EU Medical Device and IVD Regulatory Update

Transcription

1 0086 EU Medical Device and IVD Regulatory Update 0535 Sue Spencer Head of IVD NB BSI Group Kitemark Court, Davy Avenue, Knowlhill, Milton Keynes, MK5 8PP, UK Copyright 2015 BSI. All rights reserved. Hanauer Landstraße 115, Frankfurt, Germany

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 Copyright 2015 BSI. All rights reserved. 2

4 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 Copyright 2015 BSI. All rights reserved. 4

5 Impact of Immediate Actions Action Re-assessment of qualifications and scope of activities of NBs Impact 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 Copyright 2015 BSI. All rights reserved. 5

6 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 Copyright 2015 BSI. All rights reserved. 6

7 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 Joint Audits of NBs by Designating Authority, Commission (FVO) plus two other CAs Impact 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? Copyright 2015 BSI. All rights reserved. 7

8 Impact of Com. Recommendation (2013/473/EU) on audits and assessments performed by NBs Items to be verified by NB during an audit Requirements Annex I: Criteria for NBs performing design dossier and type examinations Impact 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 Copyright 2015 BSI. All rights reserved. 8

9 STEP CHANGE MDR / IVDR Clinical trials EU oversight Special NBs EUDAMED UDI Joint audits CoC audits UAV COEN - MS Electronic submission Industry in Spotlight and MORE. Copyright 2015 BSI. All rights reserved. 9

11 Elements of change new guidance being finalised MEDDEV 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 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 serious adverse event reporting Endorsed 28 May 2015 More in line with EN ISO New form in annex Copyright 2015 BSI. All rights reserved. 11

12 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,. Copyright 2015 BSI. All rights reserved. 12

13 Notified Body (NBs) re-accreditation (*) 82 NBs before 2010 for MD 75 NBs ( June 2014) 50 NBs (May 2015)? New EU implementing Regulation 920/ Number of NBs Proposed Regulations Projection? (* ) Courtesy R. Voelksen. RAPS President. November AHWP-AHC meeting, Korea Copyright 2015 BSI. All rights reserved. 13

16 Influencers and upcoming Trialogue discussions EU Commission Technical Workshop staff Political teams in Coreper Luxembourg Netherlands EU Parliament EU Council of Ministers Copyright 2015 BSI. All rights reserved. 16

19 MDR Timeline Realistic Expectations: Plan: 6 negotiation rounds and early adoption in 2 nd reading Greek Presidency Italian Presidency Council reaches agreement, (partial) general approach? Latvian Luxembourg Presidency Presidency Dutch Presidency Jan 2014 July 2014 Jan 2015 July 2015 Jan 2016 Parliament elections Parliament 1 st reading Rapporteurs appointed New Commissioners in place Begin trilogues? Entry into force? Conclude trilogues? Copyright 2015 BSI. All rights reserved. 19

20 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/ 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 reference=2012/0266 COD Council Consolidated draft for EPSCO 19 June pages with many alterations and additions Variety of snapshots on IVDR Foreseeable outcome best guess of today Copyright 2015 BSI. All rights reserved. 20

21 Chapter I - Scope and Definitions New views from Council 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 Copyright 2015 BSI. All rights reserved. 21

22 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, overarching borderline group Copyright 2015 BSI. All rights reserved. 22

23 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 New views from Council 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 Copyright 2015 BSI. All rights reserved. 23

24 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 Copyright 2015 BSI. All rights reserved. 24

25 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 New views from Council Copyright 2015 BSI. All rights reserved. 25

26 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 Copyright 2015 BSI. All rights reserved. 26

27 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 New views from Council 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 Copyright 2015 BSI. All rights reserved. 27

28 Chapter IV Notified Bodies Commission Parliament Council 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 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 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 Copyright 2015 BSI. All rights reserved. 28

29 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 New views from Council 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 Copyright 2015 BSI. All rights reserved. 29

30 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 Copyright 2015 BSI. All rights reserved. 30

31 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 New views from Council Copyright 2015 BSI. All rights reserved. 31

32 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 Copyright 2015 BSI. All rights reserved. 32

33 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 New views from Council 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 Copyright 2015 BSI. All rights reserved. 33

34 Chapter VII Vigilance and Market Surveillance Commission Parliament Council 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 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 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 Copyright 2015 BSI. All rights reserved. 34

35 Chapter VIII Cooperation, MDCG, Reference Laboratories, Registers New views from Council 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 Copyright 2015 BSI. All rights reserved. 35

36 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 Copyright 2015 BSI. All rights reserved. 36

37 Chapter IX Confidentiality, Data Protection, Funding, Penalties New views from Council Cost of joint audits fall to Commission Recoverable costs to be later defined More detail on confidentiality of data Copyright 2015 BSI. All rights reserved. 37

38 Chapter IX Confidentiality, Data Protection, Funding, Penalties Commission Aligning confidentiality with existing EU law Parliament Structure and level of fees publicly available Council Trade Secrets to be protected where possible Aligning data protection with existing EU law Allowing Member States to raise fees; system to be defined later Dissuasive nature of penalty relates to financial benefit obtained by infringement Allowing Member States to issue penalties; system to be defined later Basically all agree Copyright 2015 BSI. All rights reserved. 38

39 Chapter X Final Provisions UDI for now allowed under: GSI AISBL HIBCC ICCBBA New views from Council UDI applicable first for implantables and III (1 yr) Then IIa and IIb (3 yr) Then rest (5 yr) Copyright 2015 BSI. All rights reserved. 39

40 Chapter X Final Provisions Commission Streamlined Committee procedure Details of Delegated Acts Amendments in other legal text 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 Three years transition Further transition details Basically all agree Copyright 2015 BSI. All rights reserved. 40

42 On the IVDR Commission Proposal for a Regulation of the European parliament and of the Council on in vitro medical devices 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 Council A consolidated draft for EPSCO 19 June 2015, available in some languages only reference=2012/0267 COD Foreseeable outcome best guess of today Copyright 2015 BSI. All rights reserved. 42

43 IVDR New views from Council 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 Copyright 2015 BSI. All rights reserved. 43

44 IVDR CTS fully replaced by CS New views from Council 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! Copyright 2015 BSI. All rights reserved. 44

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