Ronald BoumansSenior Global Regulatory ConsultantTelephone: +31 70 345 85 70rboumans@emergogroup.com

Understanding Europe’s new Medical Devices Regulation (MDR)

The new Medical Devices Regulation!

Be aware of some major changesPrepare in advanceMake sure your team is preparedNB. Medical Devices Regulation: MDR

Today’s agenda

Relevance of the MDR proposalMajor concepts of the MDR

Critical items: Clinical dataPost-Market SurveillancePeriodic Safety Update ReportEUDAMEDTimelines

Before we begin…

The Hague, The Netherlands

108 Embassies in The Hague!Dutch

Parliament

Relevance of the MDR:Leading a global trend

Once upon a time…

There was a Technical File of about 12 pages…

… for a Class III device…

Those days are long gone…

Medical Devices Directive (MDD) in need of revisionStructural problems:Oversight by the Notified Bodies insufficientPost-market safetyTransparency and traceability of devicesAccess to medical expertise

But also:New types of products introducedLack of consensus among competent authoritiesNew market conceptsFurther globalization

PIP scandal was a wake up call!

MDR indicator of a global trend

More liability for the manufacturerMore clinical data neededClinical data of higher qualityMonitoring of quality and safety during product life cycleIncreased data management

It took a while to deliver…

First weaknesses identified in 2002 by MDEGModifications to MDD in 2007 (2007/47/EC)European Commission public consultation in 2008Deficiencies became clear (PIP, metal-on-metal etc.)September 2012 first version by European CommissionApril 2014 European Parliament 347 amendmentsSeptember 2015 European Council with its own versionJune 2016 current compromise textFinal version expected in Q1 of 201740 – 80 delegating and implementing acts to follow

Significant influence by IMDRF

International Medical Device Regulators Forum - IMDRF (Australia, Brazil, Canada, China, Europe, Japan, Russia, USA)Builds on Global Harmonization Task Force (GHTF)Influence can be seen in:•Introduction of UDI•Requirements for Technical File•Post Market Surveillance

MDR will likely impact future legislation in other markets

More control over industrial network

Manufacturer must control supply chain:

Prepare supply chain for unannounced audits by NBCritical supply must be part of the Technical File and the Quality Management SystemControl over distribution chain must be part of QMSCharacteristics of distribution chain may lead to design requirementsDistribution chain will have role in vigilance and PMS

Be prepared to update your QMS.

Stricter control over Notified Bodies

Less of an industry partner, more an extension of the authoritiesTighter requirements for Notified BodiesIncreased procedural requirements•Joint Assessment Teams – several competent authorities, highly trained•Less room for outsourcing expertise•More clinical expertise in-house•Opinion provided by MDCG during conformity assessment of high risk devices

Expect Notified Bodies to be more critical.

Economic Operators

Manufacturers, Authorized Representatives, Importers and Distributors (MAID)Each role well defined (articles 8-12)Economic Operators to verify if upstream supplier is in conformityAble to identify to whom deliveredReporting requirements re. VigilanceMust act in case of Field Safety Corrective Action

The manufacturer is responsible to organize and train distribution chain.

Clinical evaluation:A next step in compliance assessment

Major changes

Old: Clinical Evaluation Report Much information from literature reviewOften with data referring to devices that were not equivalentHow well did your Notified Body look into your updates to your CER?

How well did your Notified Body look

into your updates to your CER?

Major changes

New:Constantly updated set of data from subject deviceBenefit – risk evaluationPermanent updatingNotified Body will look into data AND methodology!

Notified Bodies will look into data AND

methodology.

Increase data quality requirements

MEDDEV 2.7/1 Rev. 4 already lifts the barMDR goes further: only data from equivalent devices is accepted, andThis data must adequately demonstrate compliance with the relevant requirements

Collecting this data may take longer than

you think.

Equivalent devices

Equivalence is defined in detail in Annex XIII, section 4aEquivalence = Technical (similar design), Biological (same materials/substances) and Clinical (same condition or purpose) – no significant differences in clinical performance and safetyEquivalent device of another manufacturer: full access to the technical file

Many current ‘equivalent devices’

will no longer be accepted.

Clinical Evaluation and QMS

Collection and evaluation of clinical data must be part of the QMSEach device should be part of a continuous cycle of improvement

Clinical investigations

Strict requirements for clinical investigationsSpecific requirements for vulnerable or incapacitated subjectsTimelines of reporting of Serious Adverse EventsClear rationales for sample sizes

Clinical investigations will take more

time and they will be more expensive.

Where does your current clinical data come from?Data somewhere on file…Data from previous generations of the device – still equivalent?Data from previous companiesData incomplete, because part is on floppy disk

Verify that your clinical data is still available, applicable, and valid.

Post-Market Surveillance:A giant leap forward

Post-market surveillance plan

Necessary for each devicePart of updated CERCollect information on specific subjects (incidents, trending, complaints, feedback etc.)Procedures of how to collect that informationDefine how to systematically evaluate information, including indicators, thresholds, etc.And many more…

Start your PMS plan now - it may generate valuable information.

Post-market clinical follow-up (PMCF)

Continuous process to update clinical evaluationCollect data and evaluate PMCF is part of PMS

PMCF plan

Required for each device (family)Process to update CERConfirming safety and performance, side-effects, risks, etc.Methods and procedures usedRationale for the appropriateness of these methods and proceduresObjectives, time schedule, etc.

Start developing your PMS plans now, they

may generate valuable information for your

transition to the MDR.

Vigilance and market surveillance

Reporting of incidents will have to done through EudamedAccessible to European Commission, Competent Authorities, Notified Bodies and public (limited)Keep evaluating your device against the general safety and performance characteristicsCompetent authorities will monitor compliance of devices involved in incidents and/or corrective actions

For fast and consistent reporting you need a

smart data management system

Benefit of risk determination

The clinical benefits must outweigh the risks of the deviceThe result of this analysis may change over timeAll this needs to be recorded in the PMS report

Is this REALY such a big leap forward?

The clinical benefits must outweigh the risks of the deviceThe result of this analysis may change over timeAll this needs to be recorded in the PMS report

For fast and consistent reporting, you need a

smart data management system.

Periodic Safety Update Report

Class I: periodic updated PMS report

PMS report to be updated as new clinical data is evaluatedPart of Technical FileTo be assessed by the Competent Authorities upon request

First indicator of Competent Authorities if a manufacturer has an active PMS system.

Periodic Safety Update Report

For Class lla, Class llb and Class lll:Conclusions of benefit risk determinationMain findings of PMCF reportVolumes of sales/exposure in report Would you be able to

draw up such a report based on your current

procedures/data?

Publication of Periodic Safety Update ReportsFor Class lll and llb implants:Must be uploaded to EudamedEvaluated by Notified BodyPossible conflict: freedom of information acts versus sensitive commercial data

Your annual sales data may be published.

EUDAMED:A brave new world of medical devices data

EUDAMED helps map Economic OperatorsManufacturer, Authorized Representative, Importer, and Distributor must all be listed in EUDAMEDEssential in demonstration of complianceCompetent authorities will map industry based on EUDAMEDParts will be accessible to the public

At least you may know your parallel importer.

Single Registration Number (SRN)

Every Economic Operator needs an SRN for accessing EUDAMEDMultiple roles will require multiple SRNs (e.g. Authorized Representative AND importer: two SRNs)Competent authority will verify company information before handing out SRNNo access to EUDAMED without SRNSRN must be on certificates

Be aware: no Eudamed access, no market

access.

Entering data

Economic operators can enter data in EUDAMED:•Devices•Clinical investigations•Incidents•Etc.

Upload Periodic Safety Update ReportUpload Summary of Safety and Clinical Performance ReportConfirm annuallyOld data remain available in Eudamed

Take care data quality in Eudamed is high!

Timelines: Planning in the dark

The timeline…

MDR will be adopted in Q1 2017After six months notified bodies may apply for designationAt least six months before application EUDAMED becomes operationalMDR will be applicable three years after adoptionNo ‘old’ certificates will be valid four years after application

But…

The reality…

It is not clear in what order NBs will be designated and the designating team has limited capacityAt the moment an NB is designated for the MDR it can no longer issue MDD certificatesEUDAMED is crucial for producing the SRNs, but may not be ready at the moment the first NB is designated: no certificates can be issued until EUDAMED is operational

Grandfather devices

Currently compliant, safe device, but insufficient clinical data: grandfather deviceUnder MDR clinical data via clinical investigations, but,Under MDD clinical data via PMCF study possible

Identify possible grandfather devices

now!

Continuity of supply

The transition to the MDR is a complex processNot all certificates may switch smoothly from the MDD to the MDRNo certificate, no access to the marketEmergo expects authorities will have a pragmatic approach… …but this may only be achieved after some high exposure cases

Emergo will keep you informed of

developments. Please let us know if you run

into this issue.

What can you do?

Get detailed knowledge of the MDRFind out the plans of your notified bodyAssess the level of your clinical dataStart implementing PMS measures as soon as possible

No worries - your competitors are facing the same problems…

Thank you for your attention!

Device Registration and Compliance in 24 Countries Worldwide

My contact information:Ronald BoumansEMERGO | Senior Regulatory Consultantrboumans@emergogroup.comTelephone: +31 70 345 85 70