spears-european medical device regulations — preparing … · panel discussion: european medical...

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

© 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.3

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


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…


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.

6© 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.

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


EU MDR CHANGES AREEXTENSIVE


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

9 © 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.

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.

©2017, Ombu Enterprises, LLC. All rights reserved

12

Risk Managementand

Some Friends

Dan O’Leary CBA, CQA, CQE, CRE, SSBB, CIRMPresident

Ombu Enterprises, [email protected]

OMBUENTERPRISES, LLC

mailto:[email protected]

http://www.ombuenterprises.com/


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

OMBU ENTERPRISES, LLC


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



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



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



Some Friends

17

QMS

RMS PMSS

Plans

Reports

Updates



PMSS as A Mатрешка Doll

18

The PMS System:

Plans inside plans

Reports inside reports



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



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



Connections

21

SSCP

CE

PMCF

PMS

RM

BRR

BRD

PSUR



22

Questions


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)



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


EU MDR / IVDR – Designation –Article 38-40 / 38-40

27

26 November 2017


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


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


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


List of Designated Notified Bodies

31/10/2017

oNANDO website:

New Approach Notified and Designated Organizations

http://ec.europa.eu/growth/tools-databases/nando/index.cfm?fuseaction=directive.pdf&refe_cd=93/42/EEC&requesttimeout=900


Transition periods:

MDR (Article 120) and

IVDR (Article 110)



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



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.


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


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



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


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


40

Appendix

OMBUENTERPRISES, LLC


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



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



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)]

43



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)]

44



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)]

45



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

46



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



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



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

49



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

50


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