the practical approach The upcoming EU MDR - Qserve MDR_Israel...•Better traceability of medical devices throughout the supply chain •Swift and effective response to safety problems

Copyright Qserve Group B.V.

…..the practical approach

A global leading medical device consultancy group

Europe - Amsterdam (HQ) | USA - Boston - San Francisco | China – Nanjing

The upcoming EU MDR - key changes – overview

Gert BosExecutive director & Partner

Page 2 | Copyright Qserve Group B.V. …..the practical approach

Highlights

• Objectives legal revision

• Highlights on legislative process

• 10 most critical changes

• Timelines moving forward

• Key impact

• Q&A


Objectives in legislative reform

• Consistently high level of health & safety protection for EU citizens

• Free and fair trade of medical devices throughout the EU

• Adaption to significant technological & scientific progress in the sector over last 2 decades.

Key elements:

• extending scope• better supervision of notified bodies

• clear rights manufacturers/distributors• stronger requirements medical evidence


Objectives in legislative reform

• Consistently high level of health & safety protection for EU citizens

Sufficient clinical data and performance evaluation results

• Free and fair trade of medical devices throughout the EU

= Clinical Evidence

• Adaption to significant technological & scientific progress in the sector over last 2 decades.

State of the art


Four charges to improve ad interim

• Functioning notified bodies

• Market surveillance

• Coordination on vigilance

• Communication and transparency


2010

Guidance &

interpretation

• Updated

legislation

• Updated

MEDDEV

documents

• New harmonized

standards

• State of the art

2013

Audits &

supervision

• Joint inspection

of NBs

• UAV system

• COEN

coordination

2017-2020

equirements &

transparency

• MDR / IVDR

• Clinical trials

• Special NBs

• EUDAMED

• UDI

• Supply chain

focus

• And more….

Living up to MDR/IVDR


Push on Notified Bodies

• Regulation:• Re-designation of notified bodies

• Joint assessment teams

• Strong focus on qualification,independence, clinical evaluation

• Recommendation:• Strict details on dossier assessment

• Strict details on audits

• Minimum frequency of unannounced visits


Changes to Notified Bodies

• Regulation on NB designation & recommendation on NB work• Notified Body number dropped from 87 to 57; IVD-NB relatively stable at

22; expectations for next 6-12 months: 10-15 more to go including some with IVD scope

• Some remain with reduced scope• Notified bodies under pressure and scared

• Ongoing initial reviews stifle on growing requirements on clinical data and limits to equivalence use

• Line-extension reviews getting cumbersome• Renewal halted; certificates not renewed in time• Certificates suspended without clear warning• NBs careful in accepting transfers• Waiting lists generally increasing

Expected 50% not

re-designated or with

significant scope change !

MHRA


Elements of change – new guidance MEDDEV 2.7.1 rev 4

• Clinical Evaluation Report for all classes of devices

• Benefit risk in intended use / target group

• Aligned with state of art in medical field concerned

• Inclusion of usability requirements

• Integrated in lifecycle management

• Clinical evaluation before and after clinical studies

• Expectation of larger patient numbers in studies

• Stronger focus on analysis and appraisal of data

• Qualification of evaluators

• Update (annually / 2 year / 5 year)


Element of change – shifting view on Own Brand Labeling

• Own Brand Labeler same requirements as OEM

• Access to full technical file, including e.g. sterilization validation at subcontractors of the OEM

• Access to OEM’s PMS data

• Full audit and supply chain oversight

• Unannounced audits


New MHRA guidance – OBL => virtual manufacturer


Intermezzo: the impact of a Brexit….

• Slow process; will take till Q1 2019

• Uncertainty on future is most critical impact

• Trade agreement?

• Accept new MDR / IVDR – or separate legal framework?

• Continued notified body services?

• Continued authorized rep services?

• Etc. etc.


Three key stakeholders

Commission (2012) Parliament (2014) Council (2015)


Trilogue Process

• Discussion method for negotiations between Council and EP to reachpolitical agreement

• No formal rules, it does not exist in the procedures; there is an MoUbetween EP and Council

• Trilogues, but mainly negotiations between EP and Council; CIE ‘facilitates’.


Finally MDR is published on May 5 2017


Finally MDR is published on May 5 2017

Key elements of change

20 articles

60 pages

12 annexes

Directive

MDD123 articles

175 pages

16 annexes

Regulation

MDR


Regulation EU 2017/745

101 Whereas … = Why

10 Chapters of 123 Articles = What

XVI Annexes = How

Chapter I – Scope and Definitions

Chapter II – CE Marking, Economic Operators, Reprocessing

Chapter III – Identification and Traceability of Devices

Chapter IV – Notified Bodies

Chapter V – Classification and Conformity Assessment

Chapter VI – Clinical Evaluation and Investigation

Chapter VII – Vigilance and Market Surveillance

Chapter VIII – Cooperation between Member States

Chapter IX – Confidentiality, Data Protection, Funding,

Penalties

Chapter X – Final Provisions


Regulation EU 2017/745

Annex I – General safety and performance requirements

Annex II – Technical Documentation

Annex III – EU Declaration of Conformity

Annex IV – CE Marking of Conformity

Annex V – European UDI System

Annex VI – Requirements to be met by Notified Bodies

Annex VII – Classification Criteria

Annex VIII – Conformity Assessment – QMS and Technical Documentation

Annex IX – Conformity Assessment – Type Examination

Annex X – Conformity Assessment – Product Conformity Verification

Annex XI – Procedure for Custom-made Devices

Annex XII – Certificates issued by a Notified Body

Annex XIII – Clinical Evaluation and Post-market clinical follow-up

Annex XIV – Clinical Investigations

Annex XV – Products without an intended medical purpose

Annex XVI – Correlation Table 90/385, 93/42 and Regulation

101 Whereas … = Why

10 Chapters of 123 Articles = What

XVI Annexes = How


Wider, clearer scope for EU legislation

• Products manufactured utilising non-viable human tissues or cells, or their derivatives, that have undergone substantial manipulation

• Reference human tissue donation and procurement legislation

• Certain implantable / invasive products without a medical purpose

• Clarification towards:• products that contain or consist of viable biological substances• food covered by Regulation (EC) No 178/2002


Common Specifications

• Extension of legal requirements• Authored with little input from industry

• Technical and other specification• Annex XV cosmetic implants

• Reprocessing of single use devices

• Clinical requirements

• and more……

• Will gradually replace MEDDEVs and (selected) Standards


Stronger supervision of notified bodies

• System moves from New Approach to New Legal Framework

• Stronger supervision on Notified Bodies

• Continuation of joint assessment; manual transcribed into NB annex

• Focused clinical scrutiny mechanism on high risk devices

Because of that:

• Stronger supervision by Notified Bodies


More powers for assessment

• Thorough testing and regular checks on manufacturers

• Much stricter acceptance criteria on clinical data and equivalence

• Unannounced factory inspections, including supply chain

• Rotation of notified body staff involved in assessment

• Adoption of common (technical) specifications


Clearer rights & responsibilities

• Clearer responsibilities for manufacturers, importers and distributors

• Also applicable to diagnostic services and internet sales

• Establishing a ‘qualified person’ in manufacturer or authorized rep.

• Relabeling and repackaging clarified

• Liability detailed (manufacturer and authorized rep.)


Obligations Importer & Distributor

• Verify device is CE marked & with Declaration of Conformity & AR designated

• Verify appropriate labelling & IFU, including assignment UDI & registration EUDAMED

• Appropriate storage or transport conditions

• Inform authority on (suspected) non-compliance

• Keep a register of complaints, non-conforming products, product recalls and withdrawals

• Provide other economic operators with information to investigate complaints

• Immediately forward information on complaints to manufacturer & AR

• Keep a copy of the declaration of conformity and a copy of the certificate

• Importers shall indicate name & address on the device, its packaging or in a accompanying document


Liability

• Proportionate to the risk class, type of device and the size of the enterprise, manufacturers shall have measures in place to provide sufficient financial coverage in respect of their potential liability under Directive 85/374/EEC, without prejudice to more protective measures under national law.

• Liability extended beyond manufacturer and importer to authorized representative

• Liability for notified bodies

• Liability for sponsor in clinical trial


Reprocessing of Single Use Devices (Recital 38)

• Reprocessing of SUDs only where permitted by national law, and in respect of requirements laid down in this Regulation.

• Reprocessor should be considered the manufacturer of the device.

• Member States may decide that reprocessing and re-use of SUDs within a health institution may vary from the obligations of the manufacturerdescribed in this Regulation. • In principle this is only permitted when adequate common specifications are in

place and if appropriate national regulations exist and are applied in the reprocessing of these devices which ensure AT LEAST THE SAME LEVEL OF SECURITY as in case of the corresponding initial SUDs.

• This also applies if the reprocessing is carried out by an external reprocessor on behalf of a health institution.


Extended Eudamed database

• Registration of devices and economic operators

• Comprehensive information on products available on the EU market

• Non-confidential data will be publicly available

• Public summary of safety and performance


Better traceability

• Better traceability of medical devices throughout the supply chain

• Swift and effective response to safety problems (e.g. recalls)

• phased introduction of Unique Device Identification (UDI)• UDI on label, higher packaging,

• UDI on Declaration of Conformity;

• UDI included in implant card;

• UDI central in EUDAMED database


UDI

• UDI on label, higher packaging, DoC; included in implant card, stored by health institutes;

• UDI in database before placing products on the market

• UDI on NB certificates IIb implants and III

• UDI basis for vigilance reporting

• UDI for now allowed under:

• GSI AISBL

• HIBCC

• ICCBBA

• UDI application:

• 1 yr: implantables and class III

• 3 yr: class IIa and Iib

• 5 yr: rest


Stricter requirements for clinical evidence

• Stricter requirements for clinical evidence to support assessments• Interventional clinical performance studies• Studies with invasive procedures or other risks

• Sponsor introduced

• Database for clinical studies

• Ethical consent detailed

• Continuous performance evaluation integrated in PMS


Hazardous substances

• CMR substances / endocrine disruptors > 0.1% for body contacting devices and devices in contact with medicines need justification• Justification details extensified in ER 10.4.2

• Irrespective of existing applicable environmental legislation (REACH)

• Guideline on phthalates

• Guideline on CMR / endocrine disruptors


Updated classification rules

• Keeps four risk classes; AIMD integrated

• Reclassifications:• AIMD and accessories => III

• Selected orthopaedic implants => III

• Deliberate Nano => III

• Critical care active devices => III

• Ingested, inhaled or administered rectally or vaginally and absorbed by or dispersed in the human body


Better coordination

• Better coordination between national surveillance authorities, with the Commission providing scientific, technical and logistic support• Clinical evaluation / scrutiny

• Market surveillance / vigilance

• Governance system – MedDev Coordination Group (MDCG)

• Encourage device registers


Consultations

An.IX-5.2 Pharmaceuticals• EMA for biotech, recombinant etc.

and MS for any others• 210 days after receipt of valid

documentation: opinion delivered• No way to overrule negative

opinion; any change relating to pharmaceutical: 60 day review

An.IX-5.3 Animal tissue/cells, TSE susceptible (EC 722/2012)• Consultation as per current TSE

Regulation (EDQM 4 wks, no EDQM 12 wks

An.IX-5.3 Human tissue/cells

• Consultation with human tissues and cells competent authority

• 120 days after receipt of validdocumentation: opinion delivered

• No way to overrule negative opinion, same change control as pharmaceuticals

An.IX-5.4 Substances – absorbable as per intended purpose

• EMA or MS drug authority, 150 days


Scrutiny on implantable class III devices (An.IX-5.1)

• NB clinical evaluation assessment report on risk-benefit, consistency with intended purpose and PMCF plan

• NB report, clinical evaluation docs to Commission, forwarding to expert panel

• Optional presentation of NB to expert panel

• In case no opinion will be delivered: 15 days, with motivation of decision; NB proceeds

• Opinion from expert panel in 60 days; NB proceeds

• If no opinion in 60 days. NB may proceed

• Restriction of purpose to numbers or groups of patients• Limitation to validity of certificate• Demand for specific PMCF studies• Adaptation of Instruction for use• Other restrictions


Procedure packs – art. 22

• Mix with IVD; mix with non-devices when justified

• Statement on mutual compatibility, packaging with relevant information, appropriate methods of internal monitoring, verification and validation

• Sterilization subject to NB conformity assessment

• No additional CE mark, but room for tradename, trademark

So what is different??


Procedure packs – art. 52

• …where the system or procedure pack incorporate devices which do not bear the CE marking

• …where the chosen combination of devices is not compatible in view of their original intended purpose

• …where the sterilization has not been carried out in accordance with the manufacturer's instructions

=> procedure pack shall be treated as a device in its own right; subject to Article 52. The natural or legal person shall assume the obligations incumbent on manufacturers.


Key Impact

• Private label route to fund initial developments blocked

• Clinical data requirement pre-market strongly enhanced – higher upfront investments

• Regulatory requirement much more demanding - higher upfront investments

• Portfolio rationalization strategies initiated

• New strategies to develop (proof of) concept instead of direct sales

• Ongoing mergers and acquisitions at the top

• Many SME will go out of business or will change company strategy


What to expect?

• NB’s faster to implement changes

• NB’s implement before end of transition

• NB’s too busy for all the work

• Increasing uncertainty on path forward, existence of NB, availability of services

• Expect bars to be raised and issuance of certificates to be a time-consuming effort


Resourcing at NBs, authorities, commission

• Some NB fully ready, double procedures, double the staff

• Authorities typically at 0-growth policy

• EUDAMED specs being set, expect 3 years development

• UDI to be specified in details, expect 3 years development

• Harmonization of standards, expect 2-3 years development

• Hospitals not required to use UDI

• CS: priority list in place: UDI, EUDAMED, NBs, annex XV


Thank you for your attention

Copyright Qserve Group B.V.

A global leading medical device consultancy group

Europe - Amsterdam (HQ) | USA - Boston - San Francisco | China – Nanjing

…..the practical approach

Gert BosExecutive director & Partner

the practical approach The upcoming EU MDR - Qserve MDR_Israel...•Better traceability of medical devices throughout the supply chain •Swift and effective response to safety problems

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