Qualification & Validation

QUALIFICATION &QUALIFICATION &
VALIDATIONVALIDATION

QUALIFICATION & VALIDATIONQUALIFICATION & VALIDATION
IntroductionIntroduction
• Validation is an essential part of GMP, and an elementValidation is an essential part of GMP, and an element
of QAof QA
• Basic principles include:Basic principles include:
– Safety, quality and efficacy of productsSafety, quality and efficacy of products
– Built into the product – as it cannot be "inspected or testedBuilt into the product – as it cannot be "inspected or tested
into a product"into a product"
– Critical steps in the process need to be validatedCritical steps in the process need to be validated
• Need for confidence that the product will consistentlyNeed for confidence that the product will consistently
meet predetermined specifications and attributesmeet predetermined specifications and attributes

Introduction (2)Introduction (2)
Documentation associated with validation:Documentation associated with validation:
• SOPsSOPs
• SpecificationsSpecifications
• Validation Master Plan (VMP)Validation Master Plan (VMP)
• Qualification protocols and reportsQualification protocols and reports
• Validation protocols and reportsValidation protocols and reports

Introduction (3)Introduction (3)
Validation work requires considerable resources such as:Validation work requires considerable resources such as:
• Time:Time:
– work is subject to rigorous time scheduleswork is subject to rigorous time schedules
• Money:Money:
– may need specialized personnel and expensive technologymay need specialized personnel and expensive technology
• People:People:
– collaboration of experts from various disciplinescollaboration of experts from various disciplines
– a multidisciplinary team, comprising quality assurance,a multidisciplinary team, comprising quality assurance,
engineering, production, quality control (other disciplines,engineering, production, quality control (other disciplines,
depending on the product and process to be validated)depending on the product and process to be validated)

Qualification and ValidationQualification and Validation
• Qualification and validation are essentially componentsQualification and validation are essentially components
of the same conceptof the same concept
• The termThe term qualificationqualification is normally used for equipment,is normally used for equipment,
utilities and systemsutilities and systems
• The termThe term validationvalidation is normally used for processesis normally used for processes
• In this sense, qualification is part of validationIn this sense, qualification is part of validation

Validation: Approaches to validationValidation: Approaches to validation
• Two basic approaches:Two basic approaches:
1.1. Evidence obtained through testing (prospective andEvidence obtained through testing (prospective and
concurrent validation), andconcurrent validation), and
2.2. Analysis of accumulated (historical) dataAnalysis of accumulated (historical) data
(retrospective validation)(retrospective validation)
• Whenever possible, prospective validation is preferred.Whenever possible, prospective validation is preferred.
• Retrospective validation is no longer encouragedRetrospective validation is no longer encouraged
• Retrospective validation is not applicable to sterileRetrospective validation is not applicable to sterile
productsproducts

Scope of validationScope of validation
• Validation requires an appropriate and sufficientValidation requires an appropriate and sufficient
infrastructure including:infrastructure including:
– organization,organization, documentation, personneldocumentation, personnel and financesand finances
• Involvement of management and quality assuranceInvolvement of management and quality assurance
personnelpersonnel
• Personnel with appropriate qualifications andPersonnel with appropriate qualifications and
experienceexperience
• Extensive preparation and planning before validation isExtensive preparation and planning before validation is
performedperformed
• A specific programme for validation activities in placeA specific programme for validation activities in place
• Validation done in a structured way according toValidation done in a structured way according to
documentation including procedures and protocols.documentation including procedures and protocols.

Scope of validation (2)Scope of validation (2)
• Validation should be performed:Validation should be performed:
– for new premises, equipment, utilities and systems, andfor new premises, equipment, utilities and systems, and
processes and procedures;processes and procedures;
– at periodic intervals; andat periodic intervals; and
– when major changes have been made.when major changes have been made.
• Validation in accordance with written protocols.Validation in accordance with written protocols.
• A written report on the outcome to be produced.A written report on the outcome to be produced.
• Validation over a period of time, e.g.Validation over a period of time, e.g.
– at least three consecutive batches (full production scale) toat least three consecutive batches (full production scale) to
demonstrate consistency. (Worst case situations should bedemonstrate consistency. (Worst case situations should be
considered.)considered.)

Scope of validation (3)Scope of validation (3)
• Demonstrate suitability for new manufacturing formulaDemonstrate suitability for new manufacturing formula
or methodor method
• Process, materials and equipment to prove consistentProcess, materials and equipment to prove consistent
yield of a product of the required qualityyield of a product of the required quality
• Significant changes (facilities, equipment, processes) -Significant changes (facilities, equipment, processes) -
should be validatedshould be validated
• Risk assessment approach used to determine the scopeRisk assessment approach used to determine the scope
and extent of validation neededand extent of validation needed

QualificationQualification
• Qualification should be completed before processQualification should be completed before process
validation is performedvalidation is performed
• A logical, systematic process followedA logical, systematic process followed
• Start from the design phase of the premises, equipment,Start from the design phase of the premises, equipment,
utilities and equipmentutilities and equipment
• Major equipment and critical utilities and systemsMajor equipment and critical utilities and systems
normally require IQ, OQ and PQnormally require IQ, OQ and PQ

Qualification (2)Qualification (2)
• Some equipment, utilities and systems require only IQSome equipment, utilities and systems require only IQ
and OQ as the correct operation could be consideredand OQ as the correct operation could be considered
to be a sufficient indicator of its performanceto be a sufficient indicator of its performance
• The equipment, utility and system should then beThe equipment, utility and system should then be
maintained, monitored and calibrated according to amaintained, monitored and calibrated according to a
regular scheduleregular schedule

DocumentationDocumentation
• Validation Master Plan (VMP)Validation Master Plan (VMP)
• ProtocolsProtocols
• ReportsReports
• SOPsSOPs
• Others?Others?

Validation Master Plan (VMP)Validation Master Plan (VMP)
• Contains key elements of the validation programme.Contains key elements of the validation programme.
• Concise, clear, contain at least:Concise, clear, contain at least:
– a validation policya validation policy
– organizational structure of validation activitiesorganizational structure of validation activities
– summary of facilities, systems, equipment and processessummary of facilities, systems, equipment and processes
validated (and to be validated)validated (and to be validated)
– documentation format (e.g. protocol and report)documentation format (e.g. protocol and report)
– planning and schedulingplanning and scheduling
– change control and references to existing documentschange control and references to existing documents

Qualification and validation protocolsQualification and validation protocols
• Describe the study to be performed:Describe the study to be performed:
– the objectives of the studythe objectives of the study
– the site of the studythe site of the study
– the responsible personnelthe responsible personnel
– description of SOPs to be followeddescription of SOPs to be followed
– equipment to be usedequipment to be used
– standards and criteria for the products and processesstandards and criteria for the products and processes

Qualification and validation protocols (2)Qualification and validation protocols (2)
• Protocol contents (2):Protocol contents (2):
– the processes and/or parametersthe processes and/or parameters
– sampling, testing and monitoring requirementssampling, testing and monitoring requirements
– predetermined acceptance criteria for drawing conclusionspredetermined acceptance criteria for drawing conclusions
• Description (how results will be analyzed)Description (how results will be analyzed)
• Protocol approved prior to use - changes approvedProtocol approved prior to use - changes approved
prior to implementation of the changeprior to implementation of the change

Qualification and validation reportsQualification and validation reports
• Written reports on the qualification and validationWritten reports on the qualification and validation
performedperformed
• Reflect protocols followed and include at least:Reflect protocols followed and include at least:
– title and objective of the study; reference to the protocol; detailstitle and objective of the study; reference to the protocol; details
of materialof material
– equipment, programmes and cycles used; procedures and testequipment, programmes and cycles used; procedures and test
methodsmethods
• Results evaluated, analyzed and compared against theResults evaluated, analyzed and compared against the
pre-determined acceptance criteriapre-determined acceptance criteria

Qualification and validation reports (2)Qualification and validation reports (2)
• The results should meet the acceptance criteriaThe results should meet the acceptance criteria
• Deviations and out-of-limit results should beDeviations and out-of-limit results should be
investigated. If these are accepted, this should beinvestigated. If these are accepted, this should be
justified. Where necessary further studies should bejustified. Where necessary further studies should be
performedperformed
• Responsible departments and QA to approveResponsible departments and QA to approve
completed report, including the conclusioncompleted report, including the conclusion

Qualification stagesQualification stages
• There are four stages of qualification:There are four stages of qualification:
– design qualification (DQ);design qualification (DQ);
– installation qualification (IQ);installation qualification (IQ);
– operational qualification (OQ); andoperational qualification (OQ); and
– performance qualification (PQ).performance qualification (PQ).
• All SOPs for operation, maintenance and calibrationAll SOPs for operation, maintenance and calibration
should be prepared during qualificationshould be prepared during qualification
• Training provided and records maintainedTraining provided and records maintained

Design qualificationDesign qualification: Provides documented evidence: Provides documented evidence
that the design specifications were metthat the design specifications were met
Installation qualificationInstallation qualification: Provides documented: Provides documented
evidence that the installation was complete andevidence that the installation was complete and
satisfactorysatisfactory
• During IQ:During IQ:
– Purchase specifications, drawings, manuals, spare parts listsPurchase specifications, drawings, manuals, spare parts lists
and vendor details should be verifiedand vendor details should be verified
– Control and measuring devices should be calibratedControl and measuring devices should be calibrated

Operational qualificationOperational qualification: Provides documented: Provides documented
evidence that utilities, systems or equipment and all itsevidence that utilities, systems or equipment and all its
components operate in accordance with operationalcomponents operate in accordance with operational
specificationsspecifications
• Demonstrate satisfactory operation over the normalDemonstrate satisfactory operation over the normal
operating range as well as at the limits of its operatingoperating range as well as at the limits of its operating
conditions (including worst case conditions)conditions (including worst case conditions)
• Operation controls, alarms, switches, displays and otherOperation controls, alarms, switches, displays and other
operational components should be testedoperational components should be tested

Performance qualificationPerformance qualification: Provides documented: Provides documented
evidence that utilities, systems or equipment and all itsevidence that utilities, systems or equipment and all its
components can consistently perform in accordancecomponents can consistently perform in accordance
with the specifications under routine usewith the specifications under routine use
• Test results collected over a suitable period of time toTest results collected over a suitable period of time to
prove consistencyprove consistency

RequalificationRequalification
• In accordance with a defined scheduleIn accordance with a defined schedule
• Frequency to be determined (e.g. on the basis of factorsFrequency to be determined (e.g. on the basis of factors
such as the analysis of results relating to calibration,such as the analysis of results relating to calibration,
verification and maintenance)verification and maintenance)
• Periodic and after changesPeriodic and after changes
– e.g. changes to utilities, systems, equipment; maintenancee.g. changes to utilities, systems, equipment; maintenance
work; and movementwork; and movement
• Part of change control procedurePart of change control procedure

RevalidationRevalidation
• Processes and procedures - to ensure that they remainProcesses and procedures - to ensure that they remain
capable of achieving the intended resultscapable of achieving the intended results
• Periodic revalidation, as well as revalidation afterPeriodic revalidation, as well as revalidation after
changeschanges
• In accordance with a defined scheduleIn accordance with a defined schedule
• Frequency and extent determined using a risk-basedFrequency and extent determined using a risk-based
approach together with a review of historical dataapproach together with a review of historical data

Periodic revalidationPeriodic revalidation
• To assess process changes that may occur graduallyTo assess process changes that may occur gradually
over a period of time, or because of wear of equipmentover a period of time, or because of wear of equipment
• Consideration given to:Consideration given to:
– master formulae and specificationsmaster formulae and specifications
– SOPsSOPs
– records (e.g. of calibration, maintenance and cleaning)records (e.g. of calibration, maintenance and cleaning)
– analytical methodsanalytical methods

Revalidation after changeRevalidation after change
• After change that could have an effect on the process,After change that could have an effect on the process,
procedure, quality of the product and/or the productprocedure, quality of the product and/or the product
characteristics. (Considered as part of the changecharacteristics. (Considered as part of the change
control procedure.)control procedure.)
• Extent depends on the nature and significance of theExtent depends on the nature and significance of the
change(s)change(s)
• Changes should not adversely affect product quality orChanges should not adversely affect product quality or
process characteristicsprocess characteristics

Revalidation after change (continuation)Revalidation after change (continuation)
• Changes of equipment which involve the replacementChanges of equipment which involve the replacement
of equipment on a “like-for-like” basis would notof equipment on a “like-for-like” basis would not
normally require a revalidationnormally require a revalidation
• For example, installation of a new centrifugal pump toFor example, installation of a new centrifugal pump to
replace an older model wouldreplace an older model would not necessarily requirenot necessarily require
revalidationrevalidation

Change controlChange control
• SOP followed - as changes may have an impact on aSOP followed - as changes may have an impact on a
qualified utility, system or piece of equipment, and aqualified utility, system or piece of equipment, and a
validated process and/or procedurevalidated process and/or procedure
• Describe the actions to be taken, including the need forDescribe the actions to be taken, including the need for
and extent of qualification or validationand extent of qualification or validation
• Changes should be formally requested, documentedChanges should be formally requested, documented
and approved before implementationand approved before implementation
• Records should be maintainedRecords should be maintained

PersonnelPersonnel
• Demonstrate that personnel are appropriately qualified,Demonstrate that personnel are appropriately qualified,
where relevantwhere relevant
• These include for example:These include for example:
– laboratory analysts;laboratory analysts;
– personnel following critical procedures;personnel following critical procedures;
– personnel doing data entry in computerized systems; andpersonnel doing data entry in computerized systems; and
– risk assessors.risk assessors.

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