PHARMACEUTICAL CALIBRATION & VALIDATION.ppt

PHARMACEUTICAL CALIBRATION & VALIDATION.
What is Validation?
What is calibration?
What are the types of Validation ?
Validation and calibration Basic Difference

1. 1
VALIDATION
&
CALIBRATION
M.Mitra
CDSCO(NZ)
www.pharmanotes.org

2. History
–Drug product quality was seen as the
function of the status of the product itself.
–Flawed approach-destructive tests-
individual products can not be tested.
–No statistical method was available to
ensure quality of a batch of drug.

3. History
–US FDA included some form of validation
around mid 1970s
(Process validation 21 CFR parts 210 and 211)
–Initially limited to sterile products and later
extended to other dosage forms
–This was out of a concern to develop a
verification mechanism that would need to be
applied to the process to be meaningfully
extrapolated to an entire batch

4. History
–In the Indian scene this emerged as a requirement
for those firms who wished to register with
foreign agencies.
–Followed by those requiring WHO GMP
Certification for COPP.
–Now included in the revised schedule M

5. Calibration---what is it?
–A set of operations that establish, underspecified
conditions, the relationship between values
indicated by an instrument or system for
measuring, recording, and controlling, or the
values represented by a material measure, and
the corresponding known values of a reference
standard. limits of acceptance of the results of
measuring should be established.

6. Calibration
Thekeyrequirementsforcriticalinstrumentsare
asfollows:
eachinstrumentshouldhavearecordina
permanentfile
allinstrumentsshouldbeassignedaunique
numberandtaggedwiththatnumber
thecalibrationmethodshouldbedefinedand
approved
calibrationfrequencyandprocesslimitsshouldbe
bedefinedforeachinstrument

7. Calibration
–allrecordsshallbemaintained
–eachstandardshouldbetraceabletoarecognized
standard
–Thecalibrationstandardsmustbemoreaccurate
toaclosertolerancethattheinstrumentbeing
tested
–calibrationstatusshouldbeidentifiedoneach
instrument

8. Calibration
all instruments shall be fit for the purpose
training records for all personnel involved in the
calibration must be maintained
a change control system must be in place
the instruments must meet all GMP
requirements

9. Calibration
–Frequency of calibration shall be determined by the
following:
–manufactures recommendations
–duty of the instrument
–relevant standards and regulations
–historical information
–consequence of calibration failure
–experience

10. Calibration
–Documentation
–Key documents:
Schedule date for calibration and frequency
Instrument ID
Calibration range
–others
•all records must be clear and unambiguous
•unique number must identify the instrument
•any instrument removal must be documented
•replacement instrument must have documented history
•removed instrument should be calibrated immediately to ascertain the cause or
impact of failure

11. Validation And Process Validation
-Validationstudiesshallbeanessentialpartof
GoodmanufacturingPracticesandshallbe
conductedasperthepre-definesprotocols.
Theseshallincludevalidationofprocessing
testingandcleaningprocedures.
-Awrittenreportsummarizingrecordedresults
andconclusionsshallbeprepared,documented
andmaintained.

12. Validation And Process Validation.
–Processes and procedures shall be established on he basis
of validation study and undergo periodic revalidation to
ensure that they remain capable of achieving the intended
results. Critical processes shall be validated, prospectively
or retrospectively.
–When any new master formula or method of preparation is
adopted, steps shall be taken to demonstrate its suitability
for routine processing. The defined process, using the
materials and equipment specified shall be demonstrated
to yield a product consistently of the required quality.

13. Significant changes to the manufacturing
process, including any change in equipment
or material that may affect product quality
and / or the reproducibility of the process,
shall be validated.

14. What is Validation ?
–Documentedproofthateverything,within
reasonablecertainty,thatisinvolvedinthe
manufactureofaproductisundercontrol.
–Thisincludesthefacility,theenvironment,thematerials,
theequipmentandtheprocessesincludingmanufacture
andcleaningprocedures.

15. WHY VALIDATION
–ToEstablishbydocumented
Evidencetoprovideahigh
degreeofassurancethata
plannedprocesswillconsistently
performaccordingtothe
intendedspecifiedoutcomes

16. MASTER VALIDATION PLAN
–Itisadocumentpertainingtothe“whole
facility”thatdescribeswhichEquipment.
Systems.MethodsandProcesseswillbe
validatedandwhentheywillbevalidated.
–ItalsoincludesRe-Validation-whyand
when

17. VALIDATION CONSISTS OF
–Design Qualification -DQ
–Installation Qualification -IQ
–Operational Qualification -OQ
–Performance Qualification -PQ

18. DESIGN QUALIFICATION
–Necessary when planning and choosing equipment or
systems to ensure that components selected will have
adequate capacity to function for the intended purpose.
–Example-selection of steam generator.
–Master Validation Plan must address sequence of DQ.

19. INSTALLATION QUALIFICATION
–Qualificationofapieceofequipment
shouldcheckfortherequirementsthat
arementionedintheDQ
–Compare with the purchasing information
and invoice data
–Requirements-Name,description,model,
identificationnumbers,location,utility
requirements, connections, safety
measures0fthesystem

20. IQ -continued
–DuringInstallationQualificationitshouldbeverifiedthat
thefollowingmatchesthepurchasespecification:
Drawings,
manuals,
spare parts list,
vendor address and contact number,
Other pertinent documentation.

21. Simple Example of
Installation Qualification
1.Equipment: _________________
2.Model: _________________
3.Manufacturer: _______________
4.Date of Purchase:____________

22. 1.Manual Provided/Not Provided Remarks
2.Physical DamageOK/Damage found
3.Dimensions Not / As per
requirement
4.Switches OK/Damage/Inadequate
5.Covers WorkingOK/Damage/Inadequate
6.Limit SwitchesOK/Damage/Inadequate
7.Electrical
Fittings
OK/Damage/Inadequate
8.All fasteningsOK/Damage/Inadequate

23. Thedetailsoftheequipmentshouldbe
criticallytalliedwiththeorderplaced
withthevendor.Needlesstoaddthe
orderplacedshouldbeasperthe
DesignQualification(DQ).Allcritical
componentsoftheequipmentshouldbe
tabulatedandonlyaftersuccessful
verificationshouldtheequipment
verifiedasconformingtoIQ

24. OPERATIONAL
QUALIFICATIONS
–Outlines the information required to provide
evidence that all the components of a system
or equipment operate as specified.

25. OPERATIONAL
QUALIFICATIONS
–This involves testing of all:
normal operation controls,
all alarm points,
all switches,
all displays,
interacting controls,
any other indications of operation & functions

26. OQ -continued
Specificationsandacceptancecriteriamustbe
definedforalloperation
ShouldprovidealistingofSOPs,referenceto
specificmanualinstructionsforoperation,
maintenanceandcalibration

27. Performance Qualification
–TobecarriedoutafterbothIQandOQhave
beensuccessfullycompleted
–Describestheproceduresfordemonstrating
thatasystemorpieceofequipmentcan
consistentlyperformandmeetrequired
specificationsunderroutineoperation,and
whereappropriate,underworstcase
situations.

28. PQ -continued
–Describethepreliminaryprocedurerequired
–Detailedperformancetest
–acceptancecriteriaforeachtest
–allsupportingsystemsandproceduresshouldhavebeen
validated(e.g..Steamsystemshouldbevalidatedbefore
autoclavevalidation)

29. Process Validation
Performance (How to do it)
-Process : Run the process according to SOP three
times and record all required data.
–Deviations to the procedures must be recorded
on the data record forms.
–Analytical tests : Perform the routine tests
associated with the process according to SOP,
Test results must be approved by the QC.

30. Evaluation
–Attach all data record forms and charts.
–Perform all calculations and analyses which are
predetermined and approved.
–Compare with the accepted criteria.

31. Prepare Deviation Report
–Deviation if any must be recorded and
justification for acceptance, if any, mentioned.

32. Prepare Process Validation
Report
–This must mention start date, completion date,
observations, problems encountered,
completeness of information, summary of the
deviation report, results of test, comparison with
the accepted criteria, other relevant data.
–Conclusion should take into account individual as
well as the results of three consecutive validation
runs.

33. Approval and Acceptance
–QA should review and approve the report.
–The Process must meet all specifications
–For three consecutive runs

34. Process validation
–Experimental
–Prospective validation
–Concurrent validation
–Analysis of historical data
–Retrospective validation
–Revalidation
–After change
–periodic

35. Process Validation Requirements
Type of process
Validation
Requirements
New •Everynewprocessmustbevalidated
beforeapprovalforroutineproduction
Existing
1. Process designed to
render a product sterile
•Allprocessesaffectingsterilityand
manufacturingenvironmentmustbe
validated;themostimportantisthe
sterilizationstage.
2. Non-sterile production •Low-dosetabletsandcapsules
containinghighlyactivesubstances:
validationofmixingandgranulationin
relationtocontentuniformity.
•Othertabletsandcapsules:Validation
oftabletcompressingandcapsule
fillinginrelationtouniformityof
mass.
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36. Example of Process Validation
Manufacture of Paracetamoltablets
Procedure of receipt of RM to the plant
Procedure of storage and testing
Procedure of issue of material to Prod.
Actual manufacturing:
Weighing
Sieving
mixing
Granulation
Drying

37. Example of Process Validation Contd.
Lubrication
Compression
Release & Packing
Eachoftheaboveoperationshavetobevalidated
againsttherequirementsoftheprocedureand
documented!!!!

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Thank You