WIXLIB

Structuring PERsunder IVDRHow to gather and present data, conduct literaturesearches, and moreJon Gimbel, Ph.D. – R&QExecutive DirectorRon Sills – R&QSenior Principal Specialist

ServicesMay 2020 / May 2022 Regulatory Worldwide regulatorystrategy and supportFDA regulatory submissions(510(k), PMA, De Novo, etc.)EU MDR and IVDRtechnical documentationCERs and PERsRegulatory complianceAcquisition integrationEU MDR / IVDRQuality SystemsExpert implementers experienced withmultinational companies transitioning to the EUMDR and IVDR Validated EU MDR / IVDR transition process,procedures, and toolsMock EU MDR and IVDR audits FDA and MDSAP inspectionreadiness and supportAcquisition integrationQuality system development /improvement: ISO 13485, QSR,EU MDR, IVDR Internal and supplier auditing QualityAssurance Best-in-class project management and SMEsfor all workstreamsFull service or just what you needofferings, including plandevelopment, literature search andreviews, and report writing (CER /PER, CEP / PEP, PMCF/PMPF,SSCP/SSP) Implementation of PMS / PMCF processes andplansAll clinical specialties and deviceclassifications Former notified body senior leadership on staffCapacity for 100's of CERs (nooffshoring) Strong notified body and ation Design quality engineeringand assurance Scalable team: strategic,tactical, and creative Safety risk management,including recall decisions andstrategy DHF and technical documentationremediation Manufacturing site transferComplaint files and device reporting Manufacturing quality483, warning letter, consent decreeresponses and execution NB non-conformity report correctiveaction plans and executionCONFIDENTIAL 2020 R&QCERs / PERs Analysis of data and creation ofPMS / PMCF / PMPF Plansand ReportsPMS/CER/Risk integration, includingprocess and operational teamalignmentRQTeam.comProject Management Across all R&Q projects Best-in-class, PMP-certifiedproject managers Seasoned device professionalsexclusively focused on RA/QA2

About Remote and Flex-CORE supportAvailable across all R&Q services.CONFIDENTIAL 2020 R&QRQTeam.com3

Questions Thank you for your questionssubmitted during registration! You are still able to ask questionsduring the webinar and they may beanswered in the follow-up Q&A Answers to some questions will beshared on webinar resources page If you have a question after thewebinar, you can still emailintel@rqteam.com Reminder: you will be notified via emailwhen the slides and webinar recordingare available (within 24 hours)CONFIDENTIAL 2020 R&QRQTeam.com4

Jon Gimbel, Ph.D. – R&Q Executive Director and CERBusiness Unit Lead Ph.D. in Mechanical Engineering 20 years of medical deviceresearch, design/development,regulatory, and quality systemexperienceCONFIDENTIAL 2020 R&QRQTeam.com5

Ron Sills – R&Q Senior Principal Specialist Joined R&Q in early 2019; former LeadAuditor at TUV Rheinland Authorizations for ISO 13485, ISO 9001,MDD, IVDD, CMDCAS and MDSAP Expert on sterilization technologies andvalidation, hygiene and clean roomcertification, and biocompatibility Has developed clinical evaluation reportservices, as well as providing expertresearch services for clients in the medicaldevices, pharmaceutical, and life sciencesindustriesCONFIDENTIAL 2020 R&QRQTeam.com6

Overview of today’s contentPerformance Evaluation PlanPerformance Evaluation ReportStructure tipsContents and section tipsLiterature search protocol tipsPMPFQuestionsCONFIDENTIAL 2020 R&QRQTeam.com7

Objective of the IVDR 2017/746 However a fundamental revision of that Directive(98/79/EC) is needed to establish a robust, transparent,predictable and sustainable regulatory framework for in vitrodiagnostic medical devices which ensures a high level ofsafety and health whilst supporting innovation.When interpreting the regulation, remember the objective.Does it make it more transparent? Does it provide a high level ofsafety and health? Those questions will help guide yourinterpretation.CONFIDENTIAL 2020 R&QRQTeam.com8

IVDD to IVDR transition timelineIVDDCertificates VoidMay 27, 2024YOU ARE HEREDate of ApplicationMay 26, 2022Adoption of IVDR& Entry into ForceMay 2017201820172019No more“makingavailable orputting intoservice”May 20252020202120222023202420252026Transition Period from IVDD to IVDRIVDR CertificatesCONFIDENTIAL 2020 R&QRQTeam.comSource: BSI Group, IVDD to IVDR Timeline, bsigroup.com9

Increased Emphasis on Clinical EvidenceCONFIDENTIAL 2020 R&QGreater scrutiny of Notified BodiesCompetent Authorities and Reference Laboratories involved in conformityassessment of high-risk devices resulting in elongated conformityassessment procedures. Tighter designation rules for NBs may lead to areduced number of NBs available.No "grandfathering" provisionsAll currently approved IVDs must be recertified in accordance with thenew requirements. Manufacturers with currently approved devices willhave five years to demonstrate compliance with the IVDR’s newrequirements.Increased Notified Body involvementReviews will be more focused and the requirements fordesignation and monitoring of Notified Bodies underIVDR will be considerably tightened.More stringent requirements regardingtechnical documentation and clinical evidenceContents of the technical documentation require evidenceof safety and performance proportionate with a device’sassigned risk class.RQTeam.com10

Pillars of PerformanceCONFIDENTIAL 2020 R&QRQTeam.com11

Clinical Evidence andPerformance Evaluation Pre-market performance evaluation and clinical evidence nowexplicitly required in the regulation New plans and reports are introduced (e.g., performanceevaluation plan, performance evaluation report, PMPF plan, ) Requirements similar to EU MDR and GHTF documents GHTF/SG5/N6:2012 Clinical Evidence for IVD Medical Devices – KeyDefinitions and Concepts GHTF/SG5/N7:2012 Clinical Evidence for IVD Medical Devices –Scientific Validity Determination and Performance Evaluation GHTF/SG5/N8:2012 Clinical Performance Studies for In Vitro DiagnosticMedical Devices MEDDEV 2.7/1 Rev 4 Clinical Evaluation for Medical DevicesCONFIDENTIAL 2020 R&QRQTeam.com12

Performance Evaluation Process(Annex XIII) Performance Evaluation Plan(Annex XIII Part A 1.1) Performance Evaluation Report(Annex XIII 1.3.2)PerformanceEvaluation Plan Scientific validity report(Annex XIII Part A 1.2.1) Analytical performance report(Annex XIII Part A 1.2.2) Clinical performance report(Annex XIII Part A 1.2.3) Conclusions drawn from assessmentof the clinical evidence(Article 56.3; Annex XIII 1.3.1)PMS andPMPFPerformanceEvaluationReport PMS and PMPF Plans and ReportsCONFIDENTIAL 2020 R&QRQTeam.com13

CER Structure – MEDDEV 2.7/1 rev 4 A9 Summary Scope and device description Clinical background and State of theArt Device under evaluation Demonstration of equivalenceNon-clinical dataClinical Investigation dataPMS / PMCF dataClinical literature data Analysis of the clinical data Conclusions and additionalinformationCONFIDENTIAL 2020 R&QRQTeam.com14

CER vs. PER StructureCER Summary Scope and device description Clinical background and State of theArt Device under evaluation Demonstration of equivalenceNon-clinical dataClinical investigation dataPMS / PMCF dataClinical literature data Analysis of the clinical data Conclusions and additionalinformationCONFIDENTIAL 2020 R&QPERSummaryScope and device descriptionLiterature searchClinical background and State of theArt Device under evaluation Demonstration of equivalenceScientific validity reportAnalytical performance reportClinical performance report Analysis of the clinical evidence Conclusions and additionalinformationRQTeam.com15

Performance Evaluation Plan(Annex XIII, Part A) Intended purpose, intended use, target patient groups, indications, limitations and contra-indications Characteristics of the device Analyte or marker to be determined by the device Identification of reference materials or reference measurement procedures for metrological traceability Identification of the relevant GSPRs Methods, including the statistical tools, used for the examination of performance Description of the state of the art Parameters to be used to determine the acceptability of the benefit-risk ratio For software, reference databases and other sources of data used as the basis for its decision making Outline of development phases including milestones and acceptance criteria PMPF plansTIP: The Performance Evaluation Plan should be a separate document.CONFIDENTIAL 2020 R&QRQTeam.com16

Structure of a PEP Executive Summary, Introduction, and Objectives Device Description Characteristics of the deviceSpecification of the Analyte or MarkerPerformance CharacteristicsIntended Purpose, Intended Use, and ClaimsIndications, Target Patient GroupsContraindications, Limitations, Precautions, WarningsIntended User / EnvironmentBenefitsRisk Management and Labeling Scope Identification of the Device Manufacturer Classification Status of CE Mark and Market HistoryTIPS: Align PEP and Annex II Technical Documentation content Intended use should be directly from IFUCONFIDENTIAL 2020 R&QRQTeam.com17

Structure of a PEP Literature Search Protocol State of the Art Standards, CSs, GuidanceDocuments, and BestPractice Documents Description of State of the Art CONFIDENTIAL 2020 R&QTIPS: Provide brief overview of SotA Standard and CSs should alignwith technical documentation Diagnostic alternatives andsimilar devices should informliterature searchMedical ConditionDiagnostic AlternativesSimilar DevicesSummary and ConclusionsRQTeam.com18

Structure of a PEP Demonstration of Equivalence Scientific Validity Plan Context and Type of Evaluation Data Sources Analytical Performance Plan Context and Type of Evaluation Parameters and methods used to evaluateperformance Data Sources Clinical Performance Plan Context and Type of Evaluation Parameters and methods used to evaluateperformance Data SourcesCONFIDENTIAL 2020 R&QRQTeam.comTIPS: Equivalent device should beidentified at this stage (informsliterature search) Equivalence should be based onsimilar technology andmethodology and the same analyteand intended purpose Data sources may be different foreach section All reports may include literaturedata19

Structure of a PEP Analysis of Clinical Evidence Performance and Benefits (GSPR 1,9) Safety and Risks (GSPR 1, 9) Benefit/Risk Profile and UndesirableEffects (GSPR 1, 8) Development PhasesPMS and PMPF PlansFrequency of UpdatesQualificationsReferences / Source DocumentsCONFIDENTIAL 2020 R&QRQTeam.comTIPS: See Article 56.1 for GSPRreferences PMS/PMPF plans will beupdated after evaluation Refer to MEDDEV 2.7/1 Section6.4 for concepts regardingqualifications and updatefrequency High risk – annually Lower risk – every 2-5 years Class C and D device updatedannually20

Systematic Literature Search Process Literature search protocol Search terms and databases Inclusion / exclusion criteria Appraisal criteria Execute the search Screening of articles usinginclusion-exclusion criteria Appraisal Summary and analysisCONFIDENTIAL 2020 R&QGHTF/SG5/N7:2012 Appendix BRQTeam.com21

Literature Search Protocol Introduction and Objectives Purpose of the search Reference to guidance documents Identification of Device(s) Devices covered by search Indications and claimsTIPS: Refer to the following for information on literaturesearch protocols: MEDDEV 2.7/1 Rev 4 A5 IMDRF MDCE WG/N56FINAL:2019 GHTF/SG5/N7:2012 Attach protocol to PEPCONFIDENTIAL 2020 R&QRQTeam.com22

Literature Search Protocol MethodsTIPS: Use Google Scholar to ensuresearch is capturing relevant articles General search terms can beincluded in protocol; Actual searchterms should be included in PER Search should cover initial CE markto the present State of the art will require differentsearch terms than performancesearches Databases PubMed Embase Google scholar Search strategy Search terms Operators Date rangeCONFIDENTIAL 2020 R&QRQTeam.com23