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1、Design,Control&Monitoring of SUS for Integrity Assurance,Volume 2P.Evrard,C.Masy,S.Patterson,C.Zhang and the full BPSA SUS Integrity Assurance CommitteeJuly 11,2023AGENDA Why a new document on integrity of SUS?What will you find in this document?What did we learn and what are the next steps?INTRODUC

2、TION BPSA Tech Guide-2017-Volume 1 Principles Once upon a time in February 2021 Why a Volume 2?Case studies UpdatesTHE SUS INTEGRITY ASSURANCE COMMITTEECommittee MembersEmily Alkandry,Saint-GobainSebastien Barry,SanofiRichard Bhella,CytivaMonica Cardona,Millipore SigmaJoussef Chaaban,CytivaKatie Chu

3、rch,Watson MarlowRafael Diana,CytivaRoger Hendrick,DupontNicole Hunter,Watson MarlowYves Lambeens,CytivaCharlotte Masy,GSK VaccinesNathalie Pathier,SartoriusScott Patterson,ILC DoverMark Petrich,Merck&Co.,Inc.Kevin Pickup,Thermo Fischer ScientificElke Roelandt,PfizerChanghong Zhang,Sanofi PasteurBPS

4、A FacilitatorJeanette McCoolAuthors Currently Out of the CommitteeMichael Avraam(ChargePoint Technology)Marc Hogreve,Sartorius*Alain Vanhecke,Cytiva*Patrick Evrard,Cytiva-Board Sponsor and Committee Chair*sabbatical leaveCONTENT Case study:design,qualification and validation of a SUSfor a critical a

5、pplication using QbD principles Cases studies:integrity issues with various components Updates on integrity testing technologies Handling practices and training Industry Interest Groups initiatives and regulatory landscape Case studies:specific applicationsDESIGN,QUALIFICATION AND VALIDATION OF A SU

6、S FOR A CRITICAL APPLICATIONAssessment of Criticality related to integrity Patient safety risk:Breach sterility Business risk:Massive product loss from leakDS PumpFilling station0.2 um filter train200L Sterile DS bagGrade A Isolator,Filling10L Surge bag,DP DESIGN,QUALIFICATION AND VALIDATION OF A SU

7、S FOR A CRITICAL APPLICATION URS(BPSA/BPOG template),Design Review Risk assessment matrix,e.g.,connector type,bag film,agitation type,pump tubing End user and supplier communication Sketch drawing(end user)Eng.drawing(supplier),review Prototype,Design Verification,Qualification Proof of concept,init

8、ial qualification test,and modification End user and supplier interaction Design lock-down Validation Integrated functional test(IFT),wet runs and shakedown runs Process monitoring and continuous improvementINTEGRITY ISSUES WITH VARIOUS COMPONENTS Using integrity testing result as design verificatio

9、n Integrity test allow detection of design defect during qualification and investigation Examples:molding defects,connection robustness,closureMold defect detected by pressure decayLLA1Screw cap issue using Helium spray mode 1 LLA=Luer Lock Adapter INTEGRITY ISSUES WITH VARIOUS COMPONENTS Other caus

10、es of integrity failure highlighted Leak due to chemical resistance/MOC Improper manipulation/training Impact of elevated temperature INTEGRITY TESTING TECHNOLOGIES-UPDATE Leak testing vs Integrity testing-MALL1 Correlation with barrier properties End-user experience with implementation of 100%integ

11、rity testing Updates on Helium integrity testing technology Pressure-based technologies1 MALL=Maximum Allowable Leak LimitHANDLING PRACTICES-TRAINING Training-training-training Underestimated by newcomers to the SU world List of typical tools supporting SUS integrity assurance Full life-cycle:suppli

12、er and end-userINDUSTRY INTEREST GROUPS&REGULATORY Updates from BPSA-Reliability report(s)ASTM-3 standards ASME-BPE-mapping of leak test methods PDA(TR 86)-Pharmaceutical package integrity testing BioPhorum-SUS Bag Assembly Leakage and defect toolkit Learnings from setting up ASTM standards Revision

13、 of EU GMP Annex 1SPECIFIC APPLICATIONSHigh pressure applications Risk for leaks Upstream of the filters associated to high pressure applied(eg in-situ PUPSIT)Downstream of the filters due to SUS handling or pressure being applied during filtration Pressure decay test at max pressure supported by su

14、pplier-sensitivity of 30 to 10 m NDOS depending on Applied pressure Size and type of tubing Design recommendations Avoid complex design-limit number of components and junctions Test junctions with integrity/leak testFLT02(1st product filter)FLT01(0.2 m Vent filter)MV05MV03MV01FLT04(2nd product filte

15、r)MV06MV07MV08MV09MV02MV04P01P02Pinch Valve closedPinch Valve openFillingPressurised flow pathSterile connectionFLT03(0.2 m Vent filter)SPECIFIC APPLICATIONSHandling PowdersPowders create different challenges than liquids Non-Toxic powders have less risk for operator exposure issues but open handlin

16、g will allow airborne particulate that causes several known risks Toxic powders(small percentage in bio processing)requires greater consideration of operator protection along with the same risks associated with airborne particulateSPECIFIC APPLICATIONSHandling PowdersContainment for powders(developi

17、ng a CCS)Closed powder handling using single use technology solves many issues Contained powder handling mitigates risks of airborne particulates and operator exposure risks Risk analysis for powders to develop a CCSREVIEW FEEDBACKSExcellent document,which I believe will be very valuable to users an

18、d suppliers alikeBSPA former chairThe paper looks greatBPSA DirectorSummarizing the regulatory guidelines is very helpful to IndustryBPSA former DirectorApproved!BPSA DirectorGreat pointBPSA former DirectorHelpful to see this in writing BPSA former DirectorPlease share my thanks to the author of thi

19、s great example.Well explained with visuals to support.BPSA former DirectorThe paper is excellentBPSA DirectorLEARNINGS AND KEY TAKE-HOME MESSAGES One size fits all is neither feasible nor desirable Many examples included in this new technical guide are exemplary of the most demanding applications E

20、at the dinosaur in slices Volume 2 is a 49-pages document-Sections can be read fully separately Switching from high-level principles to practical illustrations generated a lot of comments and some warm debates outside of the committee Shows the value of such illustrations NEXT STEPS-THANKS Webinar after summer Next directions to be discussed end of the year Special thanks to Jeff Carter,Cytiva Rachelle Morrow,Qosina Kirsten Strahlendorf,Sanofi Kevin Ott,BPSA BPSA Board of Directorsfor their(in-depth)reviews