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Installation Qualification, Performance Qualification and Routine Control

Miller, Arne

Publication date:2011

Document VersionPublisher's PDF, also known as Version of record

Link back to DTU Orbit

Citation (APA):Miller, A. (Author). (2011). Installation Qualification, Performance Qualification and Routine Control.Sound/Visual production (digital)

Medical Devices Sterilization for ManufacturersMedical Devices Sterilization for Manufacturers

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Validation and routine control ofValidation and routine control ofili i b i di iili i b i di isterilization by irradiationsterilization by irradiation

Arne MillerRi ø Hi h D R f L b tRisø High Dose Reference LaboratoryRisø DTUTechnical University of DenmarkDK-4000 RoskildeDenmark

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Denmark

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Content of presentation:Content of presentation:pp

InInstallationstallation Qualification Qualification -- IQIQ

Operational Operational Qualification Qualification -- OQOQ

•• Performance QualificationPerformance Qualification -- PQPQPerformance Qualification Performance Qualification PQPQ

Process Control and MonitoringProcess Control and Monitoring

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Installation qualificationInstallation qualification

undertaken to demonstrate that the sterilization equipment has undertaken to demonstrate that the sterilization equipment has q pq pbeen supplied and installed in accordance with specification.been supplied and installed in accordance with specification.

Whether or not data are “in accordance with their specification”Whether or not data are “in accordance with their specification”Whether or not data are in accordance with their specification Whether or not data are in accordance with their specification depends on agreementdepends on agreement

Measurements often the same as for Operational QualificationMeasurements often the same as for Operational QualificationMeasurements often the same as for Operational QualificationMeasurements often the same as for Operational Qualification

Responsibility:Responsibility: Facility OperatorFacility Operator

ISO 11137ISO 11137--1, sect 9.11, sect 9.1

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Operational qualificationOperational qualification

•• -- carried out by irradiating appropriate test material to carried out by irradiating appropriate test material to demonstrate the capability of the equipment to deliver the demonstrate the capability of the equipment to deliver the sterilization process that has been defined.sterilization process that has been defined.p fp f

•• -- provides baseline data to show consistent operation of the provides baseline data to show consistent operation of the facilityfacilityfacilityfacility

Responsibility: Facility OperatorResponsibility: Facility Operator

ISO 11137ISO 11137--1, sect 9.21, sect 9.2

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Operational qualification GammaOperational qualification Gammap qp q

•• dose distribution in reference dose distribution in reference d ( )d ( )product(s)product(s)

•• dose as function of dwell timedose as function of dwell time•• process interruptionprocess interruption•• process interruptionprocess interruption•• mix of productsmix of products

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OQ gamma cont..OQ gamma cont..

Gamma FacilityGamma FacilityLayoutLayout

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OQ OQ gammagammagammagammacont..cont..

Placement ofof dosimeters

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OQ Gamma cont..OQ Gamma cont..

Dose distributionDose distributionin reference productin reference product

Isodose curvesIsodose curves

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OQ gamma cont..OQ gamma cont..

Dose mappingDose mapping

Dose maps must be made with fully loaded irradiation chamberDose maps must be made with fully loaded irradiation chamber

Range of densities of reference product must cover extremes of Range of densities of reference product must cover extremes of products to be irradiatedproducts to be irradiated

Additional measurement:Additional measurement:

ff f i iff f i i−− effect of process interruptioneffect of process interruption

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OQ gamma cont..OQ gamma cont..

Dose mappingDose mapping

Dose mapping shall be carried out on a sufficient number Dose mapping shall be carried out on a sufficient number of irradiation containers to allow determination of theof irradiation containers to allow determination of theof irradiation containers to allow determination of the of irradiation containers to allow determination of the distribution and variability of dose between containersdistribution and variability of dose between containers

Dose mapping must be repeated when significant changes Dose mapping must be repeated when significant changes of the irradiation plant are madeof the irradiation plant are made e ge g source changesource changeof the irradiation plant are made, of the irradiation plant are made, e.g. e.g. source changesource change

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Operational qualification Electron beamOperational qualification Electron beam

•• CharacteristicCharacteristic parameters toparameters to bebe measuredmeasuredCharacteristicCharacteristic parameters to parameters to bebe measuredmeasured

•• dosedose distribution reference distribution reference productproduct•• scanscan widthwidthscan scan widthwidth•• energyenergy•• dosedose as as functionfunction of speed, of speed, currentcurrent, , beambeam

widthwidth•• beambeam spotspot

i t tii t ti•• processprocess interruptioninterruption

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OQ EOQ E--beam cont..beam cont..

Placement of dosimeters Placement of dosimeters in reference productin reference product

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OQ EOQ E--beam cont..beam cont..

Dose distribution Dose distribution i fi fin reference in reference productproduct

Limits for acceptable variations can bedefineddefined.

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OQ EOQ E--beam cont..beam cont..

Scan width (=extended beam width)Scan width (=extended beam width)

Limits for acceptable variationsvariations can bedefined.

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OQ EOQ E--beam cont..beam cont..

EnergyEnergy

Wedge and stack for energy measurementWedge and stack for energy measurementWedge and stack for energy measurementWedge and stack for energy measurement

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OQ EOQ E--beam cont..beam cont..

Typical depthTypical depth--dose curvedose curveTypical depthTypical depth--dose curvedose curve

Energy Energy –– range range relationshipsrelationshipsrelationshipsrelationships

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OQ EOQ E--beam cont..beam cont..

Dose as a function Dose as a function of of Dose = f(I/V*Sw)

-- beambeam currentcurrent (I)(I)-- convconv speed (V)speed (V)-- beambeam widthwidth ((SwSw))

y = 1129,8x - 0,1538R2 = 0 9996

7080

-- beambeam widthwidth ((SwSw)) R 0,9996

30405060

se, k

Gy

0102030

Do

00,000 0,010 0,020 0,030 0,040 0,050 0,060 0,070

I/(V*Sw)

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OQ EOQ E--beam cont..beam cont..

Beam spot patternBeam spot pattern

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OQ EOQ E--beam cont..beam cont..

Process interruptionProcess interruption

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OQ EOQ E--beam cont..beam cont..

EE--beam OQ should be repeated when significant changes of thebeam OQ should be repeated when significant changes of theEE beam OQ should be repeated when significant changes of the beam OQ should be repeated when significant changes of the irradiation plant are made that may influence dose or dose irradiation plant are made that may influence dose or dose distribution.distribution.

It is recommended to repeat OQ at regular intervals, e.g. annually It is recommended to repeat OQ at regular intervals, e.g. annually i d t d t t i t t tii d t d t t i t t tiin order to demonstrate consistent operation.in order to demonstrate consistent operation.

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Performance qualificationPerformance qualificationConcerns dose mapping of real productConcerns dose mapping of real product

t id tif th l ti d it d f i i d it id tif th l ti d it d f i i d ito identify the location and magnitude of minimum and maximum to identify the location and magnitude of minimum and maximum dosesdoses

andandandand

to determine the relationship between the min and max doses and the to determine the relationship between the min and max doses and the routine doseroutine dose

Responsibility: Primary ManufacturerResponsibility: Primary Manufacturer

ISO 11137ISO 11137--1, sect 9.31, sect 9.3

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Performance qualification ..cont..Performance qualification ..cont..

Purpose of dose mappingPurpose of dose mapping

-- to demonstrate that: to demonstrate that:

•• D (min)D (min) D (Steril) and D (max)D (Steril) and D (max) D (acceptable)D (acceptable)•• D (min) D (min) D (Steril) and D (max) D (Steril) and D (max) D (acceptable)D (acceptable)

•• D (min) determined by sterilization requirementsD (min) determined by sterilization requirements

•• D (max) determined by radiationD (max) determined by radiation--induced changes in productinduced changes in product

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Performance qualification ..cont..Performance qualification ..cont..

Strategies for dose mappingStrategies for dose mapping-- based on:based on:

OQ measurementsOQ measurements Inhomogeneous product distribution, orientation, voids, Inhomogeneous product distribution, orientation, voids,

i t fi t finterfaces.interfaces. ExperienceExperience

Processing categoriesProcessing categories

Limitations of dose mappingLimitations of dose mapping

Ability to measure “the true” value of D(min) or D(max)Ability to measure “the true” value of D(min) or D(max) Location of dosimeterLocation of dosimeter

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Location of dosimeterLocation of dosimeter Resolution of dosimeter systemResolution of dosimeter system

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Performance qualification ..cont..Performance qualification ..cont..Performance qualification ..cont..Performance qualification ..cont..

Examples from real lifeExamples from real lifeExamples from real life …..Examples from real life …..

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Dose map examplesDose map examplesDose map examplesDose map examples

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Measurement UncertaintyMeasurement Uncertainty

Performance qualification ..cont..Performance qualification ..cont..Measurement UncertaintyMeasurement Uncertainty

Dose mapping shall be carried out using representative irradiation Dose mapping shall be carried out using representative irradiation containers sufficient in number to determine the variability of dose containers sufficient in number to determine the variability of dose ff y fff y fbetween containersbetween containers

Practical approach:Practical approach:

Either dose map in detail 3Either dose map in detail 3--10 containers10 containers

orororor−− dose map in detail one dose map in detail one cntainercntainer−− repeat measurement of D (min) and D (max) in several (e.g. 10) repeat measurement of D (min) and D (max) in several (e.g. 10) p ( ) ( ) ( g )p ( ) ( ) ( g )

containers containers −− evaluate measurement uncertainty taking into account all evaluate measurement uncertainty taking into account all

t i t tt i t t

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uncertainty components.uncertainty components.

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Performance qualification ..cont..Performance qualification ..cont..

Setting Process LimitsSetting Process Limits

Select process parametersSelect process parametersp pp p

gamma:gamma: e.g. timer settinge.g. timer setting ee--beam:beam: e.g. conveyor speed e.g. conveyor speed

so that D(min) will exceed D(sterile) and so that D(min) will exceed D(sterile) and so that D(max) will not exceed D(acceptable)so that D(max) will not exceed D(acceptable)

Select process limits based on the measured uncertainty.Select process limits based on the measured uncertainty.

Practical approachPractical approach select process parameters so that D(min) is two standard select process parameters so that D(min) is two standard

d i ti hi h th D(d i ti hi h th D( t ilt il))

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deviations higher than D(deviations higher than D(sterilsteril))

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Performance qualification ..cont..Performance qualification ..cont..

Selection of uncertainty Selection of uncertainty limits for process controllimits for process control

Normal distribution

1

limits for process controllimits for process control0,8

0,4

0,6

Prob

abili

ty

0,2Limit based onLimit based on2 standard deviations2 standard deviations

0-4 -3 -2 -1 0 1 2 3 4

Standard deviations

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Performance qualification ..cont..Performance qualification ..cont..

Repetition of Performance Qualification Dose MapRepetition of Performance Qualification Dose Map

Only needed if product is changed Only needed if product is changed or if facility is changedor if facility is changedy gy g

review of documentation at defined intervals is recommended, review of documentation at defined intervals is recommended, e g every 3 yearse g every 3 yearse.g. every 3 yearse.g. every 3 years

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