1、BPSA Quality Test Matrices2023 UpdateJames Dean Vogel,P.E.Agenda Project Review Changes Path ForwardObjective Update the BPSA Quality Test Matrices(Last updated in 2015)Add new standards and references Remove obsolete standards and references Prioritize tests to:Required Recommended To Be Considered

2、 Complete for rollout with BPSA Summit in July August 2023 Project Gather community input from BPSA members and the industry in general.Survey.Combine information in in 5-6 teams-3-4 online meetings Test Categories and/or Component Categories Present to other teams at a face to face.Refine informati

3、on in 5-6 teams-2-3 online meetings SAB approval Board approval Presentation to Membership-TodayTeam MembersJim Sanford Paul Priebe Dan Nelson Russell Darley Nicole Hunter Charlie Zhang Robert Bob Huffman Janel Wittmayer Joe Figlio Heidi Sinkovich Nick Troise Hernan Parma Joy Xiaohui ChenNasim Mouch

4、a Jen Alejandre Craig Vincze Richard Herpers David RadspinnerGala Johnson James Hathcock Klaus Warmouth Jim Vogel Maureen Eustis Kirsten Strahlendorf Danielle ArcuriEma RajicGala johnsonJeroen Deroover,Kendall Horst Monica Cardona Mrt Sild Russell DarleyTodd AndrewsQTM HistoryPurpose:“help guide use

5、rs when making their selections and(to)facilitate qualification,validation and use of Single-Use products”Most accurate,up-to-date and emergent information QTM History2007-Initial 2015-Last Update2023-Current UpdateTest CategoriesA.PhysicalB.FunctionalC.BiologicalD.ChemicalE.RegulatoryF.Sterilizatio

6、n/SanitizationComponent Categories1.Chromatography2.Connectors,Valves and Retainers3.Containers and Film4.Sensors5.Tubing6.Filters2015Test CategoriesA.PhysicalB.FunctionalC.BiologicalD.ChemicalE.RegulatoryF.Sterilization/SanitizationComponent Categories1.Chromatography2.Connectors,Valves and Retaine

7、rs3.Containers and Film4.Sensors5.Tubing6.Filters7.Single-Use Assemblies20232023 Changes Single-Use Assembly Sheet added Tests added Manufacturer defined methods Tests deleted Links Updated Component Categories added to Test Sheets Alphabetical Listings BPSA color schemeA.Physical Tests Updates Inte

8、grity Shelf life addedTEST TYPEGENERAL DESCRIPTIONTEST REFERENCESTEST ARTICLE1Chromatography2ConnectorsValvesRetainersCon FHydrostatic Pressure Test(Shell/Seat Test)ASTM E 3251-20Final Article ASTM E 3251-20ASTM E3244-20ASTM E3244-20ASTM E3244-20ASTM ASTM E515-22ASTM ASTM D4991-99ASTM ASTM E 3251-20

9、ASTM E 3251-20ASTM E 3251-20ASTM ASTM E3336-22ASTM E3336-22ASTM E3336-22ASTM Junction Testing(barbed fittings)Single-use assembly junction connections should be qualified by the supplier to ensure they meet performance criteria as stated in their specification.The supplier shall have an established

10、testing program to substantiate performance of the mechanical connection.The testing should reference at least one of the following:(a)Pressure Testing(b)Leak Testing(c)Tracer Gas TestingManufacturer Defined MethodFinal Article Manufacturer Defined MethodManufacturer Defined MethodManufacturer Defin

11、ed MethodManufa MASMTM E1003-13(2022)ASMT COMPONE A.PHYSICAL TESTSFinal Article Hydrostatic leak testingIntegrity(Leak)TestStandard Test Method for Physical Integrity Testing of Single-Use Systems.Confirmation of integrity for components and assemblies at a given temperature.This includes pressure t

12、esting under operating conditions and at elevated pressures.Final Article A.Physical TestsTEST TYPEGENERAL DESCRIPTIONTEST REFERENCESTEST ARTICLE1Chromatography2ConnectorsValvesRetainers3Containers Film4Sensors5Tubing6Filters7Single-UseAssembliesUsed to measure manufactured product and seal barrier

13、performance of a variety of package types and forms,as well as seal and/or closure types.ASTM E3244-20ContainerASTM E3244-20Performed to ensure that functional strength requirements are met.ASTM F88-F88M&/orManufacturer Defined Method Risk AssessmentContainerASTM F88-F88M&/orManufacturer Defined Met

14、hod Risk AssessmentMicrobial ingress test of single-use systemsASTM E 3251-20ContainerASTM E 3251-20Physical integrity of single-use systemsASTM E3336-22ContainerASTM E3336-22Used to measure manufactured product and seal barrier performance of a variety of package types and forms,as well as seal and

15、/or closure types.Manufacturer Defined MethodPackagingManufacturer Defined MethodASTM D395ASTM D395ISO 815ISO 815ASTM D2240ASTM D2240ISO 868ISO 868ASTM D412ASTM D412ISO 37ISO 37Hydrostatic Pressure Test(Shell/Seat Test)ASTM E 3251-20Final Article ASTM E 3251-20ASTM E3244-20ASTM E3244-20ASTM E3244-20

16、ASTM E3244-20ASTM E3244-20ASTM E3244-20ASTM E3244-20ASTM E3244-20ASTM E515-22ASTM E515-22ASTM D4991-99ASTM D4991-99ASTM E 3251-20ASTM E 3251-20ASTM E 3251-20ASTM E 3251-20ASTM E 3251-20ASTM E 3251-20ASTM E 3251-20ASTM E 3251-20ASTM E3336-22ASTM E3336-22ASTM E3336-22ASTM E3336-22ASTM E3336-22ASTM E33

17、36-22ASTM E3336-22ASTM E3336-22Junction Testing(barbed fittings)Single-use assembly junction connections should be qualified by the supplier to ensure they meet performance criteria as stated in their specification.The supplier shall have an established testing program to substantiate performance of

18、 the mechanical connection.The testing should reference at least one of the following:(a)Pressure Testing(b)Leak Testing(c)Tracer Gas TestingManufacturer Defined MethodFinal Article Manufacturer Defined MethodManufacturer Defined MethodManufacturer Defined MethodManufacturer Defined MethodManufactur

19、er Defined MethodManufacturer Defined MethodManufacturer Defined MethodManufacturer Defined MethodASMTM E1003-13(2022)ASMTM E1003-13(2022)ASTM D3985-05(2010)e1 ASTM D3985-05(2010)e1 ASTM F1927-20ASTM F1927-20ASTM F2476 ASTM F2476 18869:201718869:2017ASTM D1599-18ASTM D1599-18ASTM D1599-18ASTM D1599-

20、18ASTM D1599-18ASTM D1599-18Manufacturer Defined MethodManufacturer Defined MethodManufacturer Defined MethodManufacturer Defined MethodManufacturer Defined MethodManufacturer Defined MethodISO1402:2021ISO 1402ISO 1402ISO 1402ISO 1402ISO 1402EN 12266-1EN 12266-1EN 12266-1EN 12266-1ISO 7241-2ISO 7241

21、-2ISO 7241-2ISO 7241-2ISO 7241-2ASTM D7192-20ASTM D7192-20(FTMS)101C-Method 2065.1(FTMS)101C-Method 2065.1 Shelf LifeDemonstrates functional performance at end of manufacturer-specified shelf life(typically does not test to failure).Manufacturer Defined MethodContainerManufacturer Defined Method*AST

22、M D792ASTM D792ISO 1187ISO 1187ASTM D624-00ASTM D624-00ASTM D1938-19ASTM D1938-19ASTM D1938-19ISO 34ISO 34ASTM D882-18ASTM D882-18ASTM D882-18Manufacturer Defined MethodManufacturer Defined MethodManufacturer Defined MethodISO 37ISO 37Thickness&Layer CompositionFilm thickness and materials compositi

23、on to be defined.ASTM D1777FilmASTM D1777*Visual Observation LibraryList of potential visual observations regarded as defects vs cosmetic imperfections.Observations should consider secondary packaging materials that may contribute to visual observations,as well as the installation state of the bio c

24、ontainer at the time such inspections would typically be performed.Manufacturer Defined MethodContainerManufacturer Defined Method*Water Vapor Transmission Rate(WVTR)The rate at which water vapor will permeate through solid material over a specified time periodASTM F1249-20FilmASTM F1249-20ASTM F124

25、9-20*Cured raw material test plaque OR Final ArticleChamber Integrity/Seal Integrity-PeelCompression set measures the residual deformation after compressive loading under specified conditions.Cured raw material test plaqueDurometer(Hardness)A measurement of the hardness of a material.Cured raw mater

26、ial test plaqueFilmSpecific GravityDensity relative to water.Cured raw material test plaque OR Final Article*Tensile StrengthDetermines resistance of loading on a jointed union/connection/fitting.Tear ResistanceTear strength measures the resistance to propagation of a rip or tear once the rip has be

27、en initiated.Film/Cured raw material test plaque or Final ArticleO2 and CO2 PermeabilityElongationA measure of a material ductility.Elastic modulus or modulus of elasticity is a measure of a materials tendency to deform when a force is applied.(Modulus at 100%,200%)COMPONENT CATEGORY APPLICABLE TO T

28、HIS TESTA.PHYSICAL TESTS*Individual components within the Single-Use Assembly are subject to test recommendations within specific categories,see section 1-6 for subassembly recommendations*Final Article Compression Set Test*Puncture ResistancePuncture resistance testing predicts the durability of th

29、e film while in use.Films with high puncture resistance correspond with materials that can absorb the energy of an impact by both resistance to deformation and increased elongation.Puncture resistance,measured in energy units,evaluates the film strength and extensibility properties.Puncture resistan

30、ce is similar to tensile toughness.Final Article Hydrostatic leak testingPressure Burst Test Characterization of device with regard to operating pressure and behavior under elevated pressure conditions at a given temperature;typically including determination of burst pressure under static pressure.F

31、inal Article Determines the steady-state rate of transmission of O2 or CO2 gases through material.FilmIntegrity(Leak)TestStandard Test Method for Physical Integrity Testing of Single-Use Systems.Confirmation of integrity for components and assemblies at a given temperature.This includes pressure tes

32、ting under operating conditions and at elevated pressures.Final Article B.Functional Tests Updates Additions General Functionality Weldability Pump LifeTEST TYPEGENERAL DESCRIPTIONTEST REFERENCESTEST ARTICLE1ChromatographyManufacturer Defined MethodManufacturer Defined MethodASTM F1980-21ASTM F1980-

33、21Accuracy/CalibrationVerification that the sensor meets the published accuracy specification,or if applicable,is properly calibratedManufacturer Defined MethodFinal ArticleAdsorbent CapacityStatic(equilibrium)and/or dynamic binding capacity of the adsorbent,determined for contacting an adsorbing su

34、bstance and the adsorbent(typically gel or membrane)under specific buffer conditions.Manufacturer Defined MethodRaw Material and/or Final ArticleManufacturer Defined MethodBacterial Retention Test(Sterilizing Grade Filters)Bacterial challenge and effluent sterility test based on standard methodology

35、.ASTM F838-05Final Article B.FUNCTIONAL TESTSAccelerated or Real Time Aging(Shelf Life)Accelerated and/or real time studies to determine the effects,if any,due to the passage of time and environmental effects on the properties of product,and on the sterile integrity of packages and the physical prop

36、erties of their component packaging materials.Final ArticleB.Functional TestsGeneral Functionality The Manufacturer/user shall establish that the Single-Use components,SUS assemblies,and SUS systems are designed for integrity and functionality,appropriately.These considerations should be maintained

37、during installation and ensured throughout the use of the item based on scientific product and process understanding for both SUS manufacturing and end user requirement.Qualification of design,manufacturing,testing and distribution should be conducted by the suppliers of Single-Use components and as

38、semblies with a planned and structured verification approach being applied throughout the system life cycle to deliver reliability of performance.Critical aspects of the SUS are typically functions,features,abilities,performance,and characteristics necessary for the manufacturing process and use,tha

39、t ensure consistent product quality and patient safety.B.Functional TestsTEST TYPEGENERAL DESCRIPTIONTEST REFERENCESTEST ARTICLE1Chromatography2ConnectorsValvesRetainers3Containers Film4Sensors5Tubing6Filters7Single-UseAssembliesManufacturer Defined MethodManufacturer Defined MethodManufacturer Defi

40、ned MethodManufacturer Defined MethodManufacturer Defined MethodManufacturer Defined MethodManufacturer Defined MethodManufacturer Defined MethodASTM F1980-21ASTM F1980-21ASTM F1980-21ASTM F1980-21ASTM F1980-21ASTM F1980-21ASTM F1980-21ASTM F1980-21Accuracy/CalibrationVerification that the sensor me

41、ets the published accuracy specification,or if applicable,is properly calibratedManufacturer Defined MethodFinal ArticleManufacturer Defined Method*Adsorbent CapacityStatic(equilibrium)and/or dynamic binding capacity of the adsorbent,determined for contacting an adsorbing substance and the adsorbent

42、(typically gel or membrane)under specific buffer conditions.Manufacturer Defined MethodRaw Material and/or Final ArticleManufacturer Defined Method*Bacterial Retention Test(Sterilizing Grade Filters)Bacterial challenge and effluent sterility test based on standard methodology.ASTM F838-05Final Artic

43、leASTM F838-05*Break at Cold Temperature TestDetermines cold crack temperature of plastic film.ISO 8570FilmISO 8570*ASTM E3231Container/FilmsASTM E3231Manufacturer Defined MethodContainer/FilmsManufacturer Defined MethodChromatographic Efficiency Test(HETP test)Characterization of separation efficie

44、ncy,typically performed on chromatography columnsManufacturer Defined MethodFinal ArticleManufacturer Defined Method*Dart DropTest method covers the determination of the energy as part of mechanical properties that causes plastic film to fail under specified conditions of impact of a free-falling da

45、rt.ASTM D1709-15FilmASTM D1709-15*Filter Integrity TestConfirms the membrane integrity(no defects,holes etc.)at given conditions of pressure/temperature.Manufacturer Defined MethodFinal Article Manufacturer Defined MethodManufacturer Defined Method*GelboDetermines the flex resistance of materials by

46、 the formation of pinholes.ASTM F392-93FilmASTM F392-93*Manufacturer Defined MethodManufacturer Defined MethodManufacturer Defined MethodManufacturer Defined MethodManufacturer Defined MethodManufacturer Defined MethodManufacturer Defined MethodManufacturer Defined MethodASTM 3051ASTM 3051ASTM 3051A

47、STM 3051ASTM 3051ASTM 3051ASTM 3051ASTM 3051Min./Max TemperatureASME BPE SD 2.4.1.2ASME BPE SD 2.4.1.2ASME BPE SD 2.4.1.2ASME BPE SD 2.4.1.2ASME BPE SD 2.4.1.2ASME BPE SD 2.4.1.2ASME BPE SD 2.4.1.2ASME BPE SD 2.4.1.2ASTM E1640-13ASTM E1640-13ASTM D3418-12e1ASTM D3418-12e1Haze and TransmittanceEvalua

48、tion of specific light transmitting and wide-angle-light-scattering properties of materials.ASTM D1003-13FilmASTM D1003-13*Kink ResistanceBend RadiusThe terms bend radius and kink resistance are used interchangeably to describe the change in the ability of a fluid to flow through the tubing when the

49、 tubing is bent.Manufacturer Defined Method(supplier-specific)Final Article Manufacturer Defined Method(supplier-specific)*ASTM D1790-14ASTM D1790-14ASTM D747ASTM D747Manufacturer Defined MethodManufacturer Defined MethodANSI/AAMI BF7ANSI/AAMI BF7ASTM D4169-14ASTM D4169-14ASTM D4169-14ASTM D4169-14A

50、STM D4169-14ASTM D4169-14ASTM D4169-14ASTM D4169-14ASTM D4728-06ASTM D4728-06ASTM D4728-06ASTM D4728-06ASTM D4728-06ASTM D4728-06ASTM D4728-06ASTM D4728-06DIN ISO 2872DIN ISO 2872DIN ISO 2872DIN ISO 2872DIN ISO 2872DIN ISO 2872DIN ISO 2872DIN ISO 2872ISTA 2AISTA 2AISTA 2AISTA 2AISTA 2AISTA 2AISTA 2A

51、ISTA 2AISTA 3AISTA 3AISTA 3AISTA 3AISTA 3AISTA 3AISTA 3AISTA 3AISTA 3BISTA 3BISTA 3BISTA 3BISTA 3BISTA 3BISTA 3BISTA 3BISTA 3EISTA 3EISTA 3EISTA 3EISTA 3EISTA 3EISTA 3EISTA 3EBPSA Recommendations for Testing,Evaluation,and Control of Particulates from Single-Use Processing EquipmentBPSA Recommendati

52、ons for Testing,Evaluation,and Control of Particulates from Single-Use Processing EquipmentBPSA Recommendations for Testing,Evaluation,and Control of Particulates from Single-Use Processing EquipmentBPSA Recommendations for Testing,Evaluation,and Control of Particulates from Single-Use Processing Eq

53、uipmentBPSA Recommendations for Testing,Evaluation,and Control of Particulates from Single-Use Processing EquipmentBPSA Recommendations for Testing,Evaluation,and Control of Particulates from Single-Use Processing EquipmentBPSA Recommendations for Testing,Evaluation,and Control of Particulates from

54、Single-Use Processing EquipmentUSP USP USP USP USP USP USP ANSI/AAMI BF7ANSI/AAMI BF7ANSI/AAMI BF7ANSI/AAMI BF7ANSI/AAMI BF7ANSI/AAMI BF7ANSI/AAMI BF7Practice for Extraction of Particulate Matter from the Surfaces of Single-Use Components and Assemblies Designed for Use in Biopharmaceutical Manufact

55、uringASTM E3230-20ASTM E3230-20ASTM E3230-20ASTM E3230-20ASTM E3230-20ASTM E3230-20ASTM E3230-20Plastic Containers Qualification of ParenteralOphthalmic-Aqueous SolutionsTests of plastic materials for use as containers for drug solutions.Tests ensure that the plastics do not change/degrade under con

56、ditions of normal use.They look for changes in physical characteristics,pH,or other changes associated with light,or chemicals.ASTM E3231Containers/FilmsASTM E3231*Product ConditioningCharacterization and Qualification of recommended conditions for conditioning the product,primarily prior to use.Thi

57、s can involve the removal(wash out)of storage solutions;or the wetting of a device.Manufacturer Defined MethodFinal ArticleManufacturer Defined Method*Pump LifeEvaluates the ability and duration tubing can withstand pumping.Manufacturer Defined MethodFinal ArticleManufacturer Defined Method*Separati

58、on TestCharacterization of separation performance and scalability of the sorbent/membranes when packed into the device(column or capsules).Manufacturer Defined MethodFinal ArticleManufacturer Defined Method*ISO 7241-2ISO 7241-2ISO 7241-2ISO 7241-2ISO 3968ISO 3968ISO 3968ISO 3968ISO 3968Manufacturer

59、Defined MethodManufacturer Defined MethodManufacturer Defined MethodManufacturer Defined MethodManufacturer Defined MethodManufacturer Defined MethodISO 815ISO 815ISO 37ISO 37IEC60534-2-3IEC60534-2-3DIN EN 1267DIN EN 1267WeldabilityCo-WeldabilitySealabilityEvaluates the ability for tubing to be ther

60、mally welded and aseptically sealed.Manufacturer Defined MethodFinal ArticleManufacturer Defined Method*B.FUNCTIONAL TESTSCOMPONENT CATEGORY APPLICABLE TO THIS TESTAccelerated or Real Time Aging(Shelf Life)Accelerated and/or real time studies to determine the effects,if any,due to the passage of tim

61、e and environmental effects on the properties of product,and on the sterile integrity of packages and the physical properties of their component packaging materials.Final Article*General FunctionalityFit for Intended UseFinal Article Cell GrowthCell Culture Growth Assessment of Single-Use MaterialTh

62、e Manufacturer/user shall establish that the Single-Use components,SUS assemblies,and SUS systems are designed for integrity and functionality,appropriately.These considerations should be maintained during installation and ensured throughout the use of the item based on scientific product and proces

63、s understanding for both SUS manufacturing and end user requirement.Qualification of design,manufacturing,testing and distribution should be conducted by the suppliers of Single-Use components and assemblies with a planned and structured verification approach being applied throughout the system life

64、 cycle to deliver reliability of performance.Critical aspects of the SUS are typically functions,features,abilities,performance,and characteristics necessary for the manufacturing process and use,that ensure consistent product quality and patient safety.*Low Temperature Brittleness Determines the te

65、mperature at which plastics and elastomers exhibit brittle failure.FilmGlass Transition TemperatureDetermines the glass transition temperature(Tg)of materials.The Tg is the temperature where the polymer goes from a hard,rigid state to a rubber-like,flexible state.Film*Microbial IngressSoil TestIdent

66、ification of external bacterias ability to breach a seal and ingress into a sterile flow path.Final Article*Individual components within the Single-Use Assembly are subject to test recommendations within specific categories,see section 1-6 for subassembly recommendationsFlow coefficient CvFinal Arti

67、cle Water Flow Rate Pressure Drop TestMeasures flow through the device.Pressure-flow testing is applied to determine the pressure loss over the device as a function of liquid flow rate.Data depends on the properties of the liquid and temperature.Typically,pressure drop for water at room temperature

68、is included for reference.Final ArticleQualify that product packaging will protect the product during shipping.Standard practice for performance testing of shipping containers and systems to provide a uniform basis of evaluating,in a laboratory,the ability of shipping units to withstand the distribu

69、tion environment.Final ArticlePackage TestingTransportationShipping IntegrityParticulate Matter Evaluates and quantifies the presence of particulates(visible and/or sub-visible)in or on a sample.Final ArticleC.Biological Updates Risk Assessment ISO 10993-1 USPTEST TYPEGENERAL DESCRIPTIONTEST REFEREN

70、CESTEST ARTICLE1Chromatography2ConnectorValvesRetainersUSP USP USP EP 2.6.14USP USP USP AAMI ST72AAMI ST72AAMI ST72BioburdenEffluent bioburden quantification of colony forming units per effluent volume(CFU/ml);identification and quantification based on standard methodology.Manufacturer Defined Metho

71、d based on USP methodologyRaw(adsorbent)material/Final ArticleManufacturer Defined Method based on USP methodologyManufacturer Defin Method based on U methodologyISO 10993-1ISO 10993-1ISO 10993-1USP USP USP ISO 10993-5ISO 10993-5ISO 10993-5USP USP USP USP USP USP ISO 10993-10ISO 10993-10ISO 10993-10

72、USP USP USP ISO 10993-11ISO 10993-11ISO 10993-11USP USP USP ISO 10993-6ISO 10993-6ISO 10993-6ISO 10993-4ASTM F756C.BIOLOGICAL TESTSC Bacterial EndotoxinQuantify bacterial endotoxins in/on a test articleFinal ArticleBiocompatibility Risk AssessmentEvaluates the interaction of SUT with blood or the bi

73、ological reactivity of animals to polymeric material.Raw Material/Final ArticleSubsections Biological ReactivityIn VitroEvaluates the response of mammalian cell cultures to extracts of polymeric materials.Raw Material/Final ArticleEvaluates the interaction of medical devices with blood or the biolog

74、ical reactivity of animals to polymeric material:Raw Material/Final Article*Individual components within the Single-Use Assembly are subject to test recommendations within specific categories,see section Acute Systemic ToxicityMuscle ImplantationHemolysisTest that measures the breakdown of red blood

75、 cells by chemical or physical means.Final Article/FilmBiological ReactivityIn Vivo Intracutaneous C.BiologicalTEST TYPEGENERAL DESCRIPTIONTEST REFERENCESTEST ARTICLE1Chromatography2ConnectorsValvesRetainers3Containers Film4Sensors5Tubing6Filters7Single-UseAssembliesUSP USP USP USP USP USP USP USP E

76、P 2.6.14EP 2.6.14USP USP USP USP USP USP USP USP AAMI ST72AAMI ST72AAMI ST72AAMI ST72AAMI ST72AAMI ST72AAMI ST72AAMI ST72BioburdenEffluent bioburden quantification of colony forming units per effluent volume(CFU/ml);identification and quantification based on standard methodology.Manufacturer Defined

77、 Method based on USP methodologyRaw(adsorbent)material/Final ArticleManufacturer Defined Method based on USP methodologyManufacturer Defined Method based on USP methodologyManufacturer Defined Method based on USP methodologyISO 10993-1ISO 10993-1ISO 10993-1ISO 10993-1ISO 10993-1ISO 10993-1ISO 10993-

78、1USP USP USP USP USP USP USP ISO 10993-5ISO 10993-5ISO 10993-5ISO 10993-5ISO 10993-5ISO 10993-5ISO 10993-5USP USP USP USP USP USP USP USP USP USP USP USP USP USP ISO 10993-10ISO 10993-10ISO 10993-10ISO 10993-10ISO 10993-10ISO 10993-10ISO 10993-10USP USP USP USP USP USP USP ISO 10993-11ISO 10993-11IS

79、O 10993-11ISO 10993-11ISO 10993-11ISO 10993-11ISO 10993-11USP USP USP USP USP USP USP ISO 10993-6ISO 10993-6ISO 10993-6ISO 10993-6ISO 10993-6ISO 10993-6ISO 10993-6ISO 10993-4ISO 10993-4ISO 10993-4ISO 10993-4ASTM F756ASTM F756C.BIOLOGICAL TESTSCOMPONENT CATEGORY APPLICABLE TO THIS TESTBacterial Endot

80、oxinQuantify bacterial endotoxins in/on a test articleFinal ArticleBiocompatibility Risk AssessmentEvaluates the interaction of SUT with blood or the biological reactivity of animals to polymeric material.Raw Material/Final Article*Subsections*Biological ReactivityIn VitroEvaluates the response of m

81、ammalian cell cultures to extracts of polymeric materials.Raw Material/Final Article*Evaluates the interaction of medical devices with blood or the biological reactivity of animals to polymeric material:Raw Material/Final Article*Individual components within the Single-Use Assembly are subject to te

82、st recommendations within specific categories,see section 1-6 for subassembly recommendationsAcute Systemic ToxicityMuscle ImplantationHemolysisTest that measures the breakdown of red blood cells by chemical or physical means.Final Article/FilmBiological ReactivityIn Vivo*Intracutaneous D.Chemical T

83、ests Updates Risk Assessment Chemical Process CompatibilityTEST TYPEGENERAL DESCRIPTIONTEST REFERENCESTEST ARTICLE1Chromatography2ConnectoValvesRetainerChemical Process CompatibilityQualification of wetted parts to show compatibility(resistance)with chemical reagents used as process liquids.Manufact

84、urer defined method typically aligned with ASTM D543-14 and/or risk assessment.Raw Material and/or Final ArticleManufacturer def method typically a with ASTM D543 and/or risk assessmManufacturer Defined MethodManufacturer Defined MethodManufacturer Def MethodASTM D543-14ASTM D543-14ASTM D543-1ASME B

85、PE SD 2.4.1.2ASME BPE SD 2.4 Conductivity TestQualification of flush effluent for hydrophilic filters.USP Final Article Elastomeric Closures for Injections A battery of tests designed to determine pertinent physicochemical extraction characteristics of elastomeric closures.(Does not apply for silico

86、nes)USP Final ArticleUSP A battery of tests specific to SiliconeEP 3.1.9EP 3.1.9A battery of tests specific to Thermoplastic ElastomersEP 3.2.9EP 3.2.9USP USP USP BPOG Extractables ProtocolBPOG Extractables ProtocolBPOG Extractab ProtocolOxidizable SubstancesQualification of flush effluent for hydro

87、phobic filters.USP Final Article pH Shift TestQualification of flush effluent for hydrophilic filters.USP Final Article Total Organic Carbon(TOC)Qualification of flush effluent for hydrophilic filters.USP Final Article D.CHEMICAL TESTSRaw Material and/or Final ArticleMaterials should be robust and c

88、ompatible with product and process fluids and should not be excessively prone to damage,which compromise structural integrity either by the shedding of any materials as solid particles which impact product quality and/or process performance.Process Compatibility(a)The physiochemical properties,mecha

89、nical strength,optical properties,and anticipated operating temperature of the Materials of construction shall be capable of withstanding the processing conditions such as temperature,pressure,and chemical corrosiveness,thus ensuring the purity and integrity of the product.(b)Materials shall be comp

90、atible with the stated bio processing conditions,cleaning/sterilizing solutions,and SIP conditions,etc.Chemical Risk AssessmentProcess CompatibilityExtractables Quantitative and qualitative characterizations of extractables in model solvents.Semivolatiles,nonvolatile impurities,and identification of

91、 unknowns.Included should be regulatory compounds of interest(e.g.,Bisphenol A(BPA,Per-and Polyfluoroalkyl substances(PFAS),nitrosamines(or N-Nitrosamines)Final ArticleEP/PhysicochemicalRaw Material or Final Article-Post SterilizationD.Chemical TestsTEST TYPEGENERAL DESCRIPTIONTEST REFERENCESTEST AR

92、TICLE1Chromatography2ConnectorsValvesRetainers3Containers Film4Sensors5Tubing6Filters7Single-UseAssembliesChemical Process CompatibilityQualification of wetted parts to show compatibility(resistance)with chemical reagents used as process liquids.Manufacturer defined method typically aligned with AST

93、M D543-14 and/or risk assessment.Raw Material and/or Final ArticleManufacturer defined method typically aligned with ASTM D543-14 and/or risk assessment.Manufacturer defined method typically aligned with ASTM D543-14 and/or risk assessment.Manufacturer defined method typically aligned with ASTM D543

94、-14 and/or risk assessment.Manufacturer defined method typically aligned with ASTM D543-14 and/or risk assessment.Manufacturer defined method typically aligned with ASTM D543-14 and/or risk assessment.*Manufacturer Defined MethodManufacturer Defined MethodManufacturer Defined MethodManufacturer Defi

95、ned MethodManufacturer Defined MethodManufacturer Defined MethodManufacturer Defined MethodASTM D543-14ASTM D543-14ASTM D543-14ASTM D543-14ASTM D543-14ASTM D543-14ASTM D543-14ASME BPE SD 2.4.1.2ASME BPE SD 2.4.1.2ASME BPE SD 2.4.1.2ASME BPE SD 2.4.1.2ASME BPE SD 2.4.1.2ASME BPE SD 2.4.1.2Conductivit

96、y TestQualification of flush effluent for hydrophilic filters.USP Final ArticleUSP*Elastomeric Closures for Injections A battery of tests designed to determine pertinent physicochemical extraction characteristics of elastomeric closures.(Does not apply for silicones)USP Final ArticleUSP USP*A batter

97、y of tests specific to SiliconeEP 3.1.9EP 3.1.9EP 3.1.9A battery of tests specific to Thermoplastic ElastomersEP 3.2.9EP 3.2.9EP 3.2.9USP USP USP USP USP USP USP BPOG Extractables ProtocolBPOG Extractables ProtocolBPOG Extractables ProtocolBPOG Extractables ProtocolBPOG Extractables ProtocolBPOG Ext

98、ractables ProtocolBPOG Extractables ProtocolOxidizable SubstancesQualification of flush effluent for hydrophobic filters.USP Final ArticleUSP*pH Shift TestQualification of flush effluent for hydrophilic filters.USP Final ArticleUSP*Total Organic Carbon(TOC)Qualification of flush effluent for hydroph

99、ilic filters.USP Final ArticleUSP*D.CHEMICAL TESTSCOMPONENT CATEGORY APPLICABLE TO THIS TESTRaw Material and/or Final ArticleMaterials should be robust and compatible with product and process fluids and should not be excessively prone to damage,which compromise structural integrity either by the she

100、dding of any materials as solid particles which impact product quality and/or process performance.Process Compatibility(a)The physiochemical properties,mechanical strength,optical properties,and anticipated operating temperature of the Materials of construction shall be capable of withstanding the p

101、rocessing conditions such as temperature,pressure,and chemical corrosiveness,thus ensuring the purity and integrity of the product.(b)Materials shall be compatible with the stated bio processing conditions,cleaning/sterilizing solutions,and SIP conditions,etc.Chemical Risk AssessmentProcess Compatib

102、ility*Extractables Quantitative and qualitative characterizations of extractables in model solvents.Semivolatiles,nonvolatile impurities,and identification of unknowns.Included should be regulatory compounds of interest(e.g.,Bisphenol A(BPA,Per-and Polyfluoroalkyl substances(PFAS),nitrosamines(or N-

103、Nitrosamines)Final Article*Individual components within the Single-Use Assembly are subject to test recommendations within specific categories,see section 1-6 for subassembly recommendationsEP/PhysicochemicalRaw Material or Final Article-Post Sterilization*E.Regulatory Updates Additions EMC PFAS Foo

104、d Contact DeletionTEST TYPEGENERAL DESCRIPTIONTEST REFERENCESTEST ARTICLE1ChromatographyElectromagnetic Compatibly(EMC)EMC requirements for immunity and emissions for sensors with active electronicsEN/IEC 61326-1Final Article PFAS and BPA Combined Chemical StatementCombined Chemical statements inclu

105、sion of components which use of restricted chemicals.EG bisphenol A and PFAS.Manufacturer Define Risk AssessmentFinal ArticleManufacturer Define Risk AssessmentREACh StatementEuropean Community Regulation on chemicals and their safe use.EC/1907/2006Raw MaterialEC/1907/2006RoHS 3 StatementRestriction

106、 of Hazardous Substances in Electric and Electronic Equipment.2002/95/ECRaw Material 2002/95/ECEMA 410/01EMA 410/01EC 1774EC 1774*Individual components within the Single-Use Assembly are subject to test recommendations within specific catego Statement of inclusion of components and processes which c

107、ontain animal-derived materials,minimizing the risk of transmitting spongiform encephalopathy agents via medicinal products.Raw Material/Final ArticleTSE BSE/Animal Origin Free StatementsE.REGULATORYE.RegulatoryTEST TYPEGENERAL DESCRIPTIONTEST REFERENCESTEST ARTICLE1Chromatography2ConnectorsValvesRe

108、tainers3Containers Film4Sensors5Tubing6Filters7Single-UseAssembliesElectromagnetic Compatibly(EMC)EMC requirements for immunity and emissions for sensors with active electronicsEN/IEC 61326-1Final ArticleEN/IEC 61326-1*PFAS and BPA Combined Chemical StatementCombined Chemical statements inclusion of

109、 components which use of restricted chemicals.EG bisphenol A and PFAS.Manufacturer Define Risk AssessmentFinal ArticleManufacturer Define Risk AssessmentManufacturer Define Risk AssessmentManufacturer Define Risk AssessmentManufacturer Define Risk AssessmentManufacturer Define Risk AssessmentManufac

110、turer Define Risk Assessment*REACh StatementEuropean Community Regulation on chemicals and their safe use.EC/1907/2006Raw MaterialEC/1907/2006EC/1907/2006EC/1907/2006EC/1907/2006EC/1907/2006EC/1907/2006EC/1907/2006RoHS 3 StatementRestriction of Hazardous Substances in Electric and Electronic Equipme

111、nt.2002/95/ECRaw Material 2002/95/EC2002/95/EC2002/95/EC2002/95/EC2002/95/EC2002/95/EC2002/95/ECEMA 410/01EMA 410/01EMA 410/01EMA 410/01EMA 410/01EMA410/01EMA410/01EMA410/01EC 1774EC 1774 EC 1774 EC 1774 EC 1774EC 1774EC 1774EC 1774*Individual components within the Single-Use Assembly are subject to

112、 test recommendations within specific categories,see section 1-6 for subassembly recommendationsCOMPONENT CATEGORY APPLICABLE TO THIS TESTStatement of inclusion of components and processes which contain animal-derived materials,minimizing the risk of transmitting spongiform encephalopathy agents via

113、 medicinal products.Raw Material/Final ArticleTSE BSE/Animal Origin Free StatementsE.REGULATORYF.Sterilization/Sanitization UpdatesTEST TYPEGENERAL DESCRIPTIONTEST REFERENCESTEST ARTICLE1Chromatography2ConnectorsValvesRetainers3Containers Film4SensorsANSI AAMI ISO 11137ANSI/AAMI/ISO 11137ANSI/AAMI/I

114、SO 11137ANSI AAMI ISO 111AAMI TIR 35AAMI TIR 35AAMI TIR 35AAMI TIR 35ISO TS 13004ISO/TS 13004ISO/TS 13004ISO TS 13004AAMI Technical Information Report 33AAMI Technical Information Report 33Moist Heat SterilizationSterilization of healthcare products.ANSI AAMI ISO 17665Final ArticleANSI/AAMI/ISO 1766

115、5ANSI/AAMI/ISO 17665ANSI/AAMI/ISO 176Sanitization Test(Bacterial Challenge Test)Evaluation of anti-microbial effectiveness and endotoxin removal with recommended cleaning protocols;i.e.clean in place(CIP).Manufacturer Defined Method based on USP methodologyFinal ArticleManufacturer Defined Method ba

116、sed on USP methodologyBPSA X-Ray Sterilization of Single-Use Bioprocess EquipmentBPSA X-Ray Sterilization of Single-Use Bioprocess EquipmentBPSA X-Ray Sterilization of Single-Use Bioprocess EquipmentBPSA X-Ray Sterilizat of Single-Use Bioproc EquipmentManufacturer Defined MethodManufacturer Defined

117、MethodManufacturer Defined MethodManufacturer Defin MethodGuidance on sterilization process material compatibilityAAMI TIR 17AAMI TIR 17AAMI TIR 17AAMI TIR 17*Individual components within the Single-Use Assembly are subject to test recommendations within specific categories,see section 1-6 for subas

118、sembly recommendatioConfirmation of manufacturers specified performance claims after sterilization process.Perform or repeat Functional and Physical Testing after worst case sterilization process.COMPONENT CATEGORY APPLICAB F.STERILIZATION/SANITATIONSterilization Process CompatibilityFinal ArticleIr

119、radiation ValidationQualify the sterilization of healthcare products by ionizing irradiation:Gamma irradiation,X-ray or E-Beam.Final ArticleF.Sterilization/SanitizationTEST TYPEGENERAL DESCRIPTIONTEST REFERENCESTEST ARTICLE1Chromatography2ConnectorsValvesRetainers3Containers Film4Sensors5Tubing6Filt

120、ers7Single-UseAssembliesANSI AAMI ISO 11137ANSI/AAMI/ISO 11137ANSI/AAMI/ISO 11137ANSI AAMI ISO 11137ANSI/AAMI/ISO 11137ANSI/AAMI/ISO 11137ANSI/AAMI/ISO 11137AAMI TIR 35AAMI TIR 35AAMI TIR 35AAMI TIR 35AAMI TIR 35AAMI TIR 35AAMI TIR 35ISO TS 13004ISO/TS 13004ISO/TS 13004ISO TS 13004ISO/TS 13004ISO/TS

121、 13004ISO/TS 13004AAMI Technical Information Report 33AAMI Technical Information Report 33*Moist Heat SterilizationSterilization of healthcare products.ANSI AAMI ISO 17665Final ArticleANSI/AAMI/ISO 17665ANSI/AAMI/ISO 17665ANSI/AAMI/ISO 17665ANSI/AAMI/ISO 17665ANSI/AAMI/ISO 17665ANSI/AAMI/ISO 17665Sa

122、nitization Test(Bacterial Challenge Test)Evaluation of anti-microbial effectiveness and endotoxin removal with recommended cleaning protocols;i.e.clean in place(CIP).Manufacturer Defined Method based on USP methodologyFinal ArticleManufacturer Defined Method based on USP methodologyManufacturer Defi

123、ned Method based on USP methodology*BPSA X-Ray Sterilization of Single-Use Bioprocess EquipmentBPSA X-Ray Sterilization of Single-Use Bioprocess EquipmentBPSA X-Ray Sterilization of Single-Use Bioprocess EquipmentBPSA X-Ray Sterilization of Single-Use Bioprocess EquipmentBPSA X-Ray Sterilization of

124、Single-Use Bioprocess EquipmentBPSA X-Ray Sterilization of Single-Use Bioprocess EquipmentManufacturer Defined MethodManufacturer Defined MethodManufacturer Defined MethodManufacturer Defined MethodManufacturer Defined MethodManufacturer Defined MethodGuidance on sterilization process material compa

125、tibilityAAMI TIR 17AAMI TIR 17AAMI TIR 17AAMI TIR 17AAMI TIR 17AAMI TIR 17*Individual components within the Single-Use Assembly are subject to test recommendations within specific categories,see section 1-6 for subassembly recommendations*Confirmation of manufacturers specified performance claims af

126、ter sterilization process.Perform or repeat Functional and Physical Testing after worst case sterilization process.COMPONENT CATEGORY APPLICABLE TO THIS TESTF.STERILIZATION/SANITATIONSterilization Process CompatibilityFinal ArticleIrradiation ValidationQualify the sterilization of healthcare product

127、s by ionizing irradiation:Gamma irradiation,X-ray or E-Beam.Final ArticleComponent Categories1.Chromatography2.Connectors,Valves and Retainers3.Containers and Film4.Sensors5.Tubing6.Filters7.Single-Use Assemblies7.Single-Use Assemblies Representative of the full assembly as the test article.for the

128、components within which are spelled out in the tables 1-6.Suitable for a Single-Use Assembly as the“test article”,It does not preclude the need for component-specific qualification testing and verification on the full assemblies;therefore,the reader should consult tabs 1 to 6(i.e.,filters,containers

129、,sensors,as applicable)as well to follow the test expectations listed for those qualify components within the assemblies.The level of lot release testing required is to be determined by the end user based on the product and process requirements where the single use assembly is utilized.7.Single-Use

130、AssembliesTEST TYPEGENERAL DESCRIPTIONTEST REFERENCESTEST ARTICLEMaterial QualificationProduct(Article)QualificationBatch/LotMaterial ChangeArticle ChangeChamber Integrity/Seal Integrity-Peel(Bags only)Used to measure manufactured product and seal barrier performance of a variety of package types an

131、d forms,as well as seal and/or closure types.Manufacturer Defined MethodPackagingOOASTM E3244-20ASTM E 3251-20ASTM E3336-22Junction Testing(barbed fittings)Single-use assembly junction connections should be qualified by the supplier to ensure they meet performance criteria as stated in their specifi

132、cation.The supplier shall have an established testing program to substantiate performance of the mechanical connection.The testing should reference at least one of the following:(a)Pressure Testing(b)Leak Testing(c)Tracer Gas TestingManufacturer Defined MethodTensile StrengthDetermines resistance of

133、 loading on a jointed union/connection/fitting.Manufacturer Defined Method OOOManufacturer Defined MethodASTM F1980-21Manufacturer Defined MethodASTM 3051Min./Max.TemperatureASME BPE SD 2.4.1.2ASTM D4169-14ASTM D4728-06DIN ISO 2872ISTA 2AISTA 3AISTA 3BISTA 3EBPSA Recommendations for Tti Elti d Ctl f

134、 The Manufacturer/user shall establish that the Single-Use components,SUS assemblies,and SUS systems are designed for integrity and functionality,appropriately.These considerations should be maintained during installation and ensured throughout the use of the item based on scientific product and pro

135、cess understanding for both SUS manufacturing and end user requirement Qualification of design manufacturing testing and distribution should be Final ArticleIntegrity(Leak)TestFinal Article OOB.FUNCTIONALStandard Test Method for Physical Integrity Testing of Single-Use Systems.Confirmation of integr

136、ity for components and assemblies at a given temperature.This includes pressure testing under operating conditions and at elevated pressures.General FunctionalityFit for Intended UseOOOOFinal ArticleQualify that product packaging will protect the product during shipping.Standard practice for perform

137、ance testing of shipping containers and systems to provide a uniform basis of evaluating,in a laboratory,the ability of shipping units to withstand the distribution environment.Package Testing/Transportation Shipping IntegrityTable 7:SINGLE USE ASSEMBLIESThe tests listed in Table 7 are representativ

138、e of the full assembly as the test article.It does not preclude the recommendation or requirement to apply tests listed for the components within which are spelled out in the tables 1-6.The tests listed in this tab under columns F to I are suitable for a Single-Use Assembly as the“test article”,unle

139、ss further specified.It does not preclude the need for component-specific qualification testing and verification on the full assemblies;therefore,the reader should consult tabs 1 to 6(i.e.,filters,containers,sensors,as applicable)as well to follow the test expectations listed for those qualify compo

140、nents within the assemblies.The level of lot release testing required is to be determined by the end user based on the product and process requirements where the single use assembly is utilized.Accelerated or Real Time Aging(Shelf Life)Accelerated and/or real time studies to determine the effects,if

141、 any,due to the passage of time and environmental effects on the properties of product,and on the sterile integrity of packages and the physical properties of their component packaging materials.Final ArticleTEST APPLICATIONA.PHYSICAL2023 Completion 7/10-7/12 BPSA Summit-7/11 presentation 7/14-SAB r

142、eview complete 7/14-QTM meeting if needed at summit.7/14 SAB comments to QTM if any.7/20-QTM meeting to address SAB comments if needed.7/21-Final to BPSA Board 7/28-BPSA Board approvalFuture QTM Updates Items did not make the cut Standard Updates Industry guidanceTopics Endotoxin/Pyrogen Free Accelerated Aging-Humidity Animal Testing Physical Joining Others?COLLABORATION,TECHNOLOGY&INNOVATION:SHAPING THE FUTURE OF SINGLE-USE JULY 10-JULY 12,FOUR SEASON HOTEL,WASHINGTON,DC