Panel Discussion: European Medical Device Regulations — Preparingfor the Storm
Moderator:Lenita Y. Sims Spears, Senior Quality Consultant/Senior Regulatory andCompliance Counsel, BioTeknicaPanelists:Karl Vahey, Vice President Manufacturing Quality, Cardinal HealthDan O’Leary, President, Ombu Enterprises LLCIbim Tariah, Technical Director, BSI Americas Inc.
MEDICAL DEVICE REGULATION
KARL VAHEYVP QA CARDINAL HEALTH
MDR Elevator Speech
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What is the EUMDR about?
• A new regulation in Europe for medical devices and invitro diagnostic products with many changescompared to the current directives
• Consolidated trilogue text of EU MDR and EU IVDRwere issued in June 2016 and was published in theOfficial Journal of the European Union in May 2017.
Why is EUMDRimportant?
• After a three-year transition period, all products mustbe CE certified to EU MDR requirements.
• There will be impacts across all Businesses and manyfunctions for the commercialized product portfolioand products in development.
• There will also be impacts to other geographies asproducts and labelling are updated.
MDR Elevator Speech
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What willsuccess looklike?
• Recertification of products within the establishedtimelines.
• Strategic investment opportunity assessment andexecution
• Partnering with Competent Authorities and NotifiedBodies to align on a practical compliance strategy
MORE ROBUST TEXT UNDERSTRONGER POLITICAL PRESSURE
A FEW FACTS…
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23 articles
60 pages
12 annexes
44occurrencesof "clinicalinvestigation“
Directivepublished1993,amended2007
MDD
97 articles
355 pages
16 annexes
142occurrences of"clinicalinvestigation“
Regulationpublished May2017, Fullimplementation2020
MDR
MDR PROGRAM OVERVIEWIMPACTS OF MDR
NPD Launch Market Cert Renewal
• More productsrequire priorapproval;
• Longer reviewtimelines &increased costs;
• Enhanced clinicalrequirements;
• Scrutiny for newproducts.
• UDI reqs;;
• New QMS reqs;
• Qualityagreements;
• Labeling reqs.
• Required PMSreporting;
• Required periodicsafety updatereports;
• Required CERupdates;
• New complainthandling reqs.
• Continued scrutinyon State of Artreqs;
• More productsrequiringsubmissions;
• Introduction of newaudits (MDSAP /Clinical).
The EU MDR release focuses onthe overall product lifecycle fromdevelopment through obsolescence.
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Requirements for CE markinghave been enhanced in eachstage of the lifecycle.
MDR PROGRAM OVERVIEWIMPACTS OF MDR
Below are examples of the specific requirements of MDR:
Regulatory Files Quality System Haz Substance Clinical Evaluation
• All Tech Filesrequire updates;
• All Declaration ofConformitiesrequire updates;
• More productfamilies requiresubmission to NB.
• SOP change to refMDR
• Post MarketSurveillance reportsfor all tech files
• Periodic SafetyUpdate Reportsrequired;
• product codesrequire analysis forhaz sub;
• Testing requiredfor any productpotentially havinghaz sub to quantifylevels;
• Can lead tomaterial changesor labeling reqs
• CER’s requirereview and ifnecessaryupdates;
• CER’s requireupdates annually;
• Post MarketClinical Follow uprequired f
• SSCP requireupdate & annualsubmission.
RA, R&D, DQE,Medical Affairs, PMV
QA Man, Ops, DQE,Medical Affairs, RA,
PMV
QA Man, RA, Ops,R&D, EHS
Medical Affairs, PMV,R&D, RA, Commercial
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EU MDR CHANGES AREEXTENSIVE
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Key EU MDR Changes Business Implications Implicated BusinessFunctions
Hazardous SubstancesIncreased Scope and Depth
of Requirements
Restricted Equivalence Claim(Class III and Implants)
Notified Body DesignReview for
Class IIb Implants
New (Up-) Classification
Expanded LabellingRequirements
(including Implant-Information)
Revenue impact from lossin portfolio
Increased Time To Market
R&DSupply Chain
R&DRegulatoryAffairsMedical AffairsQuality
EU MDR CHANGES AREEXTENSIVE
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Key EU MDR Changes Business Implications Implicated BusinessFunctions
Technical Documentation,DoCNew Format and Content
QM-System- PMS, Vigilance,PSURs, Trend Reports
ClinicalEvaluation/InvestigationSummary of Safety andPerformance
UDI and Economic Operators
Expanded LabellingRequirements(including Implant-
Information)
Administrative Burden
IncreasedTransparency andDocumentation
R&DRegulatory AffairsQualityTech. CommunicationProduction
QualityMedical AffairsRegulatory Affairs
Regulatory AffairsSupply Chain
MDR PROGRAM OVERVIEW
IMPACTS OF MDR TO INDUSTRY
Revenue
ProductLines
ProductCodes
Files toRemediate
(Risk, Design, Clinical)
1010
© Copyright 2017. All rights reserved. CARDINAL HEALTH logo , and the ESSENTIAL TO CARE are trademarks orregistered trademarks of Cardinal Health. All other marks are property of their respective owners.
Panel Discussion: European Medical Device Regulations — Preparingfor the Storm
Moderator:Lenita Y. Sims Spears, Senior Quality Consultant/Senior Regulatory andCompliance Counsel, BioTeknicaPanelists:Karl Vahey, Vice President Manufacturing Quality, Cardinal HealthDan O’Leary, President, Ombu Enterprises LLCIbim Tariah, Technical Director, BSI Americas Inc.
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12
Risk Managementand
Some Friends
Dan O’Leary CBA, CQA, CQE, CRE, SSBB, CIRMPresident
Ombu Enterprises, [email protected]
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Risk Management
• The MDR has many Risk Management requirements
– This is risk management in the sense of “how could my deviceharm the patient or user”
– It is not, as in ISO 13485:2016 Clause 0.2, “meeting applicableregulatory requirements”.
• Risk Management, in the MDR, has many friends, in the form ofrecords and reports. We will also meet some of them along the way.
13
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The RMS as QMS• The journey starts in Article 10 General Obligations of
Manufacturers
• Section 2 requires a manufacturer to establish, document,implement, and maintain a risk management system RMS, asdescribed in Annex I, Section 3
• Section 9 requires a manufacturer to establish, document,implement, maintain, keep up to date, and continually improve aquality management system, QMS
• The QMS includes:
– A strategy for regulatory compliance
– Risk management following Annex I, Section 3
– A post-market surveillance system, PMSS, following Article 8314
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Annex I
• Annex I General Safety and Performance Requirements
• Section 3 has the basic elements of the RMS such as
– A risk management plan for each device
– Analyze known and foreseeable device hazards
– Eliminate or control risks using Section 4
– Evaluate information from the post-market surveillance system,PMSS
• Section 4 provides the priority order for risk reduction measures
• Section 5 provides special considerations for risks related to useerrors
15
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ISO 14971:2007
• ISO 14971:2007 is the international standard for medical device riskmanagement
• The current Medical Device Directive, MDD, has requirements thatare not the same as the international standard
– EN ISO 14971:2012 enumerates the differences in ContentDeviations
– It is a Harmonized Standard to the MDD
• At this point, the MDR doesn’t have any Harmonized Standards
– Some of the differences carry over to the MDR, but some do not
– It is not clear what would be in a version of ISO 14971:2007harmonized to the MDR
16
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Some Friends
17
QMS
RMS PMSS
Plans
Reports
Updates
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PMSS as A Mатрешка Doll
18
The PMS System:
Plans inside plans
Reports inside reports
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Systems• The MDR has many “systems” that are part of other systems.
– The linkages are complicated, so it is best to take each system inisolation
• The systems (not all of which have the word system in the name) are:
– Quality Management System (QMS)
– Risk Management System (RMS)
– Benefit-Risk Determination (BRD)
– Benefit-Risk Ratio (BRR)
– Clinical Evaluation (CE)
– Post-market Surveillance (PMS)• Post-market Surveillance Report (PMSR)
• Periodic Safety Update Report (PSUR)
– Post-market Clinical Follow-up (PMCF)
– Summary of Safety and Clinical Performance (SSCP) 19
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QMS
• The QMS must specifically address some of these systems:
– Risk Management System (RMS)
– Clinical Evaluation (CE)
– Post-market Clinical Follow-up (PMCF)
– Post-market Surveillance (PMS)
• Post-market Surveillance Report (PMSR)
• Periodic Safety Update Report (PSUR)
20
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Connections
21
SSCP
CE
PMCF
PMS
RM
BRR
BRD
PSUR
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22
Questions
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Panel Discussion: European Medical Device Regulations — Preparingfor the Storm
Moderator:Lenita Y. Sims Spears, Senior Quality Consultant/Senior Regulatory andCompliance Counsel, BioTeknicaPanelists:Karl Vahey, Vice President Manufacturing Quality, Cardinal HealthDan O’Leary, President, Ombu Enterprises LLCIbim Tariah, Technical Director, BSI Americas Inc.
Copyright © 2012 BSI. All rights reserved.
Notified Bodies Designation &Transition Provisions under the
EU MDRIbim Tariah Ph.DBSI Group America Inc.November 1, 2017
Copyright © 2012 BSI. All rights reserved. 25
Notified Bodies Designation
(under MDR & IVDR)
Copyright © 2017 BSI. All rights reserved.
Copyright © 2012 BSI. All rights reserved. 26
EU Notified Bodies and theAIMD/MDD/IVD Directives
0
10
20
30
40
50
60
70
80
90
100
2005 2006 2007 2008 2009 2010 2011 2012 2013 2014 2015 2016 2017
To
tal-
AIM
D,M
D,IV
D
Medical Devices Notified Bodies
Copyright © 2012 BSI. All rights reserved. 27
EU MDR / IVDR – Designation –Article 38-40 / 38-40
27
26 November 2017
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Noteworthy NB DesignationTimelines
• NB Application completeness check by CA within 30 days
• CA submission of NB Assessment report to EU Commission => MDCG
• EU Commission sets up JAT within 14 Days
• JAT review of documentation submitted by CA within 90 Days
• NB close out of NCs & provision of CAPA to CA (“within a specifiedtimeframe”)
• CA close out of NB NCs => JAT (TBD)
31/10/2017
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Noteworthy NB DesignationTimelines
• JAT final opinion on CA report & Draft Designation within 21 Days =>EU Commission
• MDCG recommendation to CA within 42 Days
• CA publication in NANDO (allows 28 Days for any Objection from otherCA’s & EU Comm)
• CA publication in EUDAMED => NB’s start activities from that date(TBD)
• EU Commission publication in NANDO within 42* (if Objection raised 64Days)
31/10/2017
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Timing of Notified Body Designation(Articles 38,39, 40 & 42)
From
Start to FinishApproximately
…
Best Case =>18 Months
Realistic => 21 Months
Worse case ~ 24 Months
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List of Designated Notified Bodies
31/10/2017
oNANDO website:
New Approach Notified and Designated Organizations
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Transition periods:
MDR (Article 120) and
IVDR (Article 110)
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MDR Transition (Article 120)
05 May 2017Adoption of MDR
Entry into Force (OJEC + 20days)(25 May 2017)
NBs designation under MDR
Date of Application(26 May 2020)
MDD/AIMD certificate validity(4 years )
MDD/AIMD certificates (max 5-year expiry from issue/renewal date)
MDR certificates
Transition period3 years
Last MDD/AIMDcertificates expire
(27 May 2024)
Annex IV certificatesexpire (27 May 2022)
27 May 2025No more « placing on
the market » of devicescovered by MDD/AIMD
certificates
33
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MDR Transition (Article 120)
However, the requirementsof this Regulation relating topost-market surveillance,market surveillance,vigilance, registration ofeconomic operators and ofdevices shall apply in placeof the correspondingrequirements in thoseDirectives.
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IVDR Transition (Article 110)
05 May 2017Adoption of IVDR
Entry in to Force25 May 2017
NBs designationunder IVDR
Date of Application26 May 2022
IVDD certificatevalidity (2 years )
IVDD certificates can be issued/re-issued/renewed
IVDR certificates
Transition period5 years
No more « makingavailable or putting
into service » ofdevices covered byIVDD certificates
IVDD certificates void27 May 2024
27 May 2025
NBs can apply fordesignation26 Nov 2017
35
Copyright © 2012 BSI. All rights reserved. 36
MDR Transition (Article 120)
MDD/AIMDDcertificates void
27 May 2024
• No significant change to design or intended purpose• Post market surveillance• Market surveillance• Vigilance• Registration of economic operators and devices
36
• Class I reusable• Class III custom made implantable• Devices with no Medical Purpose (Once Common
Specifications available)
Adoption of MDR05 May 2017
Entry in to Force25 May 2017
NBs designationunder MDR
MDD/AIMDD certificate validity(4 years )
MDD/AIMDD certificates can be issued/re-issued/renewed
MDR certificates
Transition period3 years
MDD/AIMDD Annex IVcertificates void on 27 May
2022 No more « makingavailable or putting into
service » of devicescovered by MDD/AIMDD
certificates
27 May 2025
NBs can apply fordesignation26 Nov 2017
Date of Application26 May 2020
Copyright © 2012 BSI. All rights reserved. 37
Copyright © 2012 BSI. All rights reserved. 38
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Appendix
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Paradigm View
• In the paradigm model, each system has a plan and a report.
• The plan has:
– Required content
– A location as a record
• The Report has:
– Required content
– Location as a record
– Conditions to update
– Conditions to submit it
• Some systems don’t follow this model41
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Risk Management
• Required by Article 10(9e) as part of the QMS
• There is a plan for every device [Annex I, Section 3(a)]
• The is no “report”, but the solutions and results become part ofAnnex II Section 5(a)
42
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Benefit-Risk Ratio
• Benefit-Risk Determination means the analysis of all assessments ofbenefit and risk of possible relevance for the use of the device forthe intended purpose, when used in accordance with the intendedpurpose given by the manufacturer [Art. 2(24)]
• Clinical Benefit means the positive impact of a device on the healthof an individual, expressed in terms of a meaningful, measurable,patient-relevant clinical outcome(s), including outcome(s) related todiagnosis, or a positive impact on patient management or publichealth [Art. 2(53)]
• Risk means the combination of the probability of occurrence of harmand the severity of that harm [Art. 2(23)]
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Benefit-Risk Ratio
• Clinical Evaluation helps evaluate the “acceptability of the benefit-risk ratio” [Art. 61(1)]
• Post-market Surveillance helps “update the benefit-riskdetermination” [Art. 83(3a)]
• The Periodic Safety Update Report, PSUR, sets out “theconclusions of the benefit-risk determination” [Art. 86(1a)]
• To reduce risks as far as possible means the reduction of risks as faras possible without adversely affecting the benefit-risk ratio [Anx.I(2)]
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Benefit-Risk Ratio
• Evaluate the impact of information … from the post-marketsurveillance system on the overall risk, benefit-risk ratio, and riskacceptability [Anx. I(3e)]
• The Technical Documentation contains information on the benefit-risk analysis [Anx. II(5a)]
• The Post-market Surveillance Plan covers suitable indicators andthreshold values used in the continuous reassessment of thebenefit- risk analysis [Anx. III(1.1b)]
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Clinical Evaluation
• Required by Article 61 Clinical Evaluation
• The Clinical Evaluation Plan’s content is described in Annex XIV(1a)
• It is a record in Annex II(6.1c)
• The Clinical Evaluation Report’s content is described in AnnexXIV(4)
• It is a record in Annex II(6.1c)
• It is updated throughout the life cycle using PMS and PMCF data,Art. 61(11)
• For Class III and Implants, the PMCF Report is updated annually,Art. 61(11), so, presumably the Clinical Evaluation Report is alsoupdated annually
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Post-Market Surveillance
• Required by Article 83 Post-market Surveillance System of theManufacturer
• The PMS Plan’s content is described in Annex III(1.1)
– The PMS Plan includes the PMCF Plan
• It is a record under Annex II and Annex III(1.1)
• The are two reports, depending on the device class
– The PMS Report is for Class I devices
– The Periodic Summary Update Report, PSUR, is for Class IIa,IIb, and III devices
47
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Post-Market Surveillance
• Required by Article 83 Post-market Surveillance System of theManufacturer
• The PMS Report’s content is described in Article 85
– It is a record in Annex III(1.2)
– It is updated when necessary
– It is submitted to the Competent Authority upon request
• The PSUR’s content is described in Article 86
– It is a record in Annex II and Annex III(1.2)
– For Class IIa devices it is updated every two years
– For Class IIb and Class III devices it is updated annually
– For Class III and Implantable devices it is submitted to the NB48
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Post-Market ClinicalFollow-up
• Required by Article 61 Clinical Evaluation Section 11
• The PMCF Plan is required by Annex XIV(6) and Annex III(1.1b)
– The plan’s content is described in Annex XIV(6.1 & 6.2)
– The plan is a record under Annex II(6.1d)
• The PMFC Report is required by Annex XIV(7)
– The report’s content is in Annex XIV(7)
– It is a record under Annex XIV(4) and Annex II(6.1d)
– For Class III and Implants it is updated Annually
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Summary of Safety andClinical Performance
• It is required by Article 32 Summary of Safety and ClinicalPerformance
• It applies to Class III and Implantable devices
• The content is described in Article 32(2)
• The summary’s target audience is the intended user or the patient
• The summary is updated annually
• The Manufacturer submits it the NB
– The NB submits it to Eudomed, where it is publically available
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