Helt-Hansen, Jakob

Miller, Arne

Online Research Database In Technology

                       General rights Copyright and moral rights for the publications made accessible in the public portal are retained by the authors and/or other copyright owners and it is a condition of accessing publications that users recognise and abide by the legal requirements associated with these rights.  • Users may download and print one copy of any publication from the public portal for the purpose of private study or research. • You may not further distribute the material or use it for any profit-making activity or commercial gain • You may freely distribute the URL identifying the publication in the public portal   If you believe that this document breaches copyright please contact us providing details, and we will remove access to the work immediately and investigate your claim.     Downloaded from orbit.dtu.dk on: Dec 20, 2017Challenges in Validating Radiation Sterilization with Low Energy Electron IrradiationMiller, Arne; Helt-Hansen, JakobPublication date:2011Document VersionPublisher's PDF, also known as Version of recordLink back to DTU OrbitCitation (APA):Miller, A., & Helt-Hansen, J. (2011). Challenges in Validating Radiation Sterilization with Low Energy ElectronIrradiation [Sound/Visual production (digital)]. 12th Tihany Symposium on Radiation Chemistry, Zalakaros (HU),27 Aug - 1 Sep, 01/01/2011Challenges in Validating Radiation Sterilization with Low Energy Electron IrradiationArne Miller and Jakob Helt-HansenRi Hi h D R f L b tsø g  ose e erence a ora oryRisø DTUTechnical University of Denmark DK-4000 Roskilde1 DenmarkLow Energy Electron accelerators80 – 300 keV  Scanned beam or extended cathodesSelf-shieldedRisø HDRL acceleratorEnergy: 80-125 keV Beam current: 1-10 mA2Low-energy electron beam applicationsP lo ymers– Curing and crosslinkingPharmaceutical- Sterilization ofpackaging material3Electron beam tunnel Application: Surface sterilization of tubs with syringes for vaccines4Problem: • Surface sterilization of tubs is not regulated.• It concerns sterilization – or decontaminatation – of container for container of pharmaceutical product.• It is not a medical device.• It is not a pharmaceutical product.Suggested solution: • Use the international standard for Radiation St ili ti b i f d t tier za on as as s or ocumen a on5Documentation requirements for sterilization:EN ISO 11137 part 1:Sterilization of health care products – Radiation – Requirements for development, validation and routine process control of a sterilization process for medical devices.The principles of 11137 can be applied to any irradiation processeven curing and crosslinking with low energy electrons-  -- and also surface sterilization with low-energy electrons6Definition of validation (EN ISO 11137-1, 3.47):- documented procedure for obtaining, recording and interpreting the results required to establish that a processwill consistently yield product complying with predetermined specifications.Note 1: For the purpose of this part of ISO 11137, validation has at least the three main elements IQ OQ and PQ    , ,   .7Outline of EN ISO 11137-1:2006   • Calibration and measurement traceability (4)• Equipment characterization (6)• Product definition (7)• Process definition (8)• Validation (9)• Installation Qualification (9.1)• Operational Qualification (9.2)• Performance Qualification (9.3)R ti P C t l (10)• ou ne rocess on ro8ISO ASTM standards for characterization of irradiation facilities follow the 11137 outline. e.g.:ISO ASTM 51649 High energy electron accelerators(0.3 – 25 MeV)ISO ASTM 51818  Low energy electron accelerators(80 – 300 keV)9Calibration and measurement traceabilityRecommended methods for calibration of dosimeters:1) Irradiation of dosimeters at the facility of use (in-plant calibration).Dose measured with reference dosimeters.2) Irradiation of dosimeters at calibration laboratory followed by in-plant verification.Measurement traceability is not established without in-plantirradiation for calibration or verification. 10Measurement traceability chainNational Standard Reference Field Routine DosimeterReference   Dosimeter2nd Lab. Ref. FieldIrradiation at FacilityRoutine DosimeterReference DosimeterIrradiation at FacilityRoutine dosimeter11Calibration and measurement traceabilityFor Irradiation at the facility of use (in-plant calibration) dose is measured with reference dosimeters.Problem:Dose gradients within dosimeters lead to different  thickness dosimeters measuring different doses inthe same radiation field.Solution :Evaluate surface dose– Dµ – for all dosimeters.12Concept of surface dose – Dµ30 025.0.Dµ15.020.0ose, kGy5 010.0Do0.0.0 20 40 60 80 100 120 14018µm B3 50µm FWT 130µm alanineDepth in water, µm13Process definition1)  - Specifying a maximum acceptable dose.2)  - Specifying a minimum dose for obtaining a required level of sterilization.1) Maximum dose concerns Tyvek cover only.Typical maximum acceptable dose 100 kGy2) R i d l l f t ili ti t ifi d d th fequ re eve o  s er za on no  spec e – an  ere orerequired minimum  dose not specified.Users have specified required minimum dose at 15 kGy or    25 kGy.14Process definition Important question:Is low energy electron radiation effective for killing microorganisms?Study comparing effectiveness of C b lt 60 G 10 M V-10Gammao o -  amma,  eelectrons and 100 keV electronsusing b.Pumilus.-4-3-2g fraction10 MeVResult: Same effectiveness-6-5g Surviving100 keVConclusion: Dose setting methods of 11137-2 can be used.-8-7Log80 keV-90 5 10 15Dose, kGy15Installation qualification - IQ- is carried out to demonstrate that the sterilization equipment and any ancillary items has been supplied and installed in          accordance with their specification.Whether or not data are “in accordance with their specification” depends on agreement between user and       supplier.Dosimetry measurements are often the same as used forOperational Qualification.16O i l lifi i OQperat ona  qua cat on  -OQ shall demonstrate that the irradiator, asinstalled, is capable of operating and delivering appropriate doses within defined acceptance criteria.- provides baseline data to show consistent operation of the  facility17Operational qualification  - Electron beamCharacteristics to be measuredDose distribution in reference product Not relevant for low energyBeam width and homogeniety ImportantEnergy and beam penetration Energy: Not important                     Beam penetration: ImportantDose as function of speed, current and Importantbeam widthBeam spot size Not relevant for low energy – in most casesEffect of process interruption Not relevant for low energy– in most cases18  OQ is often carried out using a reference productDosedistributionRelative Dose, %110-120100-11090-10080-9070-80in reference product10060-7050-6040-5030-4020-3010-200-10High-energy example20n Y, cm4030Position50-30,0 -25,0 -20,0 -15,0 -10,0 -5,0 0,0 5,0 10,0 15,0 20,0 25,0 30,019Position X, cmBeam width – high energy beamLimits for  acceptable variations can bedefined.20OQ E-beam cont..Beam width – low energy beam Beam width  17.5 cm at 80% dose level21Beam width – low energy beamBeam wider than measurement Beam Width40455020253035Dose, kGy5101500 20 40 60 80 100 120 140Position (left to right), cm 138 cm22OQ E-beam cont..Energy   - Wedge and stack for energy measurement23OQ E-beam cont..Typical depth-dose curveEnergy – range relationships24OQ E-beam cont..Low energy  - arrangements for  measurement of depth dose25OQ E-beam cont..Low energy  - Depth dose curvesEnergy determination difficult usually  –not carried outDepth dose profiles, Crosslinking50603040se, kGy1020Dos00 20 40 60 80 100 120 140 160 180 200Depth, µm water26100 keV 125 keV 160 keV 200 keV 250 keVOQ E-beam cont..Dose as a function of - beam current- conveyor speed- beam width) Dose = K * (I/(Vl*Wb))Measured at a lowenergyaccelerator27Beam spot size.Might be relevant for scanned beamsat high-speed product movementExample of scanned and pulsed beam28Process interruption1.00Normally no problem – product is discarded at processi i 0.95nimum dosenterrupt onsProcess interruption –effect due to sparks0.90Normalized min   0.85-20 -10 0 10 200.803 tubs per minute (1.9 cm/s)6 tubs per minute (3.8 cm/s)29Position on tub, cmRepeat of OQ to be specified by operator.(A.12.4.1) The intervals for requalification of the irradiator should be chosen to provide assurance that the irradiator is i t tl ti ithi ifi ticons s en y opera ng w n spec ca ons. Different elements of OQ can be repeated at different time intervals If requalification measurements show that the IQ and/or OQ         status of the irradiator has changed, then PQ mighthave to be repeated.30Performance Qualifiaction- dose mapping of real product  PQ dose mapping is carried out to demonstrate- that minimum dose to product exceeds the dose required for the intended effect andth t i d t d t d t d- a  max mum ose o pro uc  oes no  excee  a maximum acceptable dose.In many low-energy applications OQ and PQ are combined.31PQ Dose mapRisø B3  dosimetersplaced on tubfor an isolator in a fillingline.32Dose measurement with RisøScan   Minimum dose34.7 kGy33Repeatmeasurementofi im n mumdoseRisø B3 dosimeterson 10 trays34Avoid ozone in tubD dose un erTyvek coverRisøScan + Risø B3measurement35Routine Process controlMeasurement of routine doseThe dose at a routine monitoring position shall be measured at intervals specified by the operator of the facility. The intervals shall be chosen to provide assurance that the irradiator is consistently operating within specified limits. 36Low energy E-beam- characterization and monitoring  Reference product for electron beamtunnels37Low energy electronDose monitoring Dosimeters placed on reference tub for routine dose measurementOr placedosimeters onnormal tub38Routine Process control1) Monitoring of process parametersThe process parameters (beam energy beam current beam width    ,  ,   and conveying speed) shall be monitored to provide assurance that the irradiator is consistently operating within specifications.2) Measurement of routine doseTh d i i i i i h ll b de ose at a rout ne mon tor ng pos t on s a  e measure  at intervals specified by the operator of the facility. The intervals shall be chosen to provide assurance that the irradiator is consistently operating within specified limits. 3) A l t ti ti l t l (SPC) th d d t pp y s a s ca process con ro  on e measure a a.39

Challenges in Validating Radiation Sterilization with Low Energy Electron Irradiation

http://orbit.dtu.dk/ws/files/9987368/Challenges_in_Validating_Radiation_1_.pdf

Challenges in Validating Radiation Sterilization with Low Energy Electron Irradiation

Abstract

Similar works

Full text

Available Versions

Online Research Database In Technology