eu medical device and ivd regulatory update - bsi group · joint audits under 920/2013 ec •...

Copyright © 2015 BSI. All rights reserved.

EU Medical Device and IVD Regulatory Update

Sue Spencer Head of IVD NB BSI Group

Hanauer Landstraße 115, 60314 Frankfurt, Germany

Kitemark Court, Davy Avenue, Knowlhill, Milton Keynes, MK5 8PP, UK

0086

0535

Copyright © 2015 BSI. All rights reserved. 2

Caution

• The new regulations are draft and subject to change

• Further details will be added later pre and post application through implementing and delegating legislation


Triggers for Short Term Changes to the System

• Two fold natural regulatory cycle for the IVDD compounded by the discovery of a 16 year fraud in PIP breast implants using low quality “industrial grade” silicon oil

• Stress test performed by EU Commission • Determined that changes were needed to improve early detection

and prevent this type of incident • Other high profile vigilance cases with hips, pelvic floor meshes,

pacemaker leads, etc. • Outcome: short term changes to the system

• Immediate Actions • Commission Regulation: How Competent Authorities control Notified

Bodies • Commission Recommendation: How Notified Bodies audit

Manufacturers


Impact of Immediate Actions

Action Impact Re-assessment of qualifications and scope of activities of NBs

• NBs submitted to CAs the CVs of all technical experts for high risk devices

• Reduced scope for some NBs?

“Voluntary” Joint Audits of NBs by Designating Authority, Commission (FVO) plus two other CAs

• NBs and Designating Authorities under scrutiny

• Highlights different approaches in Member States

• Some Pain and Some Gain

Monthly Vigilance Teleconferences • Increasing number of COEN requests • More open COEN requests requiring detailed

follow up


24 September 2013

COMMISSION IMPLEMENTING

REGULATION (EU) No 920/2013

of 24 September 2013 on

the designation and the supervision of notified

bodies under Council Directive 90/385/EEC on active

implantable medical devices and Council Directive 93/42/EEC on medical devices

Directs Competent Authorities how to control

Notified Bodies

COMMISSION RECOMMENDATION

(2013/473/EU) of 24 September 2013 on the

audits and assessments performed by notified

bodies in the field of medical devices

Directs Notified Bodies how to audit Manufacturers

Effective from Jan 2014


Impact of Commission Implementing Regulation 920/2013 on the designation and the supervision of notified bodies: Criteria to be met for the designation of NB Requirements Impact Joint Audits of NBs by Designating Authority, Commission (FVO) plus two other CAs

• NBs and Designating Authorities under scrutiny • Highlights different approaches in Member States • More scrutiny of competency requirements, in-house clinicians,

qualifications • Processes and procedures clarified • NBs withdrawing – check NANDO, ask your CA

NBs subject to renewal by 14 October 2016 • Helps consistency; requires CA resource

Designating Authorities shall have sufficient number of competent personnel

• Have they the qualified resource to deliver?


Impact of Com. Recommendation (2013/473/EU) on audits and assessments performed by NBs – Items to be verified by NB during an audit

Requirements Impact Annex I: Criteria for NBs performing design dossier and type examinations

• Mainly reinforcement of current good practice • Increased need for clinical studies, less reliance on equivalence

argument • Will clarify time needed for reviews

Annex II: Criteria for NBs performing QMS assessments • Mainly reinforcement of current good practice • Introduces need for on site audits of Own Brand Labellers

Annex III: Unannounced visits to manufacturers, "critical subcontractors" or “crucial suppliers”, in addition to planned audits

• Completely new requirement needing extra product and QMS assessors

• Significant increase in NB workload and resources • IAF rules require planned audit schedules so no scope for

substitution • Gone very well in general • Some SMEs feeling burden is disproportionate


STEP CHANGE 2010 2013 2016-2018

Joint audits

UAV

CoC audits

COEN - MS

EUDAMED

Electronic submission

UDI

Industry in Spotlight

MDR / IVDR

EU oversight

Clinical trials

Special NBs

and MORE….

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Our World Today: Changes 2015


Elements of change – new guidance being finalised

• MEDDEV 2.7.1 – clinical evaluation • Review on-going • NB-elements will be removed; will be picked up by NBOG • Equivalence still in, but more restricted; our explanation and examples moved to other chapters

• MEDDEV 2.7.2 – guideline authorities on approving clinical trials • Final draft circulated for endorsement by written procedure by 24 June 2015 • Definition serious adverse event clarified; further definitions added • 70 pages on validation, assessment, details of expectation, approval/denial, workflow during and

after studies, series of annexes

• MEDDEV 2.7.3 – serious adverse event reporting • Endorsed 28 May 2015 • More in line with EN ISO 14155 • New form in annex


Joint Audits Under 920/2013 EC

• Voluntary assessments continuing; mandatory assessments increasing in number

• Requirements still stepping up

• Notified Bodies • merging • stopping • suspended, de-designated (6 months transfer) • scope reductions • sales stop, specific regions stop, ….


Notified Body (NBs) re-accreditation (*)

30

40

50

60

70

80

90

2011 2012 2013 2014 2015 2016

Number of NBs

• 82 NBs before 2010 for MD • 75 NBs ( June 2014) • 50 NBs (May 2015) ?

Projection?

New EU implementing Regulation 920/2013

Proposed “Regulations”

(* )Courtesy R. Voelksen. RAPS President. November 2014. AHWP-AHC meeting , Korea


We need to establish a level playing field

Copyright © 2015 BSI. All rights reserved. 15 15 Copyright © 2012 BSI. All rights reserved.

A Look to The Future……


Influencers and upcoming Trialogue discussions

EU Parliament

EU Commission

EU Council of Ministers

Technical Workshop staff Political teams in Coreper Luxembourg Netherlands


Process


MDR Timeline – Realistic Expectations: Plan: 6 negotiation rounds and early adoption in 2nd reading

Jan 2014

July 2014

Jan 2015

July 2015

Jan 2016

Italian Presidency

Luxembourg Presidency

Parliament elections

Rapporteurs appointed

New Commissioners in place

Latvian Presidency

Council reaches agreement, (partial) general approach?

Begin trilogues?

Conclude trilogues?

Entry into force?

Dutch Presidency

Parliament 1st reading

Greek Presidency


Sources

Commission

• Proposal for a Regulation of the European parliament and of the Council on medical devices, and amending Directive 2001/83/EC, Regulation (EC) No 178/2002 and Regulation (EC) No 1223/2009

• http://ec.europa.eu/growth/sectors/ medical-devices

Parliament

• 2012/0266(COD) - 02/04/2014 Text adopted by Parliament, 1st reading/single reading

• EP adopted by 547 votes to 19, 63 abstentions

• http://www.europarl.europa.eu reference=2012/0266 COD

Council

• Consolidated draft for EPSCO 19 June 2015 400 pages with many alterations and additions

• Variety of snapshots on IVDR

Foreseeable outcome – best guess of today

http://ec.europa.eu/growth/sectors/

http://www.europarl.europa.eu/



Chapter I - Scope and Definitions

• Regulation applies to ALL clinical studies in EU on medical devices • Annex XV cosmetics comes into force when Common Specification published; list can be extended • Delineation still based on principle mode of action • Devices with non-viable human derivatives covered (2004/23/EC on donation, procurement, testing) • IVDR + MDR = MDR • Definition: pathological investigation added; control or support of conception removed; IVD added

including organ, blood and tissue donations • Cleaning, disinfection and sterilization removed from definition, but considered devices under MDR • Accessory stricter defined (specifically or directly assist in … intended purpose) • Definitions added: falsified MD, procedure pack, system, performance, safe, risk, benefit-risk

determination, compatibility, interoperability, subject, clinical evidence, clinical performance, clinical benefit, PMS, serious public health threat

• Manufacturer includes fully refurbisher • Clinical data only from peer reviewed journals

New views from Council


Chapter I - Scope and Definitions

Commission

• Scope extension: • Non-viable human cells/tissue • Non-medical implants / invasive

devices • Clarification:

• Viable biological substances • Food covered by Regulation

EC178/2002 • Reclassification:

• Ingested, inhaled or administered rectally or vaginally and absorbed by or dispersed in the human body => class III and 2001/83/EC

• Expert Borderline Group

• Definitions aligned with New Legislative Framework (NLF) and GHTF

Parliament

• Scope extension: • Devices for aesthetic purposes • Definition includes prediction of

disease • Clarification:

• Donor and patient details • Viable pharmacological /immunological

/metabolic substances • Custom made device

• Reclassification: • ingested, inhaled etc. not reclassified • Software no longer active medical

device • Expert Borderline Group

• Definitions single use & reusable

Council

• Scope extension: • Devices for aesthetic purposes:

common specifications • Cleaning, disinfection and sterilization

removed from definition, but covered • Human cells – aligned with ATMP

• Clarification: • State of art definition removed • Clinical further detailed • Adverse event reporting detailed

• Reclassification: • Ingested, inhaled etc. risk stratification • Expert Borderline Group

• Definitions aligned NLF and GHTF Non-viable human tissue (similar to ATMP), aesthetic products in list once common

specifications are defined, viable biologicals clarified, ingested etc. based on risk, over-arching borderline group


Chapter II - Operators, Reprocessing, CE marking, Free Movement

• Solution found to keep health institutions free from CE marking • Harmonized standards stay as basis of system - PoC • Common specifications to be developed under wing of Commission – PoC • Specific requirements to have risk management system, clinical evaluation, UDI • Authorised Rep needs technical documentation permanently available • Detailed QMS requirements, including regulatory compliance strategy, RM, clinical, UDI, PMS, vigilance • Liability: Patients and users may claim compensation to manufacturers • AR legally liable for defective devices • More detailed requirements importers/distributors on sharing info, registers, etc. • ‘Qualified Person’ replaced by person responsible for regulatory compliance activities; outsourcable;

such responsibilities defined in 5 bullet points • Reprocessing allowed per country, but under MDR; allowed within health institutions; negative list • ‘Implant card’ replaced by information to patient, responsibility of hospital; info in URL • Other products in procedure pack to be justified • Procedure pack: out of intended use or sterilization instructions: own CE for full pack • Replacement part changing performance / safety characteristics = device



Chapter II - Economic Operators, Reprocessing, CE marking, Free Movement

Commission

• Common Technical Specifications (CTS) introduced

• Safety and performance • Clinical evaluation • Post-market clinical follow-up

• Minimum content Declaration of Conformity / techDoc

• New concepts: • Qualified Person • Relabelling/repackaging • Implant card

• Reprocessing - non-critical use

Parliament

• CTS: broad stakeholder input • In house exemption

• in Eudamed; summary clinical data

• Liability insurance • Importer: Regulatory verification

• New Concepts:

• QP can be lawyer; Only 3 yr exp.

• Reprocessing as basic requirements; list of unsuitable devices

Council

• CTS=>CS • In house exemption

• All facilities under 1 QMS

• AR: liable… • Importer: verify DoC, CE, AR • Distributor: verify DoC, CE

• New Concepts:

• QP (Regulatory Compliance Activities) always at disposal

• Implant card details

• Reprocessing: restriction or prohibition allowed

Common Specifications on safety, performance, clinical; supply chain increasing responsibility to verify compliance, support complaint & vigilance, Qualified person on Regulatory Compliance, Implant cards, Reprocessing SUD allowed under strict conditions


Chapter III – Identification, Traceability, Registration, Clinical Summary, EUDAMED

• Medical device nomenclature – free access • UDI: device identifier and production identifier defined • UDI on label and all higher packaging and on DoC • UDI basis for vigilance and reporting • UDI data in database before placing on the market • UDI on notified body certificate for IIb implants and III • Summary of safety and clinical performance defined



Chapter III – Identification, Traceability, Registration, Clinical Summary, EUDAMED

Commission

• Supply chain traceability (+/-1)

• UDI

• Manufacturer/AR, importers registered

• High risk: Summary on safety and performance data

• Public access to EUDAMED

Parliament

• UDI: single system; to be updated with PMCF data

• Safety and full clinical performance report + layman's summary

• EUDAMED: public access to vigilance and market surveillance data

Council

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

• UDI on NB certificates IIb implants and III

• Detailed requirements on summary

All transparency measures more or less agreed


Chapter IV – Notified Bodies

• Completely rewritten ANNEX VI • 35 pages with some challenges for NBs: • Independence and impartiality valid for global group structure to which NB belongs • Top level management and those responsible for assessment cannot use medical devices… ?? • Ex-consultants cannot work for companies and competitors they served for 3 years • Liability insurance to cover withdrawals, restrictions and suspensions • More defined authorizations and responsibilities for assessment staff includig clinical experts as part

of assessment and certification decisions • Define acceptable languages • Design examination removed; assessment of technical documentation (sampling all files) • Detailed change control, reviews before and after change • UAVs, screening safety data, action on vigilance, all changes reviewed on renewal, data from

registries part of review • NB numbers remain as is! • Closer supervision



Chapter IV – Notified Bodies

Commission

• Keep national supervision of national Notified Bodies

• Stricter and detailed requirements

• Joint assessments

• Right and duty on UAV and physical or laboratory tests on devices

• Rotation of staff

Parliament

• In house expertise (admin, technical, scientific, clinical)

• Public record on subcontractors • Annual subcontractor verification

• Immediate suspension clause

• 2-year designation instead of 3-year

• Penalty for non-compliance

• Special NBs under EMA

• Standard fees per country on NB

Council

• Authority peer review

• Detail on joint assessments

• Much detail on strict NB requirements

• Annual assessment, witness audits, dossier reviews

• Sharing report on assessment

NB system continued under stricter supervision and joint assessment; high risk device NB under tighter control; increased transparency; UAV integral part of law


Chapter V – Classification and Conformity Assessment

• Disputes resolved by authority of manufacturer, not of NB • CA scrutiny on clinical for new implantable class III devices • Report withdrawal of application to all NB when before issuing of certificates • NB may impose restrictions on certificates

• Classification highlights

• Injured skin defined • IVF/ART => ALL cells, tissues, organs => class III • Rule 4 includes mucous membrane on top of injured skin • ALL total and partial implants => III • Spinal disc replacement; implantable devices in contact with spinal column =>, except screws etc. • Rule 16 restricted to X-ray imaging being IIa; MRI, ultrasound and others removed • Rule 20 aphaeresis removed • Rule 21 substances: systemic absorption III, IIa on skin, rest IIb • Rule 22 medicine inhalation IIa unless life threatening conditions: Iib • Rule 23 intergrated or incorporated diagnostic function (closed loop system, AED, …) => III



Chapter V – Classification and Conformity Assessment

Commission

• Keeps four risk classes

• Reclassifications: • Aphaeresis machines => III • AIMD and accessories => III • Selected orthopaedic implants => III • Nano => III

• Tightening conformity assessment routes

• Expert Committee involved for initial reviews of high risk devices (scrutiny as exception)

Parliament

• Stakeholder involvement in further reclassifications

• Aphaeresis machines stay IIb • Deliberate nano => III

• UAV replace regular audits in

specific cases

• Special NB for high risk devices under EMA supervision replaces scrutiny

Council

• A few more class III • Aphaeresis machines stay IIb • Deliberate nano => III

• Revised scrutiny process

• Notified Body may restrict use of

device pending PMCF

Risk classification and free choice of conformity assessment route remain, increasing reclassifications to class III, even for active devices


Chapter VI – Clinical Evaluation, Clinical Investigation

• Clinical strategy review by the expert panel of commission • Clinical evaluation on device itself may include restricted equivalency

• For implants and class III, only equivalence with own products or with fully contracted partners • For implants and class III: update PMCF report and safety summary annually • Sponsor of clinical studies needs legal representative in EU • Clinical investigation documentation detailed precisely • Protection of dignity, protection of vulnerable patients, damage compensation • EUDAMED • Timelines to start defined for different scenarios in case on no reply • Joint assessments of clinical protocols defined • Modification and early ending defined, including corrective measures from member states • New system of coordinated approval and monitoring to be evaluated 5 years after start



Chapter VI – Clinical Evaluation, Clinical Investigation

Commission

• Detailing performance of clinical evaluation – premarket and PMCF

• Introducing Sponsor, aligned with pharma clinical trial regulation

• Further strengthening of ethical approvals

Parliament

• Always clinical trial for class II products; exemption for lower risk products endorsed by CA

• High risk: summary clinical evaluation updated annually

• Detailing ethical considerations

• Delegated Act to determine content of layman’s summary

Council

• Clinical evidence linked to the use of the device, not only intended purpose

• Clinical evaluation to include comparison with current clinical practice

• Class III need clinical studies; line extensions might be exempt where equivalence is demonstrated

• Annual summary update • Minimum requirements for

clinical study • Coordination multi-country trials

Class III always clinical studies, equivalence only for line extensions; alignment with clinical trial regulation; annual clinical summary update


Chapter VII – Vigilance and Market Surveillance

• PMS suitable to analyze data on quality, performance and safety • To update risk/benefit determination, clinical evaluation, summary of safety & clinical performance

• PMS plan required • Periodic safety update report defined, including volume of sales, population of

users, and frequency of use • Vigilance in line with new MEDDEV • Electronic systems on vigilance and on market surveillance, registers, coordinating

competent authority, trend reporting, updating technical documentation based on vigilance, hazard alert systems, references to EUDAMED removed

• Details on field safety notice removed • Annual surveillance plan from member states, including inspections and UAV at

economic operators; annual summary reports • Option for joint market surveillance actions



Chapter VII – Vigilance and Market Surveillance

Commission

• EU portal for vigilance communication

• Automatic forwarding to relevant countries’ CA

• Coordinating authority for occurrences in multiple countries

• Work- and expertise-sharing

• Enhanced and co-ordinated market surveillance

Parliament

• Any incident reported instead of serious incidents

• Immediate reporting on incident with custom made device

• Periodic safety update reports

• Empowerment of inspectors, unannounced inspections

• Market surveillance data shared with stakeholders

• Immediate actions required by member states

Council

• PMS plan part of QMS, active and systematic analysis of data on quality, performance and safety

• Actively updating documentation • Periodic safety update reports

• Report serious incident involving medical device

• Annual surveillance plans from authorities, including announced and unannounced facility visits

• Hazard alert system

Streamlining vigilance reporting; more reporting; more efficient reflections; more market surveillance with (unannounced) authority inspections; periodic safety update reports


Chapter VIII – Cooperation, MDCG, Reference Laboratories, Registers • Reference labs largely removed, only as option in specific cases • Detailing of expert panels

• Advisors of Commission, free of conflict of interest • Could be laboratories

• Tasks: • provide scientific, technical and clinical assistance to the Commission and MDCG

• contribute to the development and maintenance of appropriate guidance and common specifications

• develop and review best practices clinical evaluation guidance for the state of art performance of conformity assessment procedures with regard to clinical evaluation, physico-chemical characterisation, microbiological/biocompatibility, mechanical, electrical, electronic or non-clinical toxicological testing

• contribute to development of standards at international level, ensuring that these reflect the state of the art

• provide opinions in response to consultations by manufacturers, notified bodies and Member States

• contribute to identification of concerns and emerging issues on the safety and performance of medical devices; • Manufacturers and NB pay JRC for any work done



Chapter VIII – Cooperation, MDCG, Reference Laboratories, Registers

Commission

• Medical Device Coordination Group MDCG

• Formal yet unclear role of reference labs for specific hazards or technologies

• Encourage device registers

Parliament

• Medical Devices Advisory Committee (MDAC); experts to advise MDCG; initiated by Commission

Council

• MDCG may be extended to include experts to support members

• Medical device expert panels under MDCG

• MDCG to monitor technical progress and reflect on appropriateness of legislation; to support building CS; to support classification debates

• Reference laboratories removed, but allowed under MDCG where needed

MDCG and Expert Panels; Laboratories as part of Expert Panel where needed


Chapter IX – Confidentiality, Data Protection, Funding, Penalties

• Cost of joint audits fall to Commission • Recoverable costs to be later defined • More detail on confidentiality of data



Chapter IX – Confidentiality, Data Protection, Funding, Penalties

Commission

• Aligning confidentiality with existing EU law

• Aligning data protection with existing EU law

• Allowing Member States to raise fees; system to be defined later

• Allowing Member States to issue penalties; system to be defined later

Parliament

• Structure and level of fees publicly available

• Dissuasive nature of penalty relates to financial benefit obtained by infringement

Council

• Trade Secrets to be protected where possible

Basically all agree


Chapter X – Final Provisions

• UDI for now allowed under: • GSI AISBL • HIBCC • ICCBBA

• UDI applicable first for implantables and III (1 yr) • Then IIa and IIb (3 yr) • Then rest (5 yr)



Chapter X – Final Provisions

Commission

• Streamlined Committee procedure

• Details of Delegated Acts

• Amendments in other legal text

• Three years transition

• Further transition details

Parliament

• No critical changes, just updates in line with suggested amendments

Council

• Committee can veto implementing act by not delivering an opinion

• Expert consultation required in Delegated Act drafting

Basically all agree


IVD Regulation


On the IVDR

Commission

• Proposal for a Regulation of the European parliament and of the Council on in vitro medical devices

• http://ec.europa.eu/growth/sectors/ medical-devices

Parliament

• 2012/0267(COD) - 02/04/2014 Text adopted by Parliament, 1st reading/single reading

• EP adopted by 559 votes to 14, 92 abstentions

• http://www.europarl.europa.eu reference=2012/0267 COD

Council

• A consolidated draft for EPSCO 19 June 2015, available in some languages only

Foreseeable outcome – best guess of today

http://ec.europa.eu/growth/sectors/




IVDR

• Many elements copied in from Council version of MDR: definitions, economic operators, UDI, NB system and oversight, fee structures, joint audits, UAV, vigilance, EUDAMED, authorised representative role and liability, person responsible for regulatory compliance, technical documentation instead of design dossier review, restrictions in certification scope, etc.

• Companion diagnostics, defined, EMA consultation

• Clinical (performance) evidence; (clinical) performance evaluation needs pre-approval from Competent Authorities; public summary report. The definitions have been changed and do not align with the GHTF/ IMDRF

• PMCF structure called PMPF (performance follow-up)

• In house manufacturer exclusions largely remain in place but have to be justified and transparent

• 5 years transition



IVDR

• CTS fully replaced by CS

• Laboratory to focus on analytical sensitivity using reference materials

• Batch tests for class D; enlargement of class D group RHW1, selected genetic testing

• Self- test now class C, not B

• Sampling of technical files in class B and C, review similar to D >> NB requirement

• Sterile class A: involve notified body for sterile devices

• Scrutiny class D, AFTER CE marking!


eu medical device and ivd regulatory update - bsi group · joint audits under 920/2013 ec •...

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