Sterilization & Chemical Resistance Of Healthcare Polymers

Sterilization & Chemical Resistanceof Healthcare Polymers

Key Terms & DefinitionsSterilization - A process that eliminates or kills all forms of life, including transmissible agents, ona medical device; used to prevent Hospital acquired infections (HAI’s)Sterile - Free from micro-organisms; 100% freedom from micro-organisms cannot be provenBioburden Testing - Measures the number of bacteria living on a surface that has not beensterilizedSterility Assurance Level (SAL) - Probability of a viable micro-organism on a product after ithas been sterilized normally expressed as 10-nBiological Indicators - Tests used by medical device manufacturers and healthcare providers tomonitor the efficacy of different sterilization processesSterilization Validation - A designed protocol for evaluating the effectiveness of a sterilizationprocessSterility Testing - Required during the sterilization validation process as well as for processcontrolPathogen - Infectious agents which is a microorganismEfficacy - Ability of a sterilization process to achieve a desired resultTerminal Sterilization - Process whereby a device is sterilized in its final container; The FDArequires terminal sterilization of medical devicesConfidential

SterilizationTechniques designed to kills microorganisms/ pathogensthat may cause infectionVariety of technologies usedPrimary technologies for sterilizing medical plastic parts:oooRadiation – gamma, electron beam (E-Beam)Ethylene Oxide (EtO)Steam AutoclaveConfidential

Determining Factors for SterilizationEffectivenessType of micro-organism present - Some micro-organisms arevery difficult to kill, some very easy to killNumber of micro-organisms present - Determined byBioburden testingAmount and type of organic material protecting the microorganismMedical device design - Cracks, crevices where micro-organismscan hide and collect inConfidential

Gamma SterilizationSterilization technique that uses gamma radiation to kill microorganisms present on a medical deviceoooCompatible with most plasticsDosage rate must be limited according to the materialUsed on disposable devicesValidation method(s)ooooANSI/AAMI/ISO 11137-2AAMI TIR 33ANSI/AAMI/ISO 11137-2 VDmaxAAMI/ISO 15844Gamma RadiationResin SubstrateConfidential

Application of Gamma RadiationGamma Radiation is a viable alternative to EtO Sterilization and becomethe industry standardooooooCleaner, no heat, leaves no chemical residueCan be sterilized with packagingIrradiation is generally recommended single use applicationsSignificant improvements in cycle time, inventory and overall systems costPhoto-bleaching can occurTypical dosage at 2.5 mega-rads is the same as 25 kilo-grays (Kgy)Ionizing rays of gamma radiation can cause thermoplastics to discolor oryellow; however, the effect on mechanical properties varies by materialConfidential

Polymer Compatibility to GammaRadiationRecommend using polymers with highestmolecular weight and narrow molecularweight distributionAmorphous polymers are more radiationresistant than semi-crystallineAromatic polymers are more radiationresistant than aliphaticConfidential

Potential Affects of GammaSterilization on PolymersPhysical properties of many thermoplasticschangeColor shift after exposure (i.e., yellowingeffect)Recombination - no change in propertiesCrosslinking - increased strength, decreasedelongationChain scission - loss of strength & elongationConfidential

Polymer Exposure to Gamma RadiationElongation RetentionPPSLCPPSPEPEIPETPVC, flexPSUPCHPSABSPVC, rigidPAPBTPE-UHMWHDPESEBSLSRPP, stabPA (6,12)PMMAPTFEPCMPPDose (kgray), in ambient air, at which elongation atbreak of the polymer decreases by 25%0500100015002000Confidential

Polymer Suitability to Gamma RadiationConfidential

Electron Beam (E-Beam) SterilizationOnly 5% of market (but growing)Limited penetration vs. gamma (requires multiple cycles from different angles)Less degradation to plastics than gamma (color and physical properties)Lowest energy to radiation ratioShorter exposure time than gamma (minutes vs. hours and/or days)Limited data available on effects to polymer properties and colorConfidential

Critical Radiation Doses for PolymersPolymerCritical Dose yamides300Rigid 100Silicone rubber40Polypropylene10PTFE4Confidential

Ethylene Oxide Sterilization Gas (EtO)Colorless, flammable, poison gas that kills microorganisms on a medical deviceooHighly compatible with most plasticsUsed on disposable devicesCauses Sterilization by chemical reactionValidation methodoAAMI/ISO 11135 Method CConfidential

Applications for EtO SterilizationTraditionally most widely method for disposable devices; trend ischanging to gammao Exposure to high levels of EtO recognized as a health hazardo 6 required stages of EtO (preconditioning, humidification, gassing,exposure, evacuation, post vacuum) – extensive cycle times vs.other processesMain benefits:o Sterilizes at low temperatureso Little to no effect on thermoplasticsThe major concern is the dissipation of residuals during post sterilizationprocess for medical devices maintaining contact with skin, mucous andshort-term implantsConfidential

Steam SterilizationUtilizes moist heat to kill micro-organisms on a medical deviceo Used on reusable deviceso Most plastics cannot withstand repeated steam sterilizationo Two common exposure conditions121o C for 30 minutes134o C for 20 minutesValidation methodo ISO 17665-1: 2006Confidential

Autoclave Steam SterilizationA popular sterilization method for reusable devicesThe autoclave’s pressure vessel saturates steam that damage the cell’sstructureTime and temperature is determined by the part, packaging, types ofmaterials usedTwo commonly used exposure conditions include:“Basic” 121ºC for 30 Minutes“Mid” 134ºC for 20 MinutesFew thermoplastic materials are compatible with various temperatures ofautoclaving

Steam Sterilization:Recommended Validated Exposure TimesItemWrapped InstrumentsTextile PacksWrappped UtensilesUnwrapped Non-porousItemsUnwrapped non -porousand porous items inmixed loadSource: Pacific BioLabsGravity Displacement Steam SterilizationExposureExposureExposureTime at 121C Time at 132C Time at 135C30 minutes 15 minutes 10 minutes30 minutes 25 minutes 10 minutes30 minutes 15 minutes 10 minutesDynamic Air Removal SteamExposureExposureTime at 132C Time at 135C4 minutes3 minutes4 minutes3 minutes4 minutes3 minutes3 minutes3 minutes3 minutes3 minutes10 minutes10 minutes4 minutes3 minutesUn-modified PC can withstand limited exposures to 121C,High heat PC can withstand limited exposure to 132CConfidential

Steam Sterilization CompatibleMaterials and Temperatures121 oC134 IPPSPSYHigh Heat PolycarbonatePEEKConfidential

Specific Materials and SterilizationThere is no sterilization pass/fail for specific materials used in amedical devicesTerminally sterilized devices can contain many plastic (andmetal) components that are made of different plastic materialso Different plastic materials withstand certain sterilizationtechniques differentlyo In determining the efficacy of a sterilization process the entiredevice is considered for pass/failo The determining factor for pass/fail is the sterility assurancelevel (SAL) determined for the deviceoConfidential

Sterility Assurance Levels (SAL)Used to describe the killing efficacy of a sterilizationprocessExpressed in log reduction (10-n)Example: 10-1 equals a 90% reduction in microbial populationRecommended sterility levels of terminally sterilizedproducts are typically 10-3 or 10-6 depending on the itemConfidential

SAL For Terminally Sterilized Devices10-3 SAL Examples10-6 SAL ExamplesProducts not intended to come in contact withbreached skin or compromised tissueProducts intended to come in contact with breachedskin or compromised tissueSpecimen collection or transfer devicesCardiac cathetersTopical devicesWound dressingsMucosal containing devicesPrefilled syringesProducts that cannot withstand higher SAL (e.g.,porcine heart valves, biological wound dressings)Invasive devices that enter normally sterile tissueProducts with claims of sterile fluid pathways(e.g., fluid pathways of IV sets)Surgically implanted devices (e.g. Jointreplacements, pacemakers, sutures)Components used in aseptic processingConfidentialSource: Steris

Sterilization & The FDAThe FDA’s Center for Devices and Radiological Health (CDRH) isresponsible for medical device sterilization regulationSterility of disposable medical devices is sited under FDA GMPSterilization method and process must e put in place for any medical devicemust be described in a device 510k document (FDA sterility reviewguidance document K-90-1 (2002))The FDA considers hospitals and third party sterilizers as medical devicemanufacturers and regulates them as suchConfidential

Comparison of Sterilization MethodsConsiderationsEthylene Oxide (EtO)Gamma RadiationAutoclave (Steam)Product & PackageDesignPackaging and product must bedesigned to allow gas penetrationDensity of the product load must beconsidered to ensure adequate gammapenetrationPackaging must be designed to resistmoisture damageComponent MaterialMost materials are satisfactoryDiscoloration (yellow), cross-link,physical property degradation postexposureDNA for materials with low HDT andhygroscopic. Morpoline will requirechemical compatibilityReliability ofSterilization ProcessProcess variable must be carefullymonitored and controlledBioburden control and frequenttesting is critical for long-termreliabilityVery reliableSterilization ReleaseRelease dictated by biologicalindicator tests or parametric testingresultsRelease dependent of dosemeasured/resultsRelease dictated by parametric testingresultsQuarantine PeriodQuarantined until aeration iscomplete. Testing requires between 3and 7 daysProduct may be release immediatelyProduct may be released immediately,although drying may be consideredChemical ResidualsQuarantine time must removeResults pendingNoneEconomicsGood on all volumes and load sizesGood in large volumesGood on all volumesCommonApplicationsBlood and renal care components.Applications with embeddedelectronicsFluid delivery. Pre-packagedcomponentsLab ware. Instruments and traysUsage52% (decreasing)46% (increasing)2%Confidential

Chemical ResistanceCan be a difficult problem to predict - many new chemicals and cleaners; Musttest to truly predictIn general, crystalline materials have better chemical resistance thanamorphous materialsHeat adds to the problem by aging materialsMedical parts are commonly exposed to the following:ooooooooLipids and fat emulsion (typically used as blood and drug carriers)AlcoholsIsopropyl AlcoholEthyl AlcoholHospital cleaners and other chemicals can be nastyBleach, hydrogen peroxide, saline solution, Cirex, VirexBodily fluidsVesicants (blistering agent) in chemotherapyConfidential

Data ificbiolabs.com/sterilization Making Sure Its m/bioburdentesting.aspxConfidential

Sterilization Validation -A designed protocol for evaluating the effectiveness of a sterilization process Sterility Testing - Required during the sterilization validation process as well as for process control Pathogen - Infectious agents which is a microorganism Efficacy-Ability of a s