Validation in Pharmaceutical Industry: A Deep Dive

This comprehensive presentation delves into the critical aspects of validation within the pharmaceutical industry. It covers fundamental concepts, regulatory expectations, and practical applications relevant to pharmaceutical quality assurance professionals.

Key Topics Covered:

Introduction to Validation:

Defining validation and its significance in ensuring product quality and regulatory compliance.
Exploring different types of validation: process validation, equipment validation, cleaning validation, analytical method validation, computer system validation.
Discussing the regulatory framework for validation, including guidelines from agencies like the FDA, EMA, and WHO.
Process Validation:

Examining the stages of process validation: process design, process development, and process performance qualification.
Discussing critical process parameters (CPPs) and critical quality attributes (CQAs) and their role in process understanding.
Exploring different approaches to process validation, such as design of experiments (DOE) and risk-based approaches.
Equipment Validation:

Understanding the importance of equipment validation in ensuring consistent and reliable performance.
Discussing different types of equipment validation: installation qualification (IQ), operational qualification (OQ), and performance qualification (PQ).
Exploring specific challenges and considerations for validating various types of equipment, such as analytical instruments, filling lines, and sterilization equipment.
Cleaning Validation:

Emphasizing the importance of effective cleaning procedures to prevent cross-contamination and ensure product safety.
Discussing the principles of cleaning validation, including establishing cleaning limits, selecting appropriate analytical methods, and conducting cleaning studies.
Exploring different cleaning validation approaches, such as worst-case scenarios and worst-case residues.
Analytical Method Validation:

Discussing the criticality of validated analytical methods for accurate and reliable product testing.
Exploring various analytical method validation parameters, such as accuracy, precision, specificity, linearity, range, robustness, and limit of detection/quantification.
Discussing the importance of method validation in supporting product release, stability studies, and investigations.
Computer System Validation:

Understanding the significance of computer systems in pharmaceutical manufacturing and the need for their validation.
Discussing the principles of computer system validation, including risk assessment, system design and development, installation, and ongoing maintenance.
Exploring different types of computer systems used in the pharmaceutical industry, such as manufacturing execution systems (MES), laboratory information management systems (LIMS), and electronic data capture (EDC) systems.
Validation Documentation:

Discussing the importance of comprehensive and well-documented validation protocols and reports.
Explorin

1. Shree WaranaVibhagShikshan Mandal's
Tatyasaheb Kore College of Pharmacy,
Warananagar
Created By
Miss. A. B. Patil
M. Pharm (Pharmaceutical Chemistry)
Assistant Professor
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2. •Introduction
•DifferenceBetweenCalibration&Validation
•DifferencesBetweenValidationandQualification
•ScopeofValidation
•AdvantagesofValidation
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3. Validationisanintegralpartofqualityassurance;itinvolvesthe
systematicstudyofsystems,facilitiesandprocessesaimedat
determiningwhethertheyperformtheirintendedfunctions
adequatelyandconsistentlyasspecified.
Thetermvalidationiswidelyusedinpharmaceuticalindustries.
Thistermcomesfromtheword“validorvalidity”whichmeans
“legallydefined”.
Thetermvalidationhasbeendefinedbymanydifferentauthors.
Althoughthewordingmaybedifferent,thesenseisalwaysthe
same.
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4. AccordingtotheFoodandDrugAdministration(FDA),thegoalof
validationisto:“Establishdocumentedevidencewhichprovidesa
highdegreeofassurancethataspecificprocesswillconsistently
produceaproductmeetingitspredeterminedspecificationsand
qualityattributes.”
Definitions21CFR820.3(z)-Validationmeansconfirmationby
examinationandprovisionofobjectiveevidencethattheparticular
requirementsforaspecificintendedusecanbeconsistentlyfulfilled.
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5. Qualification-Qualificationisdefinedasthe“actionofproving
thatanyequipmentworkscorrectlyandleadstotheexpected
results.”
Qualificationisalsopartofvalidationandisproductspecific.
Qualificationisoftenapart(theinitialstage)ofvalidation,butthe
individualqualificationstepsalonedonotconstituteprocess
validation.Therearefourstagesofqualification:—
Designqualification(DQ);
Installationqualification(IQ);
Operationalqualification(OQ);and
Performancequalification(PQ).
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6. Relationship Between Validation And Qualification
Validation and qualification are essentially components of the
same concept.
The term qualification is normally used for equipment, utilities
and systems.
Validation is used for processes.
In this sense, qualification is part of validation.
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7. CALIBRATION -It is process of comparing a reading on one piece of
equipment or system with another piece of equipment that has been
calibrated & referenced to a known set of parameters.
As per WHO: Calibration is set of operations that establish, under
specified conditions, the relationship between values indicated by an
instrument or system for measuring weight, temp. pH etc. , recording, &
controlling or the values represented by a material measure, & the
corresponding known values of a reference standard.
As per ICH: It is demonstration that a particular instrument or device
produces results within specified limits by comparison with those
produced by a reference or traceable standard over an appropriate range
of measurements.
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8. CALIBRATION VALIDATION
Purpose: to demonstrate that a particular
instrument or device produces results
with in specified limits by comparisons
with those produced by reference over
appropriate range of measurements
Purpose: to documented verification
that provides high degree of assurance
that a specific process, equipment,
method or a system consistently
produces a result meeting
predetermined acceptance criteria
Performance of instrument or device is
compared against a reference standard
No such reference std. are used
It is system performance checking.It is a performance analysis
methodology
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9. CALIBRATION VALIDATION
Performed periodically, to identify
drift of the measuring device or
equipment & make them accurate
No such req. performed when changes
or modifications happen to the
existing system or once revalidation
period is reached
Performed as per calibration SOP Performed as per validation protocol
Adjust the precision & accuracy of
instrument
Confirms precision & accuracy of
equipment
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10. CALIBRATION VALIDATION
Ensures that instrument/ measuring
device produce accurate results
Provides documented evidence that a
process, equipment, method or system
produces consistent results i.e.
uniform batch are produced
To confirm that the equipment or
measuring device is performing
accurately.
To confirm that the analytical method
is performing accurately.
To ensure:
•Specificity
•Linearity
•Accuracy
•Sensitivity
•It will minimize rejection loss
•Reduction in utility cost
•Help timely corrective action
•Assure consistent production
•performance
•Ensure achievement of quality goals
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11. Qualification Validation
Is mainly for equipment and
instruments.
Is mainly for:
–Manufacturing process
–Cleaning
–Computer System
–Software
–Test Methods
and sometimes for equipment used for
critical
process operations
Used to challenge the performance of
equipment.
Used to challenge the performance of
processes.
Does not demand a reproducible
outcome. Only
concerned about the proper functioning
of the system
and sub-systems.
Specifically intended to challenge
reproducible
Outcomes.
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12. Qualification Validation
Requirementsinclude:
DQ, IQ, OQ, PQ, Calibration,
Maintenance, etc
Requirements include:
1. Process Design
2. Process Verification
3. Process Confirmation
4. Process Qualification
Different types of Validation are:
1. Prospective Validation
2. Retrospective Validation
3. Concurrent Validation
Re-qualification is needed for:
1. Significant modifications critical to
the outcome
2. Post relocation
3. Software and control modifications
4. Periodic Schedule
Re-validation is needed for any changes
in:
1. Process or its environment
2. Starting material
3. Packing material
4. Steps or Procedure
5. Equipment
6 Periodic Schedule
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13. Validationdoneinastructuredwayaccordingtodocumentation
includingproceduresandprotocols.
Validationshouldbeperformedfor
Newpremises,equipment,utilitiesandsystems.,
Newprocessesandprocedures;atperiodicintervals.,
Whenevermajorchangeshavebeenmade.,
Validationinaccordancewithwrittenprotocols.
Demonstratesuitabilityfornewmanufacturingformula/method.
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14. Awrittenreportontheoutcometobeproduced.
Demonstratesuitabilityfornewmanufacturingformulaormethod
Equipment validation (also called qualification).
Facilities and utility validation (water system, air handling unit,
compressed gas system, computer systems).
Process validation.
Cleaning validation.
Analytical method validation.
Instrument calibration.
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15. Ithelpstodeterminetheworstcaseandrisksthatmayariseduring
themanufacturingofthequalityproducts.
Validationhelpstoinvestigatethedeviationscausedduringthe
process.
Deepstudyandunderstandingofthesystemandequipmentare
madepossibleduetothevalidation.
Theriskoftheregulatorynon-complianceisminimizedafterthe
validation.
Avalidatedprocessrequiredlessprocesscontrolandthefinished
producttesting.
Batchtobatchvariationisminimizedduetothevalidationof
processes,systemsandequipment.
Reducestheproductioncostoftheproduct.
Increasestheproductionofmanufacturingfacilityduetothe
minimizedreworkandrejection.
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16. Decreasesthechancesofthefailureofthebatches.
Duringtheprocesstheknowledgeofprocessincreases.
Assurestherepeatabilityoftheprocess.
Assuresthefluencyofproduction.
Assuresthattheproductiscontinuouslyaccordingtothemarketing
authorisation.
Decreasestheriskofthemanufacturingproblems.
Decreasestheexpensescausedbythefailuresinproduction.
DecreasestherisksoffailinginGMP.
Decreasestheexpensesoftheeverydayproductioneventhoughthe
validationitselfwillcreateexpense.
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