Equipment Qualification Fit for Intended Use - … Qualification ... consisting of final ... New Utilities /Equipment Qualification Request Existing Utilities /Equipment

Karem Y. Monge SepúlvedaMS Physics, CQA

Senior Scientist-Technical ServicesMylan LLC

Equipment Qualification –Fit for Intended Use

10/27-29/151

General Information

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› 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

Why Qualify an equipment?

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› 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.

Why Qualify an equipment?

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› 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’slifecycle from concept to retirement in a systematic, efficient, andeffective way.

– Provide manufacturing capability to support defined and controlledprocesses that can consistently produce product meeting definedquality requirements.

– Satisfy international regulatory expectations.

What it means “fit for intended use”?

The main objective is to reduce cost while improving

quality and safety.

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› The lifecycle of an equipment begins from the time itis requested through the end of its useful life orwhen it is disposed.

› In general, the Site shall establish a lifecycle systemcomplemented by written SOPs that require thedocumentation and testing of an equipment, fromdesign through initial testing, qualification,requalification, maintenance, and eventualretirement.

What is the equipment lifecycle approach?

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New Equipment

Decommissioning

Identify the need Impact Assessment

Qualify, Maintain, and

Monitor

Buy the equipment

Modify and/or

upgrade

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› 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 nothave a direct impact on product quality must be commissionedfollowing GEP.

– Performing an Impact Assessment

› May be integrated with a risk management process used todetermine product impact and the extent of theverification/qualification and re-qualification period.

› Defines the boundaries of what to include/exclude from theverification/qualification.

– Buying the equipment

– Qualifying, Maintaining, and Monitoring

– Decommissioning


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› Design phase that sets the equipment requirements.

› Testing phase consisting of evaluation and developmentto ensure that the equipment meets the designspecifications.

› Qualification phase to verify that the equipment meetsrequirements consistently.

› Maintenance phase that includes calibration, preventivemaintenance, change control, and formal evaluationdocumented using SOPs.

› Defining phase of requalification requirements andperiod.

› Decommissioning phase (retirement) consisting of finaltesting and formal documentation.


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GMP Significance

GEP

Identify all utilities,

equipment, and systems

Qualification Process

Confirm boundaries and

redefine if necessary

Commissioning and

Recertification required

Qualification not required

CC review may be

required

Define boundaries

Perform Impact Assessment

Direct product contact

(e.g. Air Quality)

Produces data which

impacts product release

(e.g. Building

Management System)

Provides an excipient or

produces an ingredient or

solvent

(e.g. WFI)

Process Control System with

no independent verification

(e.g. PLC)

Used in final Cleaning

or Sterilization

(e.g. Clean Steam)

Preserves product quality

(e.g. Nitrogen)

Failure or alarm has

direct effect on product

BU or SME review

direct impact

Commissioning and/or

Recertification required

Qualification not required

CC review required

GEP

YES

NO

NO

NO

NO

NO

NO

NO

NO

NO

YES

YES

YES

YES

YES

YES

YES

YES

YES

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Requalification

Study Request

Meet Acceptance

Criteria?

Execute Protocols or

Requalification SOPs

New Utilities/Equipment

Qualification Request

Existing Utilities/Equipment

Study Request (Process

and/or Utilities/Equipment

Re-design or purchase

new Utilities,

Equipment, System

Review Functional Requirement

Specification, Manufacturer’s

recommendations and drawings

Gather Utilities/Equipment

maintenance records,

or other operational data

Prepare, review, and

approve Final Report

Develop, review,

and approve Protocol

Record the deviation(s) and

ensure corrective actions

Finalize Operation SOPs

(if applicable)

Draft Operation SOPs

(if applicable)

Is Utilities/Equipment

adequate for new

application?

Are SOPs adequate

for new application?

Check existing Protocols

and Reports, are they

adequate for new

application?

Existing Requalification

SOPs?

YES

NO

NO

YES

NO

NO

YES

NO

YES

YES

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› Systematically verify that an equipment, acting singly or incombination, are fit for intended use, have been properlyinstalled, and are operating correctly.

› ASTM 2500 describes two approaches to the specification,design, and verification of the equipment that have thepotential 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.

What entails the Qualification Process?

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› Risk -Based Approach– Apply risk management to specifications, design, and verification

– ICH Q9:

› The evaluation of the risk to quality should be based on scientificknowledge and ultimately link to protection of the patient.

› The level of effort, formality, and documentation of the qualityrisk management process should be commensurate with the levelof 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.


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› Science-Based Approach– Use product and process information as the basis for making

science- and risk-based decisions. This ensures that manufacturingsystems 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


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› 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 usingfocused 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 installationand operation of the system / equipment

› Verification that the system / equipment performance meetsproduct and process user requirements


“Fit for

Intended

Use”!!!

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› 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

Requirements Specifications

and Design

Verification Acceptance

and Release

Product Knowledge

Process Knowledge

Quality

Regulatory Requirements

Good Engineering Practice

Risk Management

Design Review

Change Management

Operations and

Continuous Improvement

1. ASTME2500 - 1317

Equipment Qualification

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› 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 end-user 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

Qualification

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Qualified as Suitable for Intended Use

Commissioning – Start-Up, setting to work, physical adjustment, physical inspection, functional testing,

performance testing

FAT Verification Work

SAT Verification Work

Other Verification Work

Commissioning Verification Work

Basis for suitability (process requirements, risk control)

Solving the Terminology Conundrum (Fig. 2 )20

› Functional Requirement Specifications (FRS)

– A document that delineates the operational characteristics of theequipment as well as any design or construction details that have cGMPimplications. It is utilized as the basis for any design, Factory AcceptanceTest (FATs), Site Acceptance Test (SATs), Commissioning, and ValidationActivities.

› Enhanced Commissioning

– Commissioning documentation used to fulfill field-testing requirements forthe IQ and OQ

› Commissioning

– Systematic challenge that establishes that the equipment is manufacturedand installed properly, and that it operates in normal conditions inaccordance with the design and installation requirements and acceptancecriteria.

– Planned and systematic process for challenging and verifying that a facility,system and equipment is constructed, installed and functionally operatesthrough all normal modes and conditions in accordance with the user,design, and installation requirement and acceptance criteria.

Qualification Phases

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› Installation Qualification (Verification)– Documented verification that all key aspects of the equipment have

been properly selected, constructed, and installed in accordancewith 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 withinestablished 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

Qualification Phases

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› Enhanced Commissioning

– Identify requirements for the facility, system, equipmentto be commissioned, such as:

› Change Control, Factory Acceptance Test (FAT), FunctionalRequirements Specification (FRS), User RequirementSpecification (URS), verification of construction completion,passivation, system leak test, pressure test, system cleaning,among others

Purpose and Common Tests

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› Enhanced Commissioning– Test Plan should include:

› Identification and listing of all equipment, systems/sub-systems,critical utilities, their specifications, normal operating limits, andacceptance 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, andresolutions

› Test conditions (usually manufacturer’s recommendations) andacceptance criteria

› Commissioning Schedule

› Unique identification number.


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› IQ– Equipment/System Specifications and Installation 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.

– Equipment Drawing Verification› 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 theequipment owner.


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› IQ– General Documentation

› Review the equipment/system manuals available forinstallation, 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 (makecopies).

› Verify and document the existence of the equipment/systemFunctional Requirements and/or System Specifications thatdefine the intended application of the system.

› Verify the equipment/change parts materials that are in directcontact with the product. Document if the material used issafe, appropriate, and free of contaminants.

› Review the construction material documentation such as:material certification, passivation, welding logs/certificationsand other applicable documents.

› Verify the critical utilities such as Clean Steam and Water forInjection (WFI) pipelines.


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› IQ– Instrument Identification and Calibration Verification

› Verify and document that the equipment/system instrumentation has beencategorized as either GMP (critical/non-critical) or non-GMPinstrumentation, and calibrated within manufacturer and design specifiedranges.

› Verify that all critical instruments (manufacturer supplied) and supplementalindicators, gauges and/or instrument loops are properly identified with aninstrument number and calibration label, and have been entered into theSite Calibration Program.

› All instruments associated with critical components must be categorized ascritical.

– For example, if a conveyor is identified as a critical component of theequipment, the tachometer associated with that conveyor is a criticalinstrument.

– Assure that all the standards required to verify the calibration of theequipment are available and instructions or methodologies for thehandling, labeling, receipt, storage and replacement of them are inplace. These procedures should be in accordance with the manufacturerrecommendations and process requirements .


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› IQ– Utilities Verification

› Verify (through tests, measurements, etc.) that the requiredutilities adhere to equipment/change requirements. Theutilities must be installed and available in conformance withdesign and manufacturer specifications.

› Verify that the electrical utility includes an additional sourcepanel and a breaker. Utilities with product contact, such asWater for Injection, Clean Steam, etc, must have qualificationpackages 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 ofthe equipment/change has been properly connected and asspecified in the electrical and wiring diagrams.


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› IQ– Maintenance/Preventive Maintenance (PM) Review

› 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.

– Recommended Spare Parts List› 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 evidence.


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› OQ– Preventive Maintenance (PM) Review

› Perform an assessment of the periodic re-qualification of theequipment/system. If the equipment/system requires periodic re-qualification, verify that the re-qualification activity has been entered intothe 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 thatare 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 thatall restart conditions are met as well as the status of any set-upconfiguration.


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› 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.


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› OQ– Operational Qualification of Steam Sterilizers, Dry

Heat/Depyrogenation Ovens and Tunnels, and componentpreparation equipment, additional tests include, but are notlimited 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 followingtests:› Heat Penetration Study

› Machine ability

› Sterilization

› Humidity

› Particulate Removal.


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› 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.


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› Develop a Validation Master Plan stating the overallphilosophy and approach used by the Facility / FunctionalUnit for planning, designing, organizing, executing, andreporting validation / qualification. The plan includes thecurrent 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.

How to Maintain the Qualified State?

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› Generate a List of GMP Equipment to be re-qualifiedincluding the re-qualification schedule

– List should include the following:

– List should be complemented with the Preventive Maintenance System.


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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

Incubator Precision B1 12/15 Report #3

Thermo Forma

B2 Decommissioned

Hotpack B3 11/15 Report #5

› 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 re-qualification 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


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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).

› 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 re-qualification requirements, develop a new procedure based on the original validation exercise and current technical procedures.


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Documentation

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› 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.

How to Write an Effective Protocol?

41

› 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

› 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

› 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 should read effortlessly.


44

› 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

› 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

› 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

– Do not abbreviate normal words


47

› 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

› 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


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› 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

› 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

How to Write an Effective Protocol?Clear Concise English “The Golden Rule” Cont’d

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› 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. Avoid This.


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› 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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› 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


53

› 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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› 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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› Develop the equipment qualification protocol using thefollowing 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/systemprocess and systems operating or the processing limits forqualification purposes.

– Design/Vendor drawings– Operation and/or Maintenance Manuals– Factory Acceptance Test (FAT) documents and/or Commissioning

Documentation.

How to Structure a Test?

Change Control Manual, FAT, SAT Commissioning56

› 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 OperatingManuals, and draft Standard Operating Procedures (SOPs), asapplicable.

› 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 andoperational items affected by the change.

› Generate a protocol following the minimum formatrequirements. You should have a procedure and/or template.


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› If it is an Existing Equipment:– Evaluate the “nature of change” (e.g., upgrade, modification,

replacement, etc.) to identify the testing requirements to becovered in the qualification protocol.

› Verify the following required documentation to develop theQualification 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 toensure system/process state of control upon change controlclosure.

– If the “change” specifies current operating parameters limits, thesystem/process state of control must be established in the OQconclusion.


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› Incorporate technical content as identified in the applicablevalidation program(s).

› Provide for the inclusion of the supporting evidence (asapplicable) that can assure that the circumstances of theexecution can be reconstructed.

› Include a rationale on sampling and acceptance criteria, ifapplicable, and use (as required) a statistical base plan (e.g.AQL, sampling levels, etc) or according to the manufacturerspecifications and industrial, regulatory and/or companystandards.


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› 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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› Test Design– Some qualification activities, such as documentation and/or verification

steps, may occur either simultaneously or subsequent to commissioningactivities

– Document a rationale/justification for exceptions if any of the qualificationrequirements (e.g., tests, documentation, etc) cannot be fulfilled or is notapplicable in order to proceed with the protocol approval and qualificationexercise.

› Ex. The compressed air is an existing point of use qualified underProtocol 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 toequipment/system presentation meetings and participate in the evaluationand 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 requirementsspecifications, general design, factory acceptance test, construction,materials, operation, manufacturer recommendations, safety devices,speeds, capabilities, drawings outputs, and equipment/system limitations.


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› 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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› OQ– Preventive Maintenance

(PM) Review– Alarms Test– Controls Verification– Start-up Sequence and

Power Failure Verification– Radio Frequency (RFI) and

Electromagnetic Interference (EMI) Verification

– Functionality Test– Operational Qualification of

Steam Sterilizers, Dry Heat/Depyrogenation Ovens and Tunnels, and component preparation equipment

› PQ– Preventive Maintenance (PM)

Review

› IQ– Equipment/System

Specifications and Installation Verification

– Equipment Drawing Verification

– Equipment Change Parts Verification

– General Documentation– Instrument Identification

and Calibration Verification– Utilities Verification– Maintenance/Preventive

Maintenance (PM) Review– Recommended Spare Parts

List– Filter Installation Verification


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