgrade, modification,
replacement, etc.) to identify the testing requirements to be
covered in the qualification protocol.
›
Verify the following required documentation to develop the
Qualification Protocols (IQ/OQ/PQ):
– Original Qualification Package and/or Validation Book
– Identify the capability of the equipment/system “change” within
the required process operating variables.
– If the equipment/system “change” capabilities are out of the
system operating ranges, the Operational Qualification (OQ)
protocol must test the new operating parameters proposed to
ensure system/process state of control upon change control
closure.
– If the “change” specifies current operating parameters limits, the
system/process state of control must be established in the OQ
conclusion.
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How to Structure a Test?
› Incorporate technical content as identified in the applicable
validation program(s).
› Provide for the inclusion of the supporting evidence (as
applicable) that can assure that the circumstances of the
execution can be reconstructed.
› Include a rationale on sampling and acceptance criteria, if
applicable, and use (as required) a statistical base plan (e.g.
AQL, sampling levels, etc) or according to the manufacturer
specifications and industrial, regulatory and/or company
standards.
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How to Structure a Test?
› The applicable validation phases of Installation, Operational,
Development, Qualification/Study, and Performance
Qualifications must be sequentially executed.
– Testing related to Computer Qualifications must be completed prior
to the related equipment operational tests.
› Installation and Operational Qualification (IOQ) protocols
may be combined in a single document and identical
elements need to be documented only once.
› If all prerequisite conditions for protocol execution are not
met (e.g., a previous phase is not completed or its Technical
Report is not approved), and interim approval must be
obtained in order to start execution of a subsequent
protocol.
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›
How to Structure a Test?
Test Design
–
–
–
–
–
Some qualification activities, such as documentation and/or verification
steps, may occur either simultaneously or subsequent to commissioning
activities
Document a rationale/justification for exceptions if any of the qualification
requirements (e.g., tests, documentation, etc) cannot be fulfilled or is not
applicable in order to proceed with the protocol approval and qualification
exercise.
› Ex. The compressed air is an existing point of use qualified under
Protocol X.
Label the equipment/system (i.e., “equipment under qualification”),
including the date, phone number and name of the person responsible.
Become familiar with the equipment/system; if possible, attend to
equipment/system presentation meetings and participate in the evaluation
and selection of the equipment/system or change
Review key documents and/or publications developed by the owner,
manufacturers and distributors, such as: user and functional requirements
specifications, general design, factory acceptance test, construction,
materials, operation, manufacturer recommendations, safety devices,
speeds, capabilities, drawings outputs, and equipment/system limitations.
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How to Structure a Test?
› Interim Approval is a document that serves to document the
completion of a phase and requests the authorization to
proceed to the next phase.
› Interim approval for a subsequent protocol may be granted
provided that:
– All specified testing for the protocol is complete.
– All data for the protocol have been thoroughly reviewed,
including failed run, and all acceptance criteria have been
achieved.
– All events are resolved or an action plan for resolving them is
in place.
– All requirements of the protocol have been met.
– A compelling business necessity warrants proceeding.
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63
›
How to Structure a Test?
IQ
›
OQ
– Equipment/System
– Preventive Maintenance
(PM) Review
Specifications and
Installation Verification
– Alarms Test
– Controls Verification
– Equipment Drawing
Verification
– Start-up Sequence and
Power Failure Verification
– Equipment Change Parts
– Radio Frequency (RFI) and
Verification
Electromagnetic Interference
– General Documentation
(EMI) Verification
– Instrument Identification
– Functionality Test
and Calibration Verification
– Operational Qualification of
Steam Sterilizers, Dry
– Utilities Verification
Heat/Depyrogenation Ovens
– Maintenance/Preventive
and Tunnels, and component
Maintenance (PM) Review
preparation equipment
– Recommended Spare Parts ›
PQ
List
– Preventive Maintenance (PM)
– Filter Installation Verification
Review
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