Post Market Surveillance & Adverse Event Reporting What is an

Post Market Surveillanceand Adverse EventReportingRequirements, interpretationsand challenges for medicaldevice manufacturers andregulatory authorities.

Post Market Surveillance and Adverse Event ReportingMichael MaierMedidee Services SAwww.medidee.com• Founder & Senior Partner of Medidee Services SA‣ Swiss based consulting group specializing inworldwide Medical Devices Regulatory Affairsand Compliance programs since 12 years.• Medical Device Regulatory Affairs trainer at eventsof WMDO, RAPS, ARIAQ and others world-wide• Advisor of medical device Start-ups• Medical Device file reviewer and Lead Auditor• MBA; Degree in Medical Engineering;• Member of SGSV and SNV standardizationcommittees

Medidee in brief – www.medidee.comPre – Market support :• Regulatory pathway development• Clinical evaluation management• Design and review of Technical Files• Support of Product- and Process- V&V• Implementation of QMS• Preparing for third party audits andinspections• Supplier qualification• Software validation• Risk analysis at the product or systemlevelStrategic Management support :• Regulatory troubleshooting• Risk analysis at the organization level• Regulatory due diligence / M&A• Coaching of startups• Interim Management• Training of executives and staffPost- Market support :• EU Representative services• Periodic PMS & regulatory intelligenceresearch according defined protocols

SchedulePart 1Part 2Part 3Part 4Introduction - get clarity about the wording used- Life cycle of a medical device- Conformity assessment- GHTF documents for PMSPost Market Surveillance and Adverse Event Reporting- What is Post Market Surveillance- What is an Adverse Event- Criteria for reporting – What to report ?- Inputs to Post Market SurveillancePost Market Surveillance and Adverse Event reporting in differentjurisdictions- USA- Canada- EuropeSummary, Outlook, Risk Management

Life cycle of medical devicesDisposal ofthe deviceDevelopmentPremarketphasePostmarketphaseUseEventually repair/ refurbishmentManufacturingMarketing andsalesEnd of pre-marketconformity ass.= RegulatoryclearanceUse

Life cycle of medical devices & Principal StakeholdersUseRefurb.DisposalM,RA/CABUseDEVMFGM & S- Manufacturer develops andproduces- RA / CAB assessesconformity of developed“Result” = Medical Deviceand verifies GMP

Life cycle of medical devices & Principal StakeholdersDisposalDEVUseRefurb.M,RA/CAB,HSUseMFGM & S- RA / CAB authorizesmarketing- Manufacturer puts onmarket- Healthcare System grantsreimbursement or not

Life cycle of medical devices & Principal StakeholdersUseRefurb.DisposalU, M,RA,HSUseDEVMFGM & S- User / patients use the MD andreport Adverse Events- MFG surveys his product &product environment andreports- RA monitors, surveys themarket and enforces Reg.Action- HC system reimburses (or not)and surveys “efficacy” andliaises with RA

Life cycle of medical devices & Principal StakeholdersDisposalDEV- Manufacturer refurbishes- RA / CAB assesses conformityof refurbished“Result” and verifies GMPUseRefurb.M,RA/CABUseMFGM & S

Life cycle of medical devices & Principal Stakeholders- User disposes off- Manufacturer takes part inrecycling- RAE (e.g. environmental)legislates, surveys andenforcesUseRefurb.DisposalU, M,RAEUseDEVMFGM & S

Introduction – Post Market Surveillance & Adverse EventReportingConformity assessment:“Conformity assessment, conducted before and after a medicaldevice is placed on the market, and post-market surveillance ofdevices in actual use are complementary elements of the GHTFglobal regulatory model. They are intended to provide theobjective evidence of safety, performance, and benefits and risksto maintain public confidence.”Source: section 2.1 - Principles of Conformity Assessment for Medical Devices SG1 FinalDocument GHTF/SG1/N78:2012

Introduction: GHTF Guidance on Post MarketSurveillance and Adverse Event Reporting5 GHTF Conformity Assessment Elements should be specified byMD Regulations :1. Quality management system (QMS),2. System for Post-market Surveillance,3. Requirements for Technical Documentation,4. DoC - Declaration of Conformity,5. Registration of manufacturers & medical devices by the RA.Source: Principles of Conformity Assessment for Medical Devices SG1 Final Document GHTF/SG1/N78:2012+ Maintaining a status of conformity after the device isplaced on the market ! -> to be controlled by RA !!

Introduction: GHTF Guidance on Post MarketSurveillance and Adverse Event ReportingManufacturers system for post-marketing surveillance• PMS implemented and operational PRIOR to marketing• Process includes:• complaint handling,• post-market vigilance reporting (AE Reporting),• subsequent CAPA• RA / CAB verifies the PMS process during Audit of QMS / GMP.• RA may require specific post-marketing study of a particulardevice.• The RA monitors post-marketing study - decision on RegulatoryAction.Source: Principles of Conformity Assessment for Medical Devices SG1 Final Document GHTF/SG1/N78:2012

Introduction: GHTF Guidance on Post MarketSurveillance and Adverse Event Reporting

Post Market Surveillance & Adverse Event ReportingWhat is Post Market Surveillance :“Post Market Surveillance is a systematic procedure toreview experience gained from devices in the postproductionphase.”Source: Europe (Directives & MEDDEV 2.12)

Post Market Surveillance & Adverse Event ReportingWhat is Post Market Surveillance :“Postmarket surveillance is the systematic collection, analysis,interpretation, and dissemination of health-related data toimprove public health and reduce morbidity and mortality.”Source: USA – FDA proposal: Strengthening our National System for Medical DevicePostmarket Surveillance“PMS is the active, systematic, scientifically valid collection,analysis, and interpretation of data or other information about amarketed device.”Source: US Code of Federal Regulations: 21 CFR 822.3 - addresses PMS activity that isconducted by the manufacturer following an order from FDA

Post Market Surveillance & AdverseEvent ReportingWhat is an “Adverse Event”:“An Adverse Event is either a malfunction or a deterioration in thecharacteristics or performance of a sold medical device [includingaccessory(s) and labelling] or use error, which either has caused orcould have caused or contributed to death, or serious injury tohealth of patients or other persons.”Source: GHTF/SG4/N33R16:2007 & Definition and Glossary of Terms Used in GHTFDocuments GHTF Steering Committee Final Document GHTF/SC/N4:2012 (Edition 2)NB ! : There are more specific GHTF definitions when including “ClinicalInvestigations” in the scope of the definition.

Post Market Surveillance & AdverseEvent ReportingWhat is an Adverse Event : (USA)An adverse event is any undesirable experience associated withthe use of a medical product in a patient.Serious Adverse Event:The adverse event is serious and should be reported to FDA whenthe patient outcome is:• Death• Life-threatening• Hospitalization (initial or prolonged)• Disability or Permanent Damage• Congenital Anomaly/Birth Defect• Required Intervention to Prevent Permanent Impairment or Damage• Other Serious (Important Medical Events)http://www.fda.gov/Safety/MedWatch/HowToReport/ucm053087.htm

Post Market Surveillance & AdverseEvent ReportingWhat is an Adverse Event : (EU)INCIDENT (= Adverse Event in the context of this overview)“Any malfunction or deterioration in the characteristics and/orperformance of a device, as well as any inadequacy in the labelingor the instructions for use which, directly or indirectly, might leadto or might have led to the death of a patient, or user or of otherpersons or to a serious deterioration in their state of health.”Source: MEDDEV 2.12http://ec.europa.eu/health/medical-devices/files/meddev/2_12_1_ol_en.pdf

Post Market Surveillance & AdverseEvent ReportingReporting criteria for Incidents EU (=adverse events) :A: An event has occurred- malfunction of a deviceB: The medical device seems to be part of the cause of theINCIDENTC: The event led, or might have led todeath or serious deterioration in state of healthIncident = A+B+C = ReportingSource: MEDDEV 2.12http://ec.europa.eu/health/medical-devices/files/meddev/2_12_1_ol_en.pdf

Post Market Surveillance and Adverse Event ReportingPost Market Surveillancecan be divided in 2 parts:Vigilance part - ReactiveReaction toproblems inthe marketMonitoring part - ProactivePost Market SurveillanceMonitoring themarket for earlywarnings forproblems in themarket

Inputs to Post Market Surveillance & Adverse Event ReportingStakeholders and inputs :H : Users e.g. Hospitals report AEM : Manufacturers report AER : Pro active research of stakeholders –Manufacturers / CA / Health InsuranceCA : Information from other CARCAMInputs to Post MarketSurveillance

Post Market Surveillance & Adverse Event ReportingRoles of Stakeholders according GHTF : NationalCompetent Authorities• Establish Adverse Event Report (AER)requirements• Establish and maintain national vigilancedatabases• Evaluate AER received• Monitor mfr. Investigation and Field SafetyCorrective Actions• Exchange information between CA

Post Market Surveillance & Adverse Event ReportingRoles of Stakeholders according GHTF: Manufacturersof Medical Devices• Establish and maintain PMS system (part ofQMS/GMP)• Prepare and submit vigilance reports• As appropriate, conduct Field Safety CorrectiveActions

Post Market Surveillance & Adverse Event ReportingAuthorities’ tasks andresponsibility for Post MarketSurveillance :Examples:- US FDA- Health Canada- European Union MemberState CompetentAuthoritiesManufacturers tasks andresponsibility for Post MarketSurveillance :Examples:Manufacturer marketingproducts in- USA- Canada- European Union

Post Market Surveillance and Adverse Event reportingFurther development of PostMarket Surveillanceactivities:• 1 of the axes of the paststrategic planof the Health Products andFood Branch (HPFB) of HealthCanada.

Post Market Surveillance and Adverse Event reportingCitation:“The Marketed Pharmaceuticals and Medical Devices Bureau within MHPD*conducts the following activities related to devices:• monitoring devices incident data;• reviewing and analysing product safety data;• detecting and evaluating signals;• conducting benefit and risk assessments and making recommendations onrisk management options;• communicating product related risks to health care professionals and thepublic; and• providing policies to effectively regulate marketed health products.”End of citation.*MHPD: Marketed Health Products DirectorateSource: Health Products and Food Branch of Health Canada - Medical Devices Program - StrategicPlan 2007-2012

Post Market Surveillance and Adverse Event reportingCanada – MHPD* – Post-Market Surveillance Activities include:Analysis of :• National and foreign incident report databases and registries• Peer-reviewed literature/media• Foreign regulatory actions*Marketed Health Products Directorate of Health Canada

Post Market Surveillance and Adverse Event reportingManufacturers marketing MD in Canada:Post Market Surveillance actions of manufacturers required inthe Medical Device Regulations under:• Distribution records• Complaint handling• Mandatory Problem Reporting (Adverse Event Reporting)• Recall– Those activities are not called “Post Market Surveillance”Pro active actions of manufacturers required by applicable ISO13485 clauses – but not called Post Market Surveillance

Post Market Surveillance and Adverse Event reportingPost Market Surveillance – Activities of Competent Authoritiesof member states of the EU• Example : Germany BfArM – Bundesinstitut für Arzneimittelund Medizinprodukte- Centralised collection, analysis and evaluation of risks arisingfrom the use of medical devices in particular from incidentreports- Co-ordinating the necessary measures to be taken especially incase of FSN / FSCA- Collaboration with the competent authorities of other memberstates

Post Market Surveillance and Adverse Event reportingPost Market Surveillance – Activities of Competent Authoritiesof member states of the EU• Example : Germany BfArM – Bundesinstitut für Arzneimittelund Medzinprodukte- Overall responsible for the evaluation regarding the technicaland medical requirements and the safety of medical devices- Shall advise the competent authorities within the federalstructure of Germany and German Notified Bodies.

Post Market Surveillance and Adverse Event reportingManufacturers marketing Medical Devices in EUPost Market Surveillance actions of manufacturers required inthe Medical Device Directives :• Obligation to have a systematic procedure to reviewexperience gained from devices in the post-production phase• Obligation to implement Corrective Action• Obligation to inform competent authorities (Adverse EventReporting)Pro active actions of manufacturers required by applicable ISO13485 clauses. (Feedback)

Post Market Surveillance & Adverse Event Reporting

Post Market Surveillance & Adverse Event ReportingPost Market Surveillance – summary and outlook :• 3 Regulatory Systems – 3 interpretations of what post marketsurveillance is that vary in the detail – especially regardingthe activity of a manufacturer• ISO 14971 gives specific details for manufacturers and cangive inspiration to Competent Authorities• Adverse event reporting quite similar in the 3 discussedsystemsA universal definition of “Post Market Surveillance”listing activities of all stakeholders is still missing.

Thank you !Questions ?-> contact: Michael Maier-> www.medidee.com