Qualification of analytical instruments

Brief Introduction of Analytical Instrument which are useful for Analysis in Pharma Field as well as Biotech Field.

1. Qualification of Analytical Instruments
Presented by:-PuneetNirmal
M.Pharm1
st
year
Dept. of QUALITY ASSURANCE
ISF COLLEGE OF PHARMACY
Mobile:[phone]
Website: -www.isfcp.org
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2. Qualification ofAnalytical
Equipments
High PerformanceLiquid
Chromatography
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3. Content:
Introduction
Qualification of HPLC
Designqualification
InstallationQualification
Operationalqualification
Performancequalification
References
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4. Introduction
Qualification:Action of proving and documenting that equipment or ancillary systems are
properly installed, work correctly, and actually lead to the expectedresults.
The entire qualification consists of fourparts00:
Designqualification(DQ)
Installation Qualification (IQ)
Operational Qualification (OQ)
Performance Qualification (PQ)
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5. 1.DesignQualification(D.Q.):Itdescribetheuserrequirementsanddefinethefunctional
andoperationalspecificationsoftheinstrument.DQshouldensurethatinstrumenttobe
purchasedhavethenecessaryfunctionsandperformancethatwillenableforsuitableintended
application.
2.InstallationQualification(I.Q):ThepurposeofI.Qistochecktheinstallationsite/
environment,confirmsequipmentspecificationsandverifiestheconditionofinstalledequipment.
3.OperationalQualification(O.Q):ItincludeproceduresanddocumentationofO.Qof
analyticalinstruement.
Whenallproceduresareexecutedandallitemspasstheinspection,itisverifiedthatthesystem
operatestosatisfytheintendedpurpose.
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6. 4.Performance Qualification(P.Q):
The objective is to ensure that the instrument is performing within specified limits.
Hence docuementedverification that the equipementand ancillary system, as connected together,
can perform effectively and reproducibly based on the approved process method and specifications.
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7. Qualification ofHPLC
1. DESIGNQUALIFICATION:
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Designelement example
Maintenance •Vendor must delivermaintenance
procedure and recommendedschedule
•Instrument must include early
maintenance feedback for timely
exchange of most important
maintenance parts. •Maintenance
procedure must be supplied on
multimedia CDROM
Intendeduse Analysis of drug componentsand
impurities.
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8. Designelement Examples
User requirements specification forthe
HPLCanalysis
•Upto100samples/day•Automatedover
nightanalysis.
•Limitofquantitation:0.1%•Automated
confirmationofpeakidentityandpurity
withdiode-arraydetection
•Automatedcompoundquantizationand
printingofreport.
FUNCTIONALSPECIFICATION:
•Pump
•Detector
•Autosampler
•Columncompartment
•Computer
•Binary or highergradient
•UV/VIS Diode array,190-900nm•100
samples, 0.5µl to 5ml samplevolume
•15 to 60ºccontrolled.
•System control, data acquisition for
signals and spectra, peak integrationand
quantitation
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9. Designelement Examples
Operationalspecification •Detector: base line noise:<5 x 10-5AU
•Sampler: precision inj. Volume : <0.5%
RSD. Sample carryover:<0.5%
•Pump: precision of retain time:<0.5%
RSD.
Userinstruction •Operation manual on paper•Computer
basedtutorial
Qualification The vendor must provide proceduresand
services for IQ andOQ
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10. 2.INSTALLATIONQUALIFICATION:
Installationqualificationestablishesthattheinstrumentisreceivedasdesignandspecified.
•Itestablishesthatinstrumentisproperlyinstalledintheselectedenvironmentandthatenvironment
shouldbesuitableforoperationoftheinstrument.
•Runoftestsamplesverifiescorrectinstallationofallmodules,electricalandfluid
connections
BEFOREINSTALLATION?
Obtainmanufacturersrecommendationsforinstallationsiterequirements
Checkthesiteforthefulfillmentofthemanufacturers
Recommendation(utilitiessuchaselectricityandenvironmentconditionsuchashumidityand
temperature)
Allowsufficientshelfspacefortheequipment,SOPs,operatingmanualandsoftware.
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11. DURINGINSTALLATION?
Compareequipmentasreceived,withpurchaseorder(includingsoftware,accessories,spare
parts).
Checkdocumentationforcompleteness(operatingmanuals,maintenanceinstruction,standard
operatingprocedurefortesting,safetyandvalidationcertificate)
Checkequipmentforanydamage.
Installhardware(computer,equipment,fittingsandtubings,forfluidconnections,columnin
HPLC,powercables,dataflowandinstrumentcontroltable)
Switchontheinstrumentandensurethatallmodulespowerup
andperformanelectronicselftest.
Identifyandamakealistwithadescriptionofallhardware,includedrawingswherenecessary
Runtestsampleandcomparechromatogramprintoutwithreferencechromatogram.
Prepareaninstallationreport.
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12. 3.OPERATIONALQUALIFICATION:
It is the process of demonstrating that an instrument will function according to its operational
specification in the selected environment . It verifies that the HPLC system compiles with key
function and operational requirements as specified in the design qualification.
In operational specification the supplier must define exactly the conditions that must be observed
with varying conditions. Eg: different ambienttemperature.
Before performing all other test first perform leak test if, it is failed thenmost ofthe remaining
test will getfailed.
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13. Test parameters and acceptance criteria:
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Parameter Procedure Userlimit
Leaktesting Flow test by volumeor
weight/time
±5%
Baselinedrift ASTM (Americansociety
for testing material)
method E19.09, 20min
<2 x 10-3AU
Baselinenoise ASTM method E19.09,20
min x1
<5 x 10—5AU
Precision ofinjection
volume
6 x injection ofcaffeine
standard, RSD of peak
areas
0.3%RSD
Precision of flowrate 6 x injection ofcaffeine
standard, RSD of
retentiontimes
0.5%RSD
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14. PARAMETER PROCEDURE USERLIMIT
Detectorlinearity Inject 5standards >1.5 AU, 5%RSD
Wavelengthaccuracy Holmium oxidefilter ±1nm
Temperatureaccuracy Comparison withexternal
measuringdevice
±1ºc
Temperatureprecision Monitoring temperature
over 20mins ±0.25ºc
Auto sampler carryover Injection of large sample
after largeconcentration
<0.5%
Mobile phasecomposition
accuracy
Stepgradientfrom4to7%
B,Stepheightsrelativeto
100%withacetonetracer
±1%
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15. Baseline noise anddrift:
•DriftandbaselinenoiseareimportantfactorsforUVdetectors.Increasedbaselinenoise
considerablyreducesthesensitivity,asitisnotpossibletodistinguishbetweenlow-levelsignals
andnoise.Withincreaseddrift,itismoredifficulttointegratethesignalscorrectlybecausethe
lessstablethebaselineis,themoreinaccurateisintegration.
•Thebaselinenoiseofthedetectormainlydependsonthelamp.Thereisaconsiderableincreasein
noiseifanoldlampwithpoorlightintensityisused.Thisisalsotruewhentheflowcellsisdirty.In
additionmakesurethattheflowcellsfreefromgasbubbles.
•TomeasurethedriftofaUVdetector,alsomakesurethatallmeasuringconditionsareconstant.In
addition,itisveryimportantthatthelamphasbeenburningforseveralhoursinthedetector
environment,avoiddirectsunlight.
•Thelampintensitydecreaseswhilethelampisburning.Besides,thelampageswhenitisturnedon
andoffveryoften.
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16. Evaluating baseline noise anddrift:
•TO check noise, drift water is pumped through the cell at a flow rate of 1ml/min. The
UV signal is recorded at254nm.
•To calculate noise the measuring signal is split into 20 intervals for 1min each. For each
interval chromeleon calculates a regression based on measured values, using the method of
least square. The limit should be between <2 x 103AU.
•To calculate the drift, chromeleon calculates a regression line from all data points with in a
range of 1-21mins based on the method of least square. The slope of the regression line is the
calculated drift. The limit should be between <5 x 10—5AU.
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17. Precision of injectionvolume:
•Precision of injection volume is an important parameter for accuracy ofquantitation.
Evaluating precision of injectionvolume:
•Inject 6 standard caffeine solution and calculate height, area, average height, average
area, %RSD of height and %RSD of area which gives precision of volume and the limit
should be in between 0.3%RSD.
Detectorlinearity:
•Linearity of a detector is a critical parameter to establish for reliable and accurate
quantitativeresults.
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18. Evaluatingdetectorlinearity:
•Aseriesof5traceablestandards(caffeinesolutionofconcentrationabout0.00035to
0.35mg/ml)areinjectedandevaluated.Thedetectorlinearityiscalculatedbydetermining
thepeakareavsconcentration.%RSDcanalsobecalculatedforcheckingthedetector
linearity.Thelimitshouldbeinbetween>1.5AU,5%RSD.
Wavelengthaccuracy:
•Itisanimportantparameterforaccuracyofquantitativeandqualitativeanalysis.
Evaluatingwavelengthaccuracy:
•Traceablecaffeinestandardisusedtodeterminethewavelengthaccuracy.Caffeineis
trappedintheflowcellandaprogrammabletimetableisusedtodeterminethewavelength
maxima(205nm)andminima(273nm).Thewavelengthaccuracyisdeterminedasthe
absolutedifferencebetweenthemeasuredandcertifiedwave
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lengthvalues
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19. Temperature accuracy: Temperature fluctuations of the solvent and column can result in
considerable retention time fluctuations. Therefore, accuracy of the temperature is
important.
Evaluating temperature accuracy: 4 measuring points are used to check the temperature
accuracy of the column compartment. The check is performed with column oven sequence.
The achieved temperature is measured with external calibrated thermometer.
The achieved temperatures are compared to the set values. The difference indicates the
temperature accuracy and the limit should be in between ±1ºc
Temperature precision: Monitor temperature for 20minutes and limit should be in between
±0.25ºc
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20. Gradientmobilephasecompositionaccuracy:Itisimportantforaccurate
quantitativeanalysis.
Evaluatinggradientmobilephasecompositionaccuracy:AnAcetonetraceris
usedtodeterminegradientmobilephaseaccuracy,stabilityandlinearity.Make6
compositionsofwater+acetoneinconcentrationof0%,20%,40%,60%,80%and
100%(20%increment).
Linearrampdownfrom100%to0%isperformedwherethecompositionlinearity
isdeterminedbetweenrangesof95,75and25%.Allcompositionsaccuraciesare
calculatedastheabsolutedifferencebetweenthemeancompositionateachset
pointandthetheoreticalcomposition.
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21. 4.PERFORMANCE QUALIFICATION:
It is the process of demonstrating that an instrument consistently performs according to a
specification appropriate for its routine use.
Important here is the word consistently. The test frequency is much higher than for OQ.
Another difference is that PQ should always be performed under conditions that are
similar to routine sample analysis. For a chromatogram this means using the same
column, the same analysis conditions and the same or similar test compounds.
PQ should be performed on a daily basis or whenever the instrument isused.
The test frequency of only depends on the stability of the equipment but on everything in
thesystemthat may contribute to analysistheresultForaliquidchromatograph,thismay
bethe
49 chromatographic column or a detectorslamp
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22. Thetestcriteriaandthefrequencyshouldbedeterminedduringthedevelopmentandthe
validationoftheanalyticalmethod.
InpracticePQmeansystemstabilitytesting,wherecriticalkeysystemperformance
characteristicaremeasuredandcomparedwithdocumented,presetlimit.
Forexample,awellcharacterizedstandardcanbeinjected5or6timesandthestandard
deviationofamountsarethencomparedwithpredefinedvalue
Ifthelimitsofdetectionandquantificationsarecritical,thelampsintensityprofileor
thebaselineshouldbetestedtheyshouldusethesamecolumnandchemicalsforthe
realsample.
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23. Test shouldinclude:
•Precision of theamounts
•Precision of retentiontimes
•Resolution between twopeaks
•Peak width at halfheight
•Peaktailing
•Baselinenoise
•Wavelength accuracy of the uv/vis wavelength detector,
preferably using built-in holmium –oxidefilters
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24. References:
•http://jddtonline.info/index.php/jddt/article/view/1858
•https://www.researchgate.net/publication/8508200_Qualification_of_analytical_in
struments_for_use_in_the_pharmaceutical_industry_A_scientific_approach
•https://www.researchgate.net/publication/327886011_AN_OVERVIEW_OF_ANALY
TICAL_INSTRUMENT_QUALIFICATION_WITH_REFERENCE_OF_PHARMACEUTICAL_IND
USTRY
•https://www.ncbi.nlm.nih.gov/pmc/articles/PMC2784854/
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